Symptoms and treatment of autoimmune hemolytic anemia. Is it possible to cure hypochromic hemolytic autoimmune anemia and its symptoms Signs of autoimmune hemolytic anemia

RCHD (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical Protocols of the Ministry of Health of the Republic of Kazakhstan - 2016

Other autoimmune hemolytic anemias (D59.1), Drug-induced autoimmune hemolytic anemia (D59.0)

Orphan diseases

general information

Short description

Approved
Joint Commission on the quality of medical services
Ministry of Health and Social Development of the Republic of Kazakhstan
dated September 15, 2016
Protocol #11

Autoimmune hemolytic anemias (AIHA)- a heterogeneous group of autoaggressive diseases and syndromes caused by the destruction of red blood cells, which is caused by the uncontrolled production of antibodies against one's own red blood cells.

Correlation between ICD-10 and ICD-9 codes:

Classification

Classification:
AIHA is divided into idiopathic (primary) and symptomatic (secondary). In more than 50% of patients, the development of AIHA is secondary (Table 1).
In 10% of cases of AIHA, various drugs are the cause of hemolysis. For a list of drugs that can cause the development of autoimmune hemolysis or lead to the detection of anti-erythrocyte antibodies, see Appendix 1.

The serological properties of autoantibodies formed the basis for the division of AIHA into four forms:
With incomplete thermal agglutinins (80% of all patients);
With complete cold agglutinins (12-15% of all cases);
with thermal hemolysins;
With two-phase cold hemolysins Donat-Landsteiner (extremely rare and, as a rule, a secondary form in syphilis and viral infections).

Table 1 - Frequency and types of antibodies in secondary AIHA

Diagnostics (outpatient clinic)

DIAGNOSIS AT OUTPATIENT LEVEL (LE - H)

Diagnostic criteria:

Complaints and anamnesis:
The main syndromes in hemolytic anemia are:
normocytic anemia with rapidly increasing weakness and poor adaptation to even a moderate decrease in hemoglobin.

Depending on the level of hemoglobin, 3 degrees of severity of anemia are distinguished:
I (mild degree) - Hb more than 90 g / l;
II (medium degree) - from 90 to 70 g / l;
III (severe degree) - less than 70 g / l.

Clinically, the severity of the patient's condition does not always correspond to the level of hemoglobin: acutely developed anemia is accompanied by much more pronounced symptoms than chronic, in which there is time for the adaptation of organs and tissues. Elderly patients tolerate anemia worse than younger ones, since the compensatory capabilities of the cardiovascular system are usually reduced in them.

In a hemolytic crisis, signs of severe anemia are pronounced against the background of an acute onset:
· fever;
· stomach ache;
· headache;
Vomiting
oliguria and anuria followed by the development of shock.

Hemolysis syndrome, which can be manifested by complaints of:
icterus of the skin and visible mucous membranes (jaundice);
darkening of the urine.
· With intravascular hemolysis, the color of urine can be from pink to almost black. The color depends on the concentration of hemoglobin, the degree of heme dissociation. The color of urine in hemoglobinuria must be distinguished from hematuria, when whole red blood cells are visible on microscopic examination. The color of urine can also be red due to taking medications (antipyrine), food (beets) or with porphyria, myoglobinuria, which develops under certain conditions (massive traumatic muscle injury, electric shock, arterial thrombosis, etc.).
The appearance of sensitivity to pressure, a feeling of heaviness or pain in the left hypochondrium associated with an enlarged spleen. More often degree of increase in a spleen has insignificant or moderate character.

In more than 50% of patients, the development of AIHA is secondary, and therefore the symptoms of the underlying disease may dominate in the clinical picture (Table 1).

Physical examination:
The results of a physical examination are determined by the rate and degree of hemolysis, the presence or absence of comorbidity, diseases that caused the development of AIHA. At the compensation stage, the condition is satisfactory, there may be slight subicteric skin, visible mucous membranes, slight splenomegaly, signs of the underlying disease, for example, SLE, lymphoproliferative disease, etc. In this situation, the presence of mild AIHA may not be diagnosed.

In a hemolytic crisis:
state of moderate or severe;
pallor of the skin and mucous membranes;
Expansion of the boundaries of the heart, deafness of tones, tachycardia, systolic murmur at the apex;
shortness of breath
· weakness;
· dizziness;
Bilirubin intoxication: icterus of the skin and mucous membranes, nausea, vomiting, abdominal pain, dizziness, headaches, fever, in some cases, disorders of consciousness, convulsions;
With intracellular hemolysis: hepatosplenomegaly;
With mixed and intravascular hemolysis: change in urine due to hemoglobinuria.

Laboratory research:
Complete blood count, including platelets and reticulocytes: normochromic anemia of varying severity; reticulocytosis, leukocytosis with a shift of the leukocyte formula to the left during the crisis; in a smear of peripheral blood, as a rule, microspherocytes;
· blood chemistry:
bilirubin with fractions (hyperbilirubinemia, indirect, non-conjugated fraction predominates),
LDH (an increase in serum LDH activity by 2-8 times, depending on the intensity of hemolysis),
haptoglobin - an indicator of hemolysis;
total protein, albumin, creatinine, urea, ALT, AST, GGTP, C-reactive protein, alkaline phosphatase - assessment of the state of the liver, kidneys
Glucose - exclusion of diabetes;
· direct Coombs' test in most cases is positive, but with massive hemolysis, as well as with cold and hemolysin forms of AIHA caused by IgA or IgM autoantibodies, it may be negative.


hemosiderin in the urine - the exclusion of intravascular hemolysis;
general urinalysis (a visual assessment of the color of urine is required);
Determination of copper in daily urine, ceruloplasmin in blood serum - exclusion of Wilson-Konovalov's disease;
puncture of the bone marrow (hyperplasia and morphology of the erythroid germ, the number and morphology of lymphocytes, complexes of metastatic cells);
trepanobiopsy (if necessary) - exclusion of secondary AIHA;
Immunophenotyping of lymphocytes (with lymphocytosis of peripheral blood and remote spleen) - exclusion of secondary AIHA;
Vitamin B12, folate - exclusion of megaloblastic anemia;
· Indicators of iron metabolism (including transferrin, serum and erythrocyte ferritin) - exclusion of iron deficiency;
· extended coagulogram + lupus anticoagulant - assessment of the state of hemostasis, exclusion of APS;
Rheumatological tests (antibodies to native DNA, rheumatoid factor, antinuclear factor, antibodies to cardiolipin antigen) - exclusion of secondary AIHA;

if necessary, thyroid hormones, prostate specific antigen, tumor markers; exclusion of secondary AIHA;
Determination of the blood group according to the AB0 system, Rh factor;
blood test for HIV - if necessary, transfusion;
a blood test for syphilis - a standard examination at any level;
determination of HBsAg in blood serum by ELISA - screening for hepatitis B;
determination of total antibodies to hepatitis C virus (HCV) in blood serum by ELISA - screening for hepatitis C.

Instrumental research:
x-ray of the lungs (if necessary, CT);
FGDS;

Ultrasound of the abdominal organs and intra-abdominal lymph nodes, small pelvis, prostate, thyroid gland.

Diagnostic algorithm (Scheme 1):

Diagnostics (ambulance)

DIAGNOSTICS AND TREATMENT AT THE EMERGENCY STAGE

Diagnostic measures:
collection of complaints, anamnesis;
physical examination.

Medical treatment: no.

Diagnostics (hospital)

DIAGNOSTICS AT THE STATIONARY LEVEL

Diagnostic criteria: see ambulatory level.

Diagnostic algorithm: see ambulatory level.

List of main diagnostic measures:
general blood test (calculation of leukoformula, platelets and reticulocytes in a smear);
biochemical blood test (total bilirubin, direct bilirubin, LDH);
direct Coombs test.

List of additional diagnostic measures:
determination of the level of haptoglobin;
blood type and Rh factor;
biochemical blood test (total protein, albumin, total bilirubin, direct bilirubin, creatinine, urea, ALaT, ASAT, glucose, LDH, GGTP, C-reactive protein, alkaline phosphatase);
iron metabolism (determination of the level of serum iron, the total iron-binding capacity of serum and the level of ferritin);
determination of the concentration of folic acid and vitamin B12;
Immunophenotyping of lymphocytes (with lymphocytosis, suspected lymphoproliferative disease, ineffectiveness of corticosteroid therapy);
Serum and urine protein electrophoresis with immunofixation (with lymphocytosis, suspected lymphoproliferative disease, failure of corticosteroid therapy);
myelogram;
ELISA for markers of viral hepatitis;
ELISA for HIV markers;
ELISA for markers of herpes group viruses;
coagulogram, lupus anticoagulant;
Reberg-Tareev test (glomerular filtration rate determination);
titer of cold agglutinins;
indirect Coombs test (required for intensive hemolysis and previous transfusions of erythrocytes);
determination of hemosiderin, copper and hemoglobin in urine;
trepanobiopsy of the bone marrow with histological examination;
vitamin B12, folate;
indicators of iron metabolism (including transferrin, serum and erythrocyte ferritin);
· coagulogram + lupus anticoagulant;
rheumatological tests (antibodies to native DNA, rheumatoid
factor, antinuclear factor, antibodies to cardiolipin antigen);
Serum immunoglobulins (G, A, M) + cryoglobulins;
thyroid hormones, prostate specific antigen, tumor markers;
· general urine analysis;
x-ray of the chest;
esophagogastroduodenoscopy;
irrigoscopy / sigmoidoscopy / colonoscopy;
Ultrasound of the abdominal organs and intra-abdominal lymph nodes, small pelvis, prostate, thyroid gland;
· Ultrasound of arteries and veins;
ECG;
echocardiography;
daily monitoring of blood pressure;
24-hour ECG monitoring.

Differential Diagnosis

Differential diagnosis and rationale for additional studies:

Treatment abroad

Get treatment in Korea, Israel, Germany, USA

Get advice on medical tourism

Treatment

Drugs (active substances) used in the treatment

Groups of drugs according to ATC used in the treatment

Treatment (ambulatory)

OUTPATIENT TREATMENT (EL - H)

Treatment tactics: only in the absence of indications for hospitalization: at the outpatient stage, treatment started in the hospital often continues, monitoring of clinical and laboratory parameters with further correction of therapy.

Non-drug treatment:
ModeII. With long-term therapy with corticosteroids, regular exercise, elimination of risk factors for accidental loss of balance, falls (C), smoking cessation. In AIHA with cold antibodies avoid hypothermia.
Diet: to prevent glucocorticoid osteoporosis, adequate intake of calcium and vitamin D, limiting alcohol consumption (D).

Medical treatment:

Prednisolone;

Rituximab concentrate for solution for infusion 100 mg;
· Cyclosporine;
amlodipine;
lisinopril;
atenolol;
· torasemide;
· folic acid;
alendronate;
risedronate;
zolendronate;
alfacalcidol;
· calcium carbonate;
paracetamol;
chlorpyramine;
omeprazole;
enoxaparin;
Nadroparin;
amoxicillin/clavulanic acid;
Levofloxacin;
a solution of sodium chloride.

AIHA therapy is currently not based solely on retrospective and few prospective studies in the absence of randomized trials and does not have a high level of evidence. There is also no formal consensus on the definition of complete or partial remission. Thus, the recommendations for the treatment of AIHA described below have a level of evidence of D.

First line therapy.
Glucocorticosteroids.
Glucocorticosteroids are the first line of therapy for AIHA patients with warm antibodies. Starting dose of prednisolone or metiprednisolone 1 mg/kg (orally or intravenously). Usually within 1-3 weeks of starting therapy (conducted in a hospital), the hematocrit level increases by more than 30% or the hemoglobin level is more than 100 g / l (there is no need to normalize the hemoglobin level). If the therapeutic goal is achieved, the dose of prednisolone is reduced to 20-30 mg per day for several weeks. If these goals are not achieved by the end of the 3rd week, then second-line therapy is connected. Dose reduction of prednisolone continues at the outpatient stage. A slow decrease in the dose of prednisolone is carried out if a therapeutic effect is achieved. Reduce the dose of prednisolone start at 5-10 mg for 2-3 days and continue until the daily dose reaches 20-30 mg. Further, the withdrawal of the drug is carried out much more slowly - 2.5 mg for 5-7 days. After reaching a dose below 10-15 mg, the rate of withdrawal should be further slowed down: 2.5 mg every 2 weeks in order to completely cancel the drug. This tactic involves the duration of taking prednisolone for 3-4 months. The level of hemoglobin, reticulocytes is monitored. If within 3-4 months, when taking prednisolone at a dose of 5 mg per day, remission persists, an attempt should be made to completely cancel the drug. The desire to quickly reduce the dose from the moment of normalization of hemoglobin due to the side effects of GC (cushingoid, steroid ulcers, arterial hypertension, acne with the formation of pustules on the skin, bacterial infections, diabetes mellitus, osteoporosis, venous thrombosis) always leads to a relapse of hemolysis. In fact, patients receiving low-dose corticosteroids for more than 6 months have a lower relapse rate and a longer duration of remission compared to patients who discontinue therapy before 6 months of therapy. Concomitant therapy in steroid treatment may include bisphosphonates, vitamin D, calcium, folic acid maintenance therapy. Blood glucose levels are monitored and diabetes is actively treated, as diabetes is a large risk factor for death due to infection. The risk of pulmonary embolism should be assessed, especially in patients with AIHA and lupus anticoagulant or AIHA recurrence after splenectomy 38.

Therapy of the 1st line of corticosteroids is effective in 70-85% of patients; however, most patients require maintenance therapy with corticosteroids to maintain hemoglobin levels within 90-100 g / l, in 50% a dose of 15 mg / day or less is sufficient, and approximately 20-30% of patients require higher doses of prednisone. It is believed that GCS monotherapy is effective in less than 20% of patients. In patients with resistance to first-line therapy, the possibility of secondary AIHA should be re-evaluated, since AIHA with warm agglutinins associated with malignant tumors, UC, ovarian teratoma, or IgM is often steroid-refractory.

Second line therapy.
Splenectomy.
Splenectomy increases the risk of severe infections associated with Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae. Patients are given polyvalent pneumococcal, meningococcal, Haemophilus influenzae type b capsular polysaccharide (PRP) tetanus toxoid (TT) conjugated vaccine 2 to 4 weeks prior to splenectomy. In patients who have received rituximab in the past 6 months, vaccination may not be effective. After surgery, thromboprophylaxis with low doses of low molecular weight heparins; gradual cancellation of GCS according to the scheme described above, pneumococcal vaccine every 5 years. Patients after splenectomy should be informed about the risk of infections and the need for any febrile episode to take antibiotics from the group of penicillins or respiratory fluoroquinolones (levofloxacin); they should also be informed about the risk of venous thromboembolism.

Rituximab.


refusal of splenectomy;
advanced age with a high risk of complications of the first and second lines of therapy
contraindications to splenectomy, high risk of venous thromboembolism.


active hepatitis B and C;

Standard mode - 375 mg/m2 on days 1, 8, 15 and 22. Patients on glucocorticoid therapy prior to initiation of rituximab therapy should continue glucocorticosteroids until the first signs of response to rituximab.

Efficiency b Rituximab at standard dose for AIHA with warm antibodies: overall response 83-87%, complete response 54-60, disease-free survival in 72% at 1 year and 56% at 2 years.
The response time varies from 1 month in 87.5% to 3 months in 12.5%. With a second course, the effectiveness of rituximab may be higher compared to the first course. The response to therapy is observed in mono mode or in combination with corticosteroids, immunosuppressants and interferon-α and does not depend on primary therapy.

Therapy toxicity: The drug has a good safety profile. Very rarely, usually after the first infusion, fever, chills, rash, or sore throat. More serious reactions include serum sickness and (very rarely) bronchospasm, anaphylactic shock, pulmonary embolism, retinal artery thrombosis, infections (episodes of infection in approximately 7%), and development of fulminant hepatitis due to reactivation of hepatitis B. In rare cases, progressive multifocal leukoencephalopathy.
Rituximab at a low dose (100 mg/week for 4 weeks) as first or second line therapy produces an overall response rate of 89% (complete response rate of 67%) and a relapse-free period of 36 months in 68%. Approximately 70% of patients treated with corticosteroids and rituximab had a remission of 36 months compared with 45% of patients who received steroids alone.

Immunosuppressive drugs.
The main factor in choosing an immunosuppressive drug should be patient safety, because the expected efficacy of all drugs is low and treatment may be more dangerous for the patient than treatment of the disease (Table 2). With long-term treatment, maintenance therapy can be carried out on an outpatient basis under the supervision of a specialist.

Table 2 - AIHA immunosuppressive therapy

Algorithm of actions in emergency situations:
if a hemolytic crisis is suspected (fever, pallor, yellowness of the skin, darkening of urine, splenomegaly, cardiovascular insufficiency, anemic shock, anemic coma) - call the ambulance team for emergency transportation of the patient to the hematology department or intensive care unit, depending on the severity of the condition;
monitoring of vital functions: the frequency and nature of breathing, the frequency and rhythm of the pulse, systolic and diastolic blood pressure, the amount and color of urine;
If there are signs of impaired vital functions (acute heart failure, signs of shock, renal failure) - emergency care: providing venous access, infusion of colloidal drugs, if intravascular hemolysis is suspected - prevention of renal failure (furosemide), oxygenation with oxygen.

· doctor's consultation on X-ray endovascular diagnostics and treatment - installation of a central venous catheter from a peripheral access (PICC);
consultation of a hepatologist - for the diagnosis and treatment of viral hepatitis;
consultation of a gynecologist - during pregnancy, metrorrhagia, menorrhagia, consultation when prescribing combined oral contraceptives;
consultation of a dermatovenereologist - in case of skin syndrome;
consultation of an infectious disease specialist - in case of suspected viral infections;
consultation with a cardiologist - in case of uncontrolled hypertension, chronic heart failure, cardiac arrhythmia and conduction disturbances;
consultation of a neuropathologist - in case of acute cerebrovascular accident, meningitis, encephalitis, neuroleukemia;
consultation of a neurosurgeon - in case of acute cerebrovascular accident, dislocation syndrome;
consultation of a nephrologist (efferentologist) - in case of renal insufficiency;
consultation of an oncologist - in case of suspicion of solid tumors;
consultation of an otorhinolaryngologist - for the diagnosis and treatment of inflammatory diseases of the paranasal sinuses and middle ear;
consultation of an ophthalmologist - in case of visual impairment, inflammatory diseases of the eye and appendages;
consultation of a proctologist - with anal fissure, paraproctitis;
consultation of a psychiatrist - in case of psychoses;
· consultation of a psychologist - in case of depression, anorexia, etc.;
consultation of a resuscitator - in the treatment of severe sepsis, septic shock, acute lung injury syndrome in differentiation syndrome and terminal conditions, installation of central venous catheters.
consultation of a rheumatologist - with SLE;
consultation of a thoracic surgeon - with exudative pleurisy, pneumothorax, zygomycosis of the lungs;
consultation of a transfusiologist - for the selection of transfusion media in case of a positive indirect antiglobulin test, transfusion failure, acute massive hemolysis;
consultation of a urologist - in case of infectious and inflammatory diseases of the urinary system;
consultation of a phthisiatrician - in case of suspected tuberculosis;
consultation of a surgeon - in case of surgical complications (infectious, hemorrhagic);
consultation of a maxillofacial surgeon - in case of infectious and inflammatory diseases of the dentoalveolar system.

Preventive actions:
In secondary AIHA, adequate treatment of the underlying disease;
· in case of AIHA with cold antibodies - avoid hypothermia.

Patient Monitoring:
To monitor the effectiveness of treatment in the outpatient card, the following are noted: the general condition of the patient, indicators of a general blood test, including reticulocytes and platelets, biochemical parameters - the level of bilirubin, LDH, enzyme immunoglobulin determination of the amount of immunoglobulins on the erythrocyte membrane, direct Coombs test.

Patient's individual follow-up card

Treatment (hospital)

TREATMENT AT THE STATIONARY LEVEL

Treatment tactics (UD-B): patients are hospitalized in the hematology department, in case of violation of vital functions - in the intensive care unit.

Non-drug treatment: diet taking into account comorbidity, regimen - II.

Medical treatment:

1st line of therapy.

Glucocorticosteroids.
Glucocorticosteroids are the first line of therapy for AIHA patients with warm antibodies. Corticosteroids, usually prednisolone, are given at a starting dose of 1 mg/kg per day (50–80 mg/day) for 1 to 3 weeks until hematocrit increases by more than 30% or hemoglobin increases by more than 100 g/L. If this goal is not achieved within 3 weeks, a second line of therapy should be started, since corticosteroid therapy is considered ineffective. Increasing the dose of prednisolone to 2 mg/kg/day (90–160 mg/day) does not improve treatment outcomes, leading to the rapid development of characteristic severe complications. If the therapeutic goal is achieved, the dose of prednisolone is reduced to 20-30 mg per day. Reduce the dose of prednisolone start at 5-10 mg for 2-3 days and continue until the daily dose reaches 20-30 mg. Further, the withdrawal of the drug is carried out much more slowly - 2.5 mg for 5-7 days. After reaching a dose below 10-15 mg, the rate of withdrawal should be further slowed down: 2.5 mg every 2 weeks in order to completely cancel the drug. This tactic involves the duration of taking prednisolone for 3-4 months. The level of hemoglobin, reticulocytes is monitored. If within 3-4 months, when taking prednisolone at a dose of 5 mg per day, remission persists, an attempt should be made to completely cancel the drug. The desire to quickly reduce the dose from the moment of normalization of hemoglobin due to the side effects of GC (cushingoid, steroid ulcers, arterial hypertension, acne with the formation of pustules on the skin, bacterial infections, diabetes mellitus, osteoporosis, venous thrombosis) always leads to a relapse of hemolysis. In fact, patients receiving low-dose corticosteroids for more than 6 months have a lower relapse rate and a longer duration of remission compared to patients who discontinue therapy before 6 months of therapy.
An alternative to the long-term use of corticosteroids (up to 3-4 months) are short courses (up to 3 weeks) of the course, followed by a transition to the second line of therapy.

All patients on steroid therapy should receive bisphosphonates, vitamin D, calcium, and folic acid maintenance therapy. Blood glucose levels are monitored and diabetes is actively treated, as diabetes is a large risk factor for death due to infection. The risk of pulmonary embolism should be assessed, especially in patients with AIHA and lupus anticoagulant or AIHA recurrence after splenectomy.
Patients with particularly rapid hemolysis and very severe anemia or complex cases (Evans syndrome) are treated with methylprednisolone at a dose of 100-200 mg/day for 10-14 days or 250-1000 mg/day for 1-3 days. Therapy with high doses of corticosteroids in the literature is presented mainly in the form of a description of clinical cases. 19.20

Therapy of the 1st line of corticosteroids is effective in 70-85% of patients; however, most patients require maintenance therapy with corticosteroids to maintain hemoglobin levels within 90-100 g / l, in 50% a dose of 15 mg / day or less is sufficient, and approximately 20-30% of patients require higher doses of prednisone. It is believed that GCS monotherapy is effective in less than 20% of patients. In patients with resistance to first-line therapy, the possibility of secondary AIHA should be re-evaluated, since AIHA with warm agglutinins associated with malignant tumors, UC, ovarian teratoma, or IgM is often steroid-refractory.

Second line therapy
When choosing second-line therapy, there are several options, and when choosing each of them, it is necessary to weigh the benefit / risk in each case (Fig. 2).

Splenectomy.
Splenectomy is generally considered to be the most effective and appropriate 2nd line therapy for warm antibody AIHA.

Indications for splenectomy:
Refractoriness or intolerance to corticosteroids;
The need for continuous maintenance therapy with prednisolone at a dose of more than 10 mg / day;
Frequent relapses.
The advantages of splenectomy are rather high efficiency with partial or complete remission achieved in 2/3 of patients (38-82%, taking into account secondary forms of AIHA, in which the response is less than in idiopathic AIHA), a significant number of patients remain in remission without requiring medical intervention. for 2 years or more; the possibility of recovery is approximately 20%.
After splenectomy, patients with persistent or recurrent hemolysis often require lower doses of corticosteroids than before splenectomy.

Disadvantages of splenectomy:
Lack of reliable predictors of splenectomy outcome;
The risk of surgical complications (TELA, intra-abdominal bleeding, abdominal abscess, hematoma) - 0.5-1.6% with laparoscopic splenectomy and 6% with conventional splenectomy);
· The risk of infection is 3.3-5% (the most dangerous is pneumococcal septicemia) with a mortality rate of up to 50%.
Splenectomy increases the risk of severe infections associated with Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae. Patients are given polyvalent pneumococcal, meningococcal, Haemophilus influenzae type b capsular polysaccharide (PRP) tetanus toxoid (TT) conjugated vaccine 2 to 4 weeks prior to splenectomy. In patients who have received rituximab in the past 6 months, vaccination may not be effective.

After surgery, thromboprophylaxis with low doses of low molecular weight heparins; gradual cancellation of GCS according to the scheme described above, pneumococcal vaccine every 5 years. Patients after splenectomy should be informed about the risk of infections and the need for any febrile episode to take antibiotics from the group of penicillins or respiratory fluoroquinolones (levofloxacin); they should also be informed about the risk of venous thromboembolism.

Figure 2. Algorithm for the treatment of steroid-refractoryWAIHA.

Rituximab.
Indications for the appointment of rituximab:
resistant forms of AIHA with an increasing number of various complications;
refusal of splenectomy;
advanced age with a high risk of complications of the first and second lines of therapy;
Contraindications to splenectomy (massive obesity, technical problems), high risk of venous thromboembolism.

Contraindications to the appointment of rituximab:
drug intolerance;
active hepatitis B and C;
acute viral or bacterial infection.

Treatment "Last option” (Despair Therapy)
High-dose cyclophosphamide (50 mg/kg/day for 4 days) accompanied by a colony-stimulating factor was effective in 5 of 8 patients with highly refractory warm antibody AIHA.
Alemtuzumab has shown efficacy in the treatment of small groups of patients with refractory AIHA, however, due to its high toxicity, it is considered as a “last resort” in the treatment of severe idiopathic AIHA, refractory to all previous therapy options.
Hematopoietic stem cell transplantation. Information on the use of HSCT in AIHA with warm antibodies is limited to single cases or small groups, mainly in Evans syndrome with a complete remission of approximately 60% in allogeneic and 50% in autologous BMT.

supportive therapy.
Patients with AIHA may often require packed red cell transfusions to maintain clinically acceptable hemoglobin levels, at least until specific therapy is effective. The decision to conduct a transfusion depends not only on the level of hemoglobin, but to a greater extent on the clinical status of the patient and comorbidity (especially coronary artery disease, severe lung disease), their exacerbation, the rate of development of anemia, the presence of hemoglobinuria or hemoglobinemia, and other manifestations of severe hemolysis. RBC transfusion should not be withheld in a critical clinical situation, even in cases where a lack of individual compatibility is found, since warm autoantibodies are often panreactive. Rh-compatible erythrocyte-containing components of the first blood group can be safely administered in emergency cases if alloantibodies (occur in 12-40% of patients with AIHA) are reasonably excluded on the basis of a previous transfusion history and/or obstetric history (women who have not had pregnancies and/or previous transfusions and men without a history of transfusions). In other patients, extended phenotyping is performed with the determination of Rh subgroups (C,c,E,e), Kell, Kidd, and S / s using monoclonal IgM antibodies and the selection of a compatible red blood cell mass for transfusion. In exceptional cases, thermal autoadsorption or allogeneic adsorption methods are used to determine alloantibodies. In any case, a biological test must be carried out.

The algorithm for the treatment of AIHA with warm antibodies is shown in Figure 3.
Figure 3. Algorithm for the treatment of AIHA with warm antibodies in adults




Treatment of secondary AIHA.
AIHA with warm antibodies in SLE.
The preferred first-line therapy is steroids, the order of administration is similar to that of primary AIHA (Table 3).

Table 3 - Treatment of secondary AIHA

Hospitalization

Information

Sources and literature

1. Minutes of the meetings of the Joint Commission on the quality of medical services of the MHSD RK, 2016
   1. 1) Clinical guidelines for the diagnosis and treatment of autoimmune hemolytic anemia / ed. V.G. Savchenko, 2014.-26 p. 2) Hill Q., Stamps R., Massey E. et al. Guidelines on the management of drug-induced immune and secondary autoimmune, haemolytic anaemia, 2012. 3) Lechner K, Jager U. How I treat autoimmune hemolytic anemias in adults. Blood. 2010;16:1831–8. 4) Dussadee K, Taka O, Thedsawad A, Wanachiwanawin W. Incidence and risk factors of relapses in idiopathic autoimmune hemolytic anemia. J Med Associate Thai. 2010;93(Suppl 1):S165–S170. 5) Lechner K, Jager U. How I treat autoimmune hemolytic anemias in adults. Blood. 2010;16:1831–8. 6) Dierickx D, Verhoef G, Van Hoof A, Mineur P, Roest A, Triffet A, et al. Rituximab in autoimmune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study. J Intern Med. 2009;266:484–91. 7) Maung SW, Leahy M, O'Leary HM, Khan I, Cahill MR, Gilligan O, et al. A multi-center retrospective study of rituximab use in the treatment of relapsed or resistant warm hemolytic anemia. Br J Haematol. 2013;163:118–22. 8) Narat S, Gandla J, Hoffbrand AV, Hughes RG, Mehta AB. Rituximab in the treatment of refractory autoimmune cytopenias in adults. haematologica. 2005;90:1273–4. 9) Zanella A. et al. Treatment Of Autoimmune Hemolytic Anemias, Haematologica October 2014 99: 1547-1554. 10) Peñalver FJ, Alvarez-Larrán A, Díez-Martin JL, Gallur L, Jarque I, Caballero D, et al. Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia. Ann Hematol. 2010;89:1073–80. 11) O'Connell N, Goodyer M, Gleeson M, Storey L, Williams M, Cotter M, et al. Successful treatment with rituximab and mycophenolate mofetil of refractory autoimmune hemolytic anemia post-hematopoietic stem cell transplant for dyskeratosis congenita due to TINF2 mutation. Pediatric Transplant. 2014;18(1):E22–24. 12) Dussadee K, Taka O, Thedsawad A, Wanachiwanawin W. . Incidence and risk factors of relapses in idiopathic autoimmune hemolytic anemia. J Med Associate Thai. 2010;93(Suppl 1):S165–S170. 13) Lechner K, Jager U. How I treat autoimmune hemolytic anemias in adults. Blood. 2010;16:1831–8. 14) Murphy S, LoBuglio AF. Drug therapy of autoimmune hemolytic anemia. Semin Hematol. 1976; 15) Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol. 2002;69(4):258-271. 16) Akpek G, McAneny D, 3. Weintraub L. Akpek G, McAneny D, Weintraub L Comparative response to splenectomy in Coombs-positive auto-immune hemolytic anemia with or without associated disease. Am J Hematol. 1999;61:98–102. 17) Casaccia M, Torelli P, Squarcia S, Sormani MP, Savelli A, Troilo BM, et al. Laparoscopic splenectomy for hematologic diseases: a preliminary analysis performed on the Italian Registry of Laparoscopic Surgery of the Spleen (IRLSS). Surg Endosc. 2006;20:1214–20. 18) Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among post-splenectomy patients. J Infect. 2001;43:182–6. 19) Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect. 2001;7:657–60. 20) Borthakur G, O'Brien S, Wierda WG, et al. Immune anemias in patients with chronic lympho-cytic leukaemia treated with fludarabine, cyclo-phosphamide and rituximab–incidence and predictors. Br J Haematol. 2007;136(6):800-805. 21) Chiao EY, Engels EA, Kramer JR, et al. Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120,908 US vet-erans with hepatitis C virus infection. Arch Intern. Med. 2009;169(4):357-363.

Information

ABBREVIATIONS USED IN THE PROTOCOL:

Attached files

Attention!

• By self-medicating, you can cause irreparable harm to your health.
• The information posted on the MedElement website and in the mobile applications "MedElement (MedElement)", "Lekar Pro", "Dariger Pro", "Diseases: a therapist's guide" cannot and should not replace an in-person consultation with a doctor. Be sure to contact medical facilities if you have any diseases or symptoms that bother you.
• The choice of drugs and their dosage should be discussed with a specialist. Only a doctor can prescribe the right medicine and its dosage, taking into account the disease and the condition of the patient's body.
• The MedElement website and mobile applications "MedElement (MedElement)", "Lekar Pro", "Dariger Pro", "Diseases: Therapist's Handbook" are exclusively information and reference resources. The information posted on this site should not be used to arbitrarily change the doctor's prescriptions.
• The editors of MedElement are not responsible for any damage to health or material damage resulting from the use of this site.

- pathology of erythrocytes, the hallmark of which is the accelerated destruction of red blood cells with the release of an increased amount of indirect bilirubin. For this group of diseases, a combination of anemic syndrome, jaundice and an increase in the size of the spleen is typical. In the process of diagnosis, a general blood test, bilirubin level, feces and urine analysis, ultrasound of the abdominal organs are examined; a bone marrow biopsy, immunological studies are performed. As methods of treatment, drug, blood transfusion therapy is used; with hypersplenism, splenectomy is indicated.

ICD-10

D59 D58

General information

Hemolytic anemia (HA) is anemia caused by a violation of the life cycle of erythrocytes, namely, the predominance of the processes of their destruction (erythrocytolysis) over formation and maturation (erythropoiesis). This group of anemias is very extensive. Their prevalence is not the same in different geographical latitudes and age cohorts; on average, pathology occurs in 1% of the population. Among other types of anemia, hemolytic ones account for 11%. Pathology is characterized by a shortening of the life cycle of erythrocytes and their decay (hemolysis) ahead of time (after 14-21 days instead of 100-120 days normally). In this case, the destruction of red blood cells can occur directly in the vascular bed (intravascular hemolysis) or in the spleen, liver, bone marrow (extravascular hemolysis).

The reasons

The etiopathogenetic basis of hereditary hemolytic syndromes is genetic defects in erythrocyte membranes, their enzyme systems, or hemoglobin structure. These prerequisites determine the morphofunctional inferiority of erythrocytes and their increased destruction. Hemolysis of erythrocytes in acquired anemia occurs under the influence of internal or environmental factors, including:

• Autoimmune processes. The formation of antibodies that agglutinate red blood cells is possible with hemoblastoses (acute leukemia, chronic lymphocytic leukemia, lymphogranulomatosis), autoimmune pathology (SLE, nonspecific ulcerative colitis), infectious diseases (infectious mononucleosis, toxoplasmosis, syphilis, viral pneumonia). The development of immune hemolytic anemia can be promoted by post-transfusion reactions, preventive vaccination, hemolytic disease of the fetus.
• Toxic effect on erythrocytes. In some cases, acute intravascular hemolysis is preceded by poisoning with arsenic compounds, heavy metals, acetic acid, fungal poisons, alcohol, etc. Certain drugs (antimalarial drugs, sulfonamides, nitrofuran derivatives, analgesics) can cause destruction of blood cells.
• Mechanical damage to erythrocytes. Hemolysis of erythrocytes can be observed during heavy physical exertion (long walking, running, skiing), with DIC, malaria, malignant arterial hypertension, prosthetic heart valves and blood vessels, hyperbaric oxygen therapy, sepsis, extensive burns. In these cases, under the influence of certain factors, traumatization and rupture of the membranes of initially full-fledged erythrocytes occur.

Pathogenesis

The central link in the pathogenesis of GA is the increased destruction of erythrocytes in the organs of the reticuloendothelial system (spleen, liver, bone marrow, lymph nodes) or directly in the vascular bed. With the autoimmune mechanism of anemia, the formation of anti-erythrocyte antibodies (heat, cold) occurs, which cause enzymatic lysis of the erythrocyte membrane. Toxic substances, being the strongest oxidizing agents, destroy the erythrocyte due to the development of metabolic, functional and morphological changes in the membrane and stroma of red blood cells. Mechanical factors have a direct effect on the cell membrane. Under the influence of these mechanisms, potassium and phosphorus ions leave the erythrocytes, and sodium ions enter inside. The cell swells, with a critical increase in its volume, hemolysis occurs. The breakdown of erythrocytes is accompanied by the development of anemic and icteric syndromes (the so-called "pale jaundice"). Perhaps intense staining of feces and urine, enlargement of the spleen and liver.

Classification

In hematology, hemolytic anemias are divided into two large groups: congenital (hereditary) and acquired. Hereditary GA includes the following forms:

• erythrocyte membranopathies(- Minkowski-Choffard disease, ovalocytosis, acanthocytosis) - anemia, due to structural abnormalities of erythrocyte membranes
• fermentopenia(enzymopenia) - anemia caused by a deficiency of certain enzymes (glucose-6-phosphate dehydrogenase, pyruvate kinase, etc.)
• hemoglobinopathies- anemia associated with qualitative disturbances in the structure of hemoglobin or a change in the ratio of its normal forms (thalassemia, sickle cell anemia).

Acquired GAs are divided into:

• acquired membranopathies(paroxysmal nocturnal hemoglobinuria - Marchiafava-Mikeli b-b, spur cell anemia)
• immune (auto- and isoimmune)- due to exposure to antibodies
• toxic- anemia due to exposure to chemicals, biological poisons, bacterial toxins
• mechanical- anemia caused by mechanical damage to the structure of red blood cells (thrombocytopenic purpura, marching hemoglobinuria)

Symptoms

Hereditary membranopathies, fermentopenias and hemoglobinopathies

The most common form of this group of anemias is microspherocytosis, or Minkowski-Choffard disease. Inherited in an autosomal dominant manner; usually seen in several members of the family. The defectiveness of erythrocytes is due to a deficiency in the membrane of actomyosin-like protein and lipids, which leads to a change in the shape and diameter of erythrocytes, their massive and premature hemolysis in the spleen. Manifestation of microspherocytic GA is possible at any age (in infancy, adolescence, old age), but usually manifestations occur in older children and adolescents. The severity of the disease varies from subclinical to severe forms characterized by frequently recurring hemolytic crises. At the time of the crisis, body temperature rises, dizziness, weakness; abdominal pain and vomiting occur.

The main symptom of microspherocytic hemolytic anemia is jaundice of varying degrees of intensity. Due to the high content of stercobilin, the feces become intensely colored in a dark brown color. In patients with Minkowski-Choffard disease, there is a tendency to form stones in the gallbladder, therefore, signs of exacerbation of calculous cholecystitis often develop, attacks of biliary colic occur, and obstructive jaundice occurs when the choledochus is blocked by a calculus. With microspherocytosis, the spleen is enlarged in all cases, and in half of the patients, the liver is also enlarged. In addition to hereditary microspherocytic anemia, other congenital dysplasias often occur in children: tower skull, strabismus, saddle nose deformity, malocclusion, gothic palate, polydactyly or bradydactyly, etc. Middle-aged and elderly patients suffer from trophic leg ulcers that occur as a result of red blood cell hemolysis in the capillaries of the extremities and are difficult to treat.

Enzymopenic anemias are associated with a lack of certain erythrocyte enzymes (more often - G-6-PD, glutathione-dependent enzymes, pyruvate kinase, etc.). Hemolytic anemia may first manifest itself after an intercurrent illness or medication (salicylates, sulfonamides, nitrofurans). Usually the disease has a smooth course; typical "pale jaundice", moderate hepatosplenomegaly, heart murmurs. In severe cases, a pronounced picture of a hemolytic crisis develops (weakness, vomiting, shortness of breath, palpitations, collaptoid state). In connection with intravascular hemolysis of erythrocytes and the release of hemosiderin in the urine, the latter acquires a dark (sometimes black) color. Peculiarities of the clinical course of hemoglobinopathies - thalassemia and sickle cell anemia are the subject of independent reviews.

Acquired hemolytic anemia

Among the various acquired variants, autoimmune anemias are more common than others. For them, the common starting factor is the formation of antibodies to the antigens of their own erythrocytes. Hemolysis of erythrocytes can be both intravascular and intracellular. Hemolytic crisis in autoimmune anemia develops acutely and suddenly. It proceeds with fever, severe weakness, dizziness, palpitations, shortness of breath, pain in the epigastrium and lower back. Sometimes acute manifestations are preceded by precursors in the form of subfebrile condition and arthralgia. During the crisis, jaundice is rapidly increasing, not accompanied by skin itching, the liver and spleen are enlarged. In some forms of autoimmune anemia, patients do not tolerate cold well; at low temperatures, they may develop Raynaud's syndrome, urticaria, hemoglobinuria. Due to circulatory failure in small vessels, complications are possible in the form of gangrene of the toes and hands.

Toxic anemia occurs with progressive weakness, pain in the right hypochondrium and lumbar region, vomiting, hemoglobinuria, high body temperature. From 2-3 days jaundice and bilirubinemia join; on the 3-5th day, hepatic and renal failure occurs, the signs of which are hepatomegaly, fermentemia, azotemia, anuria. Separate types of acquired hemolytic anemia are discussed in the relevant articles: "Hemoglobinuria" and "Thrombocytopenic purpura", "Hemolytic disease of the fetus".

Complications

Each type of HA has its own specific complications: for example, cholelithiasis - with microspherocytosis, liver failure - with toxic forms, etc. Common complications include hemolytic crises, which can be triggered by infections, stress, childbirth in women. In acute massive hemolysis, the development of a hemolytic coma is possible, characterized by collapse, confusion, oliguria, and increased jaundice. The patient's life is threatened by DIC, spleen infarction, or spontaneous organ rupture. Emergency medical care requires acute cardiovascular and renal failure.

Diagnostics

Determining the form of GA based on an analysis of the causes, symptoms and objective data is within the competence of a hematologist. During the initial conversation, the family history, frequency and severity of the course of hemolytic crises are clarified. During the examination, the color of the skin, sclera and visible mucous membranes is evaluated, the abdomen is palpated to assess the size of the liver and spleen. Spleno- and hepatomegaly is confirmed by ultrasound of the liver and spleen. Laboratory diagnostic complex includes:

• Blood test. Changes in the hemogram are characterized by normo- or hypochromic anemia, leukopenia, thrombocytopenia, reticulocytosis, and accelerated ESR. In biochemical blood samples, hyperbilirubinemia is determined (an increase in the fraction of indirect bilirubin), an increase in the activity of lactate dehydrogenase. In autoimmune anemia, a positive Coombs test is of great diagnostic value.
• Urine and stool tests. Urinalysis reveals proteinuria, urobilinuria, hemosiderinuria, hemoglobinuria. The content of stercobilin was increased in the coprogram.
• Myelogram. For cytological confirmation, a sternal puncture is performed. Examination of bone marrow punctate reveals hyperplasia of the erythroid germ.

In the process of differential diagnosis, hepatitis, cirrhosis of the liver, portal hypertension, hepatolienal syndrome, porphyria, hemoblastoses are excluded. The patient is consulted by a gastroenterologist, clinical pharmacologist, infectious disease specialist and other specialists.

Treatment

Different forms of GA have their own characteristics and approaches to treatment. With all variants of acquired hemolytic anemia, care must be taken to eliminate the influence of hemolytic factors. During hemolytic crises, patients need infusions of solutions, blood plasma; vitamin therapy, if necessary - hormone and antibiotic therapy. With microspherocytosis, the only effective method leading to a 100% cessation of hemolysis is splenectomy.

In autoimmune anemia, therapy with glucocorticoid hormones (prednisolone) is indicated, which reduces or stops hemolysis. In some cases, the desired effect is achieved by the appointment of immunosuppressants (azathioprine, 6-mercaptopurine, chlorambucil), antimalarial drugs (chloroquine). In drug-resistant forms of autoimmune anemia, splenectomy is performed. Treatment of hemoglobinuria involves the transfusion of washed red blood cells, plasma substitutes, the appointment of anticoagulants and antiplatelet agents. The development of toxic hemolytic anemia dictates the need for intensive therapy: detoxification, forced diuresis, hemodialysis, according to indications - the introduction of antidotes.

Forecast and prevention

The course and outcome depend on the type of anemia, the severity of the course of crises, the completeness of pathogenetic therapy. With many acquired variants, the elimination of the causes and the full treatment leads to a complete recovery. Congenital anemia cannot be cured, but long-term remission is possible. With the development of renal failure and other fatal complications, the prognosis is unfavorable. To prevent the development of GA allows the prevention of acute infectious diseases, intoxication, poisoning. Uncontrolled independent use of drugs is prohibited. Careful preparation of patients for blood transfusions, vaccination with the entire complex of necessary examinations is necessary.

Separate idiopathic autoimmune anemia and secondary autoimmune anemia.
Secondary autoimmune hemolytic anemias develop against the background of the following diseases: rheumatoid arthritis, scleroderma, Sjögren's syndrome, lymphoproliferative diseases, other malignant diseases, fungal infections, thymomas, ulcerative colitis, B12-deficiency anemia, Kawasaki disease, primary biliary cirrhosis of the liver.

In the absence of reasons for autoimmune hemolytic anemia, idiopathic AIHA is verified.

AIHA is a hemolytic anemia that occurs as a result of a change in the function of the body's immune system, as a result of which antigens of erythrocytes are produced against their own unchanged antigens.

Etiology.
The causes of AIHA, like many other autoimmune diseases, are not clear. The influence of some trigger agent (possibly a virus or a microorganism) is discussed, as a result of which there is a breakdown of immunological tolerance to one's own antigen.

Pathogenesis.
The nature of the pathogenetic mechanisms in AIHA depends mainly on the nature of AT produced against their own unchanged erythrocyte antigens.
Loaded with antibodies (agglutinins or precipitins), erythrocytes are destroyed in the spleen, liver and bone marrow, hemolysis is carried out according to the intracellular type.
AT of the hemolysin class, when fixed on the surface of the erythrocyte, cause cell death inside the vessel.
The manifestations of the disease will be primarily determined by the mechanism of destruction of red blood cells - intracellular or intravascular.

Classification AT: according to the mechanism of action (agglutinins, hemolysins, precipitins); according to the temperature optimum of activity (thermal, cold); by serological characteristics (complete, incomplete).

clinical picture.
The most common variant is AIHA due to incomplete heat agglutinins (anemia with intracellular death of erythrocytes).
Complaints are caused by the development of tissue hypoxia (severe weakness, drowsiness, fainting, shortness of breath, palpitations).
Subfebrile or febrile body temperature is often noted.
Some patients, especially the elderly, may develop anemic precoma and coma.

Patients with heart disease are at high risk of acute left ventricular failure.
On examination: sharp pallor of the skin and visible mucous membranes. The formation of a large amount of indirect bilirubin from Hb decaying erythrocytes leads to the development of jaundice.
In 2/3 of patients, an increase in the spleen is detected, and in more than half of the patients - the liver.

In AIHA caused by the formation of the AT class of hemolysins (anemia with intravascular death of erythrocytes), patients complain of pain in the lumbar region, fever, black urine, and complaints associated with a decrease in the content of Hb (anemic syndrome).

The skin and visible mucous membranes are pale.
Enlargement of the spleen is rare, and its size is small. Diagnostics.
The combination of anemic syndrome, jaundice of the skin and/or mucous membranes, and an enlarged spleen should lead the clinician to suspect AIHA with an intracellular mechanism of RBC destruction in the first place.

Such an assumption requires an immediate study of peripheral blood with the obligatory determination of the number of reticulocytes.
There is a significant decrease in the content of erythrocytes and Hb in the blood. The color index is close to one, RBC RMS is in the range of 80-95 fl (normocytosis).
The content of reticulocytes is significantly increased.
In severe cases, normoblasts may appear in the peripheral blood.
The number of leukocytes and platelets is within the normal range. The leukocyte formula is not changed, although leukemoid reactions of the neutrophilic type can also be observed.
ESR is significantly increased. In the study of urine, the appearance of urobilin can be recorded.

Feces in patients with AIHA with an intracellular mechanism of destruction of erythrocytes acquire a darker color compared to the usual one.

To verify the diagnosis AIHA with an intracellular mechanism of erythrocyte destruction uses a test that determines the presence of AT on the surface of erythrocytes - a positive direct Coombs test (Coombs test: rabbit antiglobulin serum obtained by sensitization with human γ-globulin is added to the studied erythrocytes.
Serum does not cause agglutination of normal washed erythrocytes, but when antiglobulin serum is added to erythrocytes containing incomplete AT on their surface, protein molecules become larger and erythrocytes agglutinate).
A more sensitive test is aggregation hemagglutination reactions.
If a patient has black urine, pain in the lumbar region, and anemic complaints, it is necessary to assume the presence of AIHA with an intravascular variant of erythrocyte destruction.

This assumption is strengthened when normochromic (normocytic) anemia is detected with an increase in the number of reticulocytes.
In the study of urine, free hemoglobin is detected, and in the study of the urinary sediment, an increase in the number of epithelial cells of the renal tubules with inclusions of hemosiderin is noted.
Pathomorphology of the bone marrow: hyperplasia of the red germ of hematopoiesis of varying severity.
In severe hemolytic crises, the bone marrow is able to increase the production of red blood cells by 6-8 times.

Differential diagnosis.
AIHA with an intracellular mechanism of erythrocyte destruction must be differentiated from other anemic conditions accompanied by an increase in the number of reticulocytes: posthemorrhagic anemia; IDA against the background of iron therapy; B12DA against the background of vitamin B12 therapy; FDA during folic acid therapy.

To distinguish between these conditions, a careful study of the anamnesis and analysis of the available documentary data on the course of the disease is of great importance. An important help is the Coombs test, AIHA with intravascular destruction of erythrocytes must be differentiated from PNH (negative sucrose test and Hem's test in AIHA and positive in PNH).

Treatment.
AIHA requires immediate treatment.
First-line drugs - GCS - oral prednisolone at a dose of 1-2 mg / kg of body weight per day.
Signs of the effectiveness of treatment are the cessation of the fall of Hb, a decrease in reticulocytosis, normalization of body temperature, and improvement in the patient's well-being.

Hemoglobin begins to rise on the 3-4th day from the start of treatment.
After the normalization of peripheral blood parameters, the dose of prednisolone begins to be slowly reduced until it is completely canceled.
The recommended dose of prednisolone for patients over 70 years of age with signs of osteoporosis is 0.6 mg/kg body weight/day.
If, for some reason, the patient cannot receive GCS orally, then with parenteral administration, their dose must be increased.
If prednisolone is administered intramuscularly, its dose should be doubled, and when administered intravenously, three times compared with the oral dose.

It should also be borne in mind that when administered parenterally, prednisolone has a short-term effect.
The use of corticosteroid therapy allows you to get a lasting effect in half of the patients.
In the rest, treatment with prednisolone gives a temporary effect; dose reduction or complete withdrawal of the drug leads to the development of a relapse of the disease.

Such patients require a constant maintenance dose of prednisolone or repeated courses of therapy.

Splenectomy as a second line of therapy is indicated in the following cases:
1) lack of effect on prednisolone;
2) dependence on prednisolone at a dose of 20 mg/day or more;
3) early relapse after discontinuation of prednisolone.

In AIHA with intravascular RBC death, the effect of splenectomy is less and may be delayed.

The therapeutic effect in this case is associated with the exclusion of the spleen from the process of AT synthesis.

For patients older than 70 years and children, splenectomy is not a second-line therapy due to the high risk of developing immunodeficiency and infectious complications.

Third line therapy.
In case of ineffectiveness of splenectomy, immunosuppressants are prescribed.
In recent years, a good effect has been obtained in the treatment of AITA with cyclosporine A (sandimmune).
Initial dose of 2.5 mg/kg x 2 times a day for 6 days, followed by a decrease in the dose of cyclosporine to 3 mg/kg day and the addition of 5 mg/day of prednisolone.

The use of cyclosporine A makes it possible to obtain long-term and stable remissions of the disease.

Mycophenolate has also shown to be effective in the treatment of AIHA.
Rituximab (MabThera) 375 mg/m2 once a week for 4 weeks. Some researchers show 100% response.

Imuran (azathiolrin - 1.5 mg / kg / day for 3 months) or small doses of cyclophosphamide (2 mg / kg / day x 3 months). The response is observed in 50% of patients.

High doses of cyclophosphamide (50 mg/kg daily x 4 days) induced prolonged remissions (15 months) in 66% of patients.

Forecast.
With adequate therapeutic tactics of management, the prognosis in patients with AIHA is favorable.

Prevention. There is no effective prevention of AIHA.

Online Tests

• Drug addiction test (questions: 12)

  Whether it's prescription drugs, illegal drugs, or over the counter drugs, once you become addicted, your life begins to spiral downhill and you drag those who love you with you...

What is Autoimmune Hemolytic Anemia -

Entitled hemolytic anemia unites a group of acquired and hereditary diseases characterized by increased intracellular or intravascular destruction of red blood cells.

Autoimmune hemolytic anemias include forms of the disease associated with the formation of antibodies to self-antigens of erythrocytes.

In the general group of hemolytic anemias, autoimmune hemolytic anemias are more common. Their frequency is 1 case per 75,000-80,000 population.

What provokes / Causes of Autoimmune hemolytic anemia:

Immune hemolytic anemia can occur under the influence of anti-erythrocyte iso- and autoantibodies and, accordingly, are divided into isoimmune and autoimmune.

Isoimmune include hemolytic anemia of newborns, due to incompatibility in the ABO and Rh systems between the mother and fetus, post-transfusion hemolytic anemia.

With autoimmune hemolytic anemia, there is a breakdown of immunological tolerance to unchanged antigens of one's own erythrocytes, sometimes to antigens that have determinants similar to erythrocytes. Antibodies to such antigens are able to interact with unchanged antigens of their own erythrocytes. Incomplete heat agglutinins are the most common type of antibody that can cause the development of autoimmune hemolytic anemia. These antibodies belong to IgG, rarely - to IgM, IgA.

Immune hemolytic anemias are divided into isoimmune and autoimmune. The serological principle of differentiation of autoimmune hemolytic anemia makes it possible to distinguish forms caused by incomplete thermal agglutinins, thermal hemolysins, cold agglutinins, biphasic cold hemolysins (Donat-Landsteiner type) and erythroopsonins. Some authors distinguish a form of hemolytic anemia with antibodies against the antigen of bone marrow normoblasts.

According to the clinical course, acute and chronic variants are distinguished.

There are symptomatic and idiopathic autoimmune hemolytic anemias. Symptomatic autoimmune anemia occurs against the background of various diseases accompanied by disorders in the immunocompetent system. Most often they occur in chronic lymphocytic leukemia, lymphogranulomatosis, acute leukemia, systemic lupus erythematosus, rheumatoid arthritis, chronic hepatitis and liver cirrhosis. In cases where the appearance of autoantibodies cannot be associated with any pathological process, they speak of idiopathic autoimmune hemolytic anemia, which accounts for about 50% of all autoimmune anemias.

The formation of autoantibodies occurs as a result of a violation in the system of immunocompetent cells that perceive the erythrocyte antigen as foreign and begin to produce antibodies to it. After fixation of autoantibodies on erythrocytes, the latter are captured by cells of the reticulohistiocytic system, where they undergo agglutination and decay. Hemolysis of erythrocytes occurs mainly in the spleen, liver, and bone marrow. Autoantibodies to erythrocytes belong to different types.

According to the serological principle, autoimmune hemolytic anemias are divided into several forms:
- anemia with incomplete heat agglutinins
- anemia with thermal hemolysins
- anemia with complete cold agglutinins
- anemia with biphasic hemolysins
- anemia with agglutinins against bone marrow normoblasts

Each of these forms has some features in the clinical picture, course and serological diagnosis. The most common anemia with incomplete thermal agglutinins, accounting for 70 - 80% of all autoimmune hemolytic anemia.

Pathogenesis (what happens?) during Autoimmune hemolytic anemia:

The essence of autoimmune processes is that as a result of the weakening of the T-suppressor system of immunity, which controls autoaggression, the B-system of immunity is activated, synthesizing antibodies against unchanged antigens of various organs. T-lymphocytes-killers also take part in the implementation of autoaggression. Antibodies are immunoglobulins (Ig), most often belonging to class G, less often - M and A; they are specific and directed against a particular antigen. IgM include, in particular, cold antibodies and biphasic hemolysins. An erythrocyte carrying antibodies is phagocytosed by macrophages and destroyed in them; possible lysis of erythrocytes with the participation of complement. Antibodies of the IgM class can cause agglutination of erythrocytes directly in the bloodstream, and antibodies of the IgG class can only destroy erythrocytes in spleen macrophages. In all cases, hemolysis of erythrocytes occurs more intensely, the more antibodies are on their surface. Hemolytic anemia with antibodies to spectrin has been described.

Symptoms of Autoimmune Hemolytic Anemia:

With an acute onset of autoimmune hemolytic anemia, patients develop rapidly increasing weakness, shortness of breath and palpitations, pain in the heart area, sometimes in the lower back, fever and vomiting, intense jaundice. In the chronic course of the process, a relatively satisfactory state of health of patients is noted even with deep anemia, often severe jaundice, in most cases an increase in the spleen, sometimes the liver, alternating periods of exacerbation and remission.

Anemia is normochromic, sometimes hyperchromic, with hemolytic crises usually marked by severe or moderate reticulocytosis. Macrocytosis and microspherocytosis of erythrocytes are found in the peripheral blood, the appearance of normoblasts is possible. ESR is increased in most cases. The content of leukocytes in the chronic form is normal, in the acute form, leukocytosis occurs, sometimes reaching high numbers with a significant shift of the leukocyte formula to the left. The platelet count is usually normal.
In Fisher-Evens syndrome, autoimmune hemolytic anemia is combined with autoimmune thrombocytopenia. In the bone marrow, erythropoiesis is enhanced, megaloblasts are rarely detected. In most patients, the osmotic resistance of erythrocytes is reduced, which is due to a significant number of microspherocytes in the peripheral blood. The content of bilirubin is increased due to the free fraction, and the content of stercobilin in feces is also increased.

Incomplete heat agglutinins are detected using a direct Coombs test with polyvalent antiglobulin serum. With a positive test using antisera to IgG, IgM, etc., it is specified to which class of immunoglobulins the detected antibodies belong. If there are less than 500 fixed IgG molecules on the surface of red blood cells, the Coombs test is negative. A similar phenomenon is usually observed in patients with a chronic form of autoimmune hemolytic anemia or who have undergone acute hemolysis. Coombs-negative are also cases when antibodies belonging to IgA or IgM are fixed on erythrocytes (in relation to which polyvalent antiglobulin serum is less active).
Approximately 50% of cases of idiopathic autoimmune hemolytic anemia simultaneously with the appearance of immunoglobulins fixed on the surface of erythrocytes, antibodies to their own lymphocytes are detected.

Hemolytic anemia due to thermal hemolysins, is rare. It is characterized by hemoglobinuria with black urine, alternating periods of acute hemolytic crisis and remissions. The hemolytic crisis is accompanied by the development of anemia, reticulocytosis (in some cases, thrombocytosis) and an enlarged spleen. There is an increase in the level of free fraction of bilirubin, hemosiderinuria. When treating donor erythrocytes with papain, it is possible to detect monophasic hemolysins in patients. Some patients have a positive Coombs test.

Hemolytic anemia due to cold agglutinins(cold hemagglutinin disease) has a chronic course. It develops with a sharp increase in the titer of cold hemagglutinins. There are idiopathic and symptomatic forms of the disease. The leading symptom of the disease is an excessively increased sensitivity to cold, which manifests itself in the form of blue and whitening of the fingers and toes, ears, and tip of the nose. Disorders of the peripheral circulation lead to the development of Raynaud's syndrome, thrombophlebitis, thrombosis and trophic changes up to acrogangrene, sometimes cold urticaria. The occurrence of vasomotor disorders is associated with the formation of large intravascular conglomerates from agglutinated erythrocytes during cooling, followed by spasm of the vascular wall. These changes are combined with increased predominantly intracellular hemolysis. In some patients there is an increase in the liver and spleen. Moderately severe normochromic or hyperchromic anemia, reticulocytosis, normal leukocyte and platelet counts, increased ESR, a slight increase in the level of free fraction of bilirubin, a high titer of complete Cold agglutinins (detected by agglutination in a saline medium), sometimes signs of hemoglobinuria are observed. Characteristic is the agglutination of erythrocytes in vitro, which occurs at room temperature and disappears when heated. If it is impossible to perform immunological tests, a provocative test with cooling acquires diagnostic value (in the blood serum obtained from a finger tied with a tourniquet after lowering it into ice water, an increased content of free hemoglobin is determined).

In cold hemagglutinin disease, in contrast to paroxysmal cold hemoglobinuria, hemolytic crisis and vasomotor disorders occur only from hypothermia of the body and hemoglobinuria, which began in cold conditions, stops when the patient moves to a warm room.

The symptom complex characteristic of cold hemagglutinin disease can occur against the background of various acute infections and some forms of hemoblastoses. With idiopathic forms of the disease, complete recovery is not observed, with symptomatic forms, the prognosis depends mainly on the severity of the underlying process.

Paroxysmal cold hemoglobinuria is one of the rare forms of hemolytic anemia. It affects people of both sexes, more often children.

Patients with paroxysmal cold hemoglobinuria may experience general malaise, headache, body aches, and other discomfort after being in the cold. This is followed by chills, fever, nausea and vomiting. Urine turns black. At the same time, jaundice, an enlarged spleen and vasomotor disorders are sometimes detected. Against the background of a hemolytic crisis, patients show moderate anemia, reticulocytosis, an increase in the content of the free fraction of bilirubin, hemosiderinuria and proteinuria.

The final diagnosis of paroxysmal cold hemoglobinuria is established on the basis of the detected two-phase hemolysins according to the Donat-Landsteiner method. It is not characterized by autoagglutination of erythrocytes, which is constantly observed in cold hemagglutination disease.

Hemolytic anemia due to erythroopsonins. The existence of autoopsonins to blood cells is generally recognized. With acquired idiopathic hemolytic anemia, cirrhosis of the liver, hypoplastic anemia with a hemolytic component and leukemia, the phenomenon of autoerythrophagocytosis was found.

Acquired idiopathic hemolytic anemia, accompanied by a positive phenomenon of autoerythrophagocytosis, has a chronic course. Periods of remission, sometimes lasting a considerable time, are replaced by a hemolytic crisis, characterized by icterus of visible mucous membranes, darkening of urine, anemia, reticulocytosis and an increase in the indirect fraction of bilirubin, sometimes an increase in the spleen and liver.

In idiopathic and symptomatic hemolytic anemia, the detection of autoerythrophagocytosis in the absence of data indicating the presence of other forms of autoimmune hemolytic anemia gives reason to attribute them to hemolytic anemia caused by erythroopsonins. Diagnostic test of autoerythrophagocytosis is carried out in direct and indirect versions.

Immunohemolytic anemia associated with the use of drugs. Various drugs (quinine, dopegyt, sulfonamides, tetracycline, tseporin, etc.) that can cause hemolysis form complexes with specific heteroantibodies, then settle on erythrocytes and attach complement to themselves, which leads to disruption of the erythrocyte membrane. This mechanism of drug-induced hemolytic anemia is confirmed by the detection of complement on the erythrocytes of patients in the absence of immunoglobulins on them. Anemia is characterized by an acute onset with signs of intravascular hemolysis (hemoglobinuria, reticulocytosis, an increase in the content of the free fraction of bilirubin, increased erythropoiesis). Against the background of a hemolytic crisis, acute renal failure sometimes develops.

Hemolytic anemia, which develops with the appointment of penicillin and methyldopa, proceed somewhat differently. Introduction per day of 15,000 units or more of penicillin can lead to the development of hemolytic anemia, characterized by intracellular hyperhemolysis. Along with the general clinical and laboratory signs of hemolytic syndrome, a positive direct Coombs test is also detected (the detected antibodies are related to IgG). Penicillin, binding to the antigen of the erythrocyte membrane, forms a complex against which antibodies are produced in the body.

With prolonged use of methyldopa, some patients develop a hemolytic syndrome that has the features of an idiopathic form of autoimmune hemolytic anemia. The detected antibodies are identical with thermal agglutinins and belong to IgG.

Hemolytic anemia due to mechanical factors, is associated with the destruction of red blood cells during their passage through altered vessels or through artificial valves. Vascular endothelium changes in vasculitis, malignant arterial hypertension; at the same time, adhesion and aggregation of platelets are activated, as well as the system of blood coagulation and thrombin formation. Widespread blood stasis and thrombosis of small blood vessels (DIC) develop with traumatization of red blood cells, as a result of which they are fragmented; numerous fragments of erythrocytes (schistocytes) are found in a blood smear. RBCs are also destroyed when they pass through artificial valves (more often with multi-valve correction); described hemolytic anemia against the background of senile calcified aortic valve. The diagnosis is based on signs of anemia, an increase in the concentration of free bilirubin in the blood serum, the presence of schistocytes in a peripheral blood smear, and symptoms of the underlying disease that caused mechanical hemolysis.

(Moshkovich's disease, Gasser's syndrome) can complicate the course of autoimmune hemolytic anemia. The disease of an autoimmune nature is characterized by hemolytic anemia, thrombocytopenia, kidney damage. Disseminated lesions of vessels and capillaries are noted with the involvement of almost all organs and systems, pronounced changes in the coagulogram, characteristic of DIC.

Diagnosis of autoimmune hemolytic anemia:

Diagnosis of autoimmune hemolytic anemia put on the basis of the presence of clinical and hematological signs of hemolysis and the detection of autoantibodies on the surface of erythrocytes using the Coombs test (positive in almost 60% of autoimmune hemolysis). Differentiate the disease from hereditary microspherocytosis, hemolytic anemia associated with enzyme deficiency.

In the blood - normochromic or moderately hyperchromic anemia of varying severity, reticulocytosis, normoblasts. In some cases, microspherocytes are found in blood smears. The number of leukocytes may increase during a hemolytic crisis. The platelet count is usually within the normal range, but thrombocytopenia may occur. ESR is significantly increased. In the bone marrow, there is marked hyperplasia of the erythroid germ. The content of bilirubin in the blood, as a rule, is increased due to indirect.

Treatment for Autoimmune Hemolytic Anemia:

In acute forms of acquired autoimmune hemolytic anemia, prednisolone is prescribed in a daily dose of 60-80 mg. With inefficiency, it can be increased to 150 mg or more. The daily dose of the drug is divided into 3 parts in a ratio of 3:2:1. As the hemolytic crisis subsides, the dose of prednisolone is gradually reduced (2.5-5 mg per day) to half the original. A further reduction in the dose of the drug in order to avoid recurrence of the hemolytic crisis is carried out at 2.5 mg for 4-5 days, then in smaller doses and at longer intervals until the drug is completely discontinued. In chronic autoimmune hemolytic anemia, it is enough to prescribe 20-25 mg of prednisolone, and as the general condition of the patient and erythropoiesis indicators improve, transfer to a maintenance dose (5-10 mg). With cold hemagglutinin disease, similar therapy with prednisolone is indicated.

Splenectomy for autoimmune hemolytic anemia associated with thermal agglutinins and autoerythroopsonins can only be recommended for patients in whom corticosteroid therapy is accompanied by short-term remissions (up to 6-7 months) or there is resistance to it. In patients with hemolytic anemia caused by hemolysins, splenectomy does not prevent hemolytic crises. However, they are observed less frequently than before surgery, and are more easily stopped with the help of corticosteroid hormones.

With refractory autoimmune hemolytic anemia, immunosuppressants (6-mercaptopurine, imuran, chlorbutine, methotrexate, cyclophosphamide, etc.) can be used in combination with prednisolone.

In the stage of a deep hemolytic crisis, transfusions of erythrocyte mass, selected using an indirect Coombs test, are used; to reduce severe endogenous intoxication, gemodez, polydez and other detoxification agents are prescribed.

Treatment of hemolytic-uremic syndrome, which can complicate the course of autoimmune hemolytic anemia, includes corticosteroid hormones, fresh frozen plasma, plasmapheresis, hemodialysis, transfusion of washed or cryopreserved erythrocytes. Despite the use of a complex of modern therapeutic agents, the prognosis is often unfavorable.

Which doctors should you contact if you have Autoimmune Hemolytic Anemia:

Are you worried about something? Do you want to know more detailed information about Autoimmune Hemolytic Anemia, its causes, symptoms, treatment and prevention methods, course of the disease and diet after it? Or do you need an inspection? You can book an appointment with a doctor– clinic Eurolaboratory always at your service! The best doctors will examine you, study the external signs and help identify the disease by symptoms, advise you and provide the necessary assistance and make a diagnosis. you also can call a doctor at home. Clinic Eurolaboratory open for you around the clock.

How to contact the clinic:
Phone of our clinic in Kyiv: (+38 044) 206-20-00 (multichannel). The secretary of the clinic will select a convenient day and hour for you to visit the doctor. Our coordinates and directions are indicated. Look in more detail about all the services of the clinic on her.

(+38 044) 206-20-00

If you have previously performed any research, be sure to take their results to a consultation with a doctor. If the studies have not been completed, we will do everything necessary in our clinic or with our colleagues in other clinics.

You? You need to be very careful about your overall health. People don't pay enough attention disease symptoms and do not realize that these diseases can be life-threatening. There are many diseases that at first do not manifest themselves in our body, but in the end it turns out that, unfortunately, it is too late to treat them. Each disease has its own specific signs, characteristic external manifestations - the so-called disease symptoms. Identifying symptoms is the first step in diagnosing diseases in general. To do this, you just need to several times a year be examined by a doctor not only to prevent a terrible disease, but also to maintain a healthy spirit in the body and the body as a whole.

If you want to ask a doctor a question, use the online consultation section, perhaps you will find answers to your questions there and read self care tips. If you are interested in reviews about clinics and doctors, try to find the information you need in the section. Also register on the medical portal Eurolaboratory to be constantly up to date with the latest news and information updates on the site, which will be automatically sent to you by mail.

Other diseases from the group Diseases of the blood, hematopoietic organs and individual disorders involving the immune mechanism:

There are many varieties of anemia, some of which do not affect the functioning of the body and the well-being of a person at all. 11% is the number of all anemias, of which 5% are hemolytic characteristics of anemia. Symptoms of hemolytic anemia have their own characteristics, which distinguish this type from other types of the disease. Causes are often noted as hereditary and acquired. Treatment is carried out exclusively by a doctor.

Hemolytic anemia is a blood disease in which there is a decrease in the level of red blood cells and hemoglobin in the blood. This is associated with their destruction or hemolysis (short duration of functioning). If normally, red blood cells should function for 120 days, then with hemolytic anemia they are destroyed ahead of time.

The severity of the hemolytic process depends on how quickly the erythrocytes are destroyed. The number of red blood cells and hemoglobin is marked by the fact that the bone marrow simply does not have time to produce new cells.

Thus, with a mild form of hemolytic anemia, the level of red blood cells decreases, but in the peripheral blood, the level of hemoglobin may not be disturbed. If there is a clear imbalance between the production of red blood cells and their number in the circulating blood, then all the symptoms of the disease appear, in which the functions of the bone marrow are depleted.

Autoimmune hemolytic anemia

The most obscure form of hemolytic anemia is autoimmune. With this form of the disease, the body's antibodies are attached to the membrane of red blood cells, which is why the immune system begins to perceive these cells as foreign. As a result, the immune system attacks red blood cells, destroying them, which leads to a decrease in their number in the blood.

Why does this form of anemia develop? However, there are two causes of autoimmune hemolytic anemia:

1. Complications: hemoblastosis, nonspecific ulcerative colitis, aggressive chronic hepatitis, systemic connective tissue diseases, malignant neoplasms, immunodeficiency, liver cirrhosis, infections.
2. as an independent disease.

The disease has a progressive nature of the slow type. Clinical manifestations do not depend on the causes of its occurrence. Thus, the first symptoms of autoimmune hemolytic anemia are subfebrile temperature, aching pain in the joints, weakness and abdominal pain. Then the symptomatology intensifies and manifests itself in severe pallor and pastosity of the skin, increasing jaundice, and an increase in the size of the liver and spleen.

In 50% of cases, the disease manifests itself in an acute form, which develops rapidly. The patient may complain, but on examination, the first signs may not be expressed. The patient's complaints are:

• Cardiopalmus.
• Decreased performance.
• Increasing weakness.
• Headache.
• The temperature rises to 38-39 degrees.
• Dizziness.
• Lack of air.
• Nausea and vomiting that occur without eating food.
• Pain in the upper abdomen of a girdle character.

Externally, yellowness of the skin may increase without an increase in the size of the liver and spleen.

The prognosis for autoimmune hemolytic anemia is poor. There are no methods of effective treatment. However, there are ways to achieve a stable remission of the disease - radical splenectomy and taking hormonal drugs.

Causes of hemolytic anemia

Unfortunately, even knowing the cause of hemolytic anemia, doctors cannot always act on it in order to cure the patient. However, knowing the causes of the disease can help prevent its development.

• Hereditary defects that are displayed in the chromosome set responsible for the synthesis and vital activity of red blood cells. This defect is transmitted from parents selectively.
• Systemic or autoimmune diseases that affect the condition of the connective tissue and vascular space.
• Infectious diseases (malaria).
• Blood diseases such as leukemia.
• Massive burns or trauma.
• Operational intervention.
• Viral or bacterial diseases in acute or chronic form.
• Contact with industrial poisons or toxic substances.
• Rh-conflict pregnancy.
• Taking certain medications: antibiotics, chemotherapy drugs, anti-inflammatory drugs, sulfonamides.
• Incorrect blood transfusion according to the Rh factor or the group of belonging and its components (plasma, erythrocyte mass, etc.).
• Congenital heart defects, main vessels.
• Artificial tissue prostheses that come into contact with blood.
• Bacterial endocarditis is a disease of the valves and the inner layer of the heart.
• Diseases of the vessels of the microcirculatory bed.
• Paroxysmal nocturnal hemoglobinuria and cold hemoglobinuria provoke a chronic form of hemolytic anemia.

Symptoms of hemolytic anemia

It is important for the layman to recognize the presence of hemolytic anemia. This is determined by the following symptoms:

1. Jaundice syndrome, which manifests itself in a lemon-yellow skin color and itchy sensations. Urine becomes dark and even black, similar to meat slops. In this case, the feces remain unchanged, which distinguishes the disease from jaundice.
2. anemia syndrome. The skin and mucous membranes become pale. There are symptoms of oxygen starvation: dizziness, palpitations, decreased muscle strength, weakness, shortness of breath.
3. Syndrome of hyperthermia. A sudden rise to 38 degrees in temperature at the moment when the destruction of red blood cells occurs.
4. Hepatosplenomegaly syndrome. An increase in the organs that are responsible for the lifespan of red blood cells - the liver and spleen. To a lesser extent, the liver increases, which is marked by heaviness in the right hypochondrium. The spleen increases depending on the degree of hemolysis.

Other symptoms of hemolytic anemia are:

• Pain in the bones and abdomen.
• Pain in the kidneys.
• Loose stool.
• Violation of intrauterine development: malformations, disproportion of various parts of the body.
• Pain in the chest, resembling a myocardial infarction.

Signs appear with a life expectancy of erythrocytes for 15 days instead of 120. According to the clinical course, latent (compensated), chronic (with severe anemia) and crisis type of hemolytic anemia are distinguished. Crisis hemolytic anemia is the most severe.

Hemolytic anemia in children

With congenital or hereditary hemolytic anemia, symptoms appear almost from birth. Symptoms in children do not differ from the type of anemia, but careful care and treatment is required. Fortunately, hemolytic anemia occurs in 2 cases per 100,000.

Minkowski-Choffard hemolytic anemia is the result of a defective gene, as a result of which red blood cells change their shape, becoming more permeable to the sodium ion. The disease is expressed by anemic symptoms and anomalies in the development of the body. The prognosis of life becomes comforting after a radical splenectomy.

Another form of hemolytic anemia is a disease with a lack of G-6-PD activity. Hemolysis occurs after eating legumes or taking certain medications. Symptoms resemble hemolytic anemia, the hallmark of which is the manifestation of hemosiderinuria and hemoglobinuria.

Thalassemia is a common form of genetic hemolytic anemia in which there is excessive accumulation of globin, which leads to premature oxidation and destruction of the red blood cell membrane. The disease manifests itself in anemic syndrome, as well as in physical, psychomotor development. The lethal outcome is quite large due to the constant progression of the disease and the absence of periods of remission.

Treatment of hemolytic anemia

The course of treatment for hemolytic anemia is the most difficult, compared with other types of anemia, due to the inability of doctors to influence the processes of hemolysis. The treatment plan may include:

1. Reception of cytostatics in autoimmune hemolytic anemia.
2. Transfusion of human immunoglobulin and fresh frozen plasma.
3. Vitamin B12 and folic acid intake.
4. Reception of glucocorticoid hormones: Methylprednisolone, Dexamethasone, Cortinef, Prednisolone.
5. Prevention of complications of an infectious nature and exacerbation of chronic pathology.
6. Hemotransfusion of open erythrocytes with a decrease in their number to a minimum level.
7. Splenectomy is the removal of the spleen, which helps in improving prognosis. Not effective for various hereditary types of anemia and Minkowski-Choffard anemia.

Forecast

Which doctors give predictions for hemolytic anemia? It depends on the methods of treatment and their effectiveness in a particular case. Life expectancy can either increase or decrease as the disease progresses.