Under the name hemolitic anemias the group of the acquired and hereditary diseases which are characterized by increase by intracellular or intravascular destruction of erythrocytes integrates. Autoimmune hemolitic anemias include the disease forms connected with antibody formation to own antigens of erythrocytes.
Epidemiology In the general group of hemolitic anemias autoimmune hemolitic anemias meet more often. Frequency makes them 1 case on 75 000 — 80 000 population
Etiology and pathogeny Immune hemolitic anemias can arise under the influence of anti-erythrocyte of - and autoantibodies and, respectively, are subdivided on isoimmune and autoimmune.
The hemolitic anemias of newborns caused by incompatibility on the AVO systems and a Rhesus factor between mother and a fruit, posttransfusion hemolitic anemias belong to isoimmune. At autoimmune hemolitic anemias there is a failure of unresponsiveness to not changed antigens of own erythrocytes, sometimes — to the antigens having determinants, similar to erythrocytes. Antibodies to similar antigens are capable to enter interaction and with not changed antigens of own erythrocytes. Incomplete thermal agglutinins are the most frequent kind of the antibodies capable to cause development of autoimmune hemolitic anemias. These antibodies belong to IgG, is rare — to IgM, IgA.
Classification Immune hemolitic anemias are subdivided on isoimmune and autoimmune. The serological principle of differentiation of autoimmune hemolitic anemias allows to allocate the forms caused by incomplete thermal agglutinins, thermal hemolysins, Cold agglutinins, two-phase Cold hemolysins (like Donat — Landshteynera) and erythroopsonins. Some authors allocate a form of hemolitic anemia with antibodies against antigen of normoblasts of marrow. Autoimmune hemolitic anemias meet in the form of idiopathic and symptomatic forms against other diseases a macrocytosis and a microspherocytosis of erythrocytes, in combination with autoimmune thrombocytopenia (Fischer's syndrome — Ivensa). On a clinical current allocate acute and chronic options.
Approximate formulation of the diagnosis: 1. The acquired chronic autoimmune hemolitic anemia caused by incomplete thermal agglutinums with increase in a spleen and liver. 2. The acquired chronic autoimmune hemolitic anemia which is combined with autoimmune thrombocytopenia (Fischer's syndrome — Ivensa) with increase in a spleen, increase in an erythrogenesis in marrow. 3. The acquired acute autoimmune hemolitic anemia caused by incomplete thermal agglutinins with intensive jaundice, a high leukocytosis and a deviation to the left, small increase in a spleen and liver.
Clinic At the acute beginning of autoimmune hemolitic anemias patients have quickly increasing weakness, an asthma and heartbeat, pains in heart, sometimes in a waist, fervescence and vomiting, intensive jaundice. At the chronic course of process note rather satisfactory health of patients even at deep anemia, quite often expressed jaundice, in most cases increase in a spleen, sometimes and a liver, alternation of the periods of an aggravation and remission.
Anemia carries normokhromny, sometimes hyperchromic character, at hemolitic crises the expressed or moderate reticulocytosis is usually noted. In peripheral blood the macrocytosis and a microspherocytosis of erythrocytes is found, emergence of normoblasts is possible. SOE is in most cases increased. The maintenance of leukocytes at a chronic form happens normal, at acute — the leukocytosis reaching sometimes high figures with a considerable deviation to the left meets. Quantity of thrombocytes usually normal.
At Fischer's syndrome — Ivensa autoimmune hemolitic anemia is combined with autoimmune thrombocytopenia. In marrow eritropozz it is strengthened, megaloblasts seldom come to light. At most of patients osmotic resistance of erythrocytes is reduced that is caused by considerable number of microspherocytes in peripheral blood. Content of bilirubin is increased at the expense of free fraction, also the content of stercobilin in Calais is increased.
Incomplete thermal agglutinins are found by means of direct test of Koombs with polyvalent antiglobulinovy serum. At a positive test by means of antiserums to IgG, IgM it is etc. specified to what class of immunoglobulins the revealed antibodies belong. If on a surface of erythrocytes less than 500 fixed molecules IgG, Koombs's test it is negative. The similar phenomenon is observed usually at patients with a chronic form of autoimmune hemolitic anemia or transferred acute hemolysis. Koombs-negative there are also cases when on erythrocytes the antibodies belonging to IgA or IgM are fixed (concerning which polyvalent antiglobulinovy serum is less active).
Approximately in 50% of cases of idiopathic autoimmune hemolitic anemias along with emergence of the immunoglobulins fixed on a surface of erythrocytes antibodies to own lymphocytes come to light.
The hemolitic anemia caused by thermal hemolysins meets seldom. Of it a haemoglobinuria with release of urine of black color" alternation of the periods of acute hemolitic crisis and remissions are characteristic. Hemolitic crisis is followed by development of anemia, a reticulocytosis (in some cases a thrombocytosis) and increase in a spleen. Increase of level of free fraction of bilirubin, a gemosiderinuriya are noted. When processing donor erythrocytes papain possible to find monophase hemolysins in patients. Some patients have positive Koombs's test.
The hemolitic anemia caused by Cold agglutinins (a cold gemagglyutininovy illness) has a chronic current. It develops at sharp increase of a caption of Cold hemagglutinins. Distinguish idiopathic and symptomatic forms of a disease. The leading symptom of an illness is excessively hypersensitivity to cold which is shown in the form of a posineniye and albication of fingers of hands and legs, ears, a nose tip. Frustration of peripheric circulation lead to development of a syndrome of Reynaud, thrombophlebitises, thromboses and trophic changes up to an akrogangrena, sometimes a cold urticaria. Emergence of vasculomotor disturbances is connected with education when cooling large intravascular conglomerates from the agglutinated erythrocytes with the subsequent spasm of a vascular wall. These changes are combined with the strengthened mainly intracellular hemolysis. Increase in a liver and spleen occurs at part of patients. Moderately expressed normokhromny or hyperchromic anemia, reticulocytosis, normal quantity of leukocytes and thrombocytes, increase in SOE, slight increase of level of free fraction of bilirubin, the high caption of full Cold agglutinins (revealed by an agglutination method in the salt environment), sometimes haemoglobinuria signs are observed. The agglutination of erythrocytes of in vitro arising at the room temperature and disappearing at warming up is characteristic. At impossibility of performance of immunoassays diagnostic value is gained by provocative test with cooling (in the blood serum received from the finger drawn by a plait after its lowering in ice water the increased content of free hemoglobin is defined).
At a cold gemagglyutininovy illness unlike a paroxysmal cold haemoglobinuria hemolitic crisis and vasculomotor disturbances arise only from overcooling of a body and the haemoglobinuria which began in the conditions of cold stops with transition of the patient to the warm room.
The symptom complex inherent to a cold gemagtlyutininovy illness can arise against various acute infections and some forms of hemoblastoses. At idiopathic forms of a disease of an absolute recovery it is not observed, at symptomatic the forecast depends mainly on weight of the main process.
The paroxysmal cold haemoglobinuria is among rare forms of hemolitic anemias. People of both sexes get sick with it, children are more often.
Patients with a paroxysmal cold haemoglobinuria after stay on cold can have a febricula, a headache, an ache in a body and other unpleasant feelings. After this the fever begins, temperature increases, nausea and vomiting is noted. Urine gets black coloring. At the same time sometimes yellowness, increase in a spleen and vasculomotor disturbances come to light. Against hemolitic crisis find moderate anemia, a reticulocytosis, increase of maintenance of free fraction of bilirubin, a gemosiderinuriya and a proteinuria in patients.
The final diagnosis of a paroxysmal cold haemoglobinuria is established on the basis of the found two-phase hemolysins by Donat's method — Landshteynera. The autoagglyutination of erythrocytes which is constantly observed at cold a gemagtlyutination is not characteristic of it ache diseases.
The hemolitic anemia caused by erythroopsonins. Existence of autoopsonin to blood cells is conventional. At the acquired idiopathic hemolitic anemia, cirrhosis, hypoplastic anemia with a hemolitic component and leukoses the phenomenon of an autoeritrofagotsitoz is found.
The acquired idiopathic hemolitic anemia which is followed by a positive phenomenon of an autoeritrofagotsitoz has a chronic current. The remission periods lasting sometimes considerable time are replaced by the hemolitic crisis which is characterized by an ikterichnost of visible mucous membranes, urine darkening, anemia, a reticulocytosis and increase of indirect fraction of bilirubin, sometimes increase in a spleen and liver.
At idiopathic and symptomatic hemolitic anemias identification of an autoeritrofagotsitoz in the absence of the data indicating existence of other forms of autoimmune hemolitic anemias gives the grounds to carry them to the hemolitic anemia caused by erythroopsonins. Diagnostic test of an autoeritrofagotsitoz is carried out in direct and indirect options.
The immunohemolitic anemias caused by use of drugs. Various medical drugs (quinine, dopegit, the streptocides, tetracycline, tseporin, etc.) capable to cause hemolysis form complexes with specific heteroantibodies, then accumulate on erythrocytes and attach to themselves a complement that leads to disturbance of a membrane of erythrocytes. Such mechanism of medicamentally caused hemolitic anemias is confirmed by detection on erythrocytes of patients of a complement in the absence of immunoglobulins on them. Anemias are characterized by the acute beginning with signs of an intravascular hemolysis (a haemoglobinuria, a reticulocytosis, increase of maintenance of free fraction of bilirubin, strengthening of an erythrogenesis). Against hemolitic crisis the acute renal failure sometimes develops.
A little differently the hemolitic anemias developing at purpose of penicillin and Methyldopa proceed. Introduction during a day of 15 000 and more than A PIECE of penicillin can lead to development of the hemolitic anemia which is characterized by intracellular hyper hemolysis. Along with the general clinical laboratory signs of a hemolitic syndrome also positive direct test of Koombs is found (the revealed antibodies belong to IgG). Penicillin, contacting antigen of a membrane of erythrocytes, forms a complex against which in an organism antibodies are developed. At prolonged use Methyldopa at part of patients arises the hemolitic syndrome having lines of an idiopathic form of autoimmune hemolitic anemias. The revealed antibodies are identical with thermal agglutinins and belong to IgG.
The Gemolitiko-uremichesky syndrome (Moshkovich's illness, Gasser's syndrome) can complicate the course of autoimmune hemolitic anemias. The disease of the autoimmune nature is characterized by hemolitic anemia, thrombocytopenia, damage of kidneys. The disseminated defeat of vessels and capillaries with involvement practically of all bodies and systems, the expressed changes from a koagulogramma are noted, characteristic of the IDCS.
In the acute period of a disease the thrombocytopenic hemorrhagic syndrome which often have generalized character is observed: from a gemmoragichesky enanthesis and mucous membranes to hemorrhages in vitals, including a brain. Damage of kidneys is followed by development of an acute renal failure and uraemia, considerable accumulation in blood of nitrogenous metabolites. Anemia is, as a rule, sharply expressed, the level of hemoglobin decreases to 40 — 60 g/l.
Verification of the diagnosis Diagnosis of the acquired autoimmune hemolitic anemias is based mainly on existence of anemia, increase in an erythroblastic sprout in marrow at the expense of unripe forms eritro-and normoblasts, a citreous shade of integuments, are frequent increase in a spleen and liver, fibrinferments can meet. The specification of option of a disease demands special serological researches. They allow to reveal existence of autoantibodies on erythrocytes of the patient, hemolysins, Cold agglutinins, two-phase Cold hemolysins, erythroopsonins. See also, differential diagnostic characters in the table.
Treatment of autoimmune hemolitic anemias At acute forms the acquired autoimmune hemolitic anemias appoint Prednisolonum in a daily dose of 60 — 80 mg. At inefficiency it can be increased to 150 mg and more. The daily dose of drug is divided into 3 parts in the ratio 3:2:1. In process of subsiding of hemolitic crisis Prednisolonum dose gradually decreases (on 2,5 — 5 mg a day) to a half initial. The further dose decline of drug in order to avoid recuring of hemolitic crisis is carried out on 2,5 mg within 4 — 5 days, then in smaller doses and with big intervals before full drug withdrawal. At chronic autoimmune hemolitic anemia it is enough to appoint 20 — 25 mg of Prednisolonum, and in process of improvement of the general condition of the patient and indicators of an erythrogenesis to transfer to a maintenance dose (5 — 10 mg). At a cold gemagglyutininovy illness similar therapy is shown by Prednisolonum.
The splenectomy at autoimmune hemolitic anemia, connected with thermal agglutinins and autoeritroopsonina, can be recommended only to patients at whom corticosteroid therapy is followed by short remissions (till 6 — 7 months) or there is a resistance to it. At patients with the hemolitic anemia caused by hemolysins, the splenectomy does not prevent hemolitic crises. However they are observed less than before operation, and easier stopped by means of corticosteroid hormones.
At refractory autoimmune hemolitic anemias in combination with Prednisolonum immunodepressata can be used (6 Mercaptopurinum, an imuran, Chlorbutinum, a methotrexate, cyclophosphamide, etc.).
In a stage of deep hemolitic crisis apply transfusions of the eritrotsitny weight which is picked up by means of indirect test of Koombs; for decrease in the expressed endogenous intoxication appoint Haemodesum, Polydesum and other disintoxication means.
Treatment of a gemolitiko-uraemic syndrome which can complicate the course of autoimmune hemolitic anemias includes corticosteroid hormones, freshly frozen plasma, a plasma exchange, a hemodialysis, transfusions of the washed or cryotinned erythrocytes. Despite use of a complex of modern therapeutic means, the forecast often adverse.