HEMOLITIC ANEMIA (anemia haemolytica; Greek haima blood + lysis destruction, dissolution; anemia) — the group name of diseases which general symptom is the strengthened destruction of erythrocytes causing, on the one hand, anemia and the increased formation of decomposition products of erythrocytes with another — reaktivno the strengthened erythrocytopoiesis. Increase in decomposition products of erythrocytes is clinically shown jaundice (see) lemon a shade, increase in content in blood of the indirect (not conjugated) bilirubin (see. Hyperbilirubinemia ) and serumal iron, pleyokhromiy bile and calla, urobilinuria (see). At intravascular hemolysis (see) dobavochno arise a hypergemoglobinemia (see. Haemoglobinaemia ), haemoglobinuria (see), gemosiderinuriya. Strengthening of an erythrogenesis is demonstrated by a reticulocytosis and a polychromatophilia in peripheral blood, eritronormoblastoz marrow.
- 1 Classification
- 2 HEREDITARY HEMOLITIC ANEMIAS
- 3 the ACQUIRED HEMOLITIC ANEMIAS
- 3.1 Immunohemolitic anemias
- 3.2 The acquired membranopathies
- 3.3 Toxic hemolitic anemias
- 4 PATHOLOGICAL ANATOMY
- 5 Table. Differential and diagnostic characteristic of hemolitic anemias
G.'s Division and. on acute and chronic it was unacceptable since acute and hron, options can be observed within the same forms G. and. Also G.'s opposition to ampere-second is not justified by intracellular and intravascular localization of hemolysis as at the same form G. and. the intracellular and intravascular hemolysis can take place. G.'s division is not deprived of convention and. on caused endo-and ekzoeritrotsitarny hemolitic factors; e.g., at a paroxysmal night haemoglobinuria the main defect is localized in a membrane of erythrocytes, and the hemolitic factor (complement) is localized out of an erythrocyte.
Division of hemolitic anemias into two basic groups — the hereditary (inborn) and acquired G. is most justified and. Hereditary G. and. can be caused by pathology of either a membrane of erythrocytes, or structure or synthesis of hemoglobin, and also deficit of one of enzymes of erythrocytes. Hereditary G. and. are integrated by the genetic principle, but significantly differ on an etiology, a pathogeny and a clinical picture. To the acquired G. and. carry big group of immunohemolitic anemias, group of the acquired membranopathies, etc.
Following is offered G.'s classification and. (Yu. I. Loriye, 1967; L. I. Idelson, 1975):
I. Hereditary (inborn)
1. Membranopathies of erythrocytes:
2. Enzimopenichesky (fermentopenichesky):
a) connected with deficit of enzymes of a pentozo-phosphatic cycle;
b) connected with deficit of enzymes of glycolysis;
c) connected with deficit of the enzymes participating in education, oxidation and recovery of glutathione;
d) connected with deficit of the enzymes participating in use of ATP;
e) connected with deficit of the enzymes participating in synthesis of porphyrines.
a) hemoglobinopathies qualitative;
1. Immunohemolitic anemias:
2. The acquired membranopathies:
a) paroxysmal night Haemoglobinuria;
b) shporokletochny anemia.
3. Connected with a bruise of erythrocytes:
a) mid-flight Haemoglobinuria;
b) disease Moshkovich (synonym mikroangiopatichesky G. and.);
c) the hearts arising at prosthetics of valves.
HEREDITARY HEMOLITIC ANEMIAS
Membranopathies of erythrocytes
Membranopathies are connected with anomalies of proteinaceous or lipidic components of a cover of erythrocytes that is the reason of change of their form and their premature destruction. Earlier carried to membranopathies also so-called inborn not spherocytic G. and., which in connection with detection of deficit of enzymes of glycolysis at them were carried later to enzimopenichesky anemias.
Microspherocytic hemolitic anemia
Microspherocytic hemolitic anemia (synonym: inborn microspherocytosis, Minkowski's disease — Shoffara, a microcytemia, spherocytic anemia) it is for the first time described by Vanler and Mazius (S. Vanlair, Masius, 1871) under the name the microcytemia but as an independent disease became known after O. Minkowski (1900) and Shoffar's classical works (A. M. to Chauffard, 1907).
Statistics it is not developed. The disease is described in all parts of the world; in Europe meets more often than in America. Due to the broad use of a splenectomy by the patient from microspherocytic G. and., as a rule, conducts edges to a wedge, to recovery, increase of this disease since chances of its transfer by inheritance increase is possible (patients live up to childbearing age).
Etiology it is unknown. The essence of defect in a membrane of erythrocytes is not finalized. The disease is inherited on autosomal dominantly type.
Pathogeny. The conducting value in G.'s development and. give to the lowered contents in a membrane of erythrocytes of aktomiozinopodobny protein and to partial deprivation of a membrane of phospholipids and cholesterol that causes reduction of the general surface of erythrocytes, decrease in its index also promotes transformation of erythrocytes into microspherocytes. The secondary role is attributed to increase in permeability of a membrane for the ions of sodium increasing activity of an adenozintrifosfataza and increasing intensity of processes of glycolysis. In the conditions of the slowed-down splenic blood-groove with low pH and content of aging glucose of erythrocytes accelerates. Besides, the microspherocytes which lost plasticity of normal erythrocytes purely mechanically are late during the passing from a pulp of a spleen to venous sinusoids before narrow (with a diameter up to 3,5 mk) a time between the endothelial cells covering their surface. The termination of the strengthened hemolysis after a splenectomy, despite preservation is explained by erythrocytes of a microspherocytic form it.
Clinical picture. Despite inborn character of microspherocytic G. and., its first manifestations usually note at the advanced children's and youthful age though cases both at babies, and at old men are described. Disease differs in a big variety — from subclinical to heavy, with frequent hemolitic crises. Complaints can be absent (according to Shoffar, «patients are more yellow, than are sick») or they are caused by an anemic hypoxia, attacks of cholelithic colic. The main symptom — jaundice of skin, scleras and mucous membranes of various and non-constant intensity. Jaundice is followed by allocation intensively painted a calla and dark urine. The spleen is increased constantly, a liver — at a half of patients.
Congenital anomalies can occur at some patients: tower skull, Gothic sky, bradi-or polydactylia, cervical edges, squint, malformations of heart and vessels and others (so-called hemolitic constitution). At a course of a disease at early children's age on the roentgenogram of a skull expansion of diploichesky spaces is noted. Anemia is usually moderate, sometimes is absent owing to compensation of unsharp hemolysis by the strengthened erythrogenesis. Even at long and intensive hemolysis the erythrogenesis remains active. Heavy hemolitic crises arise more often at women. They develop gradually, within 7 — 10 days, and are provoked usually by infections, childbirth. Sometimes anemia is aggravated with sudden development of so-called aplastic (aregeneratorny) crises which are characterized by disappearance of reticulocytes from blood and erythronormoblasts from marrow, sharp reduction of jaundice and other signs of hemolysis. At a part of patients crises are followed leucio-and thrombocytopenia. Usually aplastic crises last 7 — 10 days, sometimes dragging on up to 2 months.
At a part of patients on skin of shins bilateral ulcers in the field of entocondyles are formed; they begin to live only after a splenectomy. In the mechanism of their emergence the possibility of microthromboses of a sferotsitama is not excluded. At a blood analysis reveal a microspherocytosis (spherocytosis) of erythrocytes: average diameter of erythrocytes is reduced to 6 microns and less, their thickness is increased to 2,5 — 3 microns, the average volume of erythrocytes and respectively average content of hemoglobin in an erythrocyte are usually normal or a little increased. Microspherocytes can be found at usual viewing of the painted blood smear — they have an appearance of the small intensively painted cells without the central enlightenment. Objectively microspherocytes are defined by way eritrotsitometriya (see): the top of a Price-Jones curve is displaced to the left (towards microcytes), the basis of a curve in connection with an anisocytosis broadens. The maintenance of reticulocytes is with firmness increased (to 20% and more). In punctate of marrow the expressed hyperplasia of an erythroblastic sprout with the raised number of mitoses and signs of the accelerated maturing is found. Osmotic firmness of microspherocytes is sharply reduced: hemolysis can begin at the concentration of sodium chloride close to physiological (0,70 — 0,75%). Mechanical firmness of microspherocytes is 4 — 8 times lower, than normal erythrocytes. Acid eritrogramma (see) differs in sharp shift of the main maximum to the right, increase in the general duration of hemolysis. After washing of erythrocytes from plasma the main maximum acid erythro-grams is displaced to the left, duration of hemolysis is reduced; it allows to allow existence in plasma of the substance inhibiting hemolysis of microspherocytes. At the erased microspherocytic G.'s forms and. osmotic firmness of erythrocytes should be defined with their preliminary daily incubation at t ° 37 ° (it decreases in much bigger degree, than at erythrocytes of healthy faces). Similarly investigate an acid eritrogramma of the washed erythrocytes of patients after an incubation at t ° 37 °. During 48 hours spontaneous hemolysis (autogemoliz) averages 50% whereas at healthy faces — no more than 5%. Life expectancy of microspherocytes in a circulatory bed considerably decreases. At the same time terms of circulation of normal erythrocytes in a circulatory bed of patients, and also terms of circulation of the microspherocytes poured to the recipients who are earlier subjected to a splenectomy remain normal. It confirms lack of plasma factors of hemolysis at microspherocytic G. and. About same also results serol, researches testify: direct test of Koombs (see. Koombs reaction ) it is always negative, indirect it is positive at patients, sensibilized as a result of pregnancy by a Rh-incompatible fruit or hemotransfusions. Content of free hemoglobin in plasma normal. Hemoglobin always belongs to «adult» type (A); only at babies from microspherocytic G. and. find the hemoglobin content of F corresponding to age. Level of bilirubin of serum is always increased, is preferential at the expense of the indirect (not conjugated) fraction. Expressiveness of a bilirubinemia not always corresponds to intensity of hemolysis — at good bilirubinvydelitelny function of a liver it can remain insignificant. Considerably daily release of urobilinigen with a stake and urobilin with urine increases.
Complications. Approximately at 30 — 40% of patients, is more often at intensive and long hemolysis, the pigmental stones in zhelchevydelitelny ways causing attacks of cholelithic colic are formed. Obturation of the general bilious channel causes mechanical jaundice.
Diagnosis is based on establishment of jaundice of hemolitic type, microspherocytosis and reduced osmotic, mechanical resistance of erythrocytes, a characteristic acid eritrogramma. Existence of a microspherocytosis, reduced osmotic firmness of erythrocytes, negative direct test of Koombs and datum level of free hemoglobin of plasma allows to differentiate microspherocytic G. and. from other G. and., and also from functional hyperbilirubinemias.
Treatment. The only method providing the termination of hemolysis and practical recovery of patients is the splenectomy (see). Consider that at quiet disease it is possible to refrain from operation. However as almost at all patients complications develop sooner or later, it is more correct to operate all patients after establishment of the diagnosis, except for, maybe, children of early age, old men and patients with heavy cardiovascular pathology. Operation is admissible also at pregnancy (it is better to do in combination with Caesarian section). Palindromias after a splenectomy are observed only in the presence of the spleniculus which is not noticed at operation. All signs of hyper hemolysis after operation quickly abate and usually in 3 — 4 weeks the composition of blood is completely normalized. The microspherocytosis and decrease in osmotic firmness of erythrocytes after operation remain for life, however their expressiveness decreases a little. Complications and a lethal outcome after a splenectomy are observed seldom. All conservative actions at G. and. are inefficient. Hemotransfusion of eritrotsitny weight) should be applied with the replaceable purpose only at deep anemia (hemolitic and aplastic crises). Repeated hemotransfusions are undesirable in connection with danger of an isosensitization. After a splenectomy need for hemotransfusions disappears.
Forecast after a splenectomy favorable, at failure from operation — doubtful in view of a possibility of development of the specified complications. Working ability of patients before treatment depends on weight of anemia and extent of compensation of an anemic hypoxia. Patients shall be informed on probability of transfer of a disease by inheritance (but also on a curability of a disease). Lethality low.
Prevention it is not developed. The only method of the prevention of complications is the early splenectomy.
Ovalotsitarny hemolitic anemia
Ovalotsitarnaya hemolitic anemia (synonym elliptotsitarny G. and.). For the first time existence in blood of people of erythrocytes of an oval form was described by Dresbakh (M. of Dresbach, 1904). Blood of healthy faces contains about 8 — 15% of dipsotherapies (fiziol, an ovalocytosis). The bigger percent of dipsotherapies, a so-called ovalocytosis, find in 0,02 — 0,05% of cases, and in 10 — 12% from them ovalotsitarny G. is observed and.
Etiology it is unknown. The disease is inherited on autosomal dominantly type, transmitted, apparently, by two genes, one of which is linked to genes of system a Rhesus factor. Expressivity of genes varies over a wide range.
Pathogeny it is caused by defect of a membrane of erythrocytes. The only place of destruction of erythrocytes is the spleen, but sequestration is not connected with anomaly of their form (dipsotherapies of carriers are not late in a spleen and have the normal term of circulation).
Clinical picture, complications, treatment, forecast — as at microspherocytic G. and.
Diagnosis it is put on the basis of dominance in peripheral blood of erythrocytes of an oval form taking into account G.'s symptomatology and. The average volume of erythrocytes, concentration and a hemoglobin content in erythrocytes are normal. In punctate of marrow of a cell of a red row get an oval form at a stage of polychromatophilous normoblasts. Osmotic resistance of erythrocytes usually normal, at their incubation unsharply decreases. The test of an autogemoliz is not strengthened. Life expectancy of erythrocytes is shortened, at a carriage of dipsotherapies — is normal. Serol, reactions, indicators of pigmental exchange — as at microspherocytic G. and.
Akantotsitarny hemolitic anemia
Akantotsitarnaya hemolitic anemia received the name in a form of erythrocytes — acanthocytes (grech, akantha a thorn, a prickle) have on a surface of 5 — 10 long narrow acanthoid outgrowths. Content of phospholipids and cholesterol in a membrane of erythrocytes normal, but are available shifts in fractions of phospholipids — increase in sphingomyelin and decrease in phosphatidylsincaline.
Etiology. Akantotsitarny G. and. — the rare disease of early children's age connected with inborn lack of beta lipoproteins (see. Abetalipoproteinemiya ). It is inherited on autosomal recessively type.
Pathogeny. Formation of acanthocytes and their phospholipidic anomaly are connected with finding of erythrocytes in patol, plasma — in young erythrocytes morfol, and biochemical, changes are minimum. In plasma there are no B-protein (a proteinaceous component of p-lipoproteins), triglycerides; level of cholesterol is usually lower than 50 mg / 100 ml, phospholipids — it is lower than 100 mg / 100 of ml.
Clinical picture it is characterized by moderate G.'s combination and. and steatorrheas (see) with selective disturbance of absorption of fats. The picture of blood is characteristic: erythrocytes have long narrow acanthoid outgrowths, their life expectancy is shortened, the reticulocytosis is found. Osmotic firmness of erythrocytes normal, autogemoliz after an incubation at t ° 4 ° and 37 ° it is sharply strengthened, it korrigirutsya by addition of vitamin E [the Brain (M. S. Brain), 1971]. In plasma there are no B-protein and triglycerides, the content of cholesterol and phospholipids is reduced.
Complications. A pigmental retinitis (from the outcome in a blindness) and atactic neuropathy.
Diagnosis the wedge, pictures, detection of an akantotsitarny form of erythrocytes, reticulocytosis, shortening of life expectancy of erythrocytes is put on the basis of characteristic.
Treatment it is not developed. Purpose of vitamin E is not effective.
Forecast concerning life adverse.
G. and. develop owing to deficit of various enzymes of erythrocytes. According to insufficiency of certain fermental systems allocate several groups of enzymopathies:
And., connected with deficit of enzymes of a pentozo-phosphatic cycle (deficit glyukozo-6-phosphate-degidro-genazy, deficit of a 6-fosfoglyukonatdegidrogenaza);
And., connected with deficit of enzymes of glycolysis (deficit of a pyruvatekinase, triozofosfatizomeraza, 2,3 diphosphoglycerate mutases, etc.);
And., connected with deficit of the enzymes participating in education, oxidation and recovery of glutathione (deficit of a sintetaza, reductase and peroxidase);
And., the adenozintrifosfataza connected with deficit, adenilatkinaza, ribofosfat-pirofosfatkinaza, i.e. the enzymes participating in use of ATP;
And., connected with deficit of the enzymes participating in synthesis of porphyrines. It is an erythropoietic uroporfiriya and an erythropoietic protoporphyria (see. Enzimopenichesky anemia ).
G. and., the structures connected with disturbance or synthesis of hemoglobin. Distinguish the hemoglobinopathies caused by anomaly of primary structure of hemoglobin or qualitative, napr, drepanocytic anemia (see), and caused by disturbance of synthesis of chains of hemoglobin, or quantitative — thalassemias (see), at some of them in erythrocytes find hemoglobin N, Bart hemoglobin, etc.
the ACQUIRED HEMOLITIC ANEMIAS
Immunohemolitic anemias are characterized by existence in blood of antibodies against antigens of own or poured (donor) erythrocytes.
Autoimmune hemolitic anemias can be caused by existence of thermal autoantibodies, cold agglutinins, two-phase hemolysins, and also the autoantibodies appearing at reception of some pharmaceuticals.
The Autoimmunogemolitichesky anemias caused by thermal autoantibodies
Autoimmunogemolitichesky anemias, caused by thermal autoantibodies (a synonym: pthe acquired G. and., the acquired hemolitic jaundice like Gayem — Vidalya, immunohemolitic anemia), have two forms: idiopathic and symptomatic (developing more often against the background of tumors of an adenoid tissue and big kollagenoz, napr, at a system lupus erythematosus).
Falls to the share of this form apprx. 25% of all G. and. Persons of any age are ill, it is a little woman more often than men. Ratio of idiopathic and symptomatic forms 1: 1.
Etiology it is unknown. Lack of family cases testifies to the acquired nature of a disease. At a part of patients development of a disease is connected with reception of Methyldopum.
Pathogeny: there are two theories of formation of autoantibodies: 1) primary change of a membrane of erythrocytes with education new or an exposure of the hidden (deep) antigen and the subsequent reaction immunol, systems; 2) primary change of cells (vegetative mutation) immunol, systems with antibody formation to normal antigens of erythrocytes. Thermal autoantibodies on serol, most often belong to properties to incomplete agglutinins; on the basis of immuno-chemical researches (by means of monospecific antiglobulinovy serums) they are carried to immunoglobulin G (IgG), sometimes at the same time find immunoglobulins M and A (IgM and IgA). Hemolysis of erythrocytes happens to the antibodies fixed on them by their fragmentation or an erythrophagocytosis. Destruction of erythrocytes is made in a spleen, in marrow, limf, nodes and a liver. At a part of patients erythrocytes collapse directly in a circulatory bed; find in this part of patients also full hemolysins.
Clinical picture: onset of the illness more often gradual, but maybe acute, with a picture of rough hemolysis and an anemic coma (so-called acute G. and. Lederera). The current is usually chronic, with the periods of aggravations. Complaints of patients are caused by generally anemic hypoxia. Skin is pale, icteric, sometimes the Crocq's disease clearly is expressed. Jaundice can be various intensity, the calla, an urobilinuria is followed by a pleyokhromiya. In serum the maintenance of an indirect bilirubin is increased; at quickly progressing hemolysis which is followed by anemic necroses of a liver also the conjugated fraction of bilirubin raises. The spleen is increased slightly or moderately; at a symptomatic form the sharp splenomegaly is possible (at the expense of a basic disease). The liver is increased approximately at x / z patients. At a blood analysis find normo-or hyperchromic anemia, a high reticulocytosis, sometimes normoblasts, a sharp anisocytosis of erythrocytes, existence of microspherocytes and macrocytes; the fragments of erythrocytes erythroenglobing monocytes meet. Auto-agglutination of erythrocytes is often observed. The average volume of erythrocytes is usually increased, their osmotic resistance is reduced, after an incubation of erythrocytes it decreases even more (but less, than at microspherocytic G. and.). After an incubation of erythrocytes it is strengthened also them autogemoliz. Free hemoglobin of plasma is quite often raised, especially in the presence in blood of hemolysins and at height of hemolitic crises. At a considerable and long haemoglobinaemia the level of a gaptoglobin of plasma decreases, emergence of hemoglobin and hemosiderin in urine is possible. Life expectancy of erythrocytes both own, and poured from the donor, is shortened, quite often considerably. The number of leukocytes normal or is lowered at hron, a current, but at exacerbations of a disease the considerable neutrophylic leukocytosis with shift can be observed to the left. At symptomatic autoimmune G. and. the leukocytic formula is defined by a basic disease. The number of thrombocytes normal or is lowered, sometimes sharply. In a miyelogramma note the expressed erythronormoblastic reaction. The erythrogenesis is macronormoblastic, it is frequent with existence of megaloblasts that connect with the strengthened consumption of endogenous B12 vitamin and folic to - you. The expressed thrombocytopenia can lead to development of heavy bleeding (Fischer's syndrome — Evans), sometimes along with a leukopenia (immune the sir a cytopenia).
Complications: the aplastic crises, thromboses leading to heart attacks of appropriate authorities; formation of stones in bilious ways is noted seldom.
Diagnosis became possible after introduction of diagnostic test of Koombs. It is based on establishment by the acquired G. of ampere-second by the intracellular or mixed localization of hemolysis and is confirmed by positive direct test of Koombs, intensity a cut is various, but can correspond to weight of hemolysis. Sometimes direct test happens negative or becomes positive in rather late terms of a disease. The positive indirect test of Koombs (revealing free antibodies in plasma) not a patognomonichna for autoimmune G. and., it is usually caused by existence of isoantibodies (after transfusions, at pregnancy).
Treatment: usually appoint corticosteroid hormones. The initial dose of Prednisolonum shall be not less than 1 .mg on 1 kg of weight a day inside; at a heavy current and deep anemia the dose is raised to 2 — 3 laid down on 1 kg of weight, a half it is entered parenterally. At improvement the dose of drug is gradually reduced, but so to provide increase of hemoglobin. After normalization of indicators of red blood hormones continue to enter small doses (15 — 20 mg of Prednisolonum a day); at a state gematol. remissions enter them within 2 — 3 months and only then gradually cancel. Along with hormones appoint salts of potassium, alkali. The mechanism to lay down. effects of hormones at autoimmune G. and. it is not clear. Assume the braking action on immunocompetent cells, however speed of therapeutic effect (sometimes already in 24 — 48 hours) confirms a direct impact on process of a kroverazrusheniye. Hormonal therapy provides a wedge, recovery about 75% of patients. Direct test of Koombs remains positive during a row of months and years. The negative effect of hormonal therapy can be explained or impossibility of use of sufficient doses of hormones owing to development of diabetes, a hypertension etc., or resistance to corticosteroids. In these cases the splenectomy is shown; it gives effect approximately at a half of the operated patients, but does not exclude a late recurrence of hemolysis. At failure of corticosteroid therapy apply also immunodepressants (6 Mercaptopurinum, Azathioprinum, Cyclophosphanum, etc.). There are messages on successful use of a thymectomy for children. Transfusions of blood (eritrotsitny weight) are shown only at the heavy progressing anemia. At an anemic coma in one step pour up to 750 — 1000 ml of blood (the donor is selected for indirect test of Koombs).
Forecast to thicket doubtful though the possibility of a long quiet current and even spontaneous recovery is not excluded. Working ability of patients before treatment is with firmness reduced. Predictively adverse symptoms consider existence of the expressed thrombocytopenia, positive indirect test of Koombs, hemolysins in serum. Uncontrollable hemolysis, thrombocytopenic bleedings, fibrinferments can be proximate causes of a lethal outcome.
The hemolitic anemias caused by Cold autoantibodies
Distinguish idiopathic and symptomatic forms. Symptomatic develops against the background of some limfoproliferativny processes, an infectious mononucleosis, mycoplasmal (atypical) pneumonia more often; it is possible at any age. The idiopathic form of a disease occurs seldom, more often at women and at elderly people.
Etiology it is unknown. The mechanism of formation of cold agglutinins under the influence of infectious activators is not installed.
Pathogeny: cold autoantibodies are fixed together with a complement on erythrocytes in small vessels of distal body parts (during the cooling them up to the temperature below 32 °).
Explicit hemolysis arises at an antiserum capacity 1: 1000. Cold agglutinins possess serol, specificity to antigens I or i (the last is more often at a symptomatic form). By immunochemical methods of a research they are identified as immunoglobulins M (IgM), find a combination of immunoglobulins M and G less often (IgM + IgG), H-chains are responsible for hemolitic activity. Destruction of the agglutinated erythrocytes happens both in a vascular bed, and as a result of an erythrophagocytosis in a spleen, a liver and marrow (the mixed localization of hemolysis). Agglutinates in small vessels break blood circulation in them, causing clinic of a syndrome of Reynaud (see. Reynaud disease ).
Clinical picture: the main a wedge, displays of a disease are usually moderately expressed G. and. and the disturbances of peripheric circulation arising during the cooling as Reynaud's syndrome. The Crocq's disease, seldom akrogangrena is observed. Jaundice is usually not intensive. The sizes of a liver and spleen normal or are a little increased. Disease usually hron., not progressing. Heavy hemoglobinuric crises are possible. The symptomatic form arises sharply and comes to an end with spontaneous recovery. At a blood analysis find moderate anemia. Erythrocytes are morphologically poorly changed, sometimes a small spherocytosis, an erythrophagocytosis, during the cooling erythrocytes quickly agglutinate; after warming up of a blood sample agglutinates of erythrocytes disappear. Osmotic resistance of erythrocytes is normal or a little reduced. Reticulocytosis moderate. The number of leukocytes and thrombocytes is normal or reduced. ROE can be sharply accelerated. In plasma the indirect bilirubin and free hemoglobin is raised (after cooling); in urine hemoglobin and hemosiderin can be found.
Complications can be caused by disturbance of a blood-groove in small vessels (e.g., a gangrenosis of fingers of hands and legs).
Diagnosis it is based on G.'s identification and., Reynaud's syndrome and detection of cold agglutinins in rather high caption (1: 1 000 000). Direct test of Koombs (for a research blood is taken in the ware warmed to t ° 37 °) with whole antiglobulinovy serum is always positive, from monospecific serums is positive only with anti-With'.
Treatment: corticosteroids and a splenectomy are ineffective. The favorable effect from leukeranum is described. At deep anemia transfusions of the erythrocytes washed from plasma are shown (for elimination of a complement).
Forecast concerning recovery doubtful. Working capacity can remain.
The hemolitic anemia caused by two-phase hemolysins
Hemolitic anemia, caused by two-phase hemolysins (a paroxysmal cold haemoglobinuria) — a rare disease which makes 4,6% of all immunohemolitic anemias.
Etiology. The disease develops at acute viral infections, is more rare at. syphilis.
Pathogeny. The paroxysmal cold Haemoglobinuria arises in the presence in blood of two-phase hemolysins of Donat — Landshteynera which during the cooling of an organism settle on erythrocytes and carry out hemolysis at t ° 37 °. Two-phase hemolysins have electrophoretic mobility, the relevant gamma fraction; they treat immunoglobulins G (IgG).
Clinical picture it is characterized by symptoms of a serious general condition, short wind, fever, a headache, muscle and joints pain, and also signs of a rough intravascular hemolysis (emergence of black urine, jaundice, anemia). Pernicious vomiting by bile, a liquid chair is quite often observed. The spleen and a liver are moderately increased, sensitive. The easy form of a paroxysmal cold haemoglobinuria proceeds with a subfebrile temperature and a short-term haemoglobinuria. At a blood analysis reveal sharp normokhromny anemia, basphilic stippling of erythrocytes, a polychromatophilia of erythrocytes, normoblasts, the increased quantity of reticulocytes, and also a neutrophylic leukocytosis with shift to the left, sometimes to promyelocytes and even myeloblasts. Find a hyperbilirubinemia (at the expense of not conjugated bilirubin), increase in hemoglobin up to 30 — 40 mg / 100 ml. Blood serum is painted in pink color, during the standing it becomes brown due to formation of a methemoglobin. In punctate of marrow — a picture of a reactive erythrogenesis, an erythrophagocytosis. At other researches reveal haemoglobinuria (see), a pleyokhromiya of bile, the increased release of stercobilin with a stake.
Complications: renal failure, anury.
Treatment: hold antishock events (cardiovascular means, morphine, adrenaline, Cortinum, oxygen), transfusion of odnogruppny blood (250 — 500 ml), Polyglucinum (500 — 1000 ml), appoint alkalis inside and intravenously (5% freshly cooked solution of sodium bicarbonate kapelno in the general dose of 500 — 1000 ml). For the purpose of bystreyshy clarification of plasma from hemoglobin enter osmotic diuretics — 30% solution freshly cooked sterile the solution of glucose lyophilized drug of urea for 10% in the general dose of 200 — 300 ml. Glucocorticoids are shown.
Forecast is defined by massiveness of hemolysis, a condition of function of kidneys, timeliness and efficiency of treatment. At a favorable outcome during 2 — 4 weeks there comes full the wedge, recovery. The forecast is adverse in the cases complicated by an anury and a renal failure. At a fulminant form the lethal outcome from shock and an acute anoxia within the first two days is possible.
Medicinal immunohemolitic anemia
Medicinal immunohemolitic anemia arises at the medicamentous hemolitic reactions which are carried out with the participation of antibodies.
Etiology and pathogeny. Autoantibodies can appear at reception of some medicines (penicillin, streptomycin, PASK, indometacin, pyramidon, acetphenetidiene, quinine, quinidine, etc.). Mechanism of participation of medicines in G.'s development and. can be various. At hapten the mechanism of development of G. and. drug enters connection with a component of a surface of erythrocytes and causes formation of anti-medicinal antibodies like IgG, at repeated administration of drug of an antibody are fixed on the erythrocytes blocked by it. Such is the mechanism of effect of penicillin; at the same time usual allergic reaction to penicillin it can not be observed. At formation of cell-bound immune complexes drug connects to carrier protein and stimulates antibody formation like IgM. The complex drug — an antibody damages a membrane of erythrocytes, promotes fixing on them of a complement, causing hemolysis. Such is the mechanism of effect of quinine and quinidine. But the medicine can induce formation of true autoantibodies, such, as at thermal autoimmune G. and. Such is the mechanism of action of alpha Methyldopum (dopegit). Can also be a causative factor mebedrol (Mephenaminum), a hlordiaza poksid (Elenium). After drug withdrawal all antibodies quickly disappear.
Clinical picture is defined by weight and localization of hemolysis. Forms easy and moderately severe prevail. The disease proceeds sharply, with the mixed localization of hemolysis. In serum find the antibodies agglutinating erythrocytes of the patient and healthy faces (in the presence of this drug).
Diagnosis is based on anamnestic data, positive direct test of Koombs with monospecific serums.
Treatment comes down generally to drug withdrawal, the caused G. and. Corticosteroids are effective only at G. and., caused alpha Methyldopum, but shall be applied carefully because of danger of increase of the ABP. At heavy anemia hemotransfusions are shown.
Isoimmune hemolitic anemias also the Rhesus factor of a fruit and mother can develop at newborns with incompatibility of the AB0 systems (see. hemolitic disease of newborns ), and also as a complication at hemotransfusions, too incompatible on the AB0 systems, a Rhesus factor and to its rare versions. These are posttransfusion hemolitic anemias (see. Hemotransfusion ). At isoimmune G. and. antibodies are found in serum at statement of indirect reaction of Koombs.
The acquired membranopathies
the Paroxysmal night Haemoglobinuria
the Paroxysmal night Haemoglobinuria (a synonym: Shtryubinga-Markiafava's disease, Markiafavy-Mikeli's disease) is considered as the acquired eritrotsitopatiya (heredo-familial forms of a disease are not revealed); arises owing to the vegetative mutation leading to emergence of abnormal population of erythrocytes. The monoclonal origin of this population of erythrocytes is proved. Hemolysis of erythrocytes is caused only by a complement, but is provoked by the most various, including fiziol., factors (a condition of a dream, at women — monthly); emergence of a haemoglobinuria is connected with shifts of acid-base equilibrium towards acidosis at the above-stated states. Also intercurrent infections, conditions of hypercoagulation of blood, medicines, hemotransfusion both integral (especially fresh), and plasmas can be provocative agents. The paroxysmal night Haemoglobinuria can begin a picture of a hypoplastic condition of a hemopoiesis; in some cases the characteristic picture of a disease is developed in 10 — 12 and more years after detection of hypoplasias of a hemopoiesis, sometimes after a splenectomy.
Clinical picture. The disease differs in a long current. Against the background of a haemoglobinaemia and a gemosiderinuriya there are paroxysms of a haemoglobinuria, a thicket night.
At a blood analysis reveal the expressed anemia of hypochromia type, moderate reduction of quantity of granulocytes and thrombocytes. Owing to a long gemosiderinuriya («iron diabetes») depots of iron in an organism are exhausted and the hyposideremia develops. Symptoms of hemolitic jaundice are noted: a hyperbilirubinemia (at the expense of not conjugated fraction), an urobilinuria, a pleyokhromiya of bile, a reticulocytosis. The liver and a spleen are not increased more often. Marrow giperplazirovan at the expense of elements of an erythrogenesis.
Complications. In the period of hemoglobinuric crises the disease quite often is complicated by a syndrome of hypercoagulation with the subsequent vascular fibrinferments in system of a portal vein, abdominal, brain, coronary vessels, at women, besides, and in vessels of a small pelvis that is followed. pains in a zone of thromboses. The bent to vascular fibrinferments is connected with receipt in blood of thromboplastic substances from the broken-up erythrocytes. Fibrinferments sometimes are complicated by heart attacks in various bodies; in particular fibrinferments in system of a portal vein lead to heart attacks of a spleen with development of a tromboflebitichesky splenomegaly and portal hypertensia. Transition of a paroxysmal night haemoglobinuria to a hyperplastic, myeloproliferative syndrome — an erythremic myelosis or an acute miyeloblastny leukosis is in rare instances observed.
Diagnosis the wedge, pictures of the continuous intravascular hemolysis which is followed more often by paroxysms of a night haemoglobinuria is put by means of specific laboratory tests (acid and saccharose tests), and also on the basis. Acid test, or Ham's test, is based on definition of sensitivity of erythrocytes to a complement of the fresh human serum acidified by addition of 0,2% of solution salt to - you to pH 6,5. Test is considered positive if more than 5% (sometimes to 50 — 80%) erythrocytes gemolizutsya. Saccharose test, or Hartmann's test — Jenkins, is based that erythrocytes of patients lyse in weak solution of sucrose in the presence of a complement. Test is considered positive when more than 4% of the studied erythrocytes are exposed to a lysis.
Treatment comes down to maintenance at optimum level of indicators of red blood by the systematic transfusions washed 3 — 5 times (fiziol, solution) erythrocytes or erythrocytes 7 — 10-day (term of an inactivation of a complement). Transfusion is fresher than whole blood and plasma contraindicated since it strengthens hemolysis. At a hyposideremia iron preparations in small, individually tolerant doses, in combination with anabolic hormones (Nerobolum, retabolil) are shown. At trombotichesky complications appoint heparin, sometimes in combination with fibrinolysin. Glucocorticoids (Prednisolonum) in the developed stage of a disease are contraindicated. In a hypoplastic phase of a disease all arsenal of the means applied at hypoplastic anemia — glucocorticoids, androgens, hemotransfusions is shown and transfusion of not washed fresh erythrocytes is admissible. At persistent thrombocytopenic bleedings the splenectomy is shown.
Forecast serious. The lethal outcome can come in an initial stage owing to an anemic coma against the background of thrombocytopenic bleedings, in the developed hemolitic stage — as a result of a vascular tromboticheskikh or septic complications, in rare instances from an acute leukosis.
Shporokletochny hemolitic anemia
Shporokletochnaya hemolitic anemia is described by J. A. Smith with sotr. (1964) at patients with severe forms of cirrhosis.
The etiology is unknown.
The pathogeny of a disease is connected with the excess content of cholesterol and insufficiency of phospholipids in a membrane of erythrocytes.
A clinical picture, treatment and the forecast as at microspherocytic G. and.
The diagnosis is based on detection in blood of erythrocytes with numerous small shoots.
The hemolitic anemias caused by a bruise of erythrocytes
the Mid-flight paroxysmal Haemoglobinuria
the Mid-flight paroxysmal Haemoglobinuria it is described for the first time by Fleischer (And. Fleischer, 1881) who observed it at the healthy soldier who made long pedestrian transition.
Etiology and pathogeny. Hemolysis of erythrocytes develops at physically strong young people in connection with the raised load of muscles of the lower extremities at long walking, a march, run, ski transition, and also on muscles of hands during the carrying out techniques of karate. According to Deyvidson (R. J. L. Davidson, 1964), mid-flight a haemoglobinuria arises at run on a solid surface (after run on a soft surface or with elastic insoles the Haemoglobinuria at the same persons does not develop in footwear). The contributing factor is the gipogaptoglobinemiya. In vessels of parts of a body, it is long experiencing collision with a rigid surface (feet of legs, hands), mechanical hemolysis locally develops.
Clinical picture it is characterized by soft disease, absence of fever and it is caused by intensity of an intravascular hemolysis. Heavy hemoglobinuric crises are possible, the moderate haemoglobinaemia and a haemoglobinuria, decrease in a gaptoglobin in serum is more often noted. Reference state of patients normal. Morfol, anomalies of erythrocytes are not noted.
Differential diagnosis with other gemoglobinuriya it is based on data of the anamnesis (communication of a disease with a mechanical factor, but not with cooling or drug intake) and results of erythrocyte tests (saccharose and acid). From mid-flight myoglobinurias (see) distinguishes absence of muscular pains, detection in urine of hemoglobin.
Treatment usually it is not required.
Prevention consists in change of conditions physical. loadings: sometimes it is enough to replace footwear with more elastic and to change technology of run completely to eliminate hemolysis of erythrocytes.
Disease Moshkovich (synonym mikroangiopatichesky G. and.) — the group concept designating G. and. at some patol, states caused by defeat of small vessels (arterioles) in combination with the disseminated intravascular coagulation (see. Moshkovich disease ).
The hemolitic anemias arising at prosthetics of valves of heart
At prosthetics of valves of heart G.'s development is possible and., what is caused by mechanical traumatization and a rupture of a membrane (fragmentation) of initially full-fledged erythrocytes of the patient. Develops at insufficiency of artificial valves of a left heart owing to the forced passage of blood at a systole of a ventricle through gaps between a prosthesis and a valve ring more often.
Clinical picture it is shown by intensity of an intravascular hemolysis which is more expressed at active behavior of the patient, than during the performance of a high bed rest by it. At a blood analysis find anemia, sometimes a hypochromia of erythrocytes, a reticulocytosis, a haemoglobinaemia, decrease or lack of a gaptoglobin in plasma. Existence morfol is characteristic. signs of fragmentation of erythrocytes (shistotsita, triangular and shlemovidny erythrocytes). Cases with positive direct test of Koombs are described. In urine find hemoglobin and hemosiderin.
Diagnosis it is based on data of the anamnesis, a blood analysis (signs of an intravascular hemolysis and fragmentation of erythrocytes) and urine (availability of hemoglobin and hemosiderin).
Treatment. At deep persistent anemia operation with reconstruction of a prosthesis is shown. In mild cases are limited to repeated hemotransfusions, purpose of iron preparations. Corticosteroids are not effective.
Toxic hemolitic anemias
Etiology. Numerous substances of the chemical and bacterial nature can cause hemolysis of erythrocytes. From chemical substances hemolysis (by interaction of arsenous sulfhydryl compounds), lead, salts of copper (due to oppression of a pyruvatekinase and other enzymes of eritrrtsit), potassium chlorates cause hydrogen arsenide more often and sodium, resorcin, nitrobenzene, aniline is more rare. G.'s cases are described and. at hyperbaric oxygenation, after a sting of bees, spiders.
Pathogeny. The mechanism of hemolysis can be various. Hemolysis can happen owing to the sharp oxidizing effect (as at enzimopenichesky anemias) overcoming normal protective mechanisms of erythrocytes owing to disturbance of synthesis of porphyrines, emergence of autoimmune factors, etc. Destruction of erythrocytes happens intravascularly more often. Toxic G. and. can develop at infectious diseases. The mechanism of hemolysis at some of them is known. So, Bartonella bacilliformis — plasmodiums of malaria get in erythrocytes which then eliminirutsya by a spleen. Clostridium welchii forms alpha toxin — the lecithinase interacting with lipids of a membrane of erythrocytes with formation of hemoliticly active lysolecithin. At a leushmaniosis hemolysis is connected with a splenomegaly. Also other mechanisms of hemolysis — adsorption of bacterial polysaccharides on erythrocytes with the subsequent formation of autoantibodies, destruction by bacteria of a surface layer of a membrane of erythrocytes with an exposure of T-antigen and a poliagglyutinabelnost of erythrocytes are possible.
Clinical picture and complications. On a current toxic G. and. can be acute and hron. At acute toxic G. and. there is an intravascular hemolysis which is shown by a haemoglobinaemia, a haemoglobinuria, in hard cases can be followed by the phenomena of a collapse and an anury. At hron, toxic G. and. the intracellular hemolysis bringing to gepato-and splenomegalies that is especially expressed at malaria and a visceral leushmaniosis prevails.
Treatment consists in the termination of contact with the toxic agent and use of the corresponding antidotes, and at the infectious diseases which are followed by G. and., therapies of basic process. At heavy anemia replaceable transfusions are shown. At an anury it is necessary to support a diuresis by introduction to an organism of liquid, in particular alkaline solutions. The amount of the entered liquid shall not exceed a daily urine.
Forecast. At an acute current toxic and. the lethal outcome is possible; at early detection and elimination of the reason of hemolysis the absolute recovery is observed. At hron, toxic G.' current and. the forecast also depends on early identification of a cause of illness and its elimination. The hemolysis accompanying some infectious diseases at treatment of an infection abates.
Aggregated data about the differential and diagnostic characteristic of G. and. are presented in the table.
At G. and. in connection with the increased destruction of erythrocytes are observed an anemia, jaundice (see), hyperplasia marrow (see), increase spleens (see) and liver (see), hemosiderosis (see) bodies and fabrics, multiple hemorrhages and fibrinferments of vessels, centers of extramedullary hemopoiesis (see). These changes are expressed in various degree depending on a form G. and. At all forms G. and. find fatty dystrophy of a myocardium, liver, quite often a necrobiosis and a necrosis of hepatic cells in the central departments of segments, cirrhotic changes are possible. In small vessels and capillaries reveal accumulations aggregated, sometimes gemolizirovanny erythrocytes.
Quite often observe hemorrhages in bodies and fabrics, fresh and old blood clots in vessels of portal system, lungs, a brain etc.
At hereditary G. and. on opening find the general jaundice, sometimes deformation of bones of a skull, often trophic ulcers standing. Marrow of flat and tubular bones juicy, red color, it is frequent with a rusty shade.
The spleen is considerably increased (to 3,5 kg), the capsule is thickened, there are fibrous commissures with surrounding fabrics, a cut surface of brownish-red color, heart attacks, focal growths of connecting fabric with adjournment of decomposition products of hemoglobin (so-called sclero-pigmental small knots) are frequent. Increase in a liver, limf, nodes, signs of an extramedullary hemopoiesis in bodies and fabrics in the form of dark red small knots is possible (tsvetn. fig. 4). There is a description of massive extra marrowy growths of the hemopoietic fabric in cellulose on the course of chest department of a backbone which are externally similar to tumoral educations. In a gall bladder and channels dense dark bile, often pigmental stones. At gistol, studying of marrow find its plethora, among cells cells of a red row — erythroblasts and normoblasts prevail, the quantity of myelocytes is quite often increased (tsvetn. fig. 3). There is a rassasyvaniye of a bone tissue with focal destruction of a cortical layer of a bone. In a spleen, a liver, marrow, limf, nodes the eritrofagiya but which was less expressed is constantly observed than at the acquired autoimmune G. and. Bodies and fabrics find the phenomena of a hemosiderosis, often at the same time and bezzhelezisty decomposition products of hemoglobin. Gistol, a picture at microspherocytic G. and.: follicles of a spleen are reduced, the red pulp is sharply full-blooded (tsvetn. fig. 2), venous sine in sites of a plethora have an appearance of narrow cracks. It is a lot of gemolizirovanny and breaking-up erythrocytes. Endothelium of sine always sharply giperplazirovan. In a red pulp — accumulations of unripe cells of a red row, segmentoyaderny leukocytes, lymphocytes. Sclerous changes are expressed in various degree.
At autoimmune G. and. the spleen is usually increased, however it is less, than at hereditary G. and.: weight it seldom exceeds 1 kg. At microscopic examination find a reduction of follicles, a plethora of a pulp, a hyperplasia of an endothelium of sine, signs of hemolysis of erythrocytes, sharply expressed eritrofagiya. Distinctiveness of autoimmune G. and. existence in a spleen is considerable focal (tsvetn. fig. 5) or a diffusion hyperplasia of reticular macrophages with the advent of huge forms [Rappaport, Crosby (H. Rappaport, W. H. Crosby), 1957; L. A. Danilova, 1960; J. V. Dacie, 1962; B. Pirofsky, 1969]. The specified cells show high enzymatic activity, their considerable proliferation corresponds to tension immunol, process at patients. Often observe a hemosiderosis of bodies. In gleams of tubules of kidneys erythrocytes and gemoglobinovy cylinders are sometimes visible. In marrow find a hyperplasia normo-and erythroblasts; quite often there are dystrophic changes of cells, development of sites of a hypoplasia is possible. In marrow limited educations from end-stage lymphocytes are described [André, Duhamel (R. Andre, G. Duhamel), etc., 1968]. At a symptomatic form of autoimmune G. and., developing at leukoses, described above morfol, signs of the raised kroverazrusheniye are also found (A. K. Ageev, 1964).
At a paroxysmal night haemoglobinuria on opening note signs of an anemia, quite often jaundice, multiple punctulate hemorrhages in integuments, serous and mucous membranes. Increase in the sizes and weight of kidneys, expansion of a bast layer which has brown-red color is characteristic. Often find widespread thrombosis in system of a portal vein, in a brain and its covers. Thereof in some cases reveal the centers of a softening of substance of a brain, heart attacks in various bodies, necroses of a wall of a small intestine. Unlike G. of ampere-second preferential intracellular hemolysis, there is no expressed increase in a spleen. The last is noted only at development of complications (thrombosis of a splenic vein and its intraorganic branchings, heart attacks). The liver is increased slightly. Marrow of flat and tubular bones juicy, dark red color, may contain dryish light pink or yellowish sites. At gistol, a research in kidneys constantly find massive deposits of hemosiderin in an epithelium of tubules, a thicket in their proximal departments. In gleams of tubules there can be accumulations of free hemoglobin, gemolizirovanny erythrocytes. Dystrophic changes of an epithelium and fibrosis of a stroma of kidneys are described. Adjournment of hemosiderin in other internals is observed only at appointment of hemotransfusions as the patient of large numbers. In a liver there is fatty dystrophy, quite often necroses in the central departments of segments, especially at fibrinferment of intra hepatic veins. In marrow along with a hyperplasia of nuclear cells of a red row the sites of devastation presented by an edematous stroma, lipoblasts can meet various size. Existence of fields of hemorrhages, expansion of a gleam of sine, accumulation in them of gemolizirovanny erythrocytes, eritrofagiya is characteristic. Increase in number of plasmatic and mast cells is possible. The quantity of granulocytes in marrow is reduced. Among megacaryocytes often observe degenerative forms. Other bodies and fabrics also find morfol, the changes accompanying disturbance of blood circulation. Along with fresh blood clots find in veins of various caliber also organized, with the phenomena of vascularization.
See also Anemia .
Table. Differential and diagnostic characteristic of hemolitic anemias
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Yu. I. Loriye; G. A. Alekseev (haemoglobinuria), M. P. Khokhlov (stalemate. An.), author of table Yu. I. Loriye.