Hemolitic anemias
Hemolitic anemias represent extensive bunch of the diseases differing on an aetiology, a pathogenesis, a clinical picture, treatment methods. The basic sign of hemolitic anemias is the raised erythrocytolysis and a shorting of duration of their life.
In physiological conditions lifetime of erythrocytes compounds 100-120 days. Growing old erythrocytes are exposed to a sequestration in lien sine, and also in an osteal brain. The pigment of bilirubin formed as a result of a physiological erythrocytolysis circulates in blood in the form of free (not conjugate) bilirubin which is transported in a hepatic cell where with the assistance of enzymes it is bridged to glucuronic acid. The formed bilirubin - a glucuronide (conjugate) inpours from hepatic cells into cholic courses and is excreted together with bile in an intestine.
At hemolitic anemias owing to the enhanced destruction of erythrocytes duration of their life is shortened to 12 - 14 days.
The pathological hemolysis can be mainly intracellular or intravascular. The intracellular erythrocytolysis descends in cells of reticulohistiocytic system, mainly in a lien, and is accompanied by rising in Serum of the maintenance of free bilirubin, augmentation of an egestion of an urobilin with urine and a feces, bent to formation of stones in a gallbladder and ducts. At an intravascular hemolysis haemoglobin arrives in the raised quantity in plasma and is excreted with urine in an invariable kind or in the form of a hemosiderin. Last can be postponed in an internals (hemosiderosis).
On flow the hemolysis can be acute or chronic.
All hemolitic anemias share on two big bunches: hereditary and acquired.
Hereditary hemolitic anemias are a consequence of various genetical defects in erythrocytes which become functionally defective and unstable.
The acquired, hemolitic anemias are bound to influence of the various factors promoting destruction of erythrocytes (antibody formation, hemolitic poisons, mechanical influences and so forth).
Hereditary hemolitic anemias
The hereditary microspherocytosis (spherocytic anaemia) has been described for the first time in 1900 Minkovsky, and further in more details - the Chauffard.
Aetiology and pathogenesis
At the heart of disease genetical defect of protein of a membrane of an erythrocyte lays. Available anomaly of a membrane leads to penetration into an erythrocyte of excess of ions of sodium and the raised accumulation into it of water owing to what orbicular erythrocytes (spherocytes) are formed. Spherocytes unlike biconcave normal erythrocytes do not possess ability to be deformed in narrow fields of a blood flow, for example at transition in lien sine. It conducts to retardation of progression of erythrocytes in lien sine, to eliminating of a part of a surface of an erythrocyte with formation of microspherocytes (from here the disease name - "microspherocytosis") and their gradual destruction. The blasted erythrocytes are absorbed by lien macrophages. The constant hemolysis of erythrocytes in a lien conducts to a hyperplasia of cells of its pulp and organ augmentation. In connection with the enhanced erythrocytolysis in Serum the maintenance of free bilirubin raises. Arriving in the raised quantity in an intestine bilirubin is deduced from an organism with urine and mainly with a feces in the form of a stercobilin. Daily abjection of a stercobilin at a hereditary microspherocytosis exceeds norm at 10-20 time. A consequence of the raised abjection of bilirubin in bile is pleyochromia biles and formation of pigmental stones and a gallbladder and ducts.
Pathoanatomical picture
The skin and internals at a hereditary microspherocytosis are acyanotic and icteritious. The osteal brain in flat and tubular bones is hyperplastic at the expense of an erythroidal sprout, the phenomena of an erythrophagocytosis macrophages become perceptible. In a lien sharply expressed blood filling of a pulp, a hyperplasia of an endothelium of sine, reduction of the dimensions and quantity of follicles are observed. In a liver, an osteal brain, lymph nodes the hemosiderosis is quite often taped.
Clinical picture
The clinic depends on expression of a hemolysis. In most cases first signs are taped at youthful or mature age. Disease is found in children usually at inspection concerning disease of their relatives.
Complaints out of a disease exacerbation can be absent. These patients, on a trope of the Chauffard, «more icteritious, than patients». In an exacerbation delicacy, giddiness, a fervescence become perceptible.
One of the basic clinical symptoms is the icterus which long time can remain a unique sign of disease. Expression of an icterus depends, on the one hand, on intensity of a hemolysis, and with another - from ability of a liver to a conjugation of free bilirubin with glucuronic acid. In urine bilirubin is not found, as free bilirubin does not pass through nephroses. The feces is intensively imbued in dark brown colour owing to the raised maintenance of a stercobilin.
In connection with predilection to a lithogenesis patients can have the attacks of a cloelithiasis quite often accompanied by signs of a cholecystitis. In case of an occlusion the obstructive jaundice syndrome (substantial increase of the maintenance of bilirubin, presence of cholic pigments in urine, a dermal itch, etc.) arises a stone of the general cholic duct.
Cardinal symptom of a hereditary microspherocytosis is the augmentation of a lien which usually acts from hypochondrium on 2 - 3 see At is long a proceeding hemolysis the appreciable splenomegaly in this connection patients complain of gravity in left hypochondrium, a liver is observed at uncomplicated disease of usually normal dimensions, but sometimes at patients, is long suffering a hemolitic anaemia, it is enlarged.
Bradygenesis signs, and also disturbances of a facial atomy in the form of a tower skull, a saddle-like nose, high standing of the sky, disturbance of a locating of dens, narrow orbits can be observed.
Expression of an anaemic syndrome is various. Moderate depression of haemoglobin often becomes perceptible. At some patients the anaemia in general is absent. The sharpest ischaemisation is observed in hemolitic crises.
Persons of an average and advanced age sometimes have badly curable trophic ulcers of an anticnemion bound to agglutination and an erythrocytolysis in fine capillars of extremities.
Disease flow is characterised by the so-called hemolitic crises, showing sharp intensifying of symptoms against continuously current hemolysis. The body temperature in connection with a mass erythrocytolysis thus raises, intensity of an icterus is enlarged, there are strong abdominal pains, vomiting. Hemolitic crises arise usually after intercurrent infection contaminations, a frigorism, at women in connection with pregnancy. Frequency of crises is various, at a number of patients they do not arise.
Hematological picture
The anaemia at a hereditary microspherocytosis has normochromic character. In a blood smear the microspherocytes, differing absence characteristic for normal erythrocytes of the central clarification prevail. Prevalence of microcytes on a Price-Jones curve reflecting quantitative interrelations of erythrocytes of various diameters (average diameter of a normal erythrocyte compounds 7 - 7,5 microns). At a hereditary microspherocytosis the Price-Jones curve fastigium is stretched and shifted to the left towards microcytes. The quantity of reticulocytes is enlarged. Number of leucocytes usually normally. At hemolitic crises it becomes perceptible neutrophilic a leukocytosis with alteration to the left. The quantity of thrombocytes varies within norm. In an osteal brain the expressed hyperplasia of an erythroidal sprout becomes perceptible.
The indirect bilirubin maintenance in blood is raised moderately and, as a rule, does not exceed 50 - 70 mkmol/l. The raised maintenance of an urobilin in urine and a stercobilin in a feces is defined.
The diagnosis
Hereditary microspherocytosis diagnose on the basis of disease flow (alternating of crises and remissions), a clinical picture (an icterus, a splenomegaly, pains in right hypochondrium, an anaemia), data of research of peripheric blood (a normochromic anaemia, a reticulocytosis, a microspherocytosis). The Great value has inspection of relatives of patients at which almost inaudible signs of a hemolysis or a microspherocytosis without clinical implications can be defined.
Differential diagnostics
Differential diagnostics of a hereditary microspherocytosis is reduced first of all to diagnostics of a hemolitic anaemia in general and demands an exception of variety of diseases.
The hemolitic crisis accompanied by an anaemia, leukocytosis with the expressed alteration to the left, appearance in blood of normocytes, a hyperplasia of an erythroidal sprout of an osteal brain at insignificant augmentation of quantity of undifferentiated cells, along with lien augmentation quite often gives a causing to erroneous diagnostics of some forms of leukoses, in particular an acute erythremic myelosis.
At differential diagnostics of a hereditary microspherocytosis with other hemolitic anemias it is necessary to exclude autoimmune hemolitic anemias. The correct diagnosis is promoted by the Coombs'test taping autoantibodies fixed on erythrocytes at autoimmune hemolitic anemias.
There are bunches of the hemolitic anemias caused by insufficiency of various enzymes in erythrocytes and proceeding in the form of chronic hemolitic anemias. Unlike a hereditary microspherocytosis at the given forms there is no spherocytosis in this connection these anemias have received the name not the spherocytic. In favour of the last the normal or slightly enlarged osmotic resistance of erythrocytes, autohemolysis rising, not resolve a glucose, revealing of insufficiency of various enzymes in erythrocytes testify along with absence of a spherocytosis.
Treatment
Unique method of treatment sick of a hereditary microspherocytosis is the splenectomy which appears effective in 100 % of cases. After a splenectomy at patients there comes practical treatment in spite of the fact that erythrocytes keep the pathological properties (a microspherocytosis, depression of osmotic resistance). The termination of a hemolysis after a splenectomy speaks excision of the basic base of destruction of microspherocytes.
The splenectomy is shown at frequent hemolitic crises, a sharp anemisation of patients, lien infarcts, attacks of a hepatic colic. In the presence of the conforming indications in some cases simultaneously with a splenectomy the cholecystectomia can be effected. At the easy compensated forms of disease at adults of the indication to a splenectomy it is necessary to confine. As preoperative preparation anemisation patients transfusions erythrocytes masses are shown. Appointment of glucocorticoid hormones at a hereditary microspherocytosis noneffectively.
The forecast
At a hereditary microspherocytosis the forecast rather congenial. Many patients live till an old age.
At medicogenetic consultations of the spouses, one of which is sick of a microspherocytosis, it is necessary to explain, that probability of occurrence of disease at children a little bit more low 50.
The hereditary hemolitic anemias bound to deficiency of activity of enzymes
The hereditary hemolitic anemias bound to deficiency of activity of enzymes. This impure bunch of diseases is designated also as not spherocytic hemolitic anemias. Unlike a microspherocytosis they are characterised by a normal form of erythrocytes with the tendency to a macroplanocytosis, the normal or raised osmotic resistance of erythrocytes, a recessive mode of inheritance, absence of effect from a splenectomy. At the heart of a pathogenesis of not spherocytic hemolitic anemias deficiency of activity of some enzymes of erythrocytes therefore erythrocytes become sensitive to influence of various vegetable matters, medical products lays.
The most widespread among this bunch of diseases is the acute hemolitic anaemia bound with Glucose-6-Phosphate Dehydrogenase deficiency (G6PD). According to data the WHO, in the world is about 100 million humans with deficiency of activity G6PD. Most often this anomaly meets in the countries of the Mediterranean coast (Italy, Greece), some countries of Latin America and Africa.
Aetiology and pathogenesis
Deficiency G6PD is inherited on the recessive type linked to a floor in this connection clinical implications of the given pathology are observed mainly at men.
At low activity G6PD in erythrocytes processes of restoration and metamorphosis of the oxidised glutathione into the recovered, protecting erythrocyte from blasting action of potential hemolitic agents (the phenylhydrazine, some medical products, fabaceous, etc.) are broken. The hemolysis descends mainly intravascular by.
Pathoanatomical picture
Skin and internals icteric. The augmentation and a liver and lien plethora, moderate augmentation and a swelling of nephroses becomes perceptible. It is microscopically in renal canaliculuses find haemoglobin keeping cylinders. In a liver and a lien macrophagal reaction with presence in a hemosiderin macrophage is observed.
Clinical picture
Deficiency G6PD, as a rule, shows only at influence of hemolitic agents. Provoke a hemolitic crisis antimalarial preparations, Sulfanilamidums, the analgetics some chemio preparations (a nitrofurantoin, Paraaminosalicylic acid), vitamin K, vegetative products (fabaceous, siliculose) can.
Expression of hemolitic process depends on degree of deficiency G6PD and from a dose of the accepted preparation. The hemolysis comes not at once, and through 2 - 3 days after reception of preparations. In serious cases patients have heat, sharp delicacy, an abdominal pain and a back, abundant vomiting. The expressed dyspnea, palpitation become perceptible, collaptoid state development is frequent. A characteristic symptom is abjection of dark urine, sometimes black colour that is bound to an intravascular erythrocytolysis and abjection with hemosiderin urine. In some cases owing to an occlusion of renal canaliculuses decomposition products of haemoglobin and sharp depression of a glomerular filtration development of acute renal insufficiency is possible. At objective research the icteric coloration of integuments and mucosas, lien augmentation becomes perceptible, is rarer a liver, In a week the hemolysis stops, irrespective of, reception of a preparation proceeds or not.
Hematological picture
Within first two days of a hemolitic crisis at patients the expressed normochromic anaemia with falling of a haemoglobin content to 30 g/l and more low educes. The high reticulocytosis, presence of normocytes in blood become perceptible. Feature of erythrocytes is presence at them Heinz's representing denaturated haemoglobin of little bodies. Osmotic resistance of erythrocytes normal or is raised. During a crisis the leukocytosis with alteration to the left to myelocytes and younger forms becomes perceptible. In an osteal brain the hyperplasia of an erythroidal sprout and the erythrophagocytosis phenomenon are observed.
The diagnosis
The acute hemolitic anaemia bound to deficiency G6PD, diagnose on the basis of a typical clinico-hematological picture of an acute intravascular hemolysis, communication of disease with a drug intake and the given laboratory researches taping depression of activity G6PD in erythrocytes of patients, and sometimes their relatives. At diagnostics it is necessary to consider geographical prevalence of deficiency G6PD.
Acquired hemolitic anemias
Acquired hemolitic anemias. The autoimmune hemolitic anaemia is most often meeting disease among acquired hemolitic anemias. It is caused by appearance in an organism of the patient of antibodies to own erythrocytes which agglutinate and are exposed to disintegration in cells of reticulohistiocytic system.
Aetiology and pathogenesis
Distinguish symptomatic and idiopathic autoimmune hemolitic anemias.
Symptomatic autoimmune anemias arise against the various diseases accompanied by disturbances in immunocompetent system. Most often they meet at a chronic lymphoid leukosis, a lymphogranulomatosis, paraproteinemic hemoblastoses, a system lupus erythematosus, a pseudorheumatism, chronic hepatitises and liver cirrhosises.
When appearance of autoantibodies does not manage to be bound to any pathological process, speak about an idiopathic autoimmune hemolitic anaemia which compounds about 50 % of all autoimmune anemias.
Clinical flow
On clinical flow excrete an acute and chronic autoimmune hemolitic anaemia. At acute forms of an autoimmune hemolitic anaemia patients subitaneously have a sharp delicacy, palpitation, a dyspnea, a fever, an icterus. At chronic forms disease educes gradually. The general condition of patients variates a little. The dyspnea and palpitation can be absent, despite the expressed anemisation that is bound with. Gradual acclimatisation of patients to a hypoxia. The lien augmentation is objectively taped, is rarer - a liver. At the autoimmune anaemia bound to cold agglutinins (cold agglutinins disease), become perceptible bad tolerate-most colds and development on a cold of such symptoms, as an urticaria, a Raynaud's syndrome, a hemoglobinuria.
Disease flow is characterised predilection to exacerbations (hemolitic crises) under the influence of infection contaminations, more often virus, or at cold influence.
Hematological picture
In peripheric blood normochromic or moderately hyperchromatic anaemia of various degree, a reticulocytosis, presence erythronormoblast become perceptible. The microspherocytosis of erythrocytes is quite often observed. For an autoimmune hemolitic anaemia with cold agglutinins the agglutination of erythrocytes observed right after of a capture of blood and in a smear is characteristic. At warming up agglutination disappears. Osmotic resistance of erythrocytes is in most cases lowered. The quantity of leucocytes at idiopathic forms is subject to fluctuations. In case of an acute hemolitic crisis there is a leukocytosis alteration to the left to myelocytes. At chronic forms quantity of leucocytes close to norm. The number of thrombocytes is not variated. An ESR it is strongly enlarged. In an osteal brain sharply expressed hyperplasia of an erythroidal sprout is observed.
Among laboratory signs of an increased hemolysis the augmentation of the maintenance of the indirect bilirubin, the raised egestion of a stercobilin with a feces become perceptible.
The diagnosis
The diagnosis of an autoimmune hemolitic anaemia is put on the basis of increased hemolysis signs, on the one hand, and revealings fixed on a surface of an erythrocyte of antibodies with another. The basic method of revealing on erythrocytes of autoantibodies is Coombs'test.
Differential diagnostics
At differential diagnostics of an autoimmune hemolitic anaemia it is necessary to mean hemolitic anemias of other parentage first of all
Treatment
Choice agent at treatment of an autoimmune hemolitic anaemia are glucocorticoid hormones which practically always stop or reduce a hemolysis. A necessary condition of hormonal therapy is the sufficient dosage and duration.
Hemolitic anaemia with a constant hemosiderinuria and a paroxysmal night hemoglobinuria (Marchiafava-Micheli disease)
Clinical picture
Patients complain of delicacy, giddinesses, a dyspnea, palpitation. A characteristic sign are abdominal pains of various localisation and the intensity, observed, as a rule, in a crisis and bound to capillary clottages of mesenteric pots. Clottages of peripheric pots, more often in veins of the top and inferior extremities, and also other pots (cerebral, lienal, renal) quite often become perceptible. In a crisis at patients the body temperature can raise.
Typical sign of disease is appearance of urine of the black light caused by abjection with urine of a hemosiderin and haemoglobin. Quite often the hemoglobinuria takes place at night (a paroxysmal night hemoglobinuria). This phenomenon speaks a physiological acidosis coming during a sleep, activation of a properdin and other factors intensifying a hemolysis. The hemoglobinuria is not an obligatory symptom of disease.
At objective research pallor of a skin with a small icteric shade, moderate augmentation of a lien and a liver is taped.
The anaemia has for a long time normochromic character. At appreciable losses with urine of iron in the form of haemoglobin and a hemosiderin the colour indicator becomes below norm. The quantity of reticulocytes is raised slightly. The leukopenia and a thrombocytopenia is often observed. In an osteal brain the hyperplasia of an erythroidal sprout accompanied quite often by oppression granulocytic and megakaryocytic of sprouts becomes perceptible.
The diagnosis
Marchiafava-Micheli disease can be at patients with a hemolitic anaemia, refractory to the treatment, accompanied leukocytic and trombocytic without lien substantial growth. The important diagnostic value has a microscopy of an urocheras for the purpose of revealing of a hemosiderinuria and a positive benzidine test with urine.
Among laboratory tests in diagnostics Marchiafava-Micheli disease following tests are used: the acid test of the Boor (a hemolysis of erythrocytes of the patient in acidified human Serum), the test of Crosby (intensifying of a hemolysis under the influence of Thrombinum), the saccharose test (a hemolysis of erythrocytes of patients in fresh donor blood at sucrose addition).
Treatment
The most effective method of treatment is transfusion of the erythrocytes preliminary three times washed by isotonic solution of Sodium chloridum. Such erythrocytes pour time in 4 - 5 days in number of 200 - 400 ml, and not later than 48 hours after a capture. For preventive maintenance and treatment of clottages anticoagulant therapy is shown. In a hemolitic crisis some reduction of a hemolysis is reached at introduction of plasma substitutes, in particular a dextran or Rheopolyglucin in number of 500 - 1000 ml. Iron preparations are shown at development of deficiency of iron. Apply anabolic hormones (Nerobolum), and also vitamin E and its preparations (Erevitum), making antioxidatic impact.
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