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Paroxysmal night haemoglobinuria

The Paroxysmal Night Haemoglobinuria (PNH), or Markiafava's illness — Mikeli (an illness of Shtryubinga — Markiafava), belongs to group of the acquired hemolitic anemias caused by changes of structure of a membrane of the erythrocytes proceeding with their intravascular hemolysis.

Epidemiology
The paroxysmal night haemoglobinuria is among rare forms of hemolitic anemia. On 500 000 healthy faces 1 case of this disease meets.

Etiology and pathogeny
Deficiency of structure of their membrane which causes hypersensitivity of erythrocytes to a serum complement is the cornerstone of the most expressed clinical syndrome of a paroxysmal night haemoglobinuria. Erythrocytes easily collapse a complement at optimal conditions of its action (acid medium, concentration of a complement around erythrocytes, etc.) . At a paroxysmal night haemoglobinuria leukocytes and thrombocytes, as well as erythrocytes, are also characterized by structural deficiency of their membranes. Absence on a surface of these cells of immunoglobulins speaks well for the fact that the paroxysmal night haemoglobinuria does not belong to autoagressivny diseases. The saved-up data confirm existence of two independent populations of erythrocytes — pathological (not living up to maturing) and healthy. Uniformity of defeat of a membrane of erythrocytes, leukocytes and thrombocytes is argument in favor of the fact that with the greatest probability pathological information is obtained by the general cell predecessor of a myelopoiesis. The leading role in genesis of trombotichesky complications belongs to intravascular destruction of erythrocytes and stimulation of process of coagulation by the factors which are released at their disintegration.

Classification
Allocate an idiopathic form of a paroxysmal night haemoglobinuria and a paroxysmal night haemoglobinuria in the form of the syndrome accompanying a number of diseases. Seldom also peculiar option of an idiomatic paroxysmal night haemoglobinuria which development is preceded by a hemopoiesis hypoplasia phase meets.

Approximate formulation of the diagnosis:
Paroxysmal night haemoglobinuria with intravascular hyper hemolysis, a gemosiderinuriy, iron deficiency anemia, strengthening of an erythrogenesis in marrow.

Clinic
The disease develops gradually, sometimes sharply, with developing of hemolitic crisis more often. The infection, intoxication, contact with toxic substances can precede it.
At patients weakness, an asthma, heartbeat, dizziness, yellowness of scleras and integuments, urine of dark color, headaches, sometimes abdominal pains, thrombophlebitises of various localization are noted.

Anemia, reticulocytosis, leucio-and thrombocytopenia — characteristic signs of a gemogramma. As at a paroxysmal night haemoglobinuria mainly intravascular hyper hemolysis takes place, the level of free hemoglobin of a blood plasma increases. In the period of hemolitic crisis when the system of gaptoglobin cannot connect all hemoglobin which is released at an erythrocytolysis, hemoglobin passes through the renal filter and there is a haemoglobinuria. It is a characteristic, but not obligatory symptom of an illness. More constantly the gemosiderinuriya comes to light. As a result of systematic loss of iron with urine deficit of iron which plays a part in genesis of anemia often develops.

In a miyelogramma usually find signs of strengthening of an erythrogenesis. In a marrow bioptata a hyperplasia of the hemopoietic fabric due to increase in quantity eritro-and normoblasts, accumulation of gemolizirovanny erythrocytes in gleams of expanded sine, sites of hemorrhages. Increase in number of plasmatic and mast cells is possible. The quantity of granulocytes and megacaryocytes is, as a rule, reduced. At certain patients the fields of a devastation provided by an edematous stroma, lipoblasts can come to light. Noticeable increase in fatty tissue in marrow is found out when the disease is followed by development of a hypoplasia of a hemopoiesis.

At a paroxysmal night haemoglobinuria increase in a liver and spleen at development in it of thromboses, heart attacks quite often meets. The hemosiderosis of internals, behind an exception, kidneys is uncharacteristic. Quite often there are infections and the trombotichesky complications which are a cause of death.

Verification of the diagnosis
The differential diagnostic characters inherent in autoimmune hemolitic anemias and a paroxysmal night haemoglobinuria are provided in the table.

Differential diagnosis of the acquired hemolitic anemias

Signs

Autoimmune hemolitic anemia

Paroxysmal
night haemoglobinuria

Anemia

+

+

Increase of level of free fraction
blood serum bilirubin

+

+

Fever

+

+

Koombs's test

+

-

Jaundice

+

+

Increase of level of free hemoglobin of a blood plasma

-

+

Gemosiderinuriya

-

+

Test Ham (acid)

-

+

Test Hartman (saccharose)

-

+

Increase in a spleen

±

±

Increase in a liver

±

±

Fibrinferments

±

+

 

Ham's test (acid test) and Hartman's test (saccharose test) as they are based on the sign, most characteristic of this disease — hypersensitivity of APG-defective erythrocytes to a complement are specific to a paroxysmal night haemoglobinuria.

The paroxysmal night haemoglobinuria can begin with the previous hemopoiesis hypoplasia, sometimes it arises also at later stages. At the same time cases meet emergence at various stages of an illness of signs of an intravascular hemolysis, positive acid and sugar tests. In such cases speak about APG syndrome shout hypoplastic anemia. Patients at whom development against a paroxysmal night haemoglobinuria of an acute miyeloblastny leukosis and an erythremic myelosis, a tranzitorny syndrome of a paroxysmal night haemoglobinuria at an acute miyeloblastny leukosis, an osteomyelosclerosis and metastasises of cancer in marrow was observed are described. At hereditary dizeritropoetichesky anemia with multinuclear normoblasts the positive test of Ham can come to light.

In certain cases it is necessary to carry out differential diagnosis between a paroxysmal night haemoglobinuria and autoimmune hemolitic anemia with thermal hemolysins when saccharose test can yield false positive result. The correct diagnosis is helped by the cross saccharose matching with use of blood serum of the patient and erythrocytes of the donor revealing availability of hemolysins.

Treatment of a paroxysmal night haemoglobinuria

The main method of therapy of patients with a paroxysmal night haemoglobinuria are transfusions washed (not less than 5 times) or the defrozen erythrocytes which, as a rule, are well transferred by patients for a long time and do not cause an isosensitization. Transfusions of svezhezagotovlenny whole blood or eritrotsitny weight period of storage less, 7 days are contraindicated because of a possibility of strengthening of hemolysis, development of crises of a haemoglobinuria owing to presence at these transfusion environments of leukocytes that leads to formation of antileukocytic antibodies and complement activation.

The volume and frequency of transfusions depend on a condition of the patient, degree of manifestation of anemia and the response to the carried-out hemotransfusionic therapy. At patients with a paroxysmal night haemoglobinuria at frequent transfusions anti-erythrocyte and antileukocytic antibodies can be developed.

In these cases eritrotsitny weight is selected for indirect test of Koombs, it is washed repeatedly normal saline solution.

At treatment of a paroxysmal night haemoglobinuria Nerobolum in a daily dose of 30 — 50 mg within not less than 2 — 3 months is applied. However at a number of patients after drug withdrawal or during treatment fast strengthening of hemolysis is observed. Sometimes administration of drugs of this group is followed by change of functional trials of a liver, as a rule, having reversible character.

At patients with a paroxysmal night haemoglobinuria in connection with continuous loss of iron its deficit in an organism often develops. As against administration of drugs of iron hemolysis strengthening is quite often observed, it is necessary to apply them per os and small doses. Heparin or anticoagulants of indirect action are applied at trombotichesky complications. In rare instances of a splenomegaly with development of the expressed syndrome of a hypersplenism there can be justified a splenectomy.

 
"Relative polycythemia   Partial krasnokletochny aplasia"