Thrombocytopenia

Thrombocytopenia - A group of diseases, in which the number of platelets in the blood below normal, t. it is. less 150 T in 1 l.

Reducing the number of platelets can be caused by their increased destruction or increased consumption and lack of education. The most common trobotsitopeny pathogenesis associated with increased platelet destruction.

There are hereditary and acquired thrombocytopenia. In many hereditary thrombocytopenia observed changes in various functional properties of platelets, which gives grounds to attribute the disease to a group thrombocytopathy. Described isolated cases of thrombocytopenia, related to violation of the activity of enzymes of glycolysis or the citric acid cycle (Krebs), as well as the inherited disorder the body's trombotsitopoetinov.

Acquired thrombocytopenia share of damage genesis megakaryocyte-platelet unit to immune and forms, caused by mechanical traumatization of platelets (when hemangiomas, splenomegaly and others.), inhibition of proliferation of bone marrow cells (when aplastic anemia, chemical and radiation damage to bone marrow), substitution of bone marrow tumor tissue, somatic mutation (in paroxysmal nocturnal hemoglobinuria), increased consumption of platelets (thrombosis, DIC and others.), deficient in the body cobalamin or folate.

Immune thrombocytopenia, in turn, divided into four groups:

• alloimmune, in which platelet destruction due to the incompatibility of one of the blood group systems, or transfusion recipient of foreign platelets in the presence of antibodies to them, or penetration of antibodies in the body of the child from the mother, previously immunized with antigen, its lack of, but having a child;
• transimmunnye, in which auto-antibodies Mother, suffering from autoimmune thrombocytopenia, cross the placenta and cause the development of thrombocytopenia in a child;
• geteroimmunnye, associated with the violation antigenic structure platelet influenced virus or a result of a new antigen or hapten;
• Autoimmune, where antibodies are produced against one's own unmodified antigen.

Immune thrombocytopenia They occur most frequently, and is usually seen in children geteroimmunnye options, and adults - autoimmune. In general, the most recent marked.

Depending on, directed against an antigen antibody, autoimmune thrombocytopenia can be divided into two groups:

• with anti-platelet antigen;
• with antibodies against the antigen of megakaryocytes.

If the cause can not be identified autoaggression, autoimmune thrombocytopenia is referred to as idiopathic, where, when it is a consequence of a primary disease like symptomatic.

Autoimmunnaya thrombocytopenia

The etiology and pathogenesis of autoimmune thrombocytopenia

IN 1915 g. it has been suggested, that disease is based on a violation of maturation of megakaryocytes in some factor, perhaps, located in the spleen. This hypothesis has been recognized for many years, its use in indicating the presence of a large number of bone marrow megakaryocytes young, no halo around megakaryocytes Platelet.

IN 1916 g. Kaznelson suggested, that in idiopathic autoimmune thrombocytopenia, or thrombocytopenic purpura, there is increased destruction of platelets in the spleen. However, histological examination did not confirm this assumption.

Studies with labeled platelets showed, In all cases, thrombocytopenic purpura is a sharp reduction in life expectancy of cells - a few hours instead of 7-10 days.

Proved, what in most cases thrombocytopenic purpura platelet count, produced per unit time, is not reduced, as previously assumed, and significantly increased compared to the norm - from 2 to 6 time. Increasing the number of megakaryocyte and platelet overproduction associated with increased amounts trombotsitopoetinov in response to low platelet counts in peripheral blood.

Number of activity of megakaryocytes not reduced, and increased. A large number of young megakaryocytes, rapid cleavage of platelets from megakaryocytes and their quick exit in circulation creates visually mistaken impression, that megakaryocytes when thrombocytopenic purpura inactive.

In contrast to the hereditary forms of thrombocytopenic purpura, where the reduction in life expectancy due to defective platelet membrane structure of their energy or platelets in connection with violation of the activity of enzymes of glycolysis or the citric acid cycle, the destruction of platelets in immune thrombocytopenia consequence of exposure to antibody. Where, when the amount of anti-platelet antibodies is very large or when the antibodies are directed against an antigen of megakaryocytes, absent on the surface of platelets, possible violation of megakaryocytes Education.

First JavaScript humoral factor in plasma of thrombocytopenic purpura patient proved to Harrington 1951 g. Statement by introducing plasma patient thrombocytopenic purpura, whereupon develop thrombocytopenia with appropriate short-term symptomatic.

The most common antibodies in the immune thrombocytopenia incomplete, fixed on platelets, impairing their function, contribute to their death, but do not cause agglutination.

The method tromboagglyutinatsii identified only complete antibodies, causing agglutination when mixed with the patient's serum platelet donor. Besides, antibodies often found on the cell surface, but not in serum. Therefore tromboagglyutinatsii method rarely gives a positive result with a clear negative control. Often agglutination occurs not only in the experience, but also in the control, due to platelet aggregation, virtually indistinguishable from agglutination. Therefore it is impossible to determine the use of anti-platelet antibodies, not only the method tromboagglyutinatsii, but also the direct and indirect Coombs test.

Test Steffen, It is widely used to determine the anti-platelet antibodies, It based on the definition of consumption antiglobulin. However, its sensitivity is negligible due to the insensitive method antiglobulin test. Besides, This test is most often placed in the indirect form, when used to determine the serum of patients, and therefore often gives false- a positive result when using donor sera and sera from patients with other diseases.

A more sensitive and reliable detection methods are antiplatelet antibodies, based on the determination of the ability of serum antibodies patient platelets damaging human health and the identification of the decay products of the platelet.

In the study by You could too-Siskinds It is determined by the rate of release factor 3 Platelet. Thus, most patients thrombocytopenic purpura serum antibodies detected, belonging to the class IgA (3-it subklassa). These antibodies can be eluted from extracts of spleen, remote patient thrombocytopenic purpura.

It is also used test release of platelets under the influence of serum of patients labeled serotonin.

But sensitivity of these methods is also limited to a certain extent, as they allow you to identify only serum antibodies, It is not available for all patients; Besides, these methods do not allow to differentiate from his- and autoantibodies.

Method Dickson It based on the quantitative determination of antibodies against platelet surface. Established, that the content of immunoglobulin class G on the platelet surface in a healthy person reaches 14*10^-15 g. When immune thrombocytopenia increases to the number of its 20*10^-15 - 250*10^-15 g. This method of detection of antiplatelet antibodies most informative, but it is very time consuming and therefore can not be recommended for widespread use in practice. Besides, there is a lower limit of the number of platelets, with which to investigate the number of antibodies on their surface.

With a very low platelet count (less 50000 in 1 l) Dixon method is unacceptable.

In addition to the method of Dixon, Study of antiplatelet antibodies can be performed using purified antibodies, labeled with radionuclides or enzymes, or using immunofluorescence. The latter method is very simple, but due to the fact, that normal platelets contain immunoglobulins, It is sometimes difficult to distinguish normal from disease. The use of paraformaldehyde partially eliminates nonspecific glow, leaving (According to the author) only then, which is associated with the antibody. However, even with this technique can be observed non-specific fluorescence.

Clinical manifestations of autoimmune thrombocytopenia

Most often the disease begins acutely and is characterized by recurrent or, or protracted; it is sometimes possible gradual development of the disease.

The traditional division thrombocytopenic purpura acute and chronic forms (while under chronic form of idiopathic thrombocytopenia meant, substantially, autoimmunnaya thrombocytopenia, and under acute - geteroimmunnaya) It can not be considered successful, because the nature of the first clinical manifestations of the disease, thereby preventing each case thrombocytopenic purpura in a particular form of nosology.

Idiopaticheskaya autoimmunnaya thrombocytopenia, purpura or trombotsitopenicheskaya, develops without apparent connection with any previous illnesses, as observed in symptomatic chronic lymphocytic leukemia, multiple myeloma, active hepatitis, systemic lupus erythematosus, revmatoidnom ARTHRO. In connection with the common pathogenesis of idiopathic and symptomatic autoimmune thrombocytopenia often occur in the same, but a certain influence on the nosology of the clinical course of the disease persists.

Thrombocytopenic hemorrhagic syndrome, observed in idiopathic autoimmune thrombocytopenia, characterized by bleeding in the skin and bleeding from mucous membranes. Hemorrhage may take the form of ecchymosis, often localized on the extremities, trunk, mainly on the front surface; may cause bleeding at the injection site. Petechiae usually occur in the lower extremities. Sometimes bleeding appear on the face, conjunctivitis, lips. Their appearance indicates the possibility of a brain hemorrhage. Samples for capillary fragility often positive. Increasing the size of the spleen and liver characterized.

Laboratory findings in autoimmune thrombocytopenia

In the study of peripheral blood platelet count decrease recorded (sometimes up to their complete disappearance) with normal or elevated levels of plasma clotting factors.

Talking about critical, threshold platelet count, that they exhibit signs of hemorrhagic diathesis, It does not seem possible, since this figure depends on the nature of the lesion and platelet functional state. Where, when the platelet count is greater than 50 T in 1 l, hemorrhagic diathesis rarely observed.

You may experience morphological changes of platelets - increase their, sometimes significantly, blue appearance of platelets with little graininess. May appear small forms platelets, celebrated their poikilocytosis. Reduces the number of process forms, vыyavlyaemыh in phase-kontrastnom issledovanii.

The content of erythrocytes and hemoglobin may be normal. Sometimes there hemorrhagic anemia. In some patients, there is a combination of autoimmune thrombocytopenia with autoimmune hemolytic anemia.

RBC morphology depends, whether the patient anemia and the nature of it. The degree of reticulocytosis determined by the intensity of blood loss or hemolysis. The content of leukocytes in most patients with normal or slightly increased. Leukopenia occurs while the defeat of two or three shoots hematopoiesis. Some patients revealed eosinophilia.

Most patients have an increase in the number of megakaryocytes in the bone marrow, sometimes the content does not exceed the norm. Temporary reduction in the number of megakaryocytes until their complete disappearance can be observed only in exacerbation of the disease. Often found increased megakaryocytes, dominated by young cell shape.

When thrombocytopenic purpura megakaryocytes are no different from the usual, except, around them are rarely seen platelets. This is not due to impaired platelet otshnurovki of megakaryocytes, a quick otshnurovkoy platelet circulation and to the large number of young megakaryocytes, incapable otshnurovke. Therefore wrong to say in the conclusion of impaired platelet otshnurovke thrombocytopenic purpura. Sometimes found stimulation of red bone marrow germ, associated with increased bleeding or hemolysis.

The histological specimens of bone marrow is found in most patients a normal relationship between fat and bone marrow; the number of megakaryocytes, usually, the majority of patients increases.

Bleeding time, determined by the method of Duke and especially, by metodu Ivey modifications Barhgrevinka, often increased.

The retraction of a blood clot is reduced. Blood clotting is normal in most patients. Do not change parameters and kaolin-kefalinovogo autokoagulyatsionnogo test. Often seen in autoimmune thrombocytopenia platelet functional disorders; a number of patients reduced their adhesion to glass, violated the ADF, Thrombin- and kollagenagregatsiya.

Diagnosis of idiopathic autoimmune thrombocytopenia

Diagnosis of idiopathic autoimmune thrombocytopenia, or thrombocytopenic purpura, based on characteristic clinical picture and results of laboratory tests.

The first stage of the differential diagnosis It involves the exclusion of the patient aplasia of hematopoiesis, Leukemia, paroxysmal nocturnal hemoglobinuria, B₁₂-deficiency anemia, cancer metastasis, what made sternal puncture, Bone marrow biopsy, investigated hemosiderin in urine.

In paroxysmal nocturnal hemoglobinuria in the bone marrow as a result of somatic mutation formed platelets, red blood cells and white blood cells with defective membrane, easily destroyed in peripheral blood under the influence of the complement. Although thrombocytopenia, sometimes expressed in this disease, bleeding is rare, there is a tendency to thrombotic complications.

Thrombocytopenia combined with macrocytic hyperchromic anemia occurs when the body methylcobalamin deficiency or folic acid as a result of violation of the division of cells in the bone marrow due to violation of the formation of DNA. Wherein the degree of thrombocytopenia often small and, except in the rarest of cases, bleeding in patients is not observed.

A special group of thrombocytopenia consumption, nablyudayushtiesya in thrombosis and disseminirovannom vnutrisosudistom svertыvanii Resurrection (DIC).

The second stage of diagnosis - Differentiation of clinical entities in a group of hereditary and immune thrombocytopenia.

In some instances, help in the differential diagnosis may be family history, but sometimes, especially in recessive inherited forms, the patient is the only representative of the family, suffering from this disease.

An important role in the diagnosis of hereditary thrombocytopenia play morphological analysis of platelets, determination of their functional properties, and the availability of laboratory and clinical manifestations of hereditary diseases, inherent in certain forms thrombocytopathy, flowing with idiopathic thrombocytopenic syndrome.

Violation of the functional state of platelets observed both in hereditary, and in immune thrombocytopenia, because the presence of antibodies causes not only a decrease in life expectancy of platelets, but also a violation of their function.

The number of megakaryocytes in the punctate and trepanate bone marrow in most cases, normal or high, and only occasionally during periods of acute illness or particularly severe forms reduced (the presence of antibodies antigemakariotsitarnyh).

Thus, autoimmune thrombocytopenia diagnosis is based on the following criteria:

• no signs of the disease in early childhood;
• no morphological signs and laboratory, specific to hereditary forms of thrombocytopenia;
• no clinical or laboratory evidence of the disease in blood relatives;
• the effectiveness of corticosteroid therapy (with frequent relapses in the period of cancellation);
• detected, if possible, antiplatelet antibodies using the method of Dixon, or other methods.

Indirectly, the presence of autoimmune thrombocytopenia indicate a combination of low platelet count in the blood with autoimmune hemolytic anemia, antierythrocyte identify antibodies by Coombs or agregatgemagglyutinatsionnoy sample. However, no evidence of hemolytic anemia does not exclude the autoimmune nature of thrombocytopenia.

In all cases autoimmune thrombocytopenia should be deleted symptomatic form, associated with chronic lymphocytic leukemia, systemic lupus erythematosus, active hepatitis or other diseases.