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Idiopathic Werlhof's disease - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Remission and recurrence of an acute leukosis
Inborn leukosis
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

The Idiopathic Werlhof's Disease (IWD) — primary hemorrhagic diathesis at which define decrease in number of thrombocytes in peripheral blood at the increased or normal maintenance of megacaryocytes in marrow. It is one of the most common forms of hemorrhagic diathesis. Carry those to ITP of thrombocytopenia which etiology is unknown and which are not symptoms of other diseases. According to Mueller — Eckardt (1976), among patients with a Werlhof's disease of 47% it is the share of ITP. The etiology and a pathogeny of an idiopathic Werlhof's disease are finally not found out.
The disease can develop at any age, even at chest babies though arises at children of 3 — 6 years more often. According to many authors, at children till 14 flyings the disease occurs equally often both at girls, and at boys. However at the advanced school age incidence at girls is 2 — 3 times higher, than at boys. Numerous supervision testify to a role of the infectious factor preceding development of ITP. And most often at children the disease begins after a viral infection, is more rare — after bacterial. According to J. M of Lusher and R. Syer (1977), a half of children, sick ITP, in the anamnesis had an acute respiratory viral infection postponed for 4 — 6 weeks to a disease. Numerous supervision testify to value of medicamentous drugs in development of a Werlhof's disease though consider that at children the role of this factor is less significant, than at adults (A. V. Mazurin, 1971; McClure, 1975, etc.). However it is necessary to agree with N. P. Shabalov (1982) note what in some cases it is difficult to establish that preceded a Werlhof's disease — a viral infection or medicamentous drugs which it was treated. There are messages on development of ITP in 2 — 4 weeks after preventive inoculations (AKDS, protivokorevy, administration of Y-globulin, etc.) though the total quantity of such cases is small. The listed above reasons preceding development of ITP cannot be considered as etiological factors. At the modern level of knowledge they are carried to pathogenetic factors of the immunopathological process playing a crucial role in development of a disease. And it should be noted that the vast majority of children face also infections, both inoculations, and medicamentous drugs, but not at all ITP develops.
The m of Stefanini and Dameshek (1962) put forward the concept about constitutional predisposition of patients to thrombocytopenia. V. M. Yurlov (1977) showed that at patients with a Werlhof's disease with the frequent satellite the hereditary or acquired functional inferiority of thrombocytes is. At influence of any adverse factors the available latent trombotsitopatiya creates that background on which join purely high-quality disturbances of functional activity of thrombocytes quantitative, that is thrombocytopenia develops. From these positions N. P. Shabalov (1982) concept developed on the basis of studying of genealogical and some indicators of function of thrombocytes at direct relatives in families of children, sick ITP is interesting. The author came to conclusion that at ITP there is genetic predisposition which consists in qualitative inferiority of thrombocytes (as a rule, a trombotsitopatiya like an atrombiya of I, II). It is transferred on autosomal dominantly type. Constitutional feature under the influence of various factors is implemented in the immunopathological process leading to development of ITP. Children at whom constitutional defect of thrombocytes is absent under the influence of the same factors do not get sick with ITP.
Concerning genesis of thrombocytopenia at ITP long time existed several points of view. Many authors considered that thrombocytopenia in peripheral blood is caused by decrease in marrowy products (E. N. Mosyagina and soavt., 1976; W. Dameshek, 1946). And this hypothesis was stated in 1915 E. Frank on the basis of cytomorphological researches of marrow of patients with a Werlhof's disease. However at further studying most of authors came to conclusion that at ITP quantity of megacaryocytes in marrow and products of platelets are in most cases not lowered, and, on the contrary, are increased (N. P. Shabalov, 1982; Karpatkin, 1975). And products of thrombocytes increase in comparison with norm by 2,5 — 5 times. At the same time the number of megathrombocytes (big thrombocytes) increases in peripheral blood that also confirms the raised products of thrombocytes in unit of time. And megacaryocytes of sick ITP in cultures of fabric do not differ on the functional properties from those healthy donors.
Therefore now the point of view is considered standard that thrombocytopenia at ITP is caused by the increased destruction of platelets in a peripheral bed (A. V. Mazurin, L. V. Ostrovskaya, 1976; N. R. Shulman and soavt., 1965). Depth trombotsitopenin is caused by two interconnected factors: on the one hand, number of the platelets perishing in unit of time, on the other hand, compensatory opportunities of marrow (V. G. Savchenko, 1979). Until there is a dynamic equilibrium, thrombocytopenia does not develop. In that case when destruction of platelets exceeds potentialitys of marrow to compensate shortage of thrombocytes in peripheral blood, there is thrombocytopenia (E. V. Adams and soavt., 1978).
However the reasons of the strengthened destruction of thrombocytes are finally not clear. The fact that in genesis of ITP and destruction of platelets the large role is played by immunological frustration is undoubted. In literature the extensive material devoted to immunological aspects of a pathogeny of an idiopathic Werlhof's disease is saved up. So, in a blood plasma of patients the antithrombocytic factor operating povrezhdayushche on a thrombocyte membrane is found (S. Karpatkin and soavt., 1975). And this factor has characteristics of immunoglobulin of a class G. It is established that at sick ITP the quantity of IgG fixed on a membrane of thrombocytes in comparison with healthy people (Dixon and soavt increases., 1975). According to V. G. Savchenko (1979) and I. L. Idelsona (1979), at patients on a surface of thrombocytes contains 20 — 250 * 10-15 g / a class G immunoglobulin thrombocyte whereas healthy people have these indicators much less — 14-10-15 g / a thrombocyte. However difficulties of methodical character still leave open a question of character of immune pathology at ITP which can be both autoimmune, and heteroimmune. It is accompanied by the fact that identification of the antithrombocytic antibodies testimonial of an autoaggression is labor-intensive process, and not always yielding a positive take. In this regard some authors even allocate not immune forms of an illness of Verlgof though now immune genesis of ITP is conventional. It is possible to assume that both the autoimmune, and heteroimmune responses defining the course of a disease participate in a pathogeny of ITP.
The spleen also plays an important role in development of ITP. Exactly there is an increased destruction of thrombocytes caused by immunological process (R. McMillan and soavt., 1974). It is proved that macrophages of sick ITP, received from a spleen, very actively absorb marked thrombocytes. At the same time the spleen is the main place of products of antithrombocytic antibodies at autoimmune ITP.
Thus, the immune mechanism is the cornerstone of a pathogeny of the majority of cases of ITP. L. I. Idelson (1979) and V. G. Savchenko (1979) allocate at the same time two nosological forms — autoimmune and heteroimmune ITP. At an autoimmune form antithrombocytic autoantibodies are produced in bodies of immunocompetent system with the subsequent increased destruction of platelets exceeding compensatory opportunities of a megakariotsitarny sprout. At autoimmune process of an antibody are developed against own not changed antigen of thrombocytes. It defines clinical features of ITR accepting a chronic current. At the same time the therapeutic effect can be gained only when using the immunodepressive means suppressing an autoaggression or during removal of immunocompetent body (spleen). The ITP heteroimmune form arises at disturbance of an antigenic structure of a thrombocyte, that is at formation of new complex antigen which forms under the influence of viruses, medicines (hapten) or other alien antigens (a thrombocyte + a virus, a thrombocyte + a medicine etc.).
Механизм действия аллергических антител
Fig. 22. Mechanism of action of allergic antibodies (J. Dausset, 1969)
Antibodies are developed against this complex that also leads to peripheral destruction of thrombocytes. Such mechanism defines clinical features of heteroimmune ITP, as a rule, having an acute current. At elimination of antigen from external environment and its natural elimination from an organism there comes the absolute and permanent cure in connection with the termination of the immune conflict. A classical example of heteroimmune pathology is the thrombocytopenia developing at reception of the medicines possessing properties of hapten. Quinidine, quinine, salicylates, streptocides, antibiotics from group of aminoglycosides, digitoxin, etc. belong to such drugs.
According to a hypothesis of J. F. Ackroyd, hapten which the medicine is contacts protein of thrombocytes, forming an antigenic complex a thrombocyte — hapten (fig. 22). In response to it the organism develops the antibodies leading to a lysis of thrombocytes. The termination of reception of medicine leads to the termination of antibodyformation and recovery of normal level of thrombocytes in a peripheral bed. Communication of hapten with proteins of a thrombocyte fragile.
The similar hypothesis was made by P. Miescher. According to the concept of the author, hapten contacts not thrombocytes, and proteins of plasma therefore antigen (protein + hapten) forms on which antibodies are developed. The complex formed in the course of reaction antigen (protein + hapten) + an antibody, is adsorbed on a surface of thrombocytes that leads to their destruction.
According to version S. Moeshlin (1975), hapten forms an antigenic complex with proteins of plasma. The developed antibodies are fixed on a surface of thrombocytes. At reaction of an antigenic complex with the antibodies which are on a surface of platelets there comes agglutination and a lysis of the last.
Also the ITP heteroimmune form (an acute form of an illness of Verlgof) forming with the participation of viruses or bacteria has similar mechanisms (L. I. Idelson, 1979; V. G. Savchenko, 1979).
Immune mechanisms play a part not only in ITP pathogeny, but also at many secondary symptomatic purpuras, and also primary forms (isoimmune, transimmune purpuras).
Патогенез иммунной тромбоцитопенической пурпуры
Fig. 23. Pathogeny of an immune Werlhof's disease (A. S. Shitikoda, 1982)

Thrombocytes are sensitive to influence of immune factors. Exert impact on them as the specific antithrombocytic antibodies directed against own organ-specific antigens of platelets, and nonspecific, that is not acting directly against antigens of thrombocytes (A.S. Shitikova, 1982).
Nonspecific factors are the circulating cell-bound immune complexes which Fc (part of the molecule IgG) are fixed to the corresponding receptor of a platelet membrane (3. D. Fedorova and soavt., 1981). The scheme of development of immune thrombocytopenia is presented on fig. 23. The main links of this chain is the following.

  1. The membrane of thrombocytes connects to the class G immunoglobulins which are acting as independent specific antithrombocytic antibodies or being a part of the nonspecific circulating cell-bound immune complexes.
  2. At activation of system of a complement there comes the intravascular lysis of platelets.
  3. Sequestration of thrombocytes in a spleen amplifies, and at strong immune destructions — also in a liver. Kompensatorno is activated the thrombocytopoiesis leading to emergence in peripheral blood of a large number of megathrombocytes.
  4. In the course of death of the thrombocytes connected with IgG population of V-lymphocytes is activated that causes the increased development of antithrombocytic antibodies. Thrombocytes and cell-bound immune complexes connected with their surface are englobed by macrophages and neutrocytes. At the same time from leukocytes the active substance promoting aggregation of plates is emitted.
  5. There is an activation of aggregation and secretory processes of platelets causing the increased their consumption, thrombocytopenia and decrease in functional activity of the remained thrombocytes.

In immunological process at ITP, along with humoral factors, a certain place is taken also by reactions of cellular immunity. Results of researches of I. P. Sarnitsky and L. M. Tishchenko (1979) demonstrate that at patients the imbalance in subpopulation of lymphoid cells which is characterized by sharp decrease in maintenance of T lymphocytes and increase of quantity In - and O-cells in peripheral blood is observed. According to N. P. Shabalov (1982), in a pathogeny of immunological frustration dysfunction of macrophages and a simultaneous imbalance in subpopulation of lymphoid cells are of great importance.
In bleeding pathogeny at ITP, except the main link — thrombocytopenia, the important place is taken by defeat of a vascular wall and coagulant system of blood. It is known that thrombocytes carry out angiotrofichesky function, participate in a blood coagulation and have the inhibiting influence on a fibrinolysis. Thrombocytes are natural supporters of an endothelium of vessels therefore at their deficit vascular permeability, fragility of vessels increases that leads to development of petekhialno-spotty hemorrhages. Vascular tests are positive (a plait, a pinch, can, etc.) . According to A. V. Mazurin (1971), at ITP functional disturbances of vessels (a hyperpermeability, decrease in resistance and a retraktilnost), in comparison with the morphological changes which are expressed in swelling of an endothelium of vessels have the greatest value. Such vascular changes distinguish ITP from a hemorrhagic vasculitis at which there are organic lesions. In bleeding pathogeny a certain role belongs to decrease in level of serotonin in plasma at sick ITP which has vasoconstrictive effect and stimulates aggregation of thrombocytes (N. P. Shabalov and soavt., 1975). Set of these factors (thrombocytopenia, functional disturbances of a vascular wall, decrease in level of serotonin) define one of typical symptoms of a Werlhof's disease — lengthening of a bleeding time.
In development of a hemorrhagic syndrome at ITP also disturbance of processes of a blood coagulation and fibrinolysis matters. It is proved that at patients hypocoagulation in the I phase of coagulation whereas the second and third phases remain normal is observed. In the I phase of coagulation at ITP in the period of crisis points out considerable decrease in consumption of a prothrombin defect (N. P. Shabalov, 1982). In the period of crisis also retraction of a blood clot is considerably broken. J. Salmon (1903) published the data testimonial of value of a fibrinolysis in development of a hemorrhagic syndrome at ITP. At part of patients fibrinolitic activity of blood increases that is one of the pathogenetic links defining the raised bleeding at ITP.
As it was already noted, on a current allocate acute and the ITP chronic form. Allocation of the periods of a disease is traditional: aggravations, clinical and kliniko-hematologic remission. At patients with a chronic current of ITP surely note the number of recurrence (with rare recurrence, with frequent recurrence and continuously recurrent current). The standard criterion of a chronic course of a disease is the time parameter when the Werlhof's disease proceeds more than 6 months.

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