Angiohemophilia - Practical hematology of children's age

The angiohemophilia represents a severe form of the hemorrhagic diathesis which is characterized by plentiful bleedings. In 1926 the Finnish doctor E. A. Willebrand described a disease at inhabitants of the Aland Islands under the name "pseudohemophilia". On a clinical picture hemorrhagic diathesis reminds hemophilia, but with some distinguishing characters. In particular, considerable lengthening of a bleeding time at a normal blood clotting time was observed. The disease passed from father to son and persons of both sexes (an autosomal and dominant mode of inheritance) were ill. At further studying in 1933 E. A. Willebrand and N. Iiirgens came to a conclusion that at this pathology functional capacity of thrombocytes — a constitutional thrombopathy is broken. Now it is proved that bleeding at an angiohemophilia is caused by the combined (combined) defect in system of a hemostasis. Disturbance of synthesis of a plasma component of coagulant system is primary. It was already mentioned that the factor of VIII consists of several subunits — koagulyantny part (VIIIk), Villebrand's (VIII-FV) factor and the related protein (VI11-AG), antigenic part of the VIII-FV complex. At an angiohemophilia VIII-FV antigen is absent or its activity is sharply reduced. As Villebrand's (VIII-FV) factor regulates synthesis of koagulyantny part (VIIIk), disturbance of a blood coagulation at this disease is connected with decrease of the activity of VIIIk though there is no accurate dependence between weight of hemorrhagic manifestations and activity of components. Except regulation of synthesis of koagulyantny part of a factor of VIII, Villebrand's factor controls adhesive function of thrombocytes. Normal the endothelium of a vascular wall synthesizes and contains a large number of VIII-FV necessary for adhesion of thrombocytes. Therefore the secondary mechanism causing bleeding at an angiohemophilia is disturbance of a sosudistotrombotsitarny link of a hemostasis. Besides, decrease Ristocetinum aggregation of thrombocytes whereas aggregation of the thrombocytes induced by ADF, collagen, thrombin, a kaolin and adrenaline usually remains normal is noted.
The reasons of functional inferiority of thrombocytes are not clear. It is established that at an angiohemophilia children have metabolic disturbances in thrombocytes which degree correlates with weight of a hemorrhagic syndrome (L. N. Yakunina and soavt., 1982).
The angiohemophilia takes the second place on frequency among coagulopathies, conceding only to hemophilia. It is inherited on autosomal dominantly type, with various penetrance and expressivity. Both homozygous, and heterozygous forms meet. It is noted that women are ill slightly more often. There are descriptions of autosomal and recessive option of an angiohemophilia.

T and l and c and 36. Typiform differential diagnostic characters bo) Villebrand's gezn and similar hemorrhagic diathesis

The angiohemophilia can be also acquired if it arises at advanced age and if there is no heredo-familial character of a disease. Pathologies are the cornerstone immunologic mechanisms. In blood there are antibodies which generally inhibit only that part of a complex of a factor of VIII which is responsible for functional properties of thrombocytes (adhesion and Ristocetinum aggregation).
The clinical picture of a typiform of an angiohemophilia is characterized by the hemorrhagic syndrome arising at children of early age. Plentiful bleedings of different localization are observed. Long bleedings arise at insignificant wounds and injuries, after operative measures, small on volume — an ekstration of teeth, a tonsilectomy, appendectomy. At children of more advanced age hematomas are formed. At girls during puberty uterine bleedings prevail. A hemarthrosis arises less than at hemophilia, and, as a rule, at very severe disease. Usually with age the hemorrhagic phenomena decrease. One of the most characteristic symptoms of a disease is increase in duration of bleeding. R. G. McFarlane (1941) noted that when carrying out ukolochny test bleeding proceeds so much time how many the patience of the patient and researcher allows. At the same time, bleeding duration at patients can be periodically close to normal.
Table 37. Diagnostic characteristic of various options of an angiohemophilia (3. S. Barkagan, 1980)

Tests on resistance of a vascular wall (test of a pinch, plait etc.) in the period of bleeding are positive whereas they during "the light period" can be negative. The diagnosis of an angiohemophilia is confirmed on the basis of signs of bleeding of the mixed mikrotsirkulyatorno-gematomny type, data of the heredo-familial anamnesis, changes of laboratory indicators — lengthenings of a bleeding time, decrease in adhesion of thrombocytes and Ristocetinum aggregation. Differential diagnosis is carried out with other similar forms of bleeding — hemophilia, Glantsmann's thromboasthenia, thrombocytopenia (tab. 36).
For determination of duration of bleeding by the simplest Dyyuk's method is, however it is insufficiently sensitive and quite often yields wrong results. Therefore recommend to use more sensitive methods — Ivy, Borkhgrevink, Vaaler.
Depending on weight of clinical manifestations distinguish the following forms of an illness: 1) heavy, characterized more considerably by bleeding, a hemarthrosis. It is noted at homozygous carriers of an abnormal gene, the level of a factor of VIII in blood makes 2 — 5% and below; 2) moderately severe and 3) easy — signs of bleeding are expressed moderately, there is no hemarthrosis. Patients usually are heterozygous carriers of anomaly.
It is established that the angiohemophilia proceeds differently depending on extent of disturbance of coagulative, platelet and vascular links of a hemostasis (N. to Takahaski, 1984). Allocate several clinical options of a disease (tab. 37).
In the period of bleeding in peripheral blood are noted anemia with the raised reticulocytosis, a moderate leukocytosis with a neutrocytosis.
The principles of treatment of an angiohemophilia same, as well as hemophilias A. Patogeneticheskaya replacement therapy is carried out by administration of the drugs containing anti-hemophilic globulin (a complex of a factor VIII) — cryoprecipitate, anti-hemophilic plasma. And in operation haemo drugs certain features are revealed. So, the medicamentous effect of subjects is higher, than the quantity of the entered factor is more, and activity keeps longer, than at hemophilia. It is caused by the fact that the factor of VIII-FV has a promoting effect on synthesis of VIIIk, the general activity of a factor of VIII thereby increases.
And increase of activity has character of a two-humped curve. The first peak is caused by direct administration of the drugs containing anti-hemophilic globulin, the second peak is connected with a promoting effect of a factor of Villebrand on synthesis of VIIIk. Therefore at an angiohemophilia replacement therapy is carried out in smaller volume, than at hemophilia. The reliable haemo static effect gives administration of cryoprecipitate or anti-hemophilic plasma at the rate of 15 PIECES/ml on 1 kg of body weight once a day or even once in two days.
At a preparation for surgery in 4 — 5 days prior to intervention it is necessary to carry out daily transfusions. At considerable injuries and extensive surgical interventions resort to double administration of drug in days. Introduction of a platelet concentrate at an angiohemophilia is not recommended as it does not eliminate primary coagulative defect and has no haemo static effect. The good effect is observed at administration of aminocapronic acid (to 0,2 g/kg of weight a day), synthetic contraceptives (Infecundinum) which are shown at menorrhagias. Use of aminocapronic acid and contraceptives together with cryoprecipitate in connection with threat of development of the IDCS is contraindicated (3. S. Barkagan, 1980). Adrenaline oxidation products possess positive haemo static properties — adrenoksit, Adroxonum. The last can be applied to an irrigation of the bleeding surface. At emergence of antibodies against Villebrand's factor Prednisolonum is effective.