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Hereditary coagulopathies - 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
Immunotherapy
Remission and recurrence of an acute leukosis
Inborn leukosis
Neuroleukosis
Myelosis
Lymphogranulomatosis
Gematosarkoma
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Leukopenias
Histiocytoses
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Angiopathies
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
Coagulopathies
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Angiohemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Dysfibrinogenemias
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
Thrombocytopenia
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
Trobotsitopatiya
Anemias
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

Disturbances of a coagulative link of a hemostasis at children's age more often happen hereditary genesis. Relatively less than at adults, the acquired coagulopathies — a syndrome of the disseminated intravascular coagulation, deficit the K-vitaminozavisimykh of factors caused by liver pathology, etc. are registered. Genetically determined deficit of one of blood-coagulation factors is the cornerstone of hereditary coagulopathies. As a rule, the isolated deficit of one of factors is observed, the mixed forms of deficit of different blood-coagulation factors (IX+VII, VIII+V, VII+II, VIII + are more rare than IX).
The acquired coagulopathies have more difficult multifactorial pathogeny with disturbances in various links of a hemostasis. The main groups of hereditary coagulopathies are provided to tab. 29.
At diagnosis of hereditary coagulopathies is of great importance correctly and carefully collected anamnesis which allows to reveal a hereditary factor of a disease — emergence of hemorrhagic manifestations at early age, especially at expansion of the motive sphere (1 — 2 years), existence of a hemorrhagic diater at relatives. Clinical data allow to define type of bleeding and to differentiate coagulopathies from disturbances of a platelet and vascular link of a hemostasis. Decrease in the indicators of a koagulogramma reflecting the condition of all links of coagulant system of blood (standardized partial, tromboplastinovy, kefalinovy, koalino * howling time), confirms existence of a coagulopathy. The family anamnesis and clarification of a mode of inheritance helps with definition of this or that coagulopathy. Further differential diagnosis of groups of hereditary coagulopathies is carried out on the basis of laboratory researches by process of elimination. Change above the specified indicative tests demonstrates disturbance of coagulability of blood which can be caused by a disease of any group. Diagnosis is begun with definition of a final stage of coagulation (the IV group of hereditary coagulopathies) as disturbance of this link involves change of all coagulative tests (tab. 30). For this purpose use definition of thrombin time and definition of fibrinogen in plasma. Lengthening of thrombin time and decrease in contents - fibrinogen in plasma testify to hereditary defect — and - hypo - or dysfibrinogenemias. At the same time, naturally, the tests reflecting a blood coagulation as on the internal mechanism (silicone time of coagulation, the koalinovy, kefalinovy, standardized partial tromboplastinovy time, autokoagulogramma parameters, the tromboplastinovy indicator test), and on external will be violated (a prothrombin time on Kvika).

Table 29. Hereditary coagulopathies (3. S. Barkagan, 1070)

Continuation of tab. 29

Table 30. Criteria of laboratory diagnosis of groups of hereditary coagulopathies


Koagulogramma indicators

Groups of hereditary coagulopathies

 

The I group — the isolated disturbance of the internal mechanism of coagulation (XII, XI, IX, VIII factors)

The II group — the isolated disturbance of the external mechanism of coagulation (the VII factor)

The III group — disturbance of the external and internal mechanism of coagulation (V, X, II factors)

The IV group — disturbance of a final stage of coagulation (the I factor the XIII factor)

Silicone time of coagulation of whole blood

It is extended

Normal

It is extended

Udli
neno

Holes
mal
Nov

Content of fibrinogen of plasma

Normal

Normal

Normal

Sni
wife

Norm
lny

Prothrombin time on Kvika (thromboplastin with activity in 11 — 15 c)

Normal

It is extended

It is extended

Udli
neno

Holes
mal
Nov

Partial tromboplastinovy time (norm 60 — 70 c)

It is extended

Normal

It is extended

Udli
neno

Holes
mal
Nov

The standardized partial tromboplastinovy time (norm 45-55 c)

It is extended

Normal

It is extended

Udli
neno

Holes
mal
Nov

The standardized indicator tromboplastinovy test

It is extended

Normal

It is extended

Udli
neno

Holes
mal
Nov

Autokoagulogramma parameters

Are changed

Normal

Are changed

-Ism
nena

Normal

Normal thrombin time and normal content of fibrinogen allow to exclude hereditary coagulopathies — and - hypo - and dysfibrinogenemias. At hereditary deficit of the XIII factor all indicators of a koagulogramma meet standard, and existence of hemorrhagic diathesis at normal indicators and an exception of all other forms allows to suspect a disease. In this case it is necessary to conduct purposeful research of activity of the XIII factor which is reduced. The exception of the coagulopathies caused by disturbance of a final stage of coagulation on the basis of normal thrombin time forces to carry out further diagnostic search.
Table 31. Reading the tests differentiating deficit of factors of VII, X, V, II in system of definition of a prothrombin time at normal thrombin time (3. S. Barkagan, 1980)

Designations: (+) — normalization is received, (—) — there is no normalization.
At the following stage carry out differentiation of the coagulopathies caused by disturbances of the internal and external mechanism of a blood coagulation. Factors of a prothrombin complex VII, X, V, II take part in the external mechanism of forming of prothrombinase therefore lengthening of a prothrombin time on Kvika indicates deficit of these factors. Besides, factors of X, V and II take part in the internal mechanism of coagulation therefore kefalinovy and kephalin-koalinovoye time, the standardized indicator tromboplastinovy test etc. will also be broken.
The factor of VII takes part only in the external mechanism therefore other tests are violated slightly. So, at normal thrombin time and normal content of fibrinogen lengthening of a prothrombin time on Kvinka allows to speak about deficit of factors of a prothrombin complex (VII, X, V, II). Differential diagnosis is carried out by statement of correctional tests (tab. 31). It is possible to carry out quantitative definition of factors.

Table 32. Reading results of TGT differentiating disturbances of the internal mechanism of a blood coagulation - at a normal thrombin and prothrombin time (V. P. Baluda and soavt., 1980)
Indicators at various disturbances of coagulability


Row
test

deficit of factors

Inhibitors of factors VIII, IX or XI

VIII

IX

The XI-XII

3rd plastinochny

1

Disturbance

Norm

Norm

Norm

Disturbance

2

Norm

Disturbance

Norm

Norm

Disturbance

3

Disturbance

Disturbance

Disturbance

Norm

Disturbance

4

Norm

Norm

Norm

Disturbance

Norm

5

Control

Norm

 

 

 

Table 33. Reading the test results of formation of thrombin differentiating disturbances of the internal mechanism of coagulation (3. S. Barkagan, 1980)

Designation: (-}-) — normalization is received; (—) — normalization is absent.

Table 34. Criteria of laboratory diagnosis of hereditary coagulopathies


Factor

Disease

Coagulation time

Blood clot
new
time

Protr
binovy
time

Partial trombo-

plasti-modern times

Standarti-
zirovanny partial trombo-
plastinovy time

XIII

Deficit
fibrinstabi-
lyseing
factor

Normal

Normal
Nov

Normal
Nov

Normal
Nov

Normal
Nov

I

A-gipofibrino genemiya

It is extended

It is extended

It is extended

It is extended

It is extended

VII

Gipoprokon-
vertinemiya

Normal

Normal
Nov

It is extended

Normal
Nov

Normal
Nov

X

Stewart's illness — Prauera

It is extended or normal

Normal
Nov

It is extended

It is extended

It is extended

V

Hypo -
aktselerinemiya (parahemophilia)

It is extended

Normal
Nov

It is extended

It is extended

It is extended

II

Gipoprotrom-
binemiya

It is extended or normal

Normal
Nov

It is extended

It is extended

It is extended

VIII

Hemophilia And

It is extended

Normal
Nov

Normal
Nov

It is extended

It is extended

IX

Hemophilia of B
(brlezn
Kristmasa)

It is extended

Normal
Nov

Normal
Nov

It is extended

It is extended -

XI

MOUTH insufficiency (hemophilia C)

It is extended

Normal
Nov

Normal
Nov

It is extended

It is extended

XII

Hageman's defect.

It is extended

Normal
Nov

Normal
Nov

It is extended

It is extended

Inga -

beaters of factors of VIII, IX, XI

Inhibitory forms of hemophilia

It is extended or normal

Normal
Nov

Normal
Nov

It is extended

It is extended

If the prothrombin time remains normal, it is necessary to assume the isolated disturbance of the internal mechanism of a blood coagulation. Thus (deficit of factors of XII, XI, IX, VIII) can think of group of hereditary coagulopathies on the basis of disturbance of the tests characterizing the internal mechanism of formation of prothrombinase (kaolinic, kefalinovy, a kaolin-kefalinovoye time, the indicator tromboplastinovy test, the autokoagulyatsionny test), after an exception of disturbances of a final stage of coagulation (normal thrombin time) and deficit of factors of a prothrombin complex (a normal prothrombin time). Differentiation in group is carried out by test of generation of thromboplastin (TGT) or the test of formation of thrombin (tab. 32, 33).
When carrying out TGT make 5 rows of mixes:

  1. a row (plasma) — the adsorbed patient's plasma + serum healthy + a platelet component healthy.
  2. a row (serumal) — the adsorbed plasma healthy + the patient's serum + a platelet component healthy.
  3. a row (plasma and serumal) — the adsorbed patient's plasma + the patient's serum + a platelet component healthy.
  4. a row (platelet) — the adsorbed plasma healthy + serum healthy + a platelet component of the patient.
  5. a row (control) — the adsorbed plasma healthy + serum healthy + a platelet component healthy.

Simpler in workmanship is the two-level test of formation of thrombin having approximately identical diagnostic opportunities with the test of generation of thromboplastin. Tests also allow to reveal the coagulation disturbances caused not by deficit of factors, but existence in plasma of inhibitors which appear in blood at patients and aggravate the course of a disease — inhibitory forms of hemophilia.
If there is a need, define separate inhibitors. The differentiating tests possess average sensitivity and are normalized at the level of factors more than 10% of norm that does them unsuitable for identification of easy forms of hemophilia and control of replacement therapy as at patients with hemophilia the level of factors higher than 25% of norm is considered reliable. In all similar situations it is necessary to carry out quantitative definition of scarce factors. By sensitive methods for identification of easy and latent forms of hemophilia And yes In, and also hemophilias With are the autokoagulyatsionny test and the standardized indicator tromboplastinovy test.
Considerable disturbance of indications of tests in the absence of bleeding whereas bleeding signs without disturbance of coagulative tests are typical for deficit of the XIII factor is characteristic of deficit of components of kallikrein-kinin system.



 
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