Coagulopathies

Hereditary coagulopathies and hemophilia

This group of hereditary disorders is caused by a genetically determined deficiency of plasma clotting factors, a decrease in their synthesis rate, or structural defects in protein molecules. The primary manifestation of this pathology is an increased bleeding tendency.

The most common form is hemophilia, the pathogenesis of which is based on a deficiency of factors VIII and IX, leading to impaired prothrombinase formation:

• Hemophilia A: factor VIII deficiency.
• Hemophilia B (Christmas disease): factor IX deficiency.

The disease is inherited: it affects males, whereas females act as carriers of the altered X chromosome. A characteristic feature of the clinical presentation is regular bleeding from trauma, cuts, and surgeries, as well as specific hemarthroses — hemorrhages into the joint cavities, which eventually cause muscle atrophy and skeletal deformity.

Von Willebrand disease

This disorder is inherited in a dominant manner and is more frequently diagnosed in females (60–70% of cases). The etiopathogenesis of the disorder is associated with the structural heterogeneity of antihemophilic globulin (factor VIII), which is a complex of compounds:

• Factor VIII:C — the procoagulant portion synthesized by liver cells (hepatocytes).
• Factor VIII:W (von Willebrand factor) — synthesized by megakaryocytes and vascular endothelium.

Depending on the nature of the defect, four types of the disease are distinguished. In addition to the hereditary form, there is acquired von Willebrand syndrome, which develops against the background of rheumatic diseases, systemic lupus erythematosus, amyloidosis, lymphoproliferative disorders, or DIC syndrome.

Hyperfibrinolysis and fibrinogenesis disorders

Coagulopathies caused by enhanced fibrinolysis are divided into two main groups:

1. Hereditary forms: rare, caused by a deficiency of the $\alpha_2$-antiplasmin inhibitor or an excess of tissue plasminogen activator.
2. Acquired forms: develop as a response to hypercoagulation via simultaneous activation of clotting and fibrinolysis involving factor XII.

Hemorrhagic syndrome in this case is observed in severe liver disease, malignant tumors, and surgical interventions on the urinary tract and prostate gland. Active fibrinolysis is frequently combined with the development of DIC syndrome.

Additionally, there are dysfibrinogenemias — disorders of fibrinogenesis that can be either rare hereditary molecular anomalies of factor I or acquired disorders of the conversion of fibrinogen to fibrin.

Laboratory diagnostic features and coagulation profile

Laboratory evaluation of patients with coagulopathies includes assessing the coagulation profile and specific hemostatic markers.

• In hemophilia, laboratory tests reveal a drop in factor VIII or IX concentrations, impaired prothrombinase formation, and a characteristic prolongation of the total blood clotting time.
• The dynamics of factor VIII:W allow its use as an acute-phase protein. Its level increases during stress, pregnancy, physical exertion, and acute or chronic illnesses. For instance, an elevation of this parameter in hemorrhagic vasculitis directly proves vascular endothelial damage.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Pathogenesis and classification of coagulopathies due to hyperfibrinolysis
• Differential diagnosis of the four types of von Willebrand disease
• Characteristic coagulation profile changes in various forms of hemophilia
• Acquired von Willebrand syndrome and its associations with systemic diseases
• Mechanisms of dysfibrinogenemia and the role of factor XIIIa

Other topics in Hematopoietic System Diseases

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