Hereditary Coagulopathies and Hemophilia
A group of hereditary disorders is caused by genetically determined deficiencies of plasma clotting factors, decreased synthesis rates, or structural defects in protein molecules. The primary manifestation of this pathology is increased bleeding tendency.
The most frequent form is hemophilia, the pathogenesis of which is based on a deficiency of factors VIII and IX, leading to impaired prothrombinase complex formation:
- Hemophilia A: factor VIII deficiency.
- Hemophilia B (Christmas disease): factor IX deficiency.
The condition is inherited in an X-linked recessive manner: males are affected, whereas females serve as carriers of the altered X chromosome. A hallmark of the clinical picture is regular bleeding following trauma, cuts, and surgeries, as well as specific hemarthroses—hemorrhages into joint cavities—which over time cause muscle atrophy and skeletal deformity.
von Willebrand Disease
This pathology is inherited in an autosomal dominant manner and is most 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:vW (von Willebrand factor) — synthesized by megakaryocytes and vascular endothelium.
Depending on the nature of the defect, four main types of the disease are distinguished. In addition to the hereditary form, there is acquired von Willebrand syndrome, which develops in the setting of rheumatic diseases, systemic lupus erythematosus, amyloidosis, lymphoproliferative disorders, or disseminated intravascular coagulation (DIC).
Hyperfibrinolysis and Fibrinogenesis Disorders
Coagulopathies caused by enhanced fibrinolysis are divided into two main groups:
- Hereditary forms: rare, resulting from a deficiency of the $\alpha_2$-antiplasmin inhibitor or an excess of tissue plasminogen activator.
- Acquired forms: develop as a response to hypercoagulation through the simultaneous activation of clotting and fibrinolysis involving factor XII.
In this context, hemorrhagic syndrome 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.
Additionally, there are dysfibrinogenemias—disorders of fibrinogen conversion that can present either as rare hereditary molecular anomalies of factor I or as acquired disorders of the conversion of fibrinogen into fibrin.
Laboratory Diagnostics and Coagulation Profile
Laboratory evaluation of patients with coagulopathies includes assessing a coagulation panel (coagulogram) and specific markers of the hemostatic system.
- In hemophilia, laboratory tests reveal a drop in factor VIII or IX concentrations, impaired prothrombinase formation, and a predictable prolongation of whole blood clotting time.
- The dynamics of von Willebrand factor (VIII:vW) allow it to be utilized as an acute-phase reactant. Its level rises during stress, pregnancy, physical exertion, and acute or chronic illnesses. For example, an elevation of this parameter in Henoch-Schönlein purpura directly demonstrates vascular endothelial damage.