Classification of Hemostatic Disorders
All disorders of the coagulation system can be divided into three major groups depending on the affected component:
- Vasculopathies (disorders of blood vessels). These include hemorrhagic vasculitis (e.g., Henoch-Schönlein purpura, where vessels are damaged by immune complexes) and hereditary angiopathies (e.g., hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu disease).
- Thrombocytopathies. Disorders related to alterations in platelet count or functional activity. They can be primary (genetic) or secondary (acquired).
- Coagulopathies. Conditions caused by a deficiency or impaired activity of plasma coagulation factors.
Pathogenesis of Thrombocytopathies
Platelet dysfunction is driven by the disruption of one or more intracellular processes. Key mechanisms include:
- Granule defects: impaired synthesis and storage of biologically active substances (BAS). Example: gray platelet syndrome, in which granules are virtually absent.
- Defective degranulation: failure of BAS release into the plasma upon contact with proaggregants (ADP, collagen, thromboxane A₂).
- Membranopathies: alterations in membrane structure due to glycoprotein deficiency or phospholipid imbalance.
These defects lead to reduced contact activation (adhesion and aggregation) and diminished procoagulant properties, primarily due to a shortage of platelet factor 3. Combined abnormalities are occasionally seen, such as in Wiskott-Aldrich syndrome.
Coagulopathies and the Coagulation Cascade
Coagulopathies are classified as inherited or acquired. Inherited forms are overwhelmingly dominated by factor VIII deficiency (hemophilia A, von Willebrand disease) and factor IX deficiency (hemophilia B). Acquired forms frequently arise from liver disease, obstructive jaundice, or an overdose of indirect anticoagulants (vitamin K antagonists).
The coagulation process is triggered via two pathways:
- Extrinsic pathway: initiated by tissue damage and the release of tissue factor.
- Intrinsic pathway: activated when blood comes into contact with a foreign surface.
Both pathways converge on the formation of the prothrombinase complex, which converts prothrombin into thrombin—the central enzyme that forms the fibrin clot and triggers positive feedback loops.
Disseminated Intravascular Coagulation (DIC)
Disseminated intravascular coagulation (DIC) is a severe acquired condition characterized by systemic activation of blood clotting and cellular aggregation.
Massive microthrombosis leads to consumption coagulopathy: components of the clotting and fibrinolytic systems are rapidly depleted. In the terminal stage of the syndrome, two paradoxical phenomena occur simultaneously: widespread thrombosis in some vascular beds and severe hemorrhagic diathesis in others.
Principles of Management
Treatment of hemostatic disorders is based on three main principles:
- Etiotropic therapy: elimination of the underlying cause, which may include stopping toxic drugs, treating radiation exposure, removing hemangiomas, or performing a splenectomy.
- Pathogenetic therapy: correction of the disease mechanism itself. This involves platelet transfusions, plasmapheresis, immunosuppressants, proaggregants, or antifibrinolytics (e.g., aminocaproic acid). ATP and magnesium preparations may be used to stimulate the release reaction.
- Symptomatic therapy: management of blood loss consequences (treating anemia) and restoring normal function of internal organs.