Classification of hemostasis disorders
All blood clotting disorders can be divided into three major groups depending on the affected component:
- Vasopathies (blood vessel pathology). This includes hemorrhagic vasculitis (e.g., Henoch–Schönlein purpura, where vessels are damaged by immune complexes) and hereditary angiopathies (Rendu–Osler–Weber disease, manifesting as multiple telangiectasias).
- Thrombocytopathies. Diseases associated with altered platelet count or functional activity. They can be primary (genetic) and secondary (acquired).
- Coagulopathies. Conditions caused by a deficiency or suppression of plasma coagulation factors.
Pathogenesis of thrombocytopathies
Platelet dysfunction is based on the disruption of one or more intracellular processes. Key mechanisms include:
- Granule defect: impaired synthesis and accumulation of biologically active substances (BAS). An example is gray platelet syndrome, in which granules are virtually absent.
- Impaired degranulation: a failure in the release reaction of BAS into plasma upon contact with proaggregants (ADP, collagen, thromboxane A₂).
- Membranopathies: alteration of membrane structure due to glycoprotein deficiency or phospholipid imbalance.
These defects lead to decreased contact activity (adhesion and aggregation) and a drop in procoagulant properties, primarily due to a shortage of platelet factor 3. Combined abnormalities are sometimes observed, as in Wiskott–Aldrich syndrome.
Coagulopathies and the coagulation cascade
Coagulopathies are divided into hereditary and acquired. Among hereditary ones, defects of factor VIII (hemophilia A, von Willebrand disease) and factor IX (hemophilia B) are absolute leaders. Acquired forms frequently occur in liver diseases, obstructive jaundice, or overdosage of indirect anticoagulants.
The coagulation process itself is triggered by two pathways:
- Extrinsic pathway (extrinsic pathway): starts upon tissue damage and the release of tissue factor.
- Intrinsic pathway (intrinsic pathway): activated upon blood 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.
DIC syndrome
Disseminated intravascular coagulation (DIC syndrome) is a severe acquired pathology characterized by systemic clotting of blood proteins and cell aggregation.
Due to massive microthrombosis, consumption coagulopathy develops: components of the clotting and fibrinolytic systems are rapidly depleted. In the terminal stage of the syndrome, two formally opposing phenomena are observed simultaneously: excessive thrombosis in certain vascular regions and severe hemorrhagic syndrome in others.
Principles of therapy
Treatment of hemostasis disorders is based on three principles:
- Etiotropic: elimination of the cause. This may include discontinuation of toxic drugs, radiation protection, removal of hemangiomas, or splenectomy.
- Pathogenetic: correction of the disease mechanism itself. Platelet mass transfusions, plasmapheresis, immunosuppressants, proaggregants, or antifibrinolytics (e.g., $\varepsilon$-aminocaproic acid) are used. ATP and magnesium preparations are used to stimulate the release reaction.
- Symptomatic: management of blood loss consequences (treatment of anemia) and normalization of internal organ function.
Briefly: answers to topical questions
Which diseases belong to vasopathies?
Vasopathies (vascular wall disorders) include hemorrhagic vasculitis and angiopathies.
Depending on their origin, they are classified into:
- Hereditary vasopathies — Rendu–Osler telangiectasia (Rendu–Osler–Weber disease or hereditary hemorrhagic teleangiectasia).
- Acquired vasopathies — Schönlein–Henoch hemorrhagic vasculitis (anaphylactoid purpura, immune complex vasculitis).
What are the stages in the pathogenesis of DIC syndrome?
The cited sources offer two variants for describing the stages/phases of DIC syndrome:
- Three phases of development: hypercoagulation and thrombosis; consumption coagulopathy; hypocoagulation and fibrinolysis.
- Another source indicates that there are 4 sequential stages, but only stages I–III are covered in the provided excerpt: I — hypercoagulation and thrombosis, II — progressive consumption coagulopathy, III — profound hypocoagulation and activation of fibrinolysis.
What laboratory tests are used to diagnose coagulopathies?
Diagnosis of coagulopathies involves basic laboratory screening (coagulogram) including the following main parameters:
- Activated partial thromboplastin time (APTT).
- Prothrombin time (PT).
- Thrombin time (TT).
- Fibrinogen concentration (including by the Clauss method).
- INR (International Normalized Ratio).
Additionally, a complete blood count is performed with mandatory platelet count assessment, and if necessary, specific clotting factor activity assays and molecular genetic testing.
To remember the composition of the prothrombinase complex, use the "Ten-on-Five" rule: activated factor X (10) works in tandem with factor V (5), plus calcium ions and phospholipids. Together, they convert prothrombin into thrombin.
Class and exam questions
What is the difference between primary and secondary thrombocytopathies?
Primary forms are caused by genetic defects (von Willebrand disease, Glanzmann thrombasthenia). Secondary forms develop during life due to radiation, uremia, cytostatics, or tumor processes.
Why is blood clotting impaired in liver diseases?
The liver synthesizes prothrombin complex factors (II, VII, X, V). In severe liver damage or obstructive jaundice, their deficiency occurs, leading to acquired coagulopathy.
What is the role of thrombin in the hemostasis system?
Thrombin not only converts fibrinogen into soluble fibrin, but via positive feedback also activates factors V, VIII, and XI, and stabilizes the clot through factor XIII activation.
What else to study on this topic
- Mechanisms of development of hemorrhagic vasculitis (Henoch–Schönlein purpura)
- Wiskott–Aldrich syndrome: combined platelet abnormalities
- The role of the tenase complex in the intrinsic coagulation pathway
- Pharmacotherapy of thrombocytopenias: from glucocorticosteroids to release reaction stimulators
- Pathogenesis of consumption coagulopathy in DIC syndrome
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