Hemostasis and Platelet Function Quiz

Hemostasis

• Hemostasis is the physiological arrest of hemorrhage at sites of vascular leakage
• Five systems interact to ensure hemostasis: vascular factors, platelets, coagulation system, natural coagulation inhibitors, and fibrinolytic system

Learning Objectives

• Definition and types of hemostasis
• Coagulation screening tests
• Response to vascular injury
• Disorders of primary hemostasis
• Causes of thrombocytopenia (low platelet count)
• Causes, clinical features, and management of ITP
• Causes, clinical features, and management of TTP

Coagulation Screening Tests

• Thrombocytopenia:
  • Normal platelet range: 150-400 x 10⁹/L
  • Investigation: Platelet count
  • Bleeding time: <8 minutes
• Abnormal platelet function:
  • Investigation: Bleeding time
• von Willebrand disease:
  • Investigation: Bleeding time
• Vascular and connective tissue abnormalities:
  • Investigation: Bleeding time
• Deficiencies of factors II, V, VII, or X:
  • Investigation: Prothrombin time (PT)
• Severe fibrinogen deficiency:
  • Investigation: Prothrombin time (PT) and Activated partial thromboplastin time (APTT)
• Warfarin therapy:
  • Investigation: Prothrombin time (PT) and Activated partial thromboplastin time (APTT)
• Deficiencies of factors II, V, VIII, IX, X, XI, XII:
  • Investigation: Activated partial thromboplastin time (APTT)
• Severe fibrinogen deficiency:
  • Investigation: Fibrinogen concentration
• Unfractionated heparin therapy:
  • Investigation: Activated partial thromboplastin time (APTT)
• Antibodies against clotting factors:
  • Investigation : Specific tests
• Lupus anticoagulant:
  • Investigation : Specific tests
• Hypofibrinogenemia (e.g., liver failure):
  • Investigation: Fibrinogen concentration
• Disseminated intravascular coagulation:
  • Investigation; Fibrinogen concentration

Response to Vascular Injury

• Injury to a vessel triggers a sequence of events:
  • Vessel constriction
  • Primary hemostasis: platelet plug formation
  • Secondary hemostasis: fibrin reinforcement of platelet plug
  • Remodeling and fibrinolysis: return to normal

Coagulation Pathways

• Intrinsic pathway
• Extrinsic pathway
• Common pathway

Primary Hemostasis Disorders

• Failure of initial platelet plug formation
• Causes:
  • Thrombocytopenia
  • von Willebrand disease
  • Platelet function disorders
  • Vessel wall abnormalities (e.g., hereditary hemorrhagic telangiectasia, vasculitis, scurvy)

Hereditary Hemorrhagic Telangiectasia (HHT)

• Inherited condition due to mutations in endoglin and activin receptor-like kinase genes
• Results in fragile blood vessels and organ membranes
• Telangiectasia and aneurysms common on fingertips, face, tongue, nasal passages, lungs, and gastrointestinal tract
• Often leads to larger pulmonary arteriovenous malformations (PAVMs) causing arterial hypoxaemia
• Predisposes to paradoxical embolism (stroke or cerebral abscess)

Thrombocytopenia (Low Platelet Count)

• A reduced platelet count can arise from two mechanisms:

  • Decreased or abnormal platelet production (bone marrow failure, hereditary thrombocytopathies)

  • Increased platelet consumption (immune-mediated, disseminated intravascular coagulation, sequestration)

Causes of Decreased Platelet Production

• Bone marrow failure syndromes
• Drug-induced bone marrow suppression
• Infiltrative bone marrow diseases (e.g. leukaemia, lymphoma, myeloma)
• Certain infections (e.g. HIV)
• Deficiency of haemopoietic factors (e.g. Vitamin B12, folate deficiency)

Causes of Increased Consumption of Platelets

• Immune thrombocytopenia (ITP)
• Drug-induced
• disseminated intravascular coagulation (DIC)
• Mechanical pooling
• Hypersplenism
• Thrombotic microangiopathies (e.g., haemolytic uremic syndrome, thrombotic thrombocytopenic purpura)

Idiopathic Thrombocytopenic Purpura (ITP)

• Platelet destruction by autoantibodies
• Most often directed at glycoprotein IIb/IIIa
• Not a single disorder; may be associated with other conditions (connective tissue diseases, HIV, B-cell malignancies, pregnancy)

Clinical Features and Investigations

• Presentation depends on the degree of thrombocytopenia
• Spontaneous bleeding typically occurs with platelet counts <20 x 10⁹/L
• At higher counts, patients may complain of easy bruising, epistaxis, or menorrhagia
• Many cases with counts >50 x 10⁹/L are discovered incidentally

TTP (Thrombotic Thrombocytopenic Purpura)

• Rare cause of thrombocytopenia
• Characterized by platelet aggregation and microvascular thrombosis causing renal and cerebral circulation problems
• Caused by lack of ADAMTS13 protease (cleaves von Willebrand factor) resulting in large von Willebrand factor molecules
• Clinically characterized by pentad of: thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurological symptoms, renal impairment, and fever
• Untreated TTP has high mortality
• Management: Plasma exchange

Management of Thrombocytopenia

• Treatment depends on the underlying cause
• Platelet transfusion rarely needed (often only short-lasting effect)
• First-line: glucocorticoids (e.g., prednisolone, dexamethasone)
• IV immunoglobulin (IVIg) can block antibody receptors on reticuloendothelial cells
• Anti-D given to RhD-positive patients with a spleen
• Splenectomy may be considered for persistent cases
• Other immunosuppressive therapies (e.g., rituximab, cyclosporin, tacrolimus)

Test your knowledge on hemostasis and the physiological processes involved in stopping hemorrhage. This quiz covers key concepts such as platelet count, hemostatic disorders, and factors involved in primary hemostasis. Perfect for students studying physiology or related fields.