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)