Hematopathology Lecture 5: Coagulation Disorders

Hemostasis and Blood Coagulation

• Hemostasis is the physiological arrest of hemorrhage at sites of vascular injury
• 5 systems involved in hemostasis:
  • Platelets
  • Blood vessel
  • Coagulation factors
  • Natural coagulation inhibitors
  • Fibrinolytic system

Platelets

• Produced in the bone marrow through megakaryopoiesis
• Normal platelet count in adult blood: 150-400 x 10^9/L
• Normal half-life of platelet: 7-10 days, with 1/3 of platelets trapped in the spleen
• Function in primary hemostasis through:
  • Adhesion
  • Shape changes
  • Aggregation
  • Release of mediators
• ADP and TXA2 are major positive mediators for platelet aggregation
• PGI2 (prostocycline) is a potent inhibitor of platelet aggregation

Coagulation Pathways

• All coagulation factors synthesized in the liver
• Half-life of all factors: 10-65 hours, except F7 (5-7 hours)
• Final insoluble stable fibrin strands formed

Disorders of Coagulation System

• Bleeding disorders
• Thrombosis

Bleeding Manifestations

• Petechiae: pinpoint flat red spots caused by intradermal hemorrhage
• Ecchymoses: extravasation of RBC into skin and subcutaneous tissue, 0.2-10 mm
• Hematomas: bleeding in the muscle
• Hemarthroses: bleeding in the joint
• Hemoptysis, hematemesis, hematuria, conjunctival hemorrhage, epistaxis

Investigations of Bleeding Tendency

• Sample preparation: citrated plasma using special tube containing sodium citrate as anticoagulant
• Investigations:
  • CBC (complete blood count) and blood film
  • Bleeding time (BT)
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (APTT)
  • Fibrinogen assay (FNG)

Classification of Bleeding Disorders

• Platelet disorders: reduction in platelet count (thrombocytopenia) or platelet dysfunction
• Coagulation factors disorders: inherited or acquired coagulation factors deficiency or dysfunction
• Vascular disorders: inherited or acquired
• Less frequently, disorders in inhibitors and fibrinolytic system

Platelet Disorders

• Abnormal bleeding associated with platelet disorders characterized by superficial bleeding (skin and mucous membrane) and post-traumatic
• Causes of thrombocytopenia:
  • Reduced production of platelets
  • Increased platelet consumption
  • Abnormal distribution: hypersplenism

Autoimmune Thrombocytopenic Purpura (ITP)

• Chronic autoimmune thrombocytopenia, usually in young adults, without precedent or associated illness
• Can be classified into:
  • Idiopathic thrombocytopenic purpura
  • Secondary autoimmune thrombocytopenia
  • Acute post-viral autoimmune thrombocytopenia
• Clinically: usually present with purpura overall the body, sparing abdomen, in acute or chronic pattern of presentation
• Pathogenesis: triggering factors induce autoAb production against specific antigen on platelet, which is removed by macrophage in the spleen
• Hematological findings:
  • Blood picture showing isolated thrombocytopenia usually severe < 20 x 10^9/L with many giant platelets
  • Evan's syndrome: association of ITP with warm autoimmune hemolytic anemia
  • Bone marrow: usually normal cellularity with increased or normal number of megakaryocytes

Treatment of ITP

• Acute ITP: 70-80% of cases are spontaneously recovered; some patients may require treatment mainly with prednisolone
• Chronic ITP: usually needs treatment with corticosteroid, splenectomy, IV Ig, and immunosuppression
• Platelet transfusion for life-threatening bleeding, but it is contraindicated