Hemorrhagic Diathesis due to vascular disorders Prof. C V Raghuveer MBBS Regular Batch 22nd April 2015
Synonym. Vascular Purpura • Usually mild. • Characterized by petechiae,purpuraecchymosis. • Arise due to- • damage to endothelium, • abnormalities in sub-endothelial matrix, • abnormalities in extravascular conn.tissue, • newly formed vessels.
Hereditary Causes • I. Hereditary Hemorrhagic telengectasia ( Rendu Weber Osler Syndrome) • Autosomal dominant: abnormally dilated capillaries in skin, mucosa & viscera. • Childhood • Frequent epistaxis, GIT bleeds. • II. Ehlers Danlos Syndrome; Collagen defect, fragile blood vessels.
Acquired Causes. • I. HenochSchonleinPurpura. • AnaphylactoidPurpura. • Self limiting hypersensitivity vasculitis. • Children/ young adults. • Circulating immune complexes deposited in vessel walls- (IgG+ C3+Fibrin) • Hematuria, colicky abdominal pain (GIT bleeds), poly arthralgia, acute nephritis. • Coagulation Tests Normal
Acquired Causes • II. H U S : • Infancy / Childhood. • Bleeding tendency, ARF. • Hyaline thrombi in glomerular capillaries. • III. Infectious causes : Dengue, Measles, Sepsis • IV. Drug reaction: Hypersensitivity. • V. Steroid purpura: Defective vascular support. • VI. Senile purpura: atrophy of support tissue • VII. Scurvy : Collagen synthesis defective.
Hemorrhagic Diathesis due to Platelet Disorders. • 1. Those due to Thrombocytopenia: • Due to : a) Impaired production. • b) Increased destruction. • c) Splenic sequesteration. • d) Dilutional loss. • Three Important Causes of Thrombocytopenia • 1) Drug induced. • 2) Idiopathic Thrombocytopenic Purpura (I T P) • 3) Thrombotic Thrombocytopenic Purpura (TTP)
Drug Induced Thrombocytopenia. • Depression of megakaryocyte production. • Drug-antibody complex causes destruction of platelets as an innocent by-stander. • Common drugs- indomethacin, alkylating agents, sulfonamides, PAS, Digoxin • Heparin induced thrombocytopenia: Formation of antibodies against PF4, which forms a complex with heparin which activates endothelial cells & initiates thrombus formation. • No bleeding but thrombotic tendency
I T P • Immune destruction of platelets with normal / increased M’kcytes in B.M. • Classification: • 1. Acute ITP • 2. Chronic ITP • Pathogenesis: • Acute ITP: Sudden onset , self limiting follows some viral infections in children- HCV,CMV, Inf.mononucl, HIV, URI. • Immune complexes with viral antigens elicit antibodies which cross react with platelets & kill them.
I T P contd. • Chronic ITP: • Adults, more in F, 20-40yrs, Insidious, persists for many years, peticheae, easy bruising, menorrhagia, epistaxis, melaena, hematuria. • Hepatosplenomegaly +
Lab Findings in ITP • Plat count – Decreased 10,000-50,000/micro L • Blood Smear- thrombocytopenia, occasional giant platelets+ • B M – Increased M’kcytes, non lobulated nuclei, no granularity of cytoplasm, vacuoles+ • Anti-platelet antibodies on surface of platelets or in serum ++ • Platelet survival studies- decreased markedly even to less than 1 hour (Normal: 7-10 days)
Thrombotic Thrombocytopenic Purpura (TTP) & Hemolytic Uremic Syndrome (HUS) • A group of thrombotic microangiopathy. • Characterized by : • Thrombocytopenia. • Microangiopathic hemolytic anemia. • Fibrin microthrombi in microvasculature. • Often fulminant. • Microthrombi formation is the cause for thrombocytopenia.
Pathogenesis. • TTP is initiated by endothelial injury. • Injury triggered by immunologic damage. • Injury is followed by release of vWF + other pro-coagulants by endothelium. • This results in micro-thrombi. • Associated conditions: Pregnancy, Cancer, Chemotherapy, HIV, Mitomycin C etc.
Clinical Features of T T P. • Fever. • ARF. • Neurologic deficit. • Purpura. • Lab findings : Thrombocytopenia, Coomb’s negative Hemolytic Anemia, Leukemoid reaction. • B M: Increased M’kcytes, Myeloid hyperplasia. • Microthrombi in arterioles, capillaries & venules.
Disorders of Platelet Function. • 1. Hereditary: • A) Defective platelet adhesion • i) Bernard Soulier Syndrome- deficiency of platelet membrane glycoproteins essential for adhesion. • Ii) von Willebrand Disease- defect in adhesion & Factor VIII deficiency. • B) Defective aggregation- Glanzman’s disease. Defect in primary platelet aggregation with ADP or collagen due to inherited defect in platelet primary membrane glycoproteins. • C) Disorders of platelet release reaction- after normal initial platelet aggregation with ADP or collagen, subsequent release of ADP, PG & 5-HT is defective.
Disorders of Platelet Function Contd. • 2. Acquired. • Aspirin therapy- prolonged use of aspirin leads to easy bruising and prolonged bleeding time. • Aspirin inhibits COX pathway and suppresses PG synthesis necessary for platelet aggregation & release reactions.