Module 16 Haemostatic Bleeding Disorders Acknowledgments Ministry of Health Guyana Centers for Disease Control and Prevention CDC Global AIDS Program GAP Guyana Centers for Disease Control and Prevention CDC Atlanta American Society for Clinical Pathology ASCP Learning Objectives Upon completion of this unit of instruction the student will be able to List 3 conditions associated with abnormal vascular integrity Define thrombocytopenia thrombocytosis and thrombocytopathy Learning Objectives Upon completion of this lesson the student will be able to Describe the basic defect clinical features and abnormal laboratory tests for each of the following conditions that affect platelets either quantitatively or qualitatively Idiopathic thrombocytopenic purpura ITP Thrombotic thrombocytopenic purpura TTP Storage pool defects Glanzmann s thrombasthenia Bernard Soulier disease Learning Objectives Describe the mechanisms and duration of aspirin s effect on platelet function Primary Haemostasis Response of vessel walls and platelets to injury Platelet Disorders Quantitative number Qualitative function Secondary Haemostasis Response of the plasma coagulation factors Evaluating Disorders of Haemostasis Family history Patient history Laboratory testing Bleeding Patterns Mucous membrane Recurrent hemorrhages haematomas severe bleeding Vascular Abnormalities Structural abnormality or damage Easy bruising petechiae spontaneous bleeding Platelet count and coagulation screening tests normal Diagnosis of exclusion Inherited or acquired Petechiae Sites of bleeding Inherited Vascular Disorders The main one to be discussed is HHT Hereditary Hemorrhagic Telangiectasia HHT Family history of bleeding and purple lesions Caused by a genetic mutation of a gene on chromosome 9q that codes for a protein called endoglin Endoglin is a receptor for transforming growth factor on endothelial cells HHT The role of transforming growth factor receptors in forming the lesions is unknown These lesions consist of dilated capillaries and venules lacking support as a result of abnormal connective tissue Laboratory Findings Bleeding Time BT platelet count coagulation times normal Acquired Vascular Disorders The main one to be discussed is HenochSchonlein Purpura Henoch Sch nlein Purpura The term purpura means purple It can be used to describe both petechiae and ecchymoses It can also be used as part of the name of diseases in which these symptoms occur Henoch Sch nlein Purpura Vascular damage results from deposition of immune complexes Associated with viral or bacterial infection in children Disorders of Decreased or Defective Subendothelial Supporting Tissue Senile purpura Degenerating skin inadequately supports blood vessels Scurvy Vitamin Drugs C needed for collagen synthesis Platelet Disorders Quantitative Thrombocytopenia decrease in platelets Decreased production Aplastic anemia PNH Paroxysmal nocturnal hemoglobinuria MDSs Myelodysplastic Syndromes Leukemia Lymphoma carcinoma Myelofibrosis Thrombocytopenia Decreased production Megaloblastic anemia Chemotherapy radiation therapy Viral infection Drugs Idiopathic Thrombocytopenia Increased destruction or sequestration Immune Nonimmune Immune Destruction of Platelets Specific antibodies directed against platelets Antibody sensitized platelets removed by phagocytosis in spleen Platelet destruction greater than platelet production May be secondary or idiopathic Immune Thrombocytopenia Idiopathic thrombocytopenic purpura ITP Immune mediated platelet destruction Diagnosis of exclusion Acute ITP Affects children Abrupt onset of bruising petechiae mucous membrane bleeding Resolves spontaneously Acute ITP Associated with viral infections Autoantibodies directed against platelet surface glycoproteins IIb IIIa Ib X others Chronic ITP Persistent recurrent thrombo cytopenia Women 20 50 years old Insidious onset Symptoms of mucocutaneous bleeding Chronic ITP Autoimmune condition Platelet autoantibodies directed against platelet glycoproteins Platelet production also impaired Antigenic stimulation and mode of platelet destruction unknown Chronic ITP Can be treated with steroids intravenous immunoglobulin anti D immunoglobulin or splenectomy most effective Most severe cases may require chemotherapy Secondary Immune Thrombocytopenia Cause thrombocytopenia as a secondary symptom Must be excluded before diagnosing ITP Secondary Immune Thrombocytopenia Collagen vascular diseases Lymphoproliferative disorders Drugs Many IgG alloantibody or autoantibody produced in response to drug or drug complex Reversible Secondary Immune Thrombocytopenia After blood transfusion Post transfusion purpura Alloantibodies develop Also associated with pregnancy Associated with HIV Non Immune Thrombocytopenia Thrombotic thrombocytopenic purpura TTP Result is decrease plt number through a nonimmune mechanism TTP Thrombotic thrombocytopenic purpura Rare disorder Adults but range of incidence High incidence females High mortality if untreated Many cases associated with viral illness Thrombocytopenia severe TTP Platelet thrombi in small vessels Microangiopathic hemolytic anemia Common peripheral blood findings include schistocytes polychromasia and spherocytes Severe hemolysis Organ ischemia results in neurologic abnormalities and renal failure Normal coagulation tests Pathophysiology of TTP ULvWF ultra large von Willebrand Factor normally cleaved in circulation Important because ULvWF bind with higher affinity to platelets when increased shear stress ULvWF cleaved by ADAMTS 13 When ADAMTS 13 absent ULvWF not cleaved Strings of ULvWF detach from endothelial cells 2004 American Society for Clinical Pathology Classification of TTP Congenital familial chronic relapsing Adult onset Recurrent episodes of thrombocytopenia Inherited deficiency or defect of ADAMTS 13 Acquired transient Does not tend to recur Autoantibody directed against ADAMTS 13 Haemolytic Uremic Syndrome HUS Clinically resembles TTP but seen in children Classic signs are MAHA Microangiopathic Haemolytic Anemia thrombocytopenia and renal failure HUS Bacterial toxins attach to renal endothelial cells Damaged endothelial cells release ULvWF multimers that cause production of hyaline thrombi Thrombi deposit in renal vessels HUS Laboratory tests Elevated BUN blood urea nitrogen and creatinine Decreased hemoglobin Thrombocytopenia Schistocytes in peripheral blood Disseminated Intravascular Coagulation DIC Uncontrolled proliferation of fibrin Thrombocytopenia