Hemostasis Disorders - PDF

09 Hemostasis Disorders BASIC TERMINOLOGIES 1 PETECHIAE purplish, red, pinpoint hemorrhagic spots in the skin caused by loss of capillary ability to withstand normal blood pressure and trauma 2 PURPURA Hemorrhage of blood into small areas of skin, mucous membranes, and other tissues. Appears firs...

09 Hemostasis Disorders BASIC TERMINOLOGIES 1 PETECHIAE purplish, red, pinpoint hemorrhagic spots in the skin caused by loss of capillary ability to withstand normal blood pressure and trauma 2 PURPURA Hemorrhage of blood into small areas of skin, mucous membranes, and other tissues. Appears first as red but later on turns purple and finally brownish yellow color 3 ECCHYMOSIS a form of purpura in which blood escapes into large areas of skin or mucous membranes, but not into deep tissue 4 EPISTAXIS nosebleed 5 HEMARTHROSIS leakage of blood into a joint cavity 6 HEMATEMESIS vomiting of blood 7 HEMATOMA A swelling or tumor in the tissues or a body cavity that contains blood 8 HEMATURIA. Presence of intact RBCs in the urine 9 HEMOGLOBINURIA Presence of Hb in the urine 10 HEMOPTYSIS expectoration of blood secondary to hemorrhage in the larynx, trachea, bronchi, or lungs 11 MELENA a stool containing dark red or black blood 12 MENORRHAGIA excessive menstrual bleeding BLEEDING DISORDERS DUE TO VASCULAR DEFECTS HEREDITARY 1 EHLERS- DANIOS SYNDROME The individual has hyperextensible joints and hyperplastic skin Skin, vasculature, and bones of affected individuals lack structural support The defect may lie in a peptidase enzyme deficiency that converts procollagen to collagen 2 PSEUDOXANTHOMA ELASTICUM Connective tissue elastic fibers in small arteries are calcified and structurally abnormal Subarachnoid and gastrointestinal bleeding are the most common causes of death ACQUIRED 1 SCURVY (VITAMIN C DEFICIENCY) Acquired disorder of dietary deficiency of vitamin C Ascorbic acid is required for the formation of intact structure of the vascular basement mebrane Without Vitamin C, hydroxylation of the amino acids proline and lysine cannot take place and collagen will not be formed 2 SENILE PURPURA The aging process brings about a degeneration of collagen, elastin and subcutaneous fat ALTERATIONS OF VESSEL WALL STRUCTURE HEREDITARY 1 HEREDITARY HEMORRHAGIC TELANGIECTASIA Characterized by vascular malformations and surface skin lesions called teiangiectasias The small blood vessels are focally disorganized and dilated throughout the body, their wall support is poor, and their ability to contract is diminished 2 CONGENITAL HEMANGIOMATA (KASABACH-MERITT SYNDROME) disorder associated with tumors composed of vessels that commonly swell and bleed at the surface ALTERATIONS OF VESSEL WALL STRUCTURE ACQUIRED 1 DIABETES MELLITUS The large vessels may become atherosclerotic, and the capillary basement membrane may thicken, thus blocking the normal flow of blood Most often affected are the glomerulus and retina 2 AMYLOIDOSIS can involve and obstruct the function of many organs, including the vascular system, in which there is deposition of the fibrillar protein called amyloid ENDOTHELIAL DAMAGE Damaged caused by autoimmune of infectious agents to the endothelial lining of the blood vessels may lead to hypercoagulation or hypocoagalation AUTOIMMUNE VASCULAR PURPURA Drug-induced purpura- quinine, procaine, penicillin, aspirin, sulfonamides, sedatives, coumarins Allergic purpura ________________________: purpura associated with abdominal pain secondary to GIT hemorrhaging ________________________: associated with joint pain especially in the knees and ankles INFECTIOUS PURPURA Purpura may form for several reasons Result on an inflammatory response to infection An autoimmune response Bacterial products Toxins or direct injury by infectious agent QUANTITATIVE PLATELET DISORDERS 1 THROMBOCYTOPENIA DECREASED PRODUCTION Aplastic anemia- Generalized bone marrow suppression leading to a decrease an all cell types Selective suppression of the megakaryocyte by chrolothiazide (diuretic) Thrombocytopenia with absent radius (TAR)- absent or decreased and abnormal bonemarrow megakaryocytes, congenital deformities of the arm Myelophthisic process- a space occupying lesion in the bone marrow such as metastatic tumor, fibrosis or leukemia DILUTIONAL LOSS Extensive bleed transfusion often is accompanied by thrombocytopenia, the degree of which is directly proportional Lo the number of units transfused NONIMMUNE DESTRUCTION Artificial surfaces- induce platelet adherence as well as formation of platelet microaggregates Ex. Cardiovascular prosthetic devices, vascular grafts, dialysis membranes IMMUNE PLATELET DESTRUCTION platelet destruction by immune mechanisms, associated with increased levels of IgG or complement on the platelet surfaces DISSEMINATED INTRAVASCULAR COAGULATION Platelets are consumed and destroyed HEMOLYTIC UREMIC SYNDROME AND TTP TTP- platelets aggregate and lodge in the endothelium and cause damage INCREASED PLATELET SEQUESTRATION BY SPLEEN- NORMAL IS 30-45% 2 THROMBOCYTOSIS PRIMARY uncontrolled proliferation of platelets, a characteristic of mveloproliferative disorders polycythemia vera, essential thrombocythemia, Chronic Granulomatous Leukemia SECONDARY (REACTIVE) a broad spectrum of acute and chronic illnesses illicit an increase in platelet production QUALITATIVE PLATELET DISORDERS 1 ADHESION DEFECTS BERNARD-SOULIER SYNDROME Platelets lack Gplb which is necessary for binding vWF Characterized by abnormal bleeding time and giant platelets VON WILLEBRAND'S DISEASE Lack of vWF 2 AGGREGATION DEFECTS GLANZMANN'S THROMBASTHENIA lack of Gplibilla AFIBRINOGENEMIA complete absence of fibrinogen 3 STORAGE POOL DEFECTS GRAY PLATELET SYNDROME alpha granules are missing, platelets are larger than normal and appear gray or bluegray in Wright stain WISKOTT-ALDRICH SYNDROME Characterized by a triad of thrombocytopenia, recurrent infections, and eczema Platelets lack _____________ & _____________ granules. Platelets are small. HERMANSKY-PUDLAK SYNDROME Characterized by a triad of tyrosinase-positive oculocutaneous albinism, accumulation of ceroid-like pigment in macrophages and a bleeding tendency Associated with a lack of __________________________ CHEDIAK-HIGASHI SYNDROME Characterized by albinism, recurrent infections, and giant lysosomes Beta- granule deficiency 4 ACQUIRED DEFECTS DRUGS DIET DISEASES 10 DISORDERS OF THROMBOSIS PRIMARY 1 ANTITHROMBIN-II| DEFICIENCY Principal inhibitor of thrombin is deficient 2 PROTEIN C AND S DEFICIENCY Protein C and S are Vit. K dependent glycoproteins that inactivates factors Va and Villa 3 FIBRINOLYTIC SYSTEM DISORDERS Quantitative and functional abnormalities of plasminogen Deficiency in Factor XII 4 DYSFIBRINOGENEMIA An abnormal functional fibrinogen molecule is produced and is resistant to fibrinolysis 5 HOMOCYSTINURIA Abnormal platelet-vessel wall interaction SECONDARY 1 LUPUS ANTICOAGULANT immunoglobulin directed against the phospholipid Associated with thrombosis due to prostacyclin inhibition Prolonged APTT that does not correct with normal plasma substitution 2 HEMOSTATIC PROTEIN ABNORMALITIES Postoperative states- Due to the release of tissue thromboplastin which initiates coagulation Malignancy- Release of coagulating factors by neoplastic cells Pregnancy- Placenta is rich in tissue thromboplastin 11 HEMORRHAGIC DISORDERS INTRINSIC PATHWAY DISORDERS 1 FACTOR XI DEFICIENCY (HEMOPHILIA C) Mild bleeding Autosomal 2 FACTOR VIII: C DEFICIENCY (HEMOPHILIA A) Sex-linked Factor VIlI:C is complexed with Factor VIII:vWF VIII:C is attached (carried) to VWF 3 FACTOR IX DEFICIENCY (HEMOPHILIA B, CHRISTMAS DISEASE) Sex-linked 4 VON WILLEBRAND'S DISEASE Defects of both Factor VIII: C and WF PROLONGED APTT, PROLONGED BT, NORMAL PT MOST FREQUENTLY ENCOUNTERED HEREDITARY COAGULOPATHY CBC, APTT & PT ARE RECOMMENDED FOR INITIAL WORKUP EXTRINSIC AND COMMON PATHWAY DISORDERS 1 FACTOR VII DEFICIENCY Abnormal PT, Normal APTT and thrombin time 2 FACTOR X (STUART-PROWER FACTOR) DEFICIENCY. abnormal APTT and PT, normal TCT 3 FACTOR V DEFICIENCY (OWEN'S DISEASE) abnormal APTT and PT, normal TCT 4 FACTOR II (PROTHROMBIN) DEFICIENCY abnormal APTT and PT, normal TCT 5 FACTOR I DEFICIENCY Abnormal APTT, PT and TCT Afibrinogenemia- complete absence Hypofibrinogenemia- low levels/ decreased (<100 mg/dL) Dysfibrinogenemia-Dysfunctional 6 FACTOR XIII DEFICIENCY clot dissolves in 5M urea ACQUIRED DISORDERS OF COAGULATION AND FIBRINOLYSIS DISEASE HEPATIC DISEASE VITAMIN K DEFICIENCY DESCRIPTION decreased coagulation factors (PT is a sensitive test for liver function) Vit. K is needed for gamma carboxylation of PT group DISSEMINATED INTRAVASCULAR coagulation factors and platelets are destroyed leading to COAGULATION decreased coagulation proteins PRIMARY FIBRINOGENOLYSIS Increased activation of plasmin, fibrinogen is broken down (pathologic fibrinogenolysis) SECONDARY FIBRINOGENOLYSIS Increased consumption of fibrinogen (DIC) PRIMARY SECONDARY FIBRINOGEN DECREASED DECREASED FIBRIN MONOMER NONE PRESENT FIBRIN POLYMER NONE NONE STABLE CLOT NONE NONE LAB EVALUATION OF FIBRINOLYSIS 1 WHOLE BLOOD CLOT LYSIS TIME PRINCIPLE: Whole blood will clot spontaneously when collected in a glass tube without anticoagulant. The clot should remain intact for 48 at 37°C, dissolution of the clot prior to 48 hours is indicative of excessive systemic fibrinolysis 2 EUGLOBULIN LYSIS TIME Avoids the problems that arise from plasminogen) inhibitors, a more rapid and sensitive assay of lytic activity PRINCIPLE: Euglobulins are proteins that precipitate when plasma is diluted with water and acidified. They include plasminogen, plasmin, fibrinogen, and plasminogen activators. PROCEDURE: Diluted PPP+ acid Euglobulin (precipitate) + Thrombin= clot Clot is incubated at 37°C REFERENCE RANGE: Lysis in less than 2 hours is indicative of increased fibrinolytic activity 3 PROTAMINE SULFATE GELATION TEST A test for secondary (smaller) fibrin degradation products PRINCIPLE: _____________________: Protamine sulfate replaces secondary degradation products from fibrin monomers and primary FDPs, resulting to a gel formation REFERENCE RANGE: Normally, no gel formation is seen 4 ETHANOL GELATION TEST Less sensitive but more specific than protamine sulfate test in detecting soluble fibrin monomers and polymers in plasma PRINCIPLE: 50% ethanol causes soluble fibrin monomer to dissociate, resulting in polymerization of the monomers and subsequent gel formation REFERENCE RANGE: There should be no gel formation under normal conditions 5 LATEX D-DIMER ASSAY Measures a specific fragment arising from degradation of fibrin (D-dimer) Measures fibrinolysis and not fibrinogenolyis (secondary fibrinolysis) Already positive after of DIC onset PRIMARY SECONDARY EUGLOBULIN CLOT LYSIS TIME SHORTENED NORMAL OR SLIGHTLY SHORTENED PLATELET COUNT GREATER THAN 100X109/L LESS THAN 100X109/L ANTITHROMBIN III ASSAY NORMAL DECREASED D-DIMER NEGATIVE POSITIVE ANTICOAGULANT THERAPY HEPARIN THERAPY WARFARIN THERAPY ACTION: ACTION: TREATMENT: TREATMENT: MONITORING: MONITORING: