Coagulation: Review of Diseases of Primary and Secondary Hemostasis PDF

COAGULATION: REVIEW OF DISEASES OF PRIMARY AND SECONDARY HEMOSTASIS LEARNING OBJECTIVES  Define the key components of hemostasis and identify their roles in coagulation  Know the appropriate anticoagulants used for laboratory tests evaluating hemostasis  Understand the tests of primary hemosta...

COAGULATION: REVIEW OF DISEASES OF PRIMARY AND SECONDARY HEMOSTASIS LEARNING OBJECTIVES  Define the key components of hemostasis and identify their roles in coagulation  Know the appropriate anticoagulants used for laboratory tests evaluating hemostasis  Understand the tests of primary hemostasis and what they evaluate  Understand the tests of secondary hemostasis and what they evaluate  Understand and explain the common hemostatic diseases  Using laboratory data, be able to understand where in the coagulation cascade the problem exists and determine the most likely diagnosis for the patient LECTURE OUTLINE Review of Primary Laboratory Evaluation Hemostasis Common diseases Review of Secondary Laboratory Evaluation Hemostasis Common diseases PRIMARY HEMOSTASIS LABORATORY TESTING AND COMMON DISEASES THINK. PAIR. SHARE. Explain primary hemostasis. How does it start? How does it end? Who are the key players? PRIMARY HEMOSTASIS: STEPS 1. Platelet  Endothelial injury leads to the exposure of Adhesion subendothelial collagen  Platelets adhere to exposed collagen via 2. Platelet Shape von Willebrand Factor (vWF) Platelet activation Change 3. Release of Granules 4. Aggregation PRIMARY HEMOSTASIS: STEPS 1. Platelet  Endothelial injury leads to the exposure of Adhesion subendothelial collagen  Platelets adhere to exposed collagen via 2. Platelet Shape von Willebrand Factor (vWF) Platelet activation Change  Adhesion causes platelet activation  Change their shape and release granules 3. Release of Granules 4. Aggregation PRIMARY HEMOSTASIS: STEPS 1. Platelet  Endothelial injury leads to the exposure of Adhesion subendothelial collagen  Platelets adhere to exposed collagen via 2. Platelet Shape von Willebrand Factor (vWF) Platelet activation Change  Adhesion causes platelet activation  Change their shape and release granules 3. Release of  Fibrinogen forms bridges between adjacent activated Granules platelets leading to aggregation (reversible)  Forms primary hemostatic plug 4. Aggregation LET’S REVIEW! Which of the following is a quantitative method of assessing primary hemostasis? A. Thrombogram B. vWF antigen assay C. FDPs and D-dimers D. Buccal mucosal bleeding time (BMBT) LET’S REVIEW! Which of the following is a quantitative method of assessing primary hemostasis? A. Thrombogram B. vWF antigen assay C. FDPs and D-dimers D. Buccal mucosal bleeding time (BMBT) TESTS OF PRIMARY HEMOSTASIS – PLATELETS  Quantitative – platelet number  Platelet slide estimates (blood smear)  Thrombogram – automated platelet count  Qualitative – platelet function  Buccal Mucosal Bleeding Time (BMBT)  vWF antigen assay DISORDERS OF PRIMARY HEMOSTASIS  Platelets are abnormal in….  Morphology  Number  Function ABNORMAL MORPHOLOGY  Giant platelets or “shift” platelets  Platelets that are larger than RBCs  Suggests accelerated thrombopoiesis (platelet regeneration)  May also be seen with macrothrombocytopenia (CKCS)  Mean platelet volume (MPV) is generally increased THINK. PAIR. SHARE. What are the four main causes of thrombocytopenia? THINK. PAIR. SHARE. What are the four main causes of thrombocytopenia? Think S.P.U.D.! S = Sequestration P = Production U = Utilization D = Destruction THROMBOCYTOPENIA - SEQUESTRATION  Trapping of platelets within the spleen  Usually causes a mild, transient decrease in platelet counts  Due to:  Splenomegaly (e.g., anesthetic drugs)  Splenic congestion  Splenic neoplasia THROMBOCYTOPENIA – DECREASED PRODUCTION  Bone marrow disease – often associated with other cytopenias (e.g., anemia, leukopenia)  Aplastic anemia (marrow panhypoplasia)  Toxins (bracken fern, mycotoxins) and drugs (estrogen, cephalosporins, chemotherapy)  Other causes → myelofibrosis, necrosis, inflammation, myelophthisis (replacement of marrow with neoplastic or other non-marrow cells)  Infectious diseases  Ehrlichia and other rickettsial organisms  Viral organisms → FeLV/FIV, EIAV, Parvovirus  Macrothrombocytopenia (CKCS) – nonpathogenic THROMBOCYTOPENIA – INCREASED UTILIZATION  Increased utilization = increased platelet consumption  Disseminated intravascular coagulation (DIC)  Vasculitis  Endocarditis  Hemorrhage → has to be SEVERE, acute blood loss THROMBOCYTOPENIA – DESTRUCTION  Immune-mediated thrombocytopenia (ITP) – can be primary or secondary  Marked thrombocytopenia (usually 1 million plts/uL)  Due to a neoplastic cause  Essential thrombocythemia (ET)  Acute Megakaryoblastic Leukemia (AML-M7)  Chronic myeloproliferative diseases  Patients may have an increased risk of thrombosis or hemorrhage, depending on platelet function REACTIVE (SECONDARY) THROMBOCYTOSIS Several causes:  1) Increased production  Inflammation → driven by inflammatory cytokines (e.g., IL-6)  Recovery from recent thrombocytopenia (also called a rebound thrombocytosis) → e.g., secondary to blood loss or trauma  Chemotherapeutic drugs → vinca alkaloids (e.g., vincristine)  Iron deficiency → exact mechanism is unknown REACTIVE (SECONDARY) THROMBOCYTOSIS  2) Redistribution or physiologic  Epinephrine-mediated response or exercise leading to splenic contraction and transient thrombocytosis  3) Decreased removal  Recent splenectomy causing transient thrombocytosis seen for days to weeks post-op  4) Excess cortisol  Endogenous (Cushing’s disease) or exogenous (glucocorticoid administration) ABNORMAL PLATELET FUNCTION  Platelet count is normal or elevated  Can be inherited or acquired  Abnormal platelet function associated with…  Adherence or aggregation  Surface membrane receptors  Ability to synthesize and release products CAUSES OF CONGENITAL PLATELET DYSFUNCTION  Von Willebrand Disease (vWD)  Most common inherited hemostatic disorder in dogs → dobermans, scotties, shelties, and others  Rare in other domestic animals  Deficiency or abnormality of vWF (remember it’s the glue!)  Either a quantitative (Type 1 and 3) or qualitative defect (Type 2)  Acquired vWD is uncommon in vet med TYPES OF VON WILLEBRAND DISEASE (VWD) Type vWF Clinical Severity Documented Breeds Type 1 Most common Variable Airedale, Akita, Corgi, Decreased vWF concentration (