Haemostasis and Thrombosis PDF

H A E M OSTA S I S A N D T H RO M B OS I S Normal process 1. Vasoconstriction to reduce blood flow 2. Platelet plug formation 3. Activation of clotting cascade with generation of fibrin clot formation Hemorrhagic disorders Hemophilia = defect in coagulation factor Glanzmann's thrombasthenia = defect...

H A E M OSTA S I S A N D T H RO M B OS I S Normal process 1. Vasoconstriction to reduce blood flow 2. Platelet plug formation 3. Activation of clotting cascade with generation of fibrin clot formation Hemorrhagic disorders Hemophilia = defect in coagulation factor Glanzmann's thrombasthenia = defect in platelets Ehlers Danlos syndrome = defect of collagen in vessel wall Vasculitis = inflammation of blood vessel Amyloidosis = blood vessel fragility Von Willebrand disease = primary hemostasis platelet disorder (commonest inherited bleeding disorder) Type 1 = quantitative reduction in VWF Type.3 = absence / severe reduction in VWF Qualitative mutants of VWF B. Coagulation abnormalities = secondary haemostasis Factor VIII & IX = secondary hemostasis disorder Fibrinogen, factor II, Factor X & Factor XIII deficiency = secondary haemostasis Anticoagulant drugs Heparin Low molecular weight = subcutaneous Unfractionated = intravenous Argatroban = thrombin inhibitor with a short half life Warfarin = indirect inhibitor of gamma carboxylation of vitamin K clotting factors Dabigatran = direct thrombin inhibitor = Factor II Other oral drugs = Rivaroxaban, Apixaban, Edoxaban Endothelium Normal cells express anticoagulant factors which inhibit platelet aggregation, coagulation & promote fibrinolysis After injury endothelial cells acquire procoagulant activity Platelet Platelets adhere to ECM to protect it after injury through binding of platelet receptors to VWF Adhesion leads to platelet activation done by secreted granule contents including calcium and ADP which causes changes in shape & membrane comp to activate GpIIb/IIIa GpIIv/IIIa receptors on activated platelets form birding cross-link with fibrinogen leading to platelet aggregation Thrombin Thrombin generated cross-linked fibrin and activates other coagulation factors Directly induced platelets aggregation & TxA2 production and activate endothelial cells Activates leukocytes Thrombotic disorders Pulmonary embolism is most common with 100-200/100,000 95% originate in DVT Thrombosis with Virchow’s triad = Abnormal blood flow, endothelial & hypercoagulability DVT = affects 0.02% population with 10% mortality Inherited thrombophilia = suspect un young patients 95% originate from above-knee DVTs Saddle embolus = large PE which impacts across bifurcations à acute right heart failure = sudden death Multiple small emboli = embolise fof a single large mass à pulmonary hemorrhage or pulmonary infarction Multiple emboli over time à Pulmonary hypertension & chronic right heart failure Infarction morphology Gross Infarcts are generally wedge-shaped Occluded vessel is t the apex Periphery of organ is the base Microscopy Dominant histologic characteristic is ischaemic coagulative necrosis Minutes - 4hours = no visible change 12-28 hours = cogaulative necrosis 2-3 days = inflammatory response (neutrophils then macrophages) Systemic emboli 80% arise from intracardiac mural thrombi which occur due to LV infarction Atrial dilation Atrial fibrillation Remainder come from: aortic aneurysm Atherosclerotic plaque fragments Valvular vegetations Paradoxical embolus Travel to: lower limbs, intestines, kidneys, spleen, upper limbs & brain and cause infarction SEPSIS & SHOCK Management Sepsis 6 in first hour = give cardiopulmonary support and mitigate threat of uncontrolled infection Take 3 = Blood cultures, bloods & urine output Give 3 = oxygen, fluids & antimicrobials Subsequent focus is on monitoring & supporting organ function n Surgical removal of septic foci & necrotic tissue is essential Indirect therapies aimed at modifying systemic inflammatory response can be used Mortality = 35-70% SIRS abnormal generalized inflammatory to a noxious stimulus Body temp: >38’C or 90/min Hyperventilation: RR > 20/min or PaCO2 12,00 cells/uL or F) Racial Co morbidities General = DM, autoimmune, malignancy Specific = splenectomy & transplant Pre-existing organ dysfunction/ disease Causative organism Management Brain changes are due to cytokine effect Oedema = initially vasogenic but becomes cytotoxic if cells are damaged Hypoxic ischemic encephalopathy (Hippocampus > cerebellar nuclei > watershed areas Red neurons = irreversible injury Cognitive impairment is common Also: microinfarcts & hemorrhages, ischemic infarction & septic emboli Pregnancy 1/100,000 deliveries is a cause of maternal mortality Physiological changes can mimic SIRS criteria