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Lecture 26

Introduction to Disorders of Coagulation & Hemostasis

What occurs during primary hemostasis? (1) Vascular phase: endothelial cell changes (2) Platelet phase: plt attach to injury site, formation of plt plug, support of coagulation reactions
What occurs during secondary hemostasis? The coagulation cascade
What is the physical response of blood vessels to injury? 1) vasocontriction via both neural stimulation and chemical vasocontrictors 2) elastic recoil of blood vessels
What is the anticoagulant effect of PGI2? Deters platelet aggregation
What is the anticoagulant effect of thrombomodulin? Binds thrombin and activates Protein C
What is the endothelial cell response to vessel injury? Subendothelial collagen and VWF binding sites exposed; Thrombomodulin and heparan is stripped away; PGI2 and tPA are no longer produced; tissue factor is exposed to Factor VII, initiating the coagulation cascade
What proteins are required for platelet binding to the site of vessel injury? 1) Von Willebrand Factor (VWF) 2) Platelet GP1b
(T or F) Platelet aggregation requires platelet activation and energy requiring process. True.
What platelet surface receptor is required for platelet aggregation? Glycoprotein IIbIIIa receptor
What platelet surface phospholipid is required for efficient enzymatic coagulation reactions? Phosphotidyl serine
What enzyme promotes reversal of Phosphotidyl choline (PC)/Phosphotidyl serine (PS) in the platelet bi-lipid membrane? Flipase
What is the importance of Calcium in coagulation? Catalyzes reactions by promoting attachment of enzymes and zymogens to phopholipid surface
What are the co-factors of the coagulation cascade? Factor VIII, V, III (Tissue Factor)
What are the enzymes of the coagulation cascade? Factors XIII, XII, XI, X, IX, VII, and II
What is the function of thrombin? 1)cleaves fibrinogento fibrin 2)activates plts 3)activates factor XI 4)activates factor XIII to XIIIa 5)activates Protein C when bound to thrombomodulin 6)at low levels-enhances FV and FVIII function 7)at high levels-destroys FV and FVIII
What laboratory study monitors the extrinsic pathway of the coagulation cascade? Protime (PT)
What laboratory study monitors the intrinsic pathway of the coagulation cascade? aPTT
What are the initiatiors of the coagulation cascade used in the lab aPTT assay? FXII, prekallikrein, and high molecular weight kininogen (HMWK)
(T or F) Deficiencies of FXII, Prekallikrein, and HMWK prolong the aPTT test but do not cause bleeding. True.
What coagulation factors require Vitamin K? Factor VII, IX, X, II
What is the importance of Vitamin K in coagulation? The enzymes Factor VII, IX, X, and II require gamma-carboxylation by Vit K dependent pathway. Carboxyl residues help enzymes bind to the surface.
What anticoagulant drug interferes with Vit K dependent pathways in the coagulation cascade? Coumadin (warfarin)
What are some common causes of Vitamin K deficiency? 1) poor intake 2) biliary disease 3) antibiotics interfering with Vit K metabolism in the gut
With coumadin therapy, which coagulation enzyme is inhibited first? Factor VII
What coagulation factors are monitored by PT? Measures Factor VII, V, X, II, and fibrinogen
For the lab PT assay, what initators are added to the patient's blood sample for clot formation? Thromboplastin (Tissue Factor and phospholipids) and calcium
What laboratory assay is used to monitor coumadin therapy? Prothrombin Time (PT)
What laboratory assay is used to monitor FVII deficiency? Prothrombin Time (PT)
A laboratory assay of clotting factors used to monitor the intrinsic pathway of coagulation. aPTT (activated partial thromboplastin time)
What laboratory study monitors heparin therapy? aPTT
Created by: UVAPATH4