Coagulation I/II Flashcards
Primary Hemostasis
Localized to the area of exposed subendothelial collagen
Platelet plug
Secondary Hemostasis
requires platelet membrane surfaces for efficient factor interaction
Coagulation factors circulate in the blood as
Zymogens (inactive but ready to strike)
Coagulation Factors- Zymogens
FVII, FXI, FIX, FX, Pro-Thrombin (FII)
Coagulation Factors- Procofactors
Tissue Factor (TF), FVIII, FV
Coagulation Factors are all produced in the
Liver
Tissue Factor is expressed by
DAMAGED endothelial cells
Thrombin’s activity
Activates platelet phospholid to expose phosphotidyl serine
Thrombin restructures platelet surface
Thrombin activates FVIIIa and FVa which form complex with Ca2+
FVIIIa and FVa increase FXa which cleaves more prothrombin to thrombin
Thrombin cleaves Fibrinogen to fibrin
Thrombin cleaves FXIII to FXIIIa
Vitamin K dependent Cofactors
FII, FVII, FIX, FX
have GLA domains that need to be carboxylated to gamma carboxy glutamic acid by vit K dpendent carboxlase
Mechanism of Coumadin/ Warfarin
Anti-coagulant that blocks reduction of vitamin K
Prothrombin Time (PT)
Measures Extrinsic pathway
Initiated by TF which is EXTRINSIC to circulation
Blood sample collected in citrate to remove any Ca2+, platelets are removed via centrifugation
TF is added to blood with Ca2+ and phospholipids and you measure how long it takes clot to form.
Thromboplastin
Phospholipids + TF = thromboplastin
Part of Prothrombin Time Assay for Extrinsic Pathway
Partial Thromboplastin Time (PTT)
Evaluates INTRINSIC pathway
Partial Thromboplastin
Phospholipids - TF = partial thromboplastin
Part of partial thromboplastin time for Intrinsic pathway
Heparin/ Antithrombin (AT) System
AT is Serine Protease Inhibitor (SERPIN)
Inactivates all serine protease coagulation factors by IRREVERSIBLE binding
AT by itself is very slow inhibitor of thrombin
Heparin induces conformational change in AT resulting in 10,000 fold increase in activity
AT with Heparin bind to thrombin and decrease its activity