Hemostasis, Hemophilia, Vit K Flashcards
tertiary hemostasis
-aka blood coagulation
intrinsic pathway
-aka contact activation pathway
-initiated from the blood itself after exposure of
the blood to collagen from a traumatized blood vessel
extrinsic pathway
- aka tissue activation pathway
- more important
- started by tissue injury and release of tissue factor, III
common pathway
-fibrinogen -> fibrin (via thrombin)
thrombin
- acts on fibrinogen to create fibrin monomer which can interact with other fibrin monomers to form fibrin fibers
- 4 molecules reomoved from fibrinogen -> fibrin
fibrinogen
-fibrin precursor (needs peptides removed to make fibrin monomer)
hemophilia A
- inherited coagulation disorder, intrinsic pathway
- cofactor VIII -> less Xa formed -> less thrombin
- treatment: missing factor VIII (recombinant factors) or blood transfusions
hemophilia B
- inherited coagulation disorder, intrinsic pathwat
- cofactor IX -> less Xa formed -> less thrombin
- -treatment: missing factor IX (recombinant factors) or blood transfusions
anticoagulants
- Agents that decrease Ca2+
- coumains (vit K antagonists)
- heparin and derivatives
- antithrombin-like agents (bind to thrombin, medicinal leeches = hirudin, bivalirudin)
tissue plasminogen activator
- activating plasminogen activator to plasmin (Plasmin can be effective in dissolving intravascular clots)
- Within 3 hours it can improve recovery odds of: pulmonary ebolism, myocardial infarction, stroke
- risk of hemorrhage
hemostasis
prevention of blood loss
vit K
- a co-factor in the production of an unusual amino acid, γ-carboxyglutamate (gla)
- Gla residues are part of Vitamin K-dependent proteins (VKDP)
- Addition of Gla residues confers on these proteins their capacity to bind to phospholipid surfaces in the presence of Ca2+
proteases
- endopeptidases
- exist in zymogen/inactive form
- synthesized in liver (except III, tissue factor and some VIII, antihemophylic globulin)
- present in low concentrations (except pro-thrombin, II = 1microM, and fibrinogen, I = 10microM)
protease cofactors
-also require activation
coagulation factors
-generally serine proteases
tissue factor
-a combination of phospholipids and lipoproteins released from damaged tissue that act as a proteolytic enzyme
HMWK
- High Molecular Weight Kininogen
- bound to prekallikrein and factor XII
- attracked to negatively charged surfaces such as injured blood vessel
IXa-VIIIa-phospholipid-Ca2+ complex
- aka tenase
- activate X to Xa
- where extrinsic and intrinsic pathways collaborate to start common pathway
VKDP
Vitamin K-dependent proteins
– Intrinsic pathway: Factors IX
– Extrinsic pathway: Factor VII
– Common pathway: Factor II = Prothrombin and factor X
– Anti-coagulation factors: Protein C and Protein S
vit K deficiency
-inefficient coagulation and bleeding
vit K depletors
- Warfarin/Coumadin, Dicoumarol
- inhibit production and recycling of vit K
- prescribed for elderly at risk for thrombosis for prolonged anticoagulant treatment
heparin sulfate
- facilitates the interaction of antithrombin with thrombin
- > inhibits prothrombin conversion to thrombin
- > inhibits thrombin action on fibrinogen
vWF
-Von Willebrand Factor
