Blood Coagulation & Wound Repair Flashcards
Enzymatic cascade
Series of rxns where substrate becomes catalyst of the next rxn
Zymogen
Inactive precursor form of enzyme
Vitamin K
fat soluble vitamin in which factors II, VII, IX, and X are dependent upon.
Serum
Liquid phase of clotted blood after spinning out clot
Plasma
Liquid phase of unclotted (anti-coagulated) blood (still contains clotting proteins). Cells have been centrifuged away.
Hemophilia A
Classic hemophilia. X-linked recessive disorder caused by missing or defective factor VIII (clotting factor)
Blood thinners
inhibit coagulation, prolong bleeding time, can complicate dental surgery
Warfarin
Decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase which acts to activate vitamin K. Reduction in vitamin k = reduction in synthesis of clotting factors
Thromboxane A2 or TXA2
vasoconstrictor that also increases platelet aggregation through increasing expression of the GPIIb/IIIa protein complex on platelet membranes.
ADP
stored in dense bodies inside blood platelets and is released upon platelet activation. ADP causes platelet activation/aggregation.
Gamma-carboxyglutamic acid
Requires vitamin k, post-translational modification that adds a calcium binding site to coagulation proteins
Where is vitamin k metabolized?
gut bacteria
Platelets (thrombocytes)
anuclear cell bodies derived from megakaryocytes which circulate in the vasculature.
Factor XIII (Transglutaminase)
activated by thrombin in presence of Ca, catalyzes cross linking of fibrin
Serotonin
Released upon degranulation of platelets at site of injury. Functions as a smooth muscle constrictor to immediately act to limit the loss of blood volume.
Process of coagulation
- blood flow to injury site reduced (vasoconstriction)
- Platelets stick to injury site
- Platelet plug forms
- Platelets & damaged tissue release factor VIII
- Fibrin formed, works as mesh to stop bleeding
Primary hemostasis
Vasoconstriction and platelet response
Secondary hemostasis
clotting cascase
What molecule releases important signaling molecules upon binding to collagen immediately after injury?
Platelets
What is secreted by platelets upon initial binding to collagen at site of injury?
ADP, thromboxane A2, serotonin
What molecules trigger the formation the platelet plug?
ADP, thromboxane A2
What molecules stimulate vasoconstriction upon injury?
Serotonin, thromboxane A2
What is required for fibrinogen to bind platelets?
GPIIb/IIIa must undergo conformational change to expose binding site for vWF or fibrinogen
Extrinsic pathway
- Activated by external trauma that causes blood to escape from the vascular system
- involves factor VII
- slower than intrinsic but less important
Intrinsic pathway
- activated by trauma inside the vascular system
- activated by platelets, exposed endothelium, chemicals, collagen
- Involves factors XII, XI, IX, VII
Common pathway
- Where both pathways meet and finish clot production
- Involves factos I, II, V, X
Factor I (Fibrinogen)
Cleaved by thrombin to become fibrin and forms mesh that reinforces and strengthens platelet plug
Factor II (Prothrombin)
Activated on surface of activated platelets by prothrombinase complex
von willebrand factor
Associated with subendothelial connective tissue, served as a bridge between platelet, glycoprotein GPIb/IX and collagen
Thrombomodulin
Protein on surface of endothelial cells; binds thrombin which then activates protein C
Phases of wound healing
- Hemostasis
- inflammatory
- proliferative
- remodeling
Hemostasis
Within minutes after injury platelets aggregate to form a fibrin clot which controls bleeding
Inflammatory phase
Bacteria and debris are phagocytosed and removed from injury (macrophage/neutrophil), factors are released that cause migration and division of cells involved in proliferative phase
Proliferative phase
Angiogenesis, collagen deposition, granulation tissue formation, epithelialization, wound contraction
Remodeling phase
Collagen remodeled/realigned and cells no longer needed undergo apoptosis
Fibronectin
- plasma form secreted by hepatocytes and cellular form secreted by cells as part of ECM
- Regulates platelet function
What is ACD anticoagulant used for? What does it do?
Centrifugation; Reduces the amount of calcium so there will be no regulation of binding and cascade cannot begin
Prothrombin time (PT)
test used to help detect and diagnose bleeding/clotting disorder
International Normalized Ratio (INR)
- used to monitor how well warfarin is working to prevent blood coagulation
- Effective range is 2.0 to 3.0 (lower = fast clotting, higher = slower clotting)
Hemophilia B
- X-linked recessive, due to decreased synthesis of factor IX
- Inbreeding in Europe
