Lecture 5 Flashcards
Hemostasis steps (4)
1) vascular spasm
2) primary hemostasis (platelet plug)
3) secondary hemostasis (clot)
4) fibrin deposition
Physical response to vascular injury (3)
1) vasoconstriction from neurologic and myogenic response
2) increased local pressure from pooling blood/hematoma
3) first aid pressure (push on the wound)
Platelet response to vascular injury (6)
this is the platelet plug part a.k.a. primary hemostasis
1) Adhesion - glycoprotein Ib (GPIb) binds to collagen or von Willebrand factor (vWF) which crosslinks to collagen
2) Activation - caused by agonists, subendothelium or foreign surfaces - agonists are vasoconstrictors, collagen, thrombin, ADP
3) Secretion - binding causes TxA2 release and ADP release; inhibited by aspirin and Plavix (ADP blocker)
4) Aggregation - agonist binding increases crosslinking to vWF - positive feedback loop to recruit more platelets and to fibrinogen
5) procoagulant activity - agonist binding causes phosphatidylserine to be expressed on the surface
6) retraction - actomyosin dependent contraction when the clot is formed
Final common pathway (3 steps)
1) Factor X is turned into Factor Xa
2) Factor Xa turns prothrombin into thrombin
3) thrombin turns fibrinogen into fibrin
Manufacture of clotting factors takes place in? Exception?
Liver, except VIII (endothelial cells and megakaryocytes)
Vitamin K effect on clotting factors - which ones? what effect? how blocked?
which - ii, vii, ix, x
what effect - enables Ca binding (to platelets)
blocked via warfarin (Coumadin)
Extrinsic pathway for clotting (4 steps)
1) tissue factor/factor iii (from adventitial fibroblasts) turns into iii-a
2) iii-a activates vii with help from Ca and thrombin
3) vii-a activates x
4) x-a activates the final common pathway
Xa complex for prothrombin -> thrombin conversion
components? (4) V->Va conversion requires? rate goes up by?
components - Va (accelerator); Xa (basic endopeptidase); Ca; PF-3 platelet phospholipid (phosphatidylserine)
conversion requires - thrombin
rate increase - 300,000 fold
physical and paracrine factors that endothelial cells use to prevent clotting (3)
physical (1) - they are the physical barrier that prevents platelet activation
paracrine (2) - pGI2 and NO secretion the acts as a vasodilator
Anticoagulant factors of endothelial cells (4) name/function
1) Antithrombin III - circulates
2) Tissue Factor Pathway Inhibitor - TFPI - prevents the TF, VIIa, Ca complex
3) Heparin - really only increases effectiveness of Antithrombin III; esp. in lung and liver; similar proteoheparan circulates around EC’s
4) Thrombomodulin - inactivates Va and VIIIa via help from protein C and protein S
Procoagulant factors of epithelium (1)
1) manufacture and storage of vWF
septic shock induces which cascade?
Extrinsic (by activating TF)
clot breakdown pathway (3 steps)
1) Plasminogen is converted to plasmin in the presence of Tissue plasminogen activator (tPA) and fibrin
2) plasmin breaks down fibrin into soluble fragments
3) tPA and plasmin can be inactivated
tPA by PAI (plaminogen activator inhibitor)
bleeding disorders (2 types + common characteristics)
1) platelet defects - pinpoint purplish spots and bleeding from mouth, nose and GI tract
2) coagulation defects - problems with clotting factors (Factor VIII - hemophilia A); prolonged bleeding, esp GI tract or joints
hypercoagulability (3 conditions + Virchow triad)
1) increased platelet function
2) increased clotting function (primary or secondary)
3) Virchow triad - thrombus formation (can lead to thromboembolism);
1) static or turbulent blood flow
2) endothelial injury
3) blood hypercoagulability
