Hemostasis and Clotting Cascade Flashcards
In clot removal, what does thrombin do?
activates protein C
What is INR?
international normalized ratio
ratio of pt’s PT to a normal sample, raised to the power of the ISI
0.94-1.4 for more sensitive and 2-3 for less sensitive thromboplastin preparations
What are the 4 general steps of hemostasis?
vascular spasm
formation of platelet plug
blood clot formation (coagulation)
repair of damage
What is the function of glycocalyx?
blood vessel membrane protein that repels platelets
What happens in protein C deficiency?
significantly increased risk of venous thrombosis
What is contained in the granules that platelets release?
ADP, thromboxane A2, and serotonin
What is tenase?
complex of 9a, 8a, Ca, and phopholipid surface
in intrinsic path
What form of warfarin is more active?
what enzyme is it metabolized by?
S-warfarin more active than R-warfarin
metabolized by cytochrome P2C9
What are the 2 primary causes of vascular spasm?
myogenic = direct reflex response to injury, no neurons platelet factors = serotonin and thromboxane A2 released --> vasoconstrictors
What is hemophilia A?
factor 8 deficiency –> intrinsic path inhibited
usually passed down, but 1/3 of cases are caused by a spontaneous mutation
4x more common than hemophilia B
What is a normal PT?
12-13 sec
How is the production of platelets controlled?
TPO continually secreted –> platelets have mpl receptor –> internalize and destroy TPO –> lowers amount of free TPO
NEGATIVE FEEDBACK loop
What are the 5 major functions of thrombin in the clot cascade?
- activates factors 5 and 8
- helps convert fibrinogen to fibrin
- activates platelets
- helps convert more prothrombin to thrombin
- activates factor 13 to cross link fibrin
What are the 2 enzymes needed, in order, to activate vitamin K?
vitamin K 2,3-epoxide reductase
quinone reductase
What is thrombin’s role in the intrinsic pathway of clotting cascade?
activates factor 8
How is a platelet plug formed initially (step 1)?
collagen exposed in damaged vessel wall –> von willebrand factor from plasma binds collagen –> platelets bind to VWF
What happens if you have a mutation in the TPO receptor on platelets?
polycythemia vera
What conditions might cause prolonged PT but normal PTT?
liver disease, decreased vit K, warfarin therapy, defective factor 7
What is tissue factor 3/ thromboplastin?
produced by endothelial cells when they are injured –> interacts with factor 7 to make factor 7a which initiates the extrinsic pathway
What does platelet-derived growth factor do?
promotes blood vessel growth and repair by stimulating fibroblasts to secrete stuff and differentiate into smooth muscle –> collagen deposition
What is the contributing factor to vascular spasm?
neural reflex = not necessary or sufficient
What are the 3 major steps/goals of coagulation?
- activation of thrombin activator
- activation of thrombin
- creation of fibrin from fibrinogen
What is the key difference btw primary and secondary hemostastis?
secondary makes platelet plug strong by generating a fibrin mesh on it
What generally occurs in primary hemostasis?
vasoconstriction –> platelet plug –> act as a phospholipid platform to initiate coagulation cascade
What blood vessel properties prevent blood clots?
smooth surface - prevents platelets from rupturing
membrane proteins: glycocalyx and thrombomodulin
What clotting cascade proteins are Vit K dependent and are therefore inhibited by warfarin?
factors 2, 7, 9, 10
proteins C and S
How does the phospholipid platform of platelets influence fibrin?
accelerates production of fibrin 100 to 1000 times
What does heparin do?
binds antithrombin 3 –> blocks 10a, 8a, and 2a
Once platelets go to the site of an injured vessel (VWF), what happens?
platelets swell –> ER releases calcium –> smooth muscle contraction –> granules leave platelet –> platelets stick to vessel wall and to each other
How does aspirin work?
irreversible inhibition of cyclooxygenase/COX –> inhibits platelet aggregation and prevents clot formation
What do platelet cell membranes contain (3)?
glycoproteins –> sticky
phospholipids –> activate clotting cascade
collagen receptors
What do you need to change plasminogen to plasmin?
Protein C has to inactivate tPA inhibitor –> then tPA can change plasminogen to plasmin
What is the other name for factor II?
factor IIa?
prothrombin
thrombin
What does HMWK collagen do?
activates factor 12 –> intrinsic pathway
What path does aPTT/PTT evaluate?
What are the factors tested?
intrinsic
PITT
What do activated protein C and S do?
inactivate factor 8a and factor 5a –> inhibits clotting cascade
What is the order of factors in the intrinsic path?
12 –> 11 –> 9 –>8 –> 10
How does warfarin work?
decreases amount of active vit K by inhibiting Vit K 2,3-epoxide reductase
How does ticlopidine work?
irreversibly inhibits ADP pathway involved in fibrinogen binding –> inhibits platelet aggregation and prevents clot formation
What is a normal PTT?
30-50 sec
What is the function of thrombomodulin?
blood vessel membrane protein that changes thrombin into an anticoagulant
What do platelets contain within their cytoplasm? (7)
actin and myosin mitochondria remnants of ER cyclooxygenase, thromboxane A2 fibrin stabilizing factor growth factors serotonin
What things can be released from endothelial cells to prevent clotting?
prostacyclin and NO –> prevents platelet activation and causes vasodilation
heparin –> binds antithrombin 3 –> will block 10a, 8a, and 2a
What is hemophilia B?
factor 9 deficiency
What defines hemostasis?
the steps taken by the body to limit blood loss
not just confined to the production of a blood clot!
What activates kallikrein?
factor 12a
prekallikrein –> kallikrein
How is vitamin K used in synthesizing certain clotting factors?
Vit K needed to form carboxyglutamate residues that can chelate Ca
What is the Leiden mutation?
mutation in factor V so that protein C cannot deactivate it –> have too much clotting
