MOD: Hemostatis I and II Flashcards
Platelet components
Alpha granules (protein storage eg thromboglobulin etc) and Dense granules (ATP, serotonin, calcium etc), and PF3 (platelet factor 3 surface marker) hidden in inner memb that becomes exposed when platelet activated
What are two platelet receptors
GP1B: VWF receptor (von willebrand factor), adhesion
GP2B: (mostly fibrinogen receptor), step 2 aggregation
What prevents blood from clotting in vessels?
House collagen in endoth, so when broken can come out, neg charge of both endoth and plasma prots keeps them away from ea other, thrombomodulin etc
Clotting mech:
primary hemostasis platelet adhesion
Endoth cell dmg rel collagen which binds to VWF, which concentrates platelets in dmg region
What events happen in primary hemostasis?
Platelets, adhesion & aggregation
Platelet structure
discoid if inactiv, purple on smear, pseudopodia if active
How does platelet adhesion of damaged endoth occur
subendoth collagen exposed, binds vWF, platelets also bind VWF via GP1b, platelets activated and secr granules, serotonin and ADP cause vasoconstr to slow flow,
-GP2b changes shape and binds fibrinogen, causing platelets to aggregate, forming plug
What catabolizeds von willebrand multimers?
ADAMTS13 (missing in TPP)
Von Willebrand Factor?
Multimer prot in megakaryoctyes and endoth cells, and stored in endoth cell Weibal-Palade bodies (which also hold P selectin)
- its also the primary transport protein for factor VIII in the serum (so VWF allows factor 8 to circul8)
- binds GP1b on one side and subendoth collagen on the other
What does <150k platelets mean?
>450k?
Thrombocytopoenia <150k
Thrombocytosis >450k
What are the labs to test platelets?
CBC bn 150k-450k, MPV
Periph blood smear
Bleeding time, replaced by:
Platelet fxn analyzer-100 (PFA-100), cartridge in collagen coated with ADP or epi, measure time it takes for platelets to occlude cartridge, req VWF
Sx of platelet issues?
longer clotting time on test,
mucosal bleeding, purpura, post-ob bleeding
Immune Thromobocytopenic purpura aka ITP
Autoimmune clearance of platelets via autoantibodies to them
drugs that can cause clotting issues
Aspirin COX inhibition decr TXA and inhibs platelets,
Plavix inhibs ADP receptor
Bernard-Soulier Syndrome
lack gp1b VWF receptor on plaletets, probs with adhesion so incr bleeding time on PFA-100 etc
- v v large platelets!
- usu young pt with bleeding disorder and assoc anemia
Glanzman Thrombesthenia
Def in GP2 fibrinogen receptor so plalets cant aggregte/bind
Gray Platelet syndrome
alpha storage granule deficiency, look gray, incr bleeding time, purpura and some bleeding
Von Willebrand Disease sx
-usual platelet disorder sx
Acquuired platelet issues
CPB cardiopulm bypass, myeloma ab’s on platelts, MPN incr platelet count , etc etc
Inherited VWD genetics?
Types?
all types AD except type 3 is AR
type 1 decr conc of normal VWF, most common
type 2 normal conc but abnormal VWF
type 3 complete VWF absence so low factor 8 (hemophilia A phenotype)
autoimm issues can also remove VW factor
Abnormal Ristocetin cofactor test means?
VWD!!!
Can also use VWF multimer test, large are more hemostatic
When would you not evaluate VWF?
stren exercise/stress
2nd3rd trim of pregnancy