Week 3 - Coag Flashcards
- **how does thrombin limit coag cascade?
- -activates protein _____ (esp on endothelial cells when thrombin bound to _______) which inactivates factors ___ and ____
–and also binds to ____ with heparin which acts as negative feedback loop on itself
PROMOTE - by turning fibrinogen (weak glue holding pl together) to fibrin (strong glue)
LIMIT
- -activates protein C (enhanced by binding of thrombin to thrombomodulin on ENDOTHELIAL CELLS)»_space;block factors 5a and 8a
- -binds with heparin and ATIII»_space; inactivates thrombin
primary vs hemostasis
- def
- clinical features of defects (bleeding where?)
- labs (PT/PTT)
-what factors involved in intrinsic vs extrinisc pathway
PRIMARY = WEAK PLATELET PLUG
- -platelet adhesion (Gp1b to Vwf) and aggregation (via fibringoen and gp2b3a)
- -DEFECTS = mucosal / skin bleeding (#1 = nose)»_space; low platelets / normal PT/PTT
SECONDARY = STRONG PLATELET GLUE
- -glued together by making THROMBIN»_space; converts fibrinogen (weak) to fibrin (strong)
- -DEFECTs = severe bleeding (muscles, bones)»_space; low platelets, Low PT (extrinsic - 7) and/or low PTT (intrinsic - 12, 11, 9, 8)
- **Discuss the roll of amplification in the coagulation cascade
- ex for each factor ___ activated of the extrinsic pathway, 10k ______ activated that converts fibrinogen to fibrin
- 7»_space; activates 10k thrombin
* amplification in every step of pathway (as more accumulates»_space; more signals)
Primary hemostasis –Activation of platelets via receptors –Needs \_\_\_\_\_ to initiate aggregatation –Creates a \_\_\_\_\_\_(white or red clot) –Dominant in \_\_\_\_(venous or arterial) system
Primary hemostasis –Activation of platelets via receptors –Needs vWF to aggregate –Creates a platelet plug (white clot) –Dominant in arterial system
Secondary hemostasis
–Requires the generation of _________ = factor _____
–Creation of fibrin from fibrinogen = (red or white clot)
–Dominant in the ____(venoous or arterial) syste
Secondary hemostasis
–Requires the generation of Thrombin (factor IIa)
–Creation of fibrin from fibrinogen (Red Clot)
–Dominant in the venous syste
tissue factor (TF) activates factor \_\_\_\_\_ starting \_\_\_\_\_ pathway -requires \_\_\_\_ and \_\_\_\_
VERY IMPORTANT - if don’t have it they die
- activates factor 7
- starts the clot = EXTRINSIC PATHWAY
-requires Ca2+ and phospholipid
what factors are in common pathway
2,5,1 (2x5x1 = 10)
what factors in intrinsic and extrinsic pathway
- ___pathway measured by PT
- ____ measured by PTT
IN = 12, 11 , 9, 8 - PTT (more factors/letters)
EX = 7. - PT (less letters, less factors)
- ____ initiates intrinsic pathway by activating ___ factor
- _____ initiates extrinsic pathway by activating ____ factor
- SEC»_space; 12»_space; intrinsic
- TF»_space; 7»_space; extrinsic
3 things that block thrombosis:
- heparin»_space; blocks ___ factors (10/9/2 ; 7/10 ; or 8/10)
- TFPI»_space; blocks ____
- thrombomodulin»_space; _____
*which of these anti-coags is THROMBIN (2A) a part of?
HEPARIN»_space; activate ATIII»_space; blocks 10, 9 and and 2
(hep:thromb:ATIII complex also blocks thrombin)
TFPI = blocks tissue factor»_space; block 7a, 10a
TM»_space; 2a:C/S»_space; 8 and 10
–Endothelium is an _______(anti or pro-coagulaant)
–Removing endothelium begins coagulation cascade via _____
As ______ remains on»_space; inhibition will reassert control locally
» 3D reactions in the vessel remain slow»_space; Endothelium adjacent to clot remains inhibitory
ANTI (inhibit coagulation dominates)
- TF»_space; activates 7 (extrinsic pathway)
- THROMBIN (anti-coag by activating ATIII and C/S?)
***importance of membrane in coag/anticoag cascade
–membrane thought of as ____(2D or 3D) whereas lumen is _____(2D or 3D)
–reactions are FASTER in ______ (2D/3D) - why?? ***
–membrane = 2D vs. lumen = 3D
–reactions (whether its thrombin leading to initial coag explosion or its thrombin activating anti-thrombin on intact endothelial nearby) are FASTER in 2D (FASTER ON MEMBRANE)
–because in 2D»_space; increase probability of molecules matching up properly / reacting in space
•Explain the functions of von Willebrand factor (vWF) in primary hemostasis,
- ____ receptor on platelet binds to vWF
- carrier protein for factor ______(increasing its 1/2 life)
- vWF = allows for 1st stage of PRIMARY HEMO = vwf attaches to the collagen at injury site»_space; allows for PLATELET ADHESION (tethers pls to collagen)
- via Gp1B (on plt)
- carrier protein for factor 8 (increases its half-life)
–Explain the common tests of vWF: Antigen testing, ristocetin, factor VIII level, and multimers, and explain how these tests can be used to classify von Willebrand’s disease
- which test would dx TTP or subtypes of VWD type 2
- test to order for VWD 2?
- which would diagnose bernard-soulier syndrome
- which would diagnose VWD 1 ?
- VWD 3?
*which would use to test for TTP causing MHA?
–vWF antigen = measure amount of vwf in plasma (low in VWD 1 and 3)
–restocetin cofactor (vwf:Rcoa) = tests for Gp1b def (BERNARD -SOULIER) VWF ACTIVITY/QUALITY (TYPE 2 VWD)
((risto added to patients plasma (w/ vwf but NO plts) »_space; expose to “fixed platelets”»_space; watch agglutination))
-multimer analysis - distinguish subtypes of VWD type 2, diagnose TTP (adam def» Microangiopathic hemolytic anemia)
List the steps of platelet activation during primary hemostasis
-whats Gp1b, TXA2, Gp2b3a, ADP and FIBRINOGEN
1- vasoconstrition (endo releases endothelin)
2- platelet adhesion to vWF (via GP1b)
3- platelet degranulates»_space; TXA2 (come over here guys!) and ADP»_space; puts out GP2b3a (hand out for more platelets to join)
4- platelets aggregate to eachother via gp2b3a with FIBRINOGEN in middle
•Define the role of the platelet function assay as a screen of platelet function, and when platelet aggregation studies are indicated
- -PFA-100 vs platelet aggregometry
- -indications = measure platelet _____(quantity or quality) like in VWD type ____(1,2,3)
PFA-100 = platelet function analyzer»_space; basically put blood into this fake blood vessel with fake injury and see howlong it takes to clot
platelet aggregometry - shine light into suspesion of platelet (cloudy) »_space; add agonist for plts to bind»_space; see increase transmisison of light if normal platelets (aggregates form»_space; less cloudy)
INDICATION - when symptoms of QUALITATIVE platelet disorder (VWD type 2)
•Explain how the receptors Integrin αIIbβ3 (Fibrinogen receptor - Glanzmann Thrombasthenia) and GP Ib-IX-V (vWF receptor - Bernard Soulier Syndrome) function in primary hemostasis and how their absence interferes with platelet function
______ will aggultinate with ristocetin but _____ will not
–GT - integrina2b3 def = normal platelet count but primary hemostasis bleeding (petechiae, mucosal bleeding) because NO AGGREGATTION
–BS- GP1b def = plts can’t bind to vWF (NO ADHESION)»_space; plts aggregate normally but don’t aggultinate with ristocetin
**GT will aggultinate with risto but BS syndrome will NOT
–arcidonic acid converted into _____ which is imortant for platelet aggregation and released via _____ GRANULES
–_____ also released via ______ GRANULES by platelets during degranulation phase that puts out gp 2b3a
- thromboxane A2 = call signal»_space; released via ALPHA granules
- enzyme that converts = COX = inhibited by aspirin
-ADP released via DENSE granules»_space; 2b3a
***define types 1, 2, and 3 von Willebrand’s disease (vWD) (do not worry about type 2 subtypes)
- type 1 (auto-dom, variable penetrance)»_space; NOT making ENOUGH vwf (primary due to decreased syntehsis and plasma secretion)
- type 3 (auto recessive, rare)»_space; not making ANY
- type 2 = quality problem (defect in 1 of fxns of vwf with higher circulating vwf antigen levels)
- plasma vWF circulates as _____(monomer or multimer) and converted into _____(mono or multi) by _____ enzyme
- deficient in that enzyme get ______
- multimer»_space;> monomers VIA ADAMTS13
- no adam13»_space; no Vwf»_space; can’t initiate clots get MICROANGIOPTHY?
dx? 12 yo comes in with recurrent nose bleeds and petechiae, mom says runs in the family but not as severe, inc ptt, normal pt, increased bleeding time
type 1 VWD (auto dominant)
*inc bleeding time!!! … Would be NORMAL if hemophilia
dx? 12 year old comes in with recurrent nose bleeds and petechiae. Not super severe. vWF levels are NORMAL, ristocetin acofactor activity is low
type 2 VWD = quality problem (normal vwf levels tho)
clopidrogrel (plavix) = irreversible inhibitor of _____ leading to ______
- inhibits ADP receptor»_space; can’t put out Gp2b3a»_space; platets can’t AGGREGATE
- abciximab = monoclonal AB to integrin alpha2bgeta3
dx based on platelet aggregometry:
- normal ADP and collagen curves, abnormal ristocetin curve
- abnormal ADP and acollagen curves, mildly abnormal ristocetin
- no ristocetin = no gp1b fxn = BS syndrome = NO ADHESION
- OK ristocetin, no ADP and collagen = gp2b3a problem (NO AGGREGATION)