hemostasis Flashcards
hemostasis
dilation (release and excess bleeding)
quickly followed by constriction
platelet aggregation and plug while fibrin clot forms
(loosly first and then contracts)
vascular constriction is the resutl of
myogenic response and trauma to smooth muscle organ you will get this response
constriction is proportional to the damage
what product do you see in small vessel damage that leads to constricrion
thromboxane A 2
surface proteins found on platelets
what is their function
remember platelets have no nucleus
surface protein helo to adhere the platelets with vessel injury
megakaryocytes
this is the progenitor to platelets
that never leaves the bone marrow
vesicles form around these myeloid stem cell lineage
half life of platlets
8-12 days
important for ASA tx
GPIB/IX
glycoprotein adhesion molecule
ans surface receptor
recognizes subendothelium through vWF
could
what is it exactly that GOIB/IX bind to in the subendothelieum
vWF in different places
basement membrane and collagen
or tunica media and smooth muscle in the wall of the vessel
GIIb/IIIa
fibrinogen binding protein
allows platelet can adhere to blood vessel wall and can adhere to circulating fibrinogen in the blood which is going to be an important of forming the clot
Clotting factor/Ca++ complex
multiple clotting factors that require Ca to be formed and activated
Xa/Va complex limits activation of thrombin at site of injury
whenever you have exposure to the tunica intima
Or basement membrane under the endothelium of the blood vessel
you are going to form a platelet plug
what happens in this process
they get “activated” response involves swelling up and pseudopodia allowing the platelet to move around
release clotting factors and enzyme
adhere to vWF
form thromboxane A2 which activates neighboring platlets
makes the sticky and aggregate
formation of the clot depends on what?
the balance of clotting factors
what dictates this is the floating factors found in the blood stream
when in balance we aren’t bleeding out of throwing thrombin
the process of of clotting begins with what
Process begins with formation of complex called prothrombin activator
converts prothrombin to thrombin
process requires Vit K
where is prothrombin activator made
liver
along with fibrinogen
this can be a big problem with severe liver disease
how does warfarin work
disturbes the process of vitamin K dependent factors
one of them being prothrombin
structural analog of vitamin K that can bnd upf factors
job of thrombin
Thrombin removes fibrin proteins from fibrinogen (made in liver)
Long fibrin fibers form meshwork/reticulum of clot and trap blood cells to form a firm clot
what specifically needs to happen in oder to use fibrin to clot
disulfide bridges connect the fibrin subunits on the lateral sides of the molecules. In order to convert it to fibrin, we need to break off those bonds via thrombin
charged molecules that keep fibrin from self aggregating in fibrinogen form
fibrinopeptides A and B
thrombin catalyzes the removal of these and they form fibrin
what stabilizes fibrin
initially the fibrin is unstable and held together solely by fibrin hydrogen bonds in the meshwork
fibrin stabilizing factor (part of the clotting cascade) is activated and causes covalent bonds and crosslinking to form
vitamin K dependent factors
2 7 9 10
all made by the liver
stuart factor
10a
converts prothrombin to thrombin (2a)
and thrombin activates fibrin form fribonigin (1)
factor III
part of the extrinsic pathway
thromboplastin or tissue factor
comes from exposure of the blood to tissue components outside of the blood (extrinsic)
usually phospholipids
works with factor VII to activate factor X which is the final pathway
intrinsic pathway
blood trauma from within the vessel wall
initiation is intrinsic to the blood vessel
can be activated simultaneously with the extrinsic pathway
beginning of intrinsic
factor XII
very sensitive to collagen
causes confirmation change that will activate platelets
can jump to extrinsic pathway and party with factor thre
describe the intrinsic pathway after XII
factor XII activates factor XIa the plasma thromboplastin antecedent PTA
which is Ca dependant and acvtivates christmas factor IX
(Berry christmas )
xmas factor activated X through VIII
describe the extrinsic pathway
tissue factor III combines with factor VII (proconvertin) after exposure to outside elements
which activate factor X
VIII
antihemophilic
what is the involvement of Ca in the clotting pathway
Liver carboxylates factors using vit K making factors able to bind Calcium
Carboxylation by the liver which requires Vit K makes the factor able to bind to that calcium molecule which is necessary to activate factors
which factor is most commonly involved in hemophilia
Factor VIII is most commonly involved in Hemophilia A
Factor VIII
which factor is most commonly involved in hemophilia B
- Factor IX is most commonly involved in Hemophilia B
two types of clotting disordersq
a. Failure to clot
b. Inappropriate clotting
PTT (aPTT
what is this used to measure
what factors does it accoutn for
-activate partial thromboplastin time
tttn BF
Used to monitor heparin tx
Measure of activity of factors XII, XI, IX, VIII
Factor X is the final common pathway - tested by PT and aPTT
antithrombin factors
antithrombin III
inactivates by irreversibly binding
how does heparin work
binds and concentrates antithrombin III, increases activity
- Promoting activity of anticlotting agent
- Heparin is not good as clot busting agent b/c all it’s doing is preventing the formation of further clots
this is activated by binding to excess thrombin and enhanced by binding to protein S
together what to they inactivate
iii. Protein C
iv. Activity of APC (activated protein C) enhanced by binding to protein S, and together that complex inactivates factor Va
S/APC complex
binds plasmin activator to allow clotting, activated complex cleaves creating tPA which dissolves clots
i. Measures extrinsic pathway
b. PT - Prothrombin time and INR
PT - Prothrombin time and INR measures which factors
ii. Factors I, II, V, VII, X (Vit K dependent factors)
T N L K TS
iii. Used to monitor, adjust coumadin tx
PT - Prothrombin time and INR measures which factors
used to measure heparin
PTT
activate partial thromboplastin time
what is INR
PT is converted to INR (international normalized ratio) - standardized reference point so that no matter where you get the test done, the PT that is found in that particular lab will be specific to that particular lab. The INR normalizes that value to another number that we can compare from lab to lab to provide standardization
Tests abnormality affecting conversion of fibrinogen to fibrin
Thrombin time (tests for activated factor II)
NO Thrombin time
can just get a fibrinogen level
TPA
dissolves clots
created by APC/S
antiplatelet drugs
act on platelets
ASA (platelet toxin) (NSAIDS in general)
can last 7-12 days life span of a platelet b/c permanent inhibition
Clopidogrel/Ticlodipine/plavix (inhibit platelet fxn)
Abciximab (antibody therapy)
Anticoagulant
act on clotting factors
“ Heparin (preventing further formation of clot)
“ Warfarin/Coumadin
Thrombolytics
clot busters
tPA
Streptokinase, urokinase, alteplase
molecule that is formed when fibrinogen is formed into fibrin that help track disseminated intravascular coagulation
Presence of D-dime
another test for DIC
disseminated intravascular coagulation
seen as an elevation of D dimer which is a fribrinigin breakdown product
FBP is another test of this
will also see prolong PTT and PT
this seem counterintuitive but the factors are all being taken up so it makes sense
