part 9 Flashcards
(23 cards)
thrombin
coagulation factor IIa
removes fibrinopeptides from E-domain, creates fibrine polymers
fibrinogen
coagulation factor I
factor XIII
creates crosslinks between fibrin polymers
activated by thrombin
when activated: transforms fibrinogen into fibrin
generation of thrombin: extrinsic pathway
upon contact w/ TF
generation of thrombin: intrinsic pathway
upon contact w/ foreign surfaces (like glass)
Tissue Factor
= transmembrane GP
= non-enzymatic cofactor of factor VIIa
normally absent in blood
produced by fibroblasts + SMC
expressed on monocytes + epithelial cells during inflammation
in cancer: expressed on tumor cells and tumor derived particles
prothrombin time
= INR
measures extrinsic pathway
measures clotting time in sec
take citrated plasma, add TF + phospholipids + Ca
aPTT
measures intrinsic pathway
measures clotting time in sec
take citrated plasma, add glass + phospholipids + Ca
factor VIII
availability determined by vWF
abnormal primary hemostasis
gives: petechia,
increased bleeding time,
normal PT
normal aPPT
abnormal secondary hemostasis
hematosis in joints etc
normal bleeding time
re-bleeding
prolonged PT and/or aPTT
FVIII defect
gives haemophilia A
X-linked
FIX defect
gives haemophilia B
X linked
TF pathway inhibitor
suppresses the initiation of thrombin generation
expressed on healthy tissue
antithrombin III
serine protease inhibitor
prevents diffusion of active coagulation enzymes
potentiated by heparins (when you give heparin there is no clotting)
thrombomodulin
transmembrane protein (on endothelium)
receptor and cofactor for thrombin
makes thrombin recognise protein C and activate it
protein C
pro-enzyme (serine protease)
vit. K dependant
protein S
non-enzymatic cofactor for APC (activated protein c)
vit K dependant
deactivates coagulation
FV leiden
gets activated by thrombin
SNP in exon 10
inactivation = different and less effective than normal FV
better cofactor, but can lead to DVT (gain of function)
prothrombin G2021OA
mRNA mutation of prothrombin (more stable)
more prothrombin –> coagulation more active
fibrinolysis
part of normal hemostasis
plasmin = key enzyme (created D-dimers)
high levels of D-dimer indicates thrombosis
tPA dependant plasmin generation
tPA produced by endothelial cells
converts plasminogen to plasmin
fibrin = cofactor
tPA only active when bound to fibrin
uPA dependant plasmin generation
uPA= pro-urokinase
uPA produced by endothelial cells, macrophages and epithelial cells
activated by plasmin
amplificates plasmin production
can occur in absence or presence of fibrin