Principles of Hemostasis Flashcards
define hemostasis
a complex physiological process that balances forces of coagulation and anticoagulation to protect the vasculature from uncontrolled bleeding or excessive clotting
what are the three phases of hemostasis?
primary= formation of platelet plug secondary= coagulation tertiary= fibrinolysis (vascular repair)
what are the three steps of forming a platelet plug?
platelet adhesion
platelet activation
platelet aggregation
what is von Willebrand factor?
large, heterogeneous multimeric glycoprotein.
what does von Willebrand factor do?
- protects coagulation factor VIII from rapid inactivation
- binds platelets via the glycoprotein receptor complex (causes platelets to adhere to injured part of wall)
what makes vWF bind to platelets?
change in shear rate (blood flow)
what happens to the conformation of vWF when the sheer rate changes?
it unravels
how do vWF and collagen bind platelets?
vWF via glycoprotein Ib receptor
collagen via the glycoprotein VI receptor and a2b1 integrin
what is the most common congenital bleeding disorder?
von Willebrand disease
what is von Willebrand disease?
deficiency in vWF manifests as impaired platelet function -bruise easily -bleeding gums -epistaxis
how can von Willebrand disease be treated?
transfusion of FFP, cryo, DDAVP or vWF/FVIII concentrate
how are platelets activated?
by agonists at the site of injury -collagen, thrombin, ADP and epinephrine
what happens when platelets are activated?
- change morphology
- Release the contents of their alpha granules and dense granules – ADP, serotinin, factor V, factor VIII, vWF, fibrinogen
- Release substances synthesized in the cytosol (thromboxane A2) into the environment
- **Express new negatively-charged receptors on their surface membrane
why does aspirin inhibit platelet aggregation?
it's a "cox blocker" blocks cyclooxygenase (COX)
what are the three main platelet surface receptors?
thrombin
ADP
Fibrinogen
what are the primary platelet aggregation adhesive molecules?
fibrinogen and vWF
platelet aggregation is mediated by….
the surface receptor-glycoprotein IIb/IIIa receptor
what is the fibrin stabilizing factor?
Factor VIII
what are the direct effects of aspirin on fibrinogen and FXIII?
aspirin acetylates fibrinogen-clot structure is looser and easier to lyse
the proper interaction of coagulation factors requires the presence of what?
a negatively charged phospholipid membrane
where are most coagulation factors synthesized?
the liver
which factor is the only one with extra-hepatic origin?
Factor VIII
what is the principle function of vitamin K?
catalyzes the carboxylation of glutamic acid
what does coumadin do?
inhibits carboxylation of the vitamin K dependent factors by vitamin K
which has the shortest half life of the vitamin K dependent factors?
FVII
hemophilia A is a deficiency of _____
hemophilia B is a deficiency of _____
A = FVIII B = FIX
what is also known as “Christmas disease?”
Hemophilia B
of the two models of coagulation, which is considered to be the older model?
coagulation cascade
what is the main objective of the coagulation cascade?
essence is to create thrombin
what are the three pathways of the coagulation cascade?
common, intrinsic, extrinsic
name some of the hemostatic actions of thrombin
cleavage of fibrinogen to fibrin
activates platelets
activates F V, VII, VIII, IX, XIII
what are the three overlapping stages in the cell-based model of coagulation?
initiation, amplification and propagation
in the cell-based model of coagulation, what is initiation?
a procoagulant stimulus generates enough thrombin to initiate coagulation process
in the cell-based model of coagulation, what is amplification?
platelets and coagulation factors are activated
in the cell-based model of coagulation, what is propagation?
large amounts of thrombin are generated on the activated platelet surface
prothrombin is converted to thrombin in which step of the cell-based model of coagulation?
initiation
name three regulators of coagulation
Tissue Factor Pathway Inhibitor (TFPI)
Antithrombin (AT): biggest inhibitor of thrombin in adults
Protein C (PC)
what is the primary anticoagulant action of heparin?
its ability to inhibit thrombin activity
what are some of the effects heparin on AT?
binds to AT and causes a conformational change in the molecular structure of AT (need ~ 80% to be effective)
transforms AT from a slow to a rapid inhibitor of thrombin
neonates have low levels of what?
procoagulant and anticoagulant factors
neonatal platelet counts are what percent of adults?
100%…they’re the same
what is the relationship between vWF and age?
decreases with age
the FDA has approved the use of recombinant activated factor VII for what uses?
patients with hemophilia A and B with developed inhibitors against FVIII and FIX
patients with FVII deficiency
rFVIIa has a huge affinity for what?
Tissue factor
