4 Mechanisms of Hemostasis Flashcards
What is the mechanism by which bleeding is controlled after injury?
Hemostasis
Pathological states of hemostasis can lead to what 2 things?
thrombosis or hemorrhage
What cells play a vital role in hemostasis?
endothelial
damage to endothelium leads to what?
platelet adherence, aggregation and adherence
What happens at platelet activation?
release granules, increased intracellular Ca and decreased cAMP
What provides the phospholipid substrate on much of fluid phase coagulation occurs?
platelets
Plasma coagulation causes?
solubule FIBRINOGEN becomes insoluble cross-linked polymer FIBRIN
What type of enzymes need to be activated for fluid phase coagulation?
serine proteases
Where are coagulation factors produced?
liver
Breakdown of a clot requires what?
plasmin generation from plasminogen (fibrinolysis)
Decreasing clot formation is initiated by what?
antithrombin
Protein C and S pathways
Where does much of the interaction of plasma proteins occur?
on the surface of platelets
Coagulation occurs by interactions of what three things?
plasma proteins
platelets
tissue factor
What happens to arterioles right after injury?
vasoconstriction- brief, reflex mechanisms
What part of hemostasis is formation of platelet plug? fibrin clot?
Primary Hemostasis and Secondary Hemostasis
How long do platelets circulate in the blood?
7-10 days
What provides an enormous expansion of the surface area/volume ratio in platelets?
open canalicular system
What recruits adjacent platelets to form a plug?
alpha and dense granules
What are 5 basic events in series of platelet reaction?
- adhesion
- activation
- Release Reaction
4, clot formation and retraction - support plasma coagulation
Platelet adhesion requires what factor?
plasma protein von Willebrand factor (vWf) and of course the membrane receptor for it (Ib-IX-V)
Where is von willebrand factor produced and stored?
produced and stored in endothelial cell and megakaryocytes
T-F - platelets have vWf in there alpha granules?
True
what are the 3 functions of vWf?
bind platelet receptor
bind collagen
stabilize factor VIII
What binds to glycoprotein IIb-IIIa?
fibrinogen
T-f- after activations platelets do not change shape?
False-become spherical spiny due to ADP receptors
What do dense granules contain?
ATP, ADP, calcium, serotonin
What do alpha granules contain?
coagulation factors
growth modulators
adhesive proteins
T-F - platelet granules also contain lysozymes
True
What does release of granule contents cause?
vasoconstriction, modulation of growth of vessel, cell adhesion, fluid phase coagulation
What generates arachidonic acid?
phospholipids acted upon by Phospholipase C.
What converts arachidonic acid to cyclic endoperoxide?
cyclo-oxygenase
What becomes of the endoperoxides?
prostoglandins
or Thromboxane A2
The secretion of platelet alpha granules leads to high concentrations of fibrinogen, factors V, VIII, XI, XIII which lead to and enhance what?
fibrin formation and stabilization
True or False- platelets have similarities of embryonic muscle?
True- actin myosin in platelets which organize filopodia
What do the platelet filopodias bind to?
fibrin and then contract to pull close together- drawing together the edges of the injured tissue.
What inhibits platelet aggregation
prostacyclin- made by endothelial cells
NO- also made from endothelial cells
Abnormal bleeding does not occur above what platelet count? troublesome bleeding?
> 100x10^9
<50x10^9
What factor is the main factor of activation from prothrombin to thrombin
Factor Xa
The final product of the coagulation cascade is fibrinogen to fibrin which is then cross linked by which factor?
XIII
What initiates the coagulation cascade in vivo?
tissue factor
What type of cell produces most of the coagulation factors? Exceptions?
hepatocytes—
- -exception VIII- liver endothelial cells
- exception vWf- endothelial cells and megakaryocytes
What must PROTHROMBIN(II), VII, IX, X, protein C and S have in order to be fully functional?
Vitamin K
Where does most of the Vitamin K we need come from?
gastrointestinal tract by bacteria
What step is vitamin K needed?
second step- acts as a cofactor for an enzyme that inserts a second carboxyl group into gamma carbon on glutamic residues
What are the 5 roles of thrombin?
- cleavage of fibrinogen to fibrin
- activate clotting factors (V,VIII,XI,XIII)
- activation of platelets
- activation of endothelial cells
- binds thrombomodulin and activates Protein C
What laboratory measurements evaluates the INTRINSIC and common pathways of coagulation?
activated partial thromboplastin time (APTT)
-clotting time of a mixture of citrated plasma, phospholipid, calcium and an agent to increase contact activation
What laboratory measurement evaluates the EXTRINSIC and common pathways of coagulation?
Prothrombin Time
-clotting time of citrated plasma, tissue thromboplastin, and calcium ions.
A deficiency in factors VII, X, V, prothrombin and fibrinogen can be seen through what laboratory measurement?
PT
T or F- APTT can measure a deficiency in Factors VII and XIII?
False
What are 3 basic control mechanisms of regulating clot formations?
- Blood Flow
- hepatic clearance of activated factors
- Plasma Inhibitors
What inhibits thrombin by forming a 1:1 complex between arginine residue of itself with a serene residue in active site of thrombin?
antithrombin–also note that it inhibits XIa,Xa, IXa.
free thrombin at endothelial cell surface is bound by what? what does it activate?
thrombomodulin- this complex activates protein C and Protein C with S degrades Va and VIIIa AND NO LONGER SUPPORT THROMBIN AND Xa FORMATION
What enhances fibrinolysis by degrading endogenous inhibitor of endothelial cell plasminogen activator?
APC (activated protein C) and Protein S
What inhibits extrinsic pathway tissue factor/factor VIIa/ factor Xa/ calcium complex?
Tissue factor pathway inhibitor (TFPI)
The ability to lyse or dissolve a clot primarily comes from what protein?
Plasmin- From plasminogen produced in liver
T-F –plasmin can cleave fibrinogen or fibrin?
True
Cleavage of fibrin produces what>
D-dimers
What does plasminogen activator T-PA have a high affinity for?
Fibrin
What inhibits activation of plasmin?
PAI-1 plasminogen activator inhibitor
- synthesized by endothelial cells, hepatocytes, fibroblasts and platelets
What is plasmin activity physiologically regulated by>
alpha 2 antiplasmin–binds lysine binding site on plasmin
Normal unperturbed epithelium supports what 3 things?
- antithrombin inactivation of thrombin (by heparinoids)
- APC formation (by thrombin/thrombomodulin complex
- Prostacyclin- inhibit platelet adherence/aggregation
Patients with deficiencies in factor VIII or IX have what bleeding disorder?
hemophilia
What do patients with deficiency of Protein C or antithrombin have?
increased risk of clotting because missing normal checks of clotting process.
