Chapter 22: Platelets, Blood coagulation, and hemostasis Flashcards
What are the five major components of the hemostatic system?
(1) coagulation factors
(2) Platelets
(3) coagulation inhibitors
(4) fibrinolysis
(5) Blood vessels
What is the unique process by which megakaryocytes mature?
Endomitotic synchronous replication (the expansion of the cytoplasm as the DNA is replicated without nuclear or cytoplasmic division)
How many platelets can on megakaryocyte produce?
1000-5000
How long does it take a megakaryocyte to mature from a hematopoietic stem cell to the point where it can produce platelets?
About 10 days
What growth factor controls megakarycyte activity and where is it produced?
TPO (thrombopoietin) stimulate megakaryocytes and is made constitutively in the liver and kidneys.
Why do thrombopoietin levels rise dramatically during thrombocytopenia?
Because platelets also posses the c-Mpl receptor for TPO by which they remove TPO from the circulation.
What is the normal platelet count?
250,000
What is the normal platelet lifespan?
7-10 days
What proportion of bone marrow platelet output is trapped in the normal spleen?
33% (can rise to 90% in cases of splenomegaly.
What kinds of granules to platelets posses?
alpha, dense, and lysosomes.
What is contained in alpha granules?
(1) PF4 ( a heparin antagonist)
(2) PDGF
(3) Beta-thromboglobulin
(4) fibrinogen
(5) vWF
(6) other clotting factors.
What is contained in dense granules?
Dens greanules are less common and contain
1) ADP
(2) ATP
(3) 5-hydroxytryptamine (5-HT
(4) Calcium
What do the lysosomes and peroxisomes contain?
lysosome contain hydrolytic enzymes and peroxisomes contain catalase.
What is the open canalicular system?
A series of canalicular invaginations or tunnels through the platelet that communicate with the external environment.
What antigens to platelets posses?
HPA A and B
ABO antigens
HLA class 1 but not class II
What is the primary function of platelets?
To form a mechanical hemostatic plug.
What molecule allow platelets to adhere to the ECM?
vWF
How do platelets adhere to vWF?
After making contact platelets are able to role over vWF via GP1b-XI-V. Next GP2b-IIIa is able to bind tightly to vWF and other adhesion molecule bind tightly to collagen.
How are platelets activated?
Tight binding of GPIa/IIa and other molecules facilitates a cascade that results in activation of the platelets.
From where is most vWF derived?
From the endothelial cells where it is both secreted and stored in Weibel Palade bodies.
What enzyme cleaves the ultra large vWF multimers in circulation into monomers?
ADAMTS-13
How do platelets aggregate?
Upon activation GPIIb/IIIa binds to fibrinogen creating cross bridges between platelets.
What substance contained in platelet granule plays an important positive feedback role in platelet activation?
ADP
What major secondary substance created de novo acts as a powerful positive feedback for platelet activation?
TXA2 (it also causes vasocontriction.)
What substance opposes the activity of TXA2?
prostacyclin (PGI2) (NO and PECAM-1 also inhibit platelet activation)
What platelet membrane phospholipid is important for the stimulation of the coagulation cascade?
Platelet factor 3
What two processes does platelet factor 3 facilitate?
(1) tanase involves factors IXa, VIIIa, and X in the formation of Xa
(2) Prothrombinase involves factors Xa and Va, and prothrombin to produce thrombin.
What is the role of PDGF released from the alpha granules?
PDGF stimulates the growth of vascular endothelium.
How is coagulation initiated?
TF binds to factor VIIa. This complex then activates factors IX and X. Xa in turn converts small amounts of prothrombin to thrombin, and activates VIII, and XI.
What happens during clotting amplification?
VIIIa and IXa from an intrinsic Xase complex that activates enough Xa to allow it to work with Va, PL, and Ca to form the thrombinase complex.
What is the principle role of thrombin in clotting?
Thrombin cleaves fibrinogen into active fibrin.
What does tissue factor pathway inhibitor do?
it inhibits tissue factor, Xa, and VIIa to stop clot formation
What is the role of antithrombin?
Antithrombin links proteases like thrombin together thus inactivating them.
What is the role of protein C?
Protein C is able to destroy activated factors V and VIII.
What is the role of protein S?
Protein S enhances the activity of protein C.
How are proteins C and S activated?
Thrombin binds to thrombomodulin and the complex formed is able to activate vitamin K dependent proteins C and S.
How are activated clotting factors disposed of ?
The liver and other reticuloendothelial cells.
How is fibrinolysis stimulated?
tissue plasminogen activator released from endothelial cells converts plasminogen to plasmin which cleaves fibrin.
What fibrinolytic agents can be used therapeutically?
(1) tPA
(2) streptokinas
(3) urokinase
What can plasmin cleave?
Plasmin can cleave fibrinogen, fibrin, factor V, Factor VIII and many other proteins.
How is plasmin inactivated?
by PAI, alpha 2 antiplasmin, and alpha 2 macroglobulin.
What does a thrombin time testing for?
deficiency or abnormality in fibrinogen or inhibition of thrombin.
What is a prothrombin time testing for?
Deficiency in clotting factors VII, X, V , II
What is partial thrombplastin time testing for?
deficiency in clotting factors XII, XI, IX, VIII, X, V, II, fibrinogen.
