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Essential Hematology > Chapter 22: Platelets, Blood coagulation, and hemostasis > Flashcards

Chapter 22: Platelets, Blood coagulation, and hemostasis Flashcards

1
Q

What are the five major components of the hemostatic system?

A

(1) coagulation factors
(2) Platelets
(3) coagulation inhibitors
(4) fibrinolysis
(5) Blood vessels

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2
Q

What is the unique process by which megakaryocytes mature?

A

Endomitotic synchronous replication (the expansion of the cytoplasm as the DNA is replicated without nuclear or cytoplasmic division)

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3
Q

How many platelets can on megakaryocyte produce?

A

1000-5000

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4
Q

How long does it take a megakaryocyte to mature from a hematopoietic stem cell to the point where it can produce platelets?

A

About 10 days

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5
Q

What growth factor controls megakarycyte activity and where is it produced?

A

TPO (thrombopoietin) stimulate megakaryocytes and is made constitutively in the liver and kidneys.

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6
Q

Why do thrombopoietin levels rise dramatically during thrombocytopenia?

A

Because platelets also posses the c-Mpl receptor for TPO by which they remove TPO from the circulation.

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7
Q

What is the normal platelet count?

A

250,000

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8
Q

What is the normal platelet lifespan?

A

7-10 days

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9
Q

What proportion of bone marrow platelet output is trapped in the normal spleen?

A

33% (can rise to 90% in cases of splenomegaly.

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10
Q

What kinds of granules to platelets posses?

A

alpha, dense, and lysosomes.

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11
Q

What is contained in alpha granules?

A

(1) PF4 ( a heparin antagonist)
(2) PDGF
(3) Beta-thromboglobulin
(4) fibrinogen
(5) vWF
(6) other clotting factors.

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12
Q

What is contained in dense granules?

A

Dens greanules are less common and contain

1) ADP
(2) ATP
(3) 5-hydroxytryptamine (5-HT
(4) Calcium

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13
Q

What do the lysosomes and peroxisomes contain?

A

lysosome contain hydrolytic enzymes and peroxisomes contain catalase.

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14
Q

What is the open canalicular system?

A

A series of canalicular invaginations or tunnels through the platelet that communicate with the external environment.

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15
Q

What antigens to platelets posses?

A

HPA A and B
ABO antigens
HLA class 1 but not class II

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16
Q

What is the primary function of platelets?

A

To form a mechanical hemostatic plug.

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17
Q

What molecule allow platelets to adhere to the ECM?

A

vWF

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18
Q

How do platelets adhere to vWF?

A

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.

19
Q

How are platelets activated?

A

Tight binding of GPIa/IIa and other molecules facilitates a cascade that results in activation of the platelets.

20
Q

From where is most vWF derived?

A

From the endothelial cells where it is both secreted and stored in Weibel Palade bodies.

21
Q

What enzyme cleaves the ultra large vWF multimers in circulation into monomers?

A

ADAMTS-13

22
Q

How do platelets aggregate?

A

Upon activation GPIIb/IIIa binds to fibrinogen creating cross bridges between platelets.

23
Q

What substance contained in platelet granule plays an important positive feedback role in platelet activation?

A

ADP

24
Q

What major secondary substance created de novo acts as a powerful positive feedback for platelet activation?

A

TXA2 (it also causes vasocontriction.)

25
Q

What substance opposes the activity of TXA2?

A

prostacyclin (PGI2) (NO and PECAM-1 also inhibit platelet activation)

26
Q

What platelet membrane phospholipid is important for the stimulation of the coagulation cascade?

A

Platelet factor 3

27
Q

What two processes does platelet factor 3 facilitate?

A

(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.

28
Q

What is the role of PDGF released from the alpha granules?

A

PDGF stimulates the growth of vascular endothelium.

29
Q

How is coagulation initiated?

A

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.

30
Q

What happens during clotting amplification?

A

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.

31
Q

What is the principle role of thrombin in clotting?

A

Thrombin cleaves fibrinogen into active fibrin.

32
Q

What does tissue factor pathway inhibitor do?

A

it inhibits tissue factor, Xa, and VIIa to stop clot formation

33
Q

What is the role of antithrombin?

A

Antithrombin links proteases like thrombin together thus inactivating them.

34
Q

What is the role of protein C?

A

Protein C is able to destroy activated factors V and VIII.

35
Q

What is the role of protein S?

A

Protein S enhances the activity of protein C.

36
Q

How are proteins C and S activated?

A

Thrombin binds to thrombomodulin and the complex formed is able to activate vitamin K dependent proteins C and S.

37
Q

How are activated clotting factors disposed of ?

A

The liver and other reticuloendothelial cells.

38
Q

How is fibrinolysis stimulated?

A

tissue plasminogen activator released from endothelial cells converts plasminogen to plasmin which cleaves fibrin.

39
Q

What fibrinolytic agents can be used therapeutically?

A

(1) tPA
(2) streptokinas
(3) urokinase

40
Q

What can plasmin cleave?

A

Plasmin can cleave fibrinogen, fibrin, factor V, Factor VIII and many other proteins.

41
Q

How is plasmin inactivated?

A

by PAI, alpha 2 antiplasmin, and alpha 2 macroglobulin.

42
Q

What does a thrombin time testing for?

A

deficiency or abnormality in fibrinogen or inhibition of thrombin.

43
Q

What is a prothrombin time testing for?

A

Deficiency in clotting factors VII, X, V , II

44
Q

What is partial thrombplastin time testing for?

A

deficiency in clotting factors XII, XI, IX, VIII, X, V, II, fibrinogen.

Essential Hematology (22 decks)

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