Coagulation Flashcards

1
Q

What protects from traumatic blood loss and arrests hemorrhage at the site of injury?

A

Hemostasis and Coagulation

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2
Q

What are the stages of coagulation?

A
  1. Platelet activation (aggregation)
  2. Coagulation (blood clot)
  3. Clot Retraction (fibrinolysis)
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3
Q

Platelets

A

not true cells, cytoplasmic fragments of megakaryocytes
no nuclei, have bodies and granules containing platelet activating and clotting factors

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4
Q

Megakaryocyte

A

immediate precursor of platelets

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5
Q

What is the normal concentration of platelets in the blood?

A

250,000 per cubic mm

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6
Q

How long do platelets remain functional?

A

7-10 days

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7
Q

Thrombopoietin

A

glycoprotein produced by the liver
stimulates production and differentiation of megakaryocyte

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8
Q

Where do platelets aggregate selectively?

A

In damaged blood vessels

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9
Q

dense bodies

A

vesicles in each platelet containing pre-made chemicals
ADP and Ca2+

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10
Q

granules

A

vesicles for all invasive purposes
von Willebrand factor
fibrinogen

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11
Q

What contracts to cause clot retraction?

A

actin microfilaments and myosin intrinsic factor

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12
Q

activated platelets + fibrinogen =

A

platelet aggregation

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13
Q

When a blood vessel is damaged, the endothelium is disrupted and an underlying layer of what is exposed?

A

collagen

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14
Q

How are circulating platelets activated?

A

exposed collagen
contact with collagen is facilitated by vWF released by damaged endothelial cells and other activated platelets

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15
Q

What do activated platelets do?

A

change shape
release soluble factors that activate other circulating platelets (ADP and TXA2)

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16
Q

Glycoprotein Ia and Glycoprotein VI

A

bind collagen
facilitate loose platelet adhesion

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17
Q

Glycoprotein Ib-V-IX

A

binds to vWF anchored on collagen
facilitates strong platelet adhesion

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18
Q

Glycoprotein IIb/IIIa

A

activated when other glycoprotein receptors are engaged with their ligands
when activated captures fibrinogen

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19
Q

Normal Hemostasis process

A
  1. Adhesion
  2. Amplification
  3. Aggregation
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20
Q

Amplification

A

Glycoprotein IIb/IIIA activation
platelets release ADP
a few adhered platelets recruit more platelets to the site

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21
Q

ADP receptors

A

P-type purinergic receptors
binding of ADP to P2Y12 activates glycoprotein IIb/IIIa on circulating platelets

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22
Q

Thromboxane/prostaglandin endoperoxide receptor

A

binding of TXA2 to this induces platelets to change shape
TXA2 generated in activated platelets via cyclooxygenases

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23
Q

Formation of a platelet plug

A
  1. exposed collagen binds and activates platelets
  2. release of platelet factors
  3. attracts more platelets
  4. aggregate into platelet plug
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24
Q

Intact endothelium releases prostacyclin (PGI2) which inhibits?

A

platelet adhesion

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25
Q

Initial platelet adhesion to collagen creates a local accumulation of what?

A

ADP and TXA2 that may overcome PGI2

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26
Q

Thrombocytopenia

A

bleeding disorder caused by insufficient platelets
platelet count is less than 100,000/mm3
one type is heparin-induced

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27
Q

clot formation

A

15-20 seconds after major injury and about 1 minute with minor injury
traps RBC, WBC, proteins and lipids

28
Q

What is the key conversion in clot formation?

A

fibrinogen (soluble, globular) -> fibrin (insoluble, fibrous)

29
Q

What catalyzes the conversion of fibrinogen to fibrin?

A

Thrombin

30
Q

What signals for the conversion of prothrombin to thrombin?

A

Activated factor 10

31
Q

Factor 1

A

fibrinogen

32
Q

Factor 2

A

prothrombin

33
Q

Factor IV

A

calcium ions

34
Q

Extrinsic pathway

A

starts with tissue factor released outside plasma in damaged tissue
tissue factor activates factor VII which then activates factor 10

35
Q

What are examples of positive feedback in the extrinsic clotting cascade?

A

thrombin->5->5a->Xa->prothrombin->thrombin
Xa->Tissue factor->VIII->VIIIa->X->Xa

36
Q

Intrinsic pathways

A

activated platelets->12 (in plasma) ->11->9->10->thrombin

37
Q

Factor 13

A

induces the cross-linking of fibrin

38
Q

Activated clotting factors have short?

A

half-lives

39
Q

Thrombin t1/2

A

less 1 min; activity limited to area near the damage

40
Q

Protease-activated receptor-1

A

a platelet receptor

41
Q

Thrombin cleaves a segment a PAR-1 to expose what?

A

a tethered ligand that binds and activates the receptor
implies platelets can be activated by thrombin

42
Q

What do several clotting factors chelate?

A

calcium

43
Q

Vitamin K dependent clotting factors

A

II
VII
IX
x
all chelate calcium

44
Q

There is lots of this on platelet aggregates

A

Ca2+

45
Q

gamma-carboxyglutamic acid

A

carboxylated glutamate
driven by vitamin K oxidation
di-carboxylic acid chelates Ca2+
activated platelets release and bind Ca2+
enable clotting factors to accumulate on platelet aggregates

46
Q

What oxidizes Vitamin KH2 and reduces glutamic acid?

A

carboxylase

47
Q

Why is a constant supply of reduced vitamin K needed?

A

aged circulating clotting factors are constantly bein removed from blood; newly synthesized clotting factors require modification

48
Q

Prothrombin time

A

measure the quantity and quality of clotting factors in plasma
specifically tests the extrinsic pathway reaction
Patient’s plasma + Ca2+ + tissue factor
normal range 11-13.5 seconds

49
Q

International normalized ratio

A

[PT patient/ PT mean normal]^ISI

normal is 0.8-1.1

50
Q

ISI

A

indicates how a particular batch of tissue factor compares to an internationally standardized tissue factor

51
Q

Activated partial thromboplastin time

A

intrinsic pathway reaction
Patient’s plasma + Ca2+ + kaolin + cephalin
normal 24-36 s

52
Q

Hemophilia

A

bleeding disorder
inherited change in clotting factor
disrupts the entire sequence of chemical reactions necessary for clotting

53
Q

What 3 factors enhance thrombosis

A

loss of endothelial cell function
slow/turbulent blood flow
hypercoagulability state

54
Q

What are the 3 fates of a thrombus?

A

lyse= dissolve
organize= fibroblasts and new capillaries grow in to replace the thrombus with vascular connective tissue, allows some blood flow past the obstruction
embolus= break off and fragment floats to lodge downstream

55
Q

Thrombosis

A

interplay among endothelium, platelets, and clotting factors PGI2 vs ADP, TXA2

obstructive blood clots

56
Q

Thrombus removal

A

Plasminogen->plasminogen activator->plasmin

57
Q

Plasminogen

A

a plasma proenzyme

58
Q

Plasmin

A

proteolytic enzyme

59
Q

Anticoagulants

A

Reagents which interfere with thrombogenesis
includes heparin and ethylene tetraacetic acid

60
Q

Fibrinolysis

A

process by which the fibrin clot is removed from the site of vascular injury during the healing process

damaged endothelial cells release tissue plasminogen activator

61
Q

D-dimer

A

digested fibrin
indicator of thrombosis

62
Q

Prostacyclin (PGI2)

A

arachidonic acid metabolite
eicosanoid produced by healthy endothelial cells
prevents platelet activation and clumping

63
Q

epoprostenol

A

synthetic form of prostacyclin used as an anti-platelet agent

64
Q

Antithrombin

A

protease inhibitor found in plasma
inactivates factors Xa, IIa, IXa, VIIa, XIa, XIIa
inefficient by itself
effects both intrinsic and extrinsic factors

65
Q

Heparin

A

produced by basophils and mast cells
polysaccharides
binds to antithrombin and increases activity by 500-1000 fold

66
Q

Protein C

A

vitamin K depenendent serine protease
deals with Ca2+
activated by thrombin
degrades factor Va and factor VIIIa