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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
Initial platelet adhesion to collagen creates a local accumulation of what?
ADP and TXA2 that may overcome PGI2
26
Thrombocytopenia
bleeding disorder caused by insufficient platelets platelet count is less than 100,000/mm3 one type is heparin-induced
27
clot formation
15-20 seconds after major injury and about 1 minute with minor injury traps RBC, WBC, proteins and lipids
28
What is the key conversion in clot formation?
fibrinogen (soluble, globular) -> fibrin (insoluble, fibrous)
29
What catalyzes the conversion of fibrinogen to fibrin?
Thrombin
30
What signals for the conversion of prothrombin to thrombin?
Activated factor 10
31
Factor 1
fibrinogen
32
Factor 2
prothrombin
33
Factor IV
calcium ions
34
Extrinsic pathway
starts with tissue factor released outside plasma in damaged tissue tissue factor activates factor VII which then activates factor 10
35
What are examples of positive feedback in the extrinsic clotting cascade?
thrombin->5->5a->Xa->prothrombin->thrombin Xa->Tissue factor->VIII->VIIIa->X->Xa
36
Intrinsic pathways
activated platelets->12 (in plasma) ->11->9->10->thrombin
37
Factor 13
induces the cross-linking of fibrin
38
Activated clotting factors have short?
half-lives
39
Thrombin t1/2
less 1 min; activity limited to area near the damage
40
Protease-activated receptor-1
a platelet receptor
41
Thrombin cleaves a segment a PAR-1 to expose what?
a tethered ligand that binds and activates the receptor implies platelets can be activated by thrombin
42
What do several clotting factors chelate?
calcium
43
Vitamin K dependent clotting factors
II VII IX x all chelate calcium
44
There is lots of this on platelet aggregates
Ca2+
45
gamma-carboxyglutamic acid
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
What oxidizes Vitamin KH2 and reduces glutamic acid?
carboxylase
47
Why is a constant supply of reduced vitamin K needed?
aged circulating clotting factors are constantly bein removed from blood; newly synthesized clotting factors require modification
48
Prothrombin time
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
International normalized ratio
[PT patient/ PT mean normal]^ISI normal is 0.8-1.1
50
ISI
indicates how a particular batch of tissue factor compares to an internationally standardized tissue factor
51
Activated partial thromboplastin time
intrinsic pathway reaction Patient’s plasma + Ca2+ + kaolin + cephalin normal 24-36 s
52
Hemophilia
bleeding disorder inherited change in clotting factor disrupts the entire sequence of chemical reactions necessary for clotting
53
What 3 factors enhance thrombosis
loss of endothelial cell function slow/turbulent blood flow hypercoagulability state
54
What are the 3 fates of a thrombus?
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
Thrombosis
interplay among endothelium, platelets, and clotting factors PGI2 vs ADP, TXA2 obstructive blood clots
56
Thrombus removal
Plasminogen->plasminogen activator->plasmin
57
Plasminogen
a plasma proenzyme
58
Plasmin
proteolytic enzyme
59
Anticoagulants
Reagents which interfere with thrombogenesis includes heparin and ethylene tetraacetic acid
60
Fibrinolysis
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
D-dimer
digested fibrin indicator of thrombosis
62
Prostacyclin (PGI2)
arachidonic acid metabolite eicosanoid produced by healthy endothelial cells prevents platelet activation and clumping
63
epoprostenol
synthetic form of prostacyclin used as an anti-platelet agent
64
Antithrombin
protease inhibitor found in plasma inactivates factors Xa, IIa, IXa, VIIa, XIa, XIIa inefficient by itself effects both intrinsic and extrinsic factors
65
Heparin
produced by basophils and mast cells polysaccharides binds to antithrombin and increases activity by 500-1000 fold
66
Protein C
vitamin K depenendent serine protease deals with Ca2+ activated by thrombin degrades factor Va and factor VIIIa

HPP 2 (11 decks)

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