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Block 7; Week 4-Michelle > Fung-Coagulation > Flashcards

Fung-Coagulation Flashcards

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1
Q

What is hemostasis?

A

balance between clotting and thrombosis
Precisely orchestrated process involving platelets, clotting factors and endothelium
Occurs at the site of vascular injury and culminates in the formation of a blood clot

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2
Q

What are the 2 types of disorders of hemostasis?

A

Hemorrhagic

Thrombotic

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3
Q

What are the normal steps of hemostasis?

A
  1. vasoconstriction
  2. platelet aggregation
  3. fibrin formation
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4
Q

What’s involved in vasoconstriction?

A

Purpose: reduces blood flow to the area
MOA: mediated by reflex neurogenic mechanisms, augmented by secretion of endothelin
Lasts how long? Transient!

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5
Q

What is primary hemostasis?

A

aggregation of platelets on endothelium

beginnings of a clot

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6
Q

What is secondary hemostasis?

A

cascade of reaction b/c of exposure of tissue factor @ site of vascular injury
thrombin formation

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7
Q

What are the 3 layers of blood vessels?

A

Intima: endothelium
Media: smooth muscle
Adventitia: CT

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8
Q

What is the role of vascular endothelium in hemostasis?

A

Inhibiting platelets
Suppressing coagulation
Promoting fibrinolysis
Modulating vascular tone and permeability

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9
Q

What are antithrombotic agents?

A 
heparin
Protein C & Protein S
Tissue Plasminogen Activator
Prostacyclin
Nitric Oxide
Thrombomodulin
Protein C receptor
Tissue Factory Pathway Inhibitor (TFPI)
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10
Q

What are prothrombotic agents?

A 
Factor V
Tissue Factor
Plastinogen Activator INhibitor-1 (PAI-1)
Thromboxane
Platelet Activating Factor
vWF
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11
Q

WHich substance is released after vascular injury?

Which layers of the blood vessel mediate vasoconstriction?

A

Tissue Factor

Media & Adventitia

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12
Q

The presence of which 2 things sets the stage for platelet adherence & activation?

A

collagen

vWF

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13
Q

What is the role of heparin in the body?

A

anti-thrombin

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14
Q

What is the role of prostacyclin & NO in the body?

A

vasodilators…that’s why they are anti-thrombotic

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15
Q

Where do platelets come from? What do they consist of?

A

come from megakaryocytic
consist of no nucleus, but have a cytoskeleton & cytoplasmic granules
alpha & dense granules

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16
Q

Which are more numerous in platelets–alpha or dense granules?

A

alpha are more numerous!

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17
Q

What does GP Ib/V/IX on the cytoskeleton of the platelet bind?

A

vwf

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18
Q

What does GpIIb/IIIa bind?

A

fibrinogen

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19
Q

What does GP1c/IIa bind?

A

fibronectin

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20
Q

WHat does CD62P (P selection) do?

A

these are adhesion molecules

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21
Q

What does the thrombin receptor on platelets do?

A

initiates platelet activation

along with ADP (found in dense granules)

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22
Q

What does the GP1a/2a bind?

A

collagen

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23
Q

What are the red cell antigens on platelets?

A

ABO, P, I, i Le (no Rh)

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24
Q

Which substances are found in the alpha granules (more numerous)?

A 
alpha: 
vwf
fibrinogen
Factor V
Promotes Angiogenesis: VEGF, EGF, PDGF
Inhibits Angiogenesis: angiostatin, thrombospondin, endostatin
INflammatory Factors: PF-4, IL-8, CCL5
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25
Which substances are found in dense granules?
ATP ADP Calcium Serotonin
26
Describe platelet adhesion & aggregation after vascular injury.
Collagen & vwf exposed after injury Unactivated Platelets adhere to gp1b receptor on vwf GP2b3a receptor on platelets active & bind fibrinogen that cross links & causes aggregation!
27
Describe all that is involved in the activation of platelets.
shape change release of granules, including ADP in the dense ones initiation of thromboxane A2 pathway (recruits more platelets) GP2b/3a receptor active--fibrinogen welcome!
28
Describe how the coagulation pathways interact.
Extrinsic pathway activated by the presence of tissue factor. 7--7a 7a will activate factor 10 & apparently 9 (crossover to intrinsic) Proximity of factors 11 & 12 activates 12--12a. 12a causes 11--11a 11a causes 9--9a. 9a activates 10--10a too.
29
Once 10a is active...what happens?
prothrombin w/ 10a-->thrombin (2a) thrombin causes fibrinogen--fibrin. 13a causes fibrin to cross link.
30
What makes up the prothombinase complex?
Va & 10a
31
What makes up the tenase complex?
8a, 10a, Ca++
32
Which coagulation factor is fibrinogen?
Factor 1
33
Which coagulation factor is prothrombin?
Factor 2
34
Which coagulation factor is anti hemophilic factor? Where is it made?
Factor 8 | made in the Kupffer cells of the liver
35
Where are most coagulation factors made?
liver
36
What is the coagulation factor for hagemann factor?
factor 12
37
Which coagulation factor is fibrin stabilizing factor?
Factor 13
38
Where does vwf come from?
endothelial cells | megakaryocytes
39
Give a summary of primary hemostasis?
``` Collagen & vwf exposed after injury Circulating platelets adhere & become activated. Shape change. GpIIb (fibrinogen receptor) exposed. Degranulate. Thrombaxane A2 pathway Release ADP More platelets recruited Activation of intrinisc pathway. Fibrinogen cleaved to fibrin. Clot formed. ```
40
What are 4 important coagulation regulators?
Antithrombin Activated protein C (APC) Tissue Factor Pathway Inhibitor Plasmin
41
What does antithrombin regulate?
``` thrombin factor 9a factor 10a factor 11a factor 12a ```
42
What composes the activated protein C complex?
thrombin thrombomodulin Protein C Protein S
43
What does tissue factor pathway inhibitor regulate?
tissue factor 7a 10a
44
What does plasmin do?
degrades fibrin
45
What are the 4 thing that seem to activate 10--10a?
7a 9a 8a 5a
46
With feedback inhibition, what does thrombin inhibit?
conversion of 8-8a & 5-5a
47
What are the labs that can help you evaluate platelets?
Platelet count Bleeding time Platelet aggregometry (function tests) Platelet flow cytometry
48
What are the labs that can help you evaluate coagulation?
aPTT PT Thrombin time Others
49
When should you order a bleeding time test? What is a normal range?
only used when a patient has a hx of excessive bleeding | Normal range: 1.5-9.5 min
50
When do you see prolongations in bleeding time?
``` von Willebrand disease Inherited platelet disorders Uremia Aspirin ingestion Low platelet counts (<100,000) ```
51
What is platelet aggregometry?
in vitro evaluation of platelet aggregation stir plasma subject to agonists look for aggregation--if present you will have more light transmitted thru vial.
52
Which agonists to aggregation are added to the plasma in the platelet aggregometry studies?
``` ADP Epinephrine Arachidonate Collagen Ristocetin aka vwf ```
53
What's the deal with platelet flow cytometry? What is it used to diagnose?
**looks at cell surface markers by using fluorescently labeled antibodies Used to diagnose: platelet surface glycoprotein deficiencies disorders of platelet activation
54
How do you measure platelets via platelet count? What is a normal range?
automated counter | 140K-400K
55
Which pathways does Prothrombin Time (PT) evaluate? How is this test done?
used to evaluate extrinsic & common pathways Used to monitor warfarin therapy! tissue factor & thromboplastin added w/ Ca++. Measure the time to clot.
56
What is the reference range for normal PT times?
11-13.5 seconds
57
Prolongation of PT can be caused by which factor deficiencies/inhibitors?
``` Factor 7 Factor 10 Factor 5 Factor 2 Fibrinogen ```
58
T/F INR is helpful in monitoring warfarin therapy along with PT.
True.
59
Which pathways is activated partial thromboplastin time (aPTT) used to evaluate? How is it done?
intrinsic & common | phospholipid is added to plasma w/ Ca++
60
What is normal value for aPTT?
27-35 seconds
61
Which factor deficiencies/inhibitors could cause aPTT prolongation? Which therapy is it used to monitor?
``` Monitors heparin, hirudin, & argatroban therapy Factor XII Factor XI Factor IX Factor VIII Factor X Factor V Factor II Fibrinogen ```
62
What is thrombin time (TT) used to test? How is it done?
tests presence of functional fibrinogen | thrombin added to plasma & time to clot is measured
63
What is a normal TT range? What might cause TT prolongation?
15-19 seconds heparin, hirudin, argatroban problems with fibrinogen
64
What are mixing studies used to determine?
deficiency or inhibitor? | done when PT, PTT, or TT is off
65
What is the process involved in a mixing study?
MIx patient's plasma with normal plasma... If better: deficiency If not better: inhibitor present
66
What forms D dimers? What is the significance of their lab presence?
plasmin mediated degradation of fibrin forms | fibrin is goin down!
67
What is another name for the von willebrand factor assay? How is it done?
aka Ristocetin cofactor assay patient plasma added to formalin fixed normal platelets in presence of ristocetin if normal: platelet agglutination If vwf deficient: decreased aggregation
68
What is the anti-10a assay used to measure?
monitor heparin
69
When do you do factor assays?
after mixing study shows that there is a factor deficiency
70
What are the characteristics of platelet type bleeding?
petechiae common mucosal bleeding common more often in females
71
What are the characteristics of coagulation type bleeding?
hemarthroses deep hematomas delayed bleeding more often in males
72
Excessive bleeding due to platelet defects is seen in which conditions?
``` von willebrand disease bernard soulier syndrome glanzmann thrombastenia platelet storage pool disorders drugs ITP TTP HUS HIT ```
73
What are some disorders that cause excessive bleeding due to coagulation defects?
``` von willebrand disease Hemophilia A Hemophilia B Liver Disease Vit K Deficiency DIC ```
74
How is it that von willebrand disease is both a platelet defect & coagulation defect bleeding disorder?
vwf circulates bound to factor 8 to prevent its early degradation in vwf deficiency--factor 8 gets destroyed earlier.

Block 7; Week 4-Michelle (5 decks)

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