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38 Cards in this Set

  • Front
  • Back

Name three things that can activate procoagulant substances.

1. Tissue injury


2. Blood vessel rupture


3. Trauma to the blood (i.e. sepsis)


____________ on platlets adhere to subendothelial _____________

GPIa receptors


Subendothelial collagen

What is von Wildebrand factor?

A substance that leaks from the plasma into damaged tissue.



Adhere to GP1b receptors on platlets

Adherence to the vessel wall stimulates platlets to: (2)

Release thromboxane A2 (TXA2) and degranulate

Name two functions of TXA2

Promotes platlet aggregation



Potent vasoconstrictor

What substances are released during degranulation?

Dense granules release: (pro-aggregants)


ADP, 5-HT, Histamine, and Calcium



Alpha granules release:


vWF, fibrinogen, factors (V, VII, XI, XIII), PAI-1

How does platlet aggregation occur?

Fibrinogen binds to GPIIb/IIIa receptors and promotes aggregation.

The intrinsic pathway is also known as the ___________ pathway and is triggered via ______

Contact activation pathway



Contact activation of factor XII with collagen

Describe the steps of the contact activation pathway

1. Collagen activates factor XII


2. Factor XIIa activates factor XI


3. Factor XIa activates factor IX [TF-VIIa also activates factor IX]*


4. Factor IXa activates binds factor VIIIa to form the tenase complex.


5. Factor IXa-VIIIa complex (tenase) activates factor X



*From extrinsic pathway

The extrinsic pathways is also known as the ____________ pathway. Why?

Tissue factor pathway

What is the role of tissue factor (TF)?

Found in nonvascular cell membranes and the membranes of damaged endothelium.



TF activates factor VII

Describe the extrinsic pathway (Tissue Facor pathway)

TF activates factor VII.



Factor VIIa-TF complex activates factor X

What are the steps of the final common pathway?

Factor Xa binds factor V


Factor Xa-Va complex activates prothrombin (Factor II) *


Thrombin (IIa) activates fibrinogen (FI) to form Fibrin (Ia)



*TF-Va complex also activates factor IX

In addition to activating fibrin, thrombin plays an important positive feedback role.



Name four positive feedback roles of thrombin.

1. Further platlet activation


2. Further activation of factor V


3. Release of factor VIII from vWF & activation of factor VIII


4. Activation of factor XI

Prothrombin (factor II) is synthesized in the __________ and requires __________

Liver


Vitamin K

What is the role of calcium in the coagulation cascade?

Required for the activation for factor IX



Required for activation of factor X (both pathways)



Required to form Va-Xa complex (prothrombinase complex)



Required for activation of thrombin.

How is fibrin stabilized?

Thrombin activates factor XIII (also known as fibrin stabilizing factor)



Factor XIIIa stabilizes fibrin

Vitamin K is required for the synthesis of which clotting factors?

Factor II (Prothrombin)


VII


IX


X

Where is vitamin K synthesized?

In the intestine by bacteria

How does the endothelial surface prevent clot formation?

1. Prevents contact activation (intrinsic pathway)


2. Glycocalix repels clotting factors and platlets


3. Thrombomodulin (endothelial membrane receptor) binds thrombin

What is the role of antithrombin III?

Removes thrombin and other clotting factors from the blood.

How does heparin work?

Enhances the action of antithrombin III


by a thousand fold

What is the role of proteins C and S?

Proteins C and S inactivate factors Va and VIIIa

Proteins C and S require _________ for synthesis

Vitamin K

____________ trapped in the fibrin clot is activated by __________ to become _________

Plasminogen


tPA


Plasmin

___________ is an enzyme that clears the clot over a period of ___________

Plasmin


Several days

What does prothrombin time (PT) assess?

Measures integrity of extrinsic pathway (TF)


Factors V, VII, X, prothrombin, fibrinogen

Normal range for PT

11-13 sec

PT is normalized to form _________, which is used to assess ___________

INR


Warfarin

Normal INR


0.8-1.7


2-3 is target for warfarin therapy

Activated Partial Thromboplastin Time (aPTT) measures what?

Integrity of intrinsic pathway (contact activation)



Factors VIII, IX, XI



Used to monitor unfractionated heparin


Normal aPTT

30-35sec

What does Activated Clotting Time measure?

Integrity of intrinsic pathway


Used to monitor high dose heparin

Normal ACT

90-120 sec

What does thrombin time measure?

Conversion of fibrinogen to fibrin



Used to screen for abnormal fibrinogen levels



Monitors therapy with fibrinolytic agents

What does bleeding time measure

Platlet number and function


useful for assessing von Wildebrand disease

Normal bleeding time

2.0-8.5



>10 abnormal

Prolonged bleeding time with normal platlet counts implies what?

Impaired platlet function (due to NSAID for example)