4.2 CHESNEY Principles of Coagulation

Question 1

Vasoconstriction

Answer 1

“reflex” constriction, ATP driven is the vessels first response to injury

Question 2

Primary Hemostatsis

Answer 2

• Primary hemostatic plug, with platelet adhesion and fibrinogen, fibrinogen has not yet been polymerized
• Fragile and if not stablized could get washed away by blood eventually

Question 3

Secondary Hemostatsis

Answer 3

-See fibrin deposit and stabilization of the clot, driven by tissue factor which activates VII

Question 4

Antithrombotic Counter-Regulation

Answer 4

• Here to make sure clotting only takes place where it is needed and keeps clot from becoming to big
• t-Pa (fibrinolysis and thrombomodulin (blocks coag cascade) are released by non-damaged endothelial cells on borders of damage to help keep clot from getting too big

Question 5

Plasma vs Serum

Answer 5

Plasma: use an anti-coag when it is taken to prevent use of clotting factors

-Serum: has gone through coagulation and does not have any clotting factors left

Question 6

PT Time

Answer 6

Measure of Extrinsic Pathway: factor VII and common pathway

–VII is a serine protease

-Plasma is taken and rabbit brain thrombopastin and Ca w/ tissue factor are added and machine measures when clott occurs

–Normal time ~12 sec

• If PTT time is normal but the PT time is long then there is a problem with factor VII
• Neither PTT or PT measure factor XIII b/c time stops immediately after a clot is formed

Question 7

PTT Time

Answer 7

-Measure of the intrinsic pathway and common pathway, Intrinsic pathway includes XII, XI, IX, VIII

–VIII is a cofactor, XI and IX are serine proteases, V is also a cofactor

• Only XI, IX and VIII deficiencies cause a bleeding disorder, deficiency of XII will not lead to bleeding. XII def will prolong PTT but it will not cause a bleeding disorder
• Factor XIII (transamylase) is not measured, responsible for cross-linking of fibrin to increase tensile strength
• Neither test is very sensitive for fibrinogen, but fibrinogen deficiency will prolong both times, any common pathway deficiency will prolong both times.

Question 8

Warfarin and Vitamin K

Answer 8

• factors II (prothrombin) VII, IX, X, protein S and C are all relient on vitamin K for formation
• Warfarin blocks their formation
• Become unalbe to bind Ca and therefore bind membrane

Question 9

Fragment 1.2

Answer 9

• What is cleaved off of prothrombin during thrombin formation
• Do not know what it does, but has a one to one relationship with thrombin formation, good measure for thrombin formation
• Increased thrombin means a procoag state
• Warfarin will block prothrombin from binding factor V

Question 10

vWF def and Hemophilia association with VIII

Answer 10

• Both diseases can be associated with low VIII (hemophilia is the lowest)
• vWF (made by endothelial tiss) is a carrier of VIII, when vWF is absent VIII does not last well alone in circulation, but when vWF is given to patients with def of vWF will see a rise in VIII as it is synthesized by the liver and binds to vWF
• Hemophilia with VIII def will always be low b/c VIII is acutally def

Question 11

Actions of Heparin

Answer 11

• heparin can bin antithrombin III (confirmation change) and increase its affinity for thrombin
• antithrombin is an anti-serine protease

Question 12

Protein C

Answer 12

-Binds Thrombomodulin Thombin complex along with protein S (cofactor) to platelet surface and inactivates factor V and factor VIII (both are cofactors)

Question 13

TPAI

Answer 13

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-Is inhibited by Protein C which leads to more fibrolysis

Question 14

D-Dimer

Answer 14

• Means that there is cross-linking fibrin formation, they are a product of plasmin breakdown of fibrin
• Fragment D and Y are negative feedback inhibitors and slow down clotting and inhibit platelets
• Presence of D-Dimer means that there has been clot formation

Question 15

Endothelial Actions

Answer 15

Just know endothelial can be pro and anti thrombotic