section 6 - anti thrombotic therapy

Question 1

describe generally DIC

Answer 1

• initation of clotting process leading to excessive fibrinolysis (bleeding/hemorrhage) and excessive clotting (ischemia and MI)

Question 2

pathophysiology of DIC and resultant secondary fibrinolysis

Answer 2

acute episode -> whenever overwhelming stimulation of coagulation

Question 3

list causes of DIC

Answer 3

• bacterial infeciton
• intravascualr parasites
• surgery
• major tissue trauma
• casting of legs
• bruns
• snake venom
• APL
• pregnancy

Question 4

clinical symptoms of DIC

Answer 4

• oozing from microvasculature bleeds
• multiple bleeding sites
• organ damage from fibrin deposition

Question 5

what is the therapeutic purpose of anti-thrombotics

Answer 5

to limit/prevent clotting by suppressing the synthesis or function of various hemostatic constituents

Question 6

name the three categories of anti-thrombotics

Answer 6

• anti platelets
• anti coagulants
• thrombolytics

Question 7

describe warfarin

Answer 7

• arrests vit K in storage form = unable to add second carboxyl group to factors
• it K dependent factors nonfunctional
• monitored monthly by PT and INR

Question 8

how are patients with venous thrombosis most frequently treated

Answer 8

• initially with Unfractionated Heparin (UFH)
• followed by long term anticoagulants (Warfarin)

Question 9

describe the method of action for UFH

Answer 9

• causes conformational change in antithrombin molecule -> increases inhibotory effect
• irreversible complex with FIIa, IXa, Xa, and XIa

Question 10

how does Heparin therapy effect circulating levels of Antithrobmin

Answer 10

decreases AT levels = increased chances of thrombosis
- heparin may cause HIT

Question 11

monitoring of heparin therapy

Answer 11

by APTT or anti-Xa assay

Question 12

describe the method of action for Low Molecular Weight Heparin (LMWH)

Answer 12

• from UFH by depolymerization = heparins of uniform molecular mass
• greater impact of Xa inhibition
• monitored by Chromogenic anti-Xa heparin assay

Question 13

describe the method of action for Fondaparinux

Answer 13

• synthetic form of active sequence UFH and LMWH
• binds to AT and increases affinity for Xa
• inhibition specific for Xa

Question 14

describe the action of direct Xa inhibitors

Answer 14

• do not require AT to express anticoagulant activity
• inhibition specific for Xa
• monitor with drug-specific version of anti-Xa

Question 15

describe direct thrombin inhibitors

Answer 15

• neutralize thrombin by binding active sites
• can impact fibrin-bound thrombin increasing effectiveness
• monitored by APTT
• substitute for heparin

Question 16

describe the method of action for anti-platelet agents
- list methods of action

Answer 16

• reduce platelet activation and function
• inhibits cyclooxygenase => aspirin
• binds platelet membrane ADP receptor
• glycoprotein inhibitors bind GpIIb-IIIa
• inhibits thrombin related aggregation (PAR-1)
• inhibits platelet aggregation and increase dilation

Question 17

list the anti-coagulants method of action

Answer 17

• multiple factor inhibition
• direct thrombin inhibitor
• direct Xa inhibition

Question 18

describe the action of thrombolytics generally

Answer 18

activation of plasminogen to dissolve clot formation

Question 19

describe agents that convert plasminogen to plasmin directly

Answer 19

serine proteases: streptokinase and urokinase
- monitored by euglobulin clot lysis
- causes hypofibrinogenemia

Question 20

describe tPA as an antithrombotic aka a thrombolytic

Answer 20

• fibrin specificity and affinity
• binding of tPA to clot = shape change = more plasminogen activation = clot dissolved
• activate plasminogen in absence of fibrin