Coagulation Disorders

Question 0

Heparin: Mechanism

Answer 0

Binds to, and enhances the activity of antithrombin III
- Neutralizes thrombin within seconds and inhibition of fibrin formation
- Inhibition of activated factor Xa
Prolongs clotting time in-vivo and in-vitro
- In-vitro prevents clotting in a test tube

Question 1

Heparin

Answer 1

Naturally occurring
Measured in units of activity determined by its ability to prevent clotting
Administered parenterally

Question 2

Heparin: Pharmacokinetics

Answer 2

Given by injection
   - IM injections cause hematoma
   - SC bioavailability: 30-70%
Binds to plasma protein and endothelial cells
   - IV loading dose; monitor
Does not traverse the placenta
Renal excretion

Question 3

Heparin: Use

Answer 3

Pregnancy
Situations requiring rapid onset
Evolving stroke
Deep Vein thrombosis
Prevents coagulation
   - Heart-lung dialysis
Venous thrombosis
   - Post-operative
Acute myocardial infarction
   - As adjunct to thrombolytic therapy

Question 4

Heparin: Adverse Effects

Answer 4

Hemorrhage
- GI tract, urinary tract, soft tissue
Heparin- induced thrombocytopenia
- Patients develop antibodies to platelets
Hypersensitivity reactions
Osteporosis

Question 5

Heparin: Antidotes

Answer 5

Protamine sulfate

Question 6

LMW Heparins: Advantages

Answer 6

Can be given on fixed-dose schedule

aPTT monitoring not required

Question 7

Warfarin: Mechanism

Answer 7

Vitamin K antagonist
   - Inhibits formation of prothrombin and several clotting factors
       - Synthesis of these factors require vitamin K
absorbed rapidly from GI tract
Lowering of prothrombin occurs slowly
Extensively plasma protein bound
Narrow therapeutic index
Readily crosses membranes
Metabolized by hepatic cells
Delayed anticoagulant effect
   - Not useful in emergencies
   - Effect lasts for days after discontinuation

Question 8

Warfarin: Monitoring

Answer 8

Prothrombin time (
International normalized ration

Question 9

Warfarin: Adverse effects

Answer 9

Hemorrhage
Skin necrosis, purple toe syndrome
Pregnancy risk category X

Question 10

Warfarin: Drug interaction (drugs that diminish the effects)

Answer 10

Cholestyramine
P450 Inducers
- Oral contraceptives
- Vitamin K

Question 11

Warfarin: Antidote

Answer 11

Vitamin K1
   - Antagonizes warfarin action
   - Given oral, IV
   - Anaphylactoid reactions
   - Vitamin K3 not effective
Infusion of fresh whole blood, plasma

Question 12

Antiplatelet drugs

Answer 12

Aspirin

Clopidogrel