Thanks to Dr. Lewis for today’s Morning Report!
Coumadin-induced Coagulopathy
Coumadin
- Antithrombic effect: blocks activation of vitamin K → interferes with hepatic carboxylation of coagulation factors II, VII, IX and X → impairs the extrinsic and common pathway
- Prothrombic effect: Blocks activation of protein C and S
- Circulating half-life of 36-42 hours
- Metabolized in the liver
- Desired INR 2.0 to 3.0 in most cases
High Risk of Bleeding
- > 75 years
- Concurrent antiplatelet use
- Polypharmacy
- Liver or renal disease
Reversal of Coumadin-induced Coagulopathy
Vitamin K1
- Administration of vitamin K → turns on the endogenous activation of the coagulation factors
- Time to effect after administration is 24 hours regardless of route, duration of effect is days
- Asymptomatic patients with INR 4.5 to 10: Oral vitamin K 1.0 to 2.0 mg
- Asymptomatic patients with INR>10, low risk of bleed: Oral vitamin K 2.0-5 mg (+/- FFP)
- IV vitamin K has risk of anaphylactic reactions, independent of dose and should be limited to life-threatening situations
Fresh Frozen Plasma
- Immediate effect, duration of effect 12-24 hours
- Contains vitamin K dependent factors II, VII and X, lacks sufficient levels of IX
- ABO matched vs. Universal donor FFP derived from AB+ donors exists, takes 20-30 minutes to defrost
- INR> 10 no significant bleeding/or low-moderate risk of bleeding: FFP 10-15 ml/kg + Vitamin K 2.0 – 5 mg po
- Each 250 mL unit of plasma produces only small change in activity of individual clotting factors → need 3-4 units of FFP to achieve meaningful increase in coagulation factor levels
- Rapid transfusion of large volumes can lead to cardiogenic lung edema and noncardiogenic lung edema known as transfusion-related acute lung injury (TRALI).
- Specific factor quantities and volume of each unit may be varied, leading to an unpredictable response
Prothrombin Complex Concentrates
- Immediate effect, duration of effect 12-24 hrs
- 2 types available: 4 factor (II, VII, IX, and X) and 3 factor (II, IX and X) which should be supplemented with FFP or recombinant VIIa, does not require blood group matching
- Administered at dose of 50 IU/kg IV, contains higher amounts of vitamin-K dependent (concentration of factors in FFP only 4% of 4F PCC) clotting proteins per unit/volume, faster infusion times
- If PCC unavailable for life-threatening bleed give 5-10 mg diluted Vitamin K in D5W or D5 infused 1 mg/min + FFP
- Overall cost comparable to FFP
Recombinant factor VIIa
- Used off-label for patients with serious coumadin-associated bleeding
- rFVIIa can quickly correct supratherapeutic INRs with doses ranging from 10 to 90 μg/kg
- Very expensive (approx 5 K for average dose), short half-life, elevated risk of thrombosis
References:
- Zareh M, Davis A. et al. Reversal of Warfarin-Induced Hemorrhage in the Emergency Department. West J Emerg Med. 2011 November; 12(4): 386–392.
- Su M. Chapter 59. Anticoagulants. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011.
- Slattery DE, Pollack, Jr. CV. Chapter 234. Anticoagulants, Antiplatelet Agents, and Fibrinolytics. In: Tintinalli JE, Stapczynski JS, Cline DM, Ma OJ, Meckler GD, eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 8th ed. New York: McGraw-Hill; 2014
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Jay Khadpe MD
- Editor in Chief of "The Original Kings of County"
- Assistant Professor of Emergency Medicine
- Assistant Residency Director
- SUNY Downstate / Kings County Hospital
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