Morning Report: 12/12/2013 - The Original Kings of County

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

The views expressed on this blog are the author's own and do not reflect the views of their employer. Please read our full disclaimer here. Any references to clinical cases refer to patients treated at a virtual hospital, Janus General Hospital.

Bio
Latest Posts

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