A review on INR reversal in patients taking coumadin..
Fresh Frozen Plasma:
Prepared from single units of whole blood. It contains the majority of all major coagulation factors, but essentially no cells (eg, red blood cells or white blood cells) nor platelets. In addition to the all major coagulation factors, it also contains protein C, S, antithrombin III, thrombomodulin, and approximately 500mg of fibrinogen.
The dose of FFP required to achieve the desired reversal of the INR has not been clearly established, however time to administration (limited by thawing time) and dose of FFP both play a role in rapid reversal of elevated INR levels. Based on previous studies, 3-4 units of FFP are needed to have an appreciable effect on INR.
The INR of FFP can be as low as 1.3, thus calling into question the utility of transfusion in cases of bleeding patients with mildly elevated INR. Illustrating this point, one study on the use of FFP with minimally prolonged INR (1.1-1.85) was performed in 121 patients. Of these, correction of the INR to normal was achieved in only one patient (0.8%). The results of this study concluded that FFP should not be used to treat bleeding or prophylaxis for invasive procedures in patients with INR<2.0.
Duration of action: 6-8 hours
Prothrombin Complex Concentrates (PCC):
Derived from human plasma and contain the vitamin K dependent coagulation factors II, VII, IX, and X at varying concentrations. Also contains proteins C and S. The nonactivated PCC products available in the US (Bebulin® and Profilnine®) contain only negligible amounts of Factor VII (a the key clotting factor in trauma) and are thus referred to as 3-factor products.
PCC was initially indicated for coumadin reversal in patients with head bleed. These indications have expanded to include warfarin reversal in other sources of bleeding. Despite successful utilization of PCC outside of the United States, PCC use is not widespread within the US, especially in the trauma patient.
Dose: (maximum not to exceed 120ml)
Goal of normilation of INR to <1.2 within 1 hour
Initial INR 2-2.5 (administer 0.9-1.3ml/kg)
Onset of action: rapid, significant INR decline within 10 minutes
Duration: 6-8 hours
* Half lives may be significantly reduced in severe hepatocellular damage, DIC, or extended catabolic metabolism
Recombinant FACTOR VIIa (rFVIIa):
rFVIIa for rapid reversal of INRs remains controversial due in part to the safety concerns regarding the risk of thromboembolic events. To date, there are currently no prospective, randomized controlled trials on the use of rFVIIa for traumatically injured patients on warfarin.
Prepared from plasma and contains fibrinogen, von Willebrand factor, factor VIII, factor XIII and fibronectin. Cryoprecipitate is the only adequate fibrinogen concentrate available for intravenous use and is generally indicated for bleeding or immediately prior to an invasive procedure in patients with significant hypofibrinogenemia (<100)
Vitamin K (phytonadione):
Oral administration of vitamin K is preferred as it provides the most predictable response to therapy. Intravenous vitamin K should be administered slowly (over at least 30 minutes) to avoid potential anaphylactic reactions. Subcutaneous and intramuscular administration of vitamin K should be avoided due to erratic absorption.
Onset of action- increased coagulation factors oral 6-10hours, IV 1-2 hours.
INR normalization oral 24-48 hours, IV 12-14 hours
In Prosthetic-Valve Patients, patients with atrial fibrillation, and recent history of PE/DVT the reversal of anticoagulation with vitamin K remains an area of controversy. There are no clear recommendations of dosage of vitamin K in these patients. May consider low dose of vitamin K as clinical scenario dictates.
Vitamin K Dosing for Elevated INR in Patients on Warfarin (Based on American College of Chest Physican- 2012 Guidelines)
INR < 4.5 without bleeding
-Lower dose or omit next dose
INR 4.5 – 10 without bleeding
-Preferred: Omit next 1-2 doses
-Alternatively, omit 1-2 doses and give Vitamin K 1-2.5 mg po (per 2008 guidelines)
INR>10 without bleeding
– Give Vitamin K (2.5-5 mg po)
Minor bleeding at any INR elevation
-Hold warfarin, administer 2.5-5mg, monitor INR closely
Serious bleeding at any elevation of INR
-Give FFP 4 units IV OR PCC
-Vitamin K 10mg by slow IV infusion
-May repeat as needed
Additional ACCP Recommendations
• Level 1
– Fresh Frozen Plasma (FFP) should be used for emergent reversal of elevated INRs.
• Level 2
– Dosing of phytonadione (Vitamin K) should be based on the patient’s current INR, risk
of bleeding, and future need for anticoagulation
– Reversal of warfarin with Vitamin K should be reserved only for the most serious
bleeding events or patients who will not be restarted on warfarin.
– Vitamin K should be administered either orally or intravenously (IV) only.
– Oral Vitamin K is the safest and most reliable route.
– IV Vitamin K should be reserved for rapid reversal in serious bleeding events only.
– Subcutaneous and intramuscular administration of Vitamin K should be avoided.
• Level 3
-Initial dose of FFP based on risk of bleeding:
-Low to moderate risk – FFP 2 units
– High risk or active bleeding – FFP 4 units
-INR should be rechecked 1 hour after administration of FFP.
-Prothrombin Complex Concentrate (PCC) should be administered to patients on
warfarin with an INR >2 AND evidence of intracranial hemorrhage on CT scan
-Check INR 30 minutes after administration
-Vitamin K should not be administered to patients with prosthetic heart valves, only low doses (1mg) should be used if absolutely necessary.