From the Guidelines
When the International Normalized Ratio (INR) is high, vitamin K, specifically phytonadione, is the primary treatment to reverse anticoagulation, and it should be administered orally or intravenously depending on the severity of the elevation and the presence of bleeding. For mild to moderate elevations without bleeding, oral phytonadione at doses of 1-5 mg can be given, which can take approximately 24 hours to reduce the INR to a normal range 1. In cases of severe elevations or active bleeding, intravenous phytonadione (1-5 mg) should be administered, which can start to reduce the INR within 2 hours and achieve a normal range within 24 hours 1. Additionally, prothrombin complex concentrate (PCC) at 25-50 units/kg can be given to rapidly correct the INR, especially in emergency situations with life-threatening bleeding, as it provides a more rapid reversal compared to fresh frozen plasma (FFP) 1. The choice of product depends on the urgency of the situation, with oral phytonadione taking 24-48 hours to fully reverse anticoagulation, while IV administration works within 6-12 hours, and PCC providing the most rapid reversal within minutes 1. It is crucial to monitor the INR after administration and adjust treatment accordingly to avoid overcorrection, which could put patients at risk for thrombotic events, especially those on warfarin for conditions like atrial fibrillation or mechanical heart valves 1. Key considerations include:
- The route of administration: oral for mild cases, intravenous for severe cases or active bleeding
- The dose: 1-5 mg for oral or intravenous phytonadione
- The use of PCC for rapid reversal in emergency situations
- Monitoring of INR to avoid overcorrection and thrombotic risks.
From the FDA Drug Label
The coagulant effects of phytonadione tablets are not immediate; improvement of international normalized ratio (INR) may take 1 to 8 hours The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2.5 mg to 10 mg or up to 25 mg initially. Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged.
Phytonadione is the product to give when INR is high, with a recommended dose of 2.5 mg to 10 mg or up to 25 mg initially. The dose may be repeated if INR remains prolonged after 6 to 8 hours 2.
- Key considerations:
- Dose: 2.5 mg to 10 mg or up to 25 mg initially
- Administration: Oral
- Monitoring: Evaluate INR after 6 to 8 hours and repeat dose if necessary
- Caution: Phytonadione tablets are not a clotting agent, and overzealous therapy with vitamin K1 may restore conditions which originally permitted thromboembolic phenomena 2.
From the Research
Products for Reversing High INR
When the International Normalized Ratio (INR) is high, it indicates an increased risk of bleeding. Several products can be used to reverse this condition, including:
- Prothrombin complex concentrates (PCCs) 3, 4, 5, 6
- Fresh frozen plasma (FFP) 3, 4, 5, 7
- Vitamin K (phytonadione) 3, 4, 5, 6, 7
- Recombinant activated factor VII (FVIIa) 4
- Activated PCC (aPCC) 6
Characteristics of Each Product
- PCCs offer a rapid reversal of warfarin, particularly in life-threatening bleeding situations 3, 5
- FFP is a standard treatment for reversing warfarin, but it may take longer to reverse INR compared to PCCs or FVIIa 4, 7
- Vitamin K is often used in combination with other products to reverse warfarin 3, 4, 5, 6, 7
- FVIIa is a rapid-acting agent, but it may have a higher risk of INR rebound and is more expensive than PCCs 4
- aPCC contains the same four factors as four-factor PCC, but with factor VII in an activated form 6
Clinical Evidence
Studies have shown that PCCs can rapidly reverse INR and reduce the risk of bleeding in patients with warfarin-associated intracranial hemorrhage 3, 5 FFP and vitamin K are effective in reversing warfarin, but may take longer to achieve INR reversal compared to PCCs or FVIIa 4, 7 The choice of product depends on the clinical situation, including the presence of bleeding, need for surgery, and INR level 6