What is the management for a 30-year-old patient with diabetes mellitus (DM), hypertension (HTN), and atrial fibrillation (AF) taking metformin, amlodipine, and warfarin, presenting with lower gastrointestinal (GI) bleeding and an elevated international normalized ratio (INR)?

Management of Lower GI Bleeding with Supratherapeutic INR

For this patient with active lower GI bleeding and INR 6-7, immediately administer 4-factor prothrombin complex concentrate (PCC) 50 U/kg IV plus vitamin K 5-10 mg by slow IV infusion, provide volume resuscitation with normal saline and transfuse packed red blood cells as needed for hemodynamic support. 1, 2

Immediate Reversal of Anticoagulation

In cases of unstable gastrointestinal hemorrhage, anticoagulation should be reversed with prothrombin complex concentrate and vitamin K (strong recommendation, moderate quality evidence). 1

• For INR 6-7 with active bleeding, the recommended PCC dose is 50 U/kg IV based on the dosing algorithm: INR >6 requires 50 U/kg. 2
• Co-administer vitamin K 5-10 mg by slow IV infusion over 30 minutes—this is essential because factor VII in PCC has only a 6-hour half-life, requiring vitamin K to stimulate endogenous production of vitamin K-dependent factors. 1, 2
• PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma, making it the superior choice for urgent reversal. 2

Why PCC Over Fresh Frozen Plasma

• PCC has faster onset of action (5-15 minutes vs. hours for FFP), no need for ABO blood type matching, minimal risk of fluid overload, and lower risk of transmitting infections. 2
• In the landmark INCH trial, 67% of PCC-treated patients achieved INR ≤1.2 within 3 hours versus only 9% of FFP-treated patients. 2
• Fresh frozen plasma should only be used if PCC is unavailable. 2

Volume Resuscitation and Blood Product Support

Provide aggressive volume resuscitation with normal saline (not lactated Ringer's) and transfuse packed red blood cells for hemodynamic support and oxygen-carrying capacity. 1, 2

• Normal saline is preferred for initial resuscitation in acute GI bleeding—lactated Ringer's is not specifically indicated and normal saline remains the standard crystalloid. 1
• Transfuse packed RBCs based on hemodynamic status, rate of bleeding, and presence of comorbid conditions (coronary artery disease, chronic heart failure). 1, 2
• The presence of coagulopathy (INR >1.5) should prompt correction with PCC and vitamin K as outlined above. 1

Monitoring and Follow-Up

• Recheck INR 15-60 minutes after PCC administration to assess degree of correction. 2
• Monitor INR serially every 6-8 hours for the next 24-48 hours, as some patients require over a week to clear warfarin and may need additional vitamin K. 2
• Monitor hemoglobin every 4-6 hours until stable and bleeding source is controlled. 2

Warfarin Management

Warfarin should be interrupted at presentation and held completely until bleeding is controlled. 1

• Warfarin has a long half-life and its anticoagulant effect can persist for 3-5 days after discontinuation. 1
• Warfarin should be restarted 7 days after lower GI bleeding has stopped (based on large retrospective study showing that restarting between 7-15 days reduces thromboembolic events and mortality with no increase in rebleeding). 1
• Starting warfarin before 7 days resulted in a twofold increase in rebleeding. 1

Bridging Anticoagulation Considerations

• This patient has atrial fibrillation without high-risk features (no prosthetic valve, no recent VTE <3 months). 1
• Bridging with low molecular weight heparin is NOT recommended for patients with low-to-moderate thrombotic risk (strong recommendation, moderate quality evidence). 1
• Bridging should only be considered at 48 hours after hemostasis in patients with high thrombotic risk (prosthetic metal mitral valve, AF with prosthetic valve or mitral stenosis, <3 months after VTE). 1

Critical Pitfalls to Avoid

• Do not use vitamin K alone without PCC in active bleeding—vitamin K takes 12-24 hours to work, which is too slow for unstable hemorrhage. 2
• Do not exceed 10 mg of vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for days. 2
• Do not restart warfarin until bleeding is completely controlled, the source is identified and treated, and the patient is hemodynamically stable. 2
• Be aware that PCC use increases thrombotic risk during the recovery period—thromboprophylaxis must be considered as early as possible after bleeding control is achieved. 2

Why "Purified Protein Factor" is the Correct Answer

The question's reference to "purified protein factor" is terminology for 4-factor prothrombin complex concentrate (PCC), which contains concentrated amounts of factors II, VII, IX, and X—the vitamin K-dependent clotting factors depleted by warfarin. 2 This is the definitive treatment for warfarin-associated major bleeding with elevated INR.