What should a patient with gastrointestinal (GI) bleeding on warfarin (coumarin) be given after receiving red blood cells and intravenous (IV) vitamin K (phylloquinone)?

From the Guidelines

For a patient with GI bleeding on warfarin who has already received red blood cells and IV vitamin K, prothrombin complex concentrate (PCC) should be administered as the next step, specifically a combination of 4-factor PCC and low-dose vitamin K (<5 mg), as recommended by the joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines 1. The recommended dose of PCC is not explicitly stated in terms of units/kg in the provided guidelines, but it is emphasized that 4-factor PCC is preferred due to its more complete coagulation factor replacement. If PCC is unavailable, fresh frozen plasma (FFP) can be considered, though it has several disadvantages compared to PCC, including the need for ABO matching, a slower onset of action, and a higher risk of fluid overload and transmitting infection 1. After the acute bleeding is controlled, the underlying cause of the GI bleed should be identified and treated, and the patient's anticoagulation strategy should be reassessed, considering the balance between thromboembolic risk and bleeding risk. PCC works by rapidly replacing the vitamin K-dependent clotting factors depleted by warfarin, allowing for immediate reversal of anticoagulation, while the previously administered vitamin K enables the body to resume its own production of these factors. The use of low-dose vitamin K (<5 mg) is recommended to reduce the risk of hypercoagulopathy, especially in patients for whom early re-anticoagulation is necessary, based on evidence from randomized trials that the optimal doses of vitamin K for normalization of INR are between 1 and 2.5 mg 1. It's also important to note that current guidelines do not recommend normalizing INR in all patients as it may delay endoscopy for life-threatening bleeding, and the administration of vitamin K does not result in immediate correction of coagulopathy 1. Therefore, the management of GI bleeding in patients on warfarin should prioritize urgent reversal of anticoagulation with PCC and low-dose vitamin K, followed by reassessment of the patient's anticoagulation strategy.

From the FDA Drug Label

If minor bleeding progresses to major bleeding, give 5 to 25 mg (rarely up to 50 mg) parenteral vitamin K1. In emergency situations of severe hemorrhage, clotting factors can be returned to normal by administering 200 to 500 mL of fresh whole blood or fresh frozen plasma, or by giving commercial Factor IX complex Packed red blood cells may also be given if significant blood loss has occurred

After administering red blood cells and IV vitamin K for GI bleeding on warfarin, a patient should be given:

• Fresh frozen plasma (200 to 500 mL) to return clotting factors to normal,
• or commercial Factor IX complex to achieve the same effect,
• as these options can help control the bleeding in emergency situations of severe hemorrhage 2. Note that packed red blood cells may also be given if significant blood loss has occurred.

From the Research

Management of GI Bleeding on Warfarin

After administering red blood cells and IV vitamin K to a patient with GI bleeding on warfarin, the next steps in management are crucial. The following points outline the key considerations:

• The patient's coagulopathy should be reversed, and the optimal timing of endoscopy should be determined 3.
• The use of specific reversal agents, such as prothrombin complex concentrates, may be considered to reverse the anticoagulant effect of warfarin 4.
• The risk of rebleeding should be assessed, and strategies to prevent recurrent GI bleeding should be implemented, such as the use of proton-pump inhibitors and the identification of risk factors for bleeding 4, 5.
• The decision to resume anticoagulation therapy should be made on an individual basis, taking into account the patient's thrombotic risk and the risk of recurrent bleeding 6.
• The patient's values and preferences should be incorporated into the decision-making process, and a framework for decision-making should be used to guide the management of anticoagulant-associated GI bleeding 6.

Key Considerations

Some key considerations in the management of GI bleeding on warfarin include:

• The severity of bleeding and the intensity of anticoagulation 3.
• The patient's thrombotic risk and endoscopy findings 3.
• The use of vitamin K1 and its potential effects on rebleeding 7.
• The risk of gastrointestinal bleeding associated with oral anticoagulation therapy, including the location of GI bleeding and prevention strategies 5.