87 – What is the most optimal management of a patient with elevated coagulation parameters, such as high INR, undergoing emergency orthopaedic surgery?

Marc Carrier, Alex C. Spyropoulos.

Response/Recommendation: In patients on vitamin K antagonist (VKA) with an elevated international normalized ratio (INR) requiring emergency orthopaedic surgery, we suggest correction to an INR ≤ 1.5.

Strength of Recommendation: Limited.

Rationale: The prothrombin time (PT) test measures the extrinsic and common coagulation pathways. The PT correlates to the degree of inhibition of factors II, V, VII, X, and fibrinogen which are synthesized by the liver. The INR is an expression of the results of a PT in a standardized testing environment allowing for universal standardization of anticoagulant therapy1-3. The most common reason for an isolated elevated INR is VKA anticoagulation therapy (e.g., warfarin). However, a prolonged PT and elevated INR can also occur in vitamin K deficiency, lupus anticoagulants, extrinsic pathway coagulation factor deficiencies, disseminated intravascular coagulation, bile duct obstruction, malabsorption, malnutrition, and other conditions1. Furthermore, other anticoagulants, including the direct oral anticoagulants (e.g., rivaroxaban), hirudin, argatroban, and heparin, may also prolong the PT.

VKA are widely used for variety of different clinical indications including primary prevention of stroke for patients with atrial fibrillation and for the acute treatment or secondary prevention of venous thromboembolism (VTE). VKA inhibit hepatic production of the vitamin K-dependent coagulation factors (II, VII, IX, X), protein C and S. The clinical effect is measured by the INR. Previous studies have reported that the use of VKA was associated with a delay in time-to-surgery and higher mortality for patients requiring emergency orthopaedic procedures4-7. Furthermore, these patients experience increased surgical blood loss and higher risk of red blood cell transfusions8, highlighting the importance of reversing the anticoagulation effect prior to emergency surgery.

Current VTE guidelines presented by the American Society of Hematology and the American College of Chest Physicians do not provide direction on the correction of INR for patients on VKA undergoing emergency surgery2,9. Although current literature still lacks consensus regarding the most appropriate management strategy for VKA reversal in patients undergoing emergency orthopaedic surgery, recommendations for the management of major bleeding episodes related to VKA have been published. In patients on VKA with elevated INR and major bleeding complications, the clinical practice guidelines suggest using 4-factor prothrombin complex concentrates (PCC) rather than fresh-frozen plasma (FFP) in addition to cessation of VKA and administration of intravenous vitamin K2.

Vitamin K (phytonadione) may be given orally, intravenously, or subcutaneously depending on the value of the INR and the desired time frame for anticoagulant reversal. In stable, semi-urgent cases (within 24 to 36 hours), low-dose oral administration (1 to 2.5 mg) is preferred10-13. Although intravenous administration of vitamin K is associated with a risk of anaphylactoid reaction, it has a more rapid effect and may be more effective in the truly emergent case. For urgent surgical procedures that can be delayed for six to 12 hours, the anticoagulant effect of warfarin can be effectively reversed with 10 mg of intravenous vitamin K14-16. For patients requiring emergent surgical procedures (within less than 6 hours), 4-Factor PCC containing factors II, VII, IX, and X or FFP is required to rapidly reverse the anticoagulant effect of VKA17,18. The concentration of coagulation factors in PCC is approximately 25 times greater than that available in FFP, allowing for it to be administered in small volumes of fluid14. The reversal of anticoagulation with PCC or FFP is temporary and decreases after six hours due to the short half-life of factor VII. Therefore, it is recommended that vitamin K be administered concurrently to ensure sustained reversal effect. Previous observational studies have shown that reversing the effect of VKA to an INR ≤ 1.5 using vitamin K and/or PCC or FFP is safe and effective in patients requiring emergency orthopaedic surgery17,19-23.

Although it is widely recognized that the use of VKA is associated with a delay in time to surgery as well as morbidity and mortality in patients requiring emergency orthopaedic surgery, existing studies have not defined the optimal management strategy to reverse the anticoagulant effect of VKA. Notwithstanding, based on the proven efficacy and safety of vitamin K, 4 factors PCC and FFP in the management of major bleeding episodes and the reassuring observational data in patients requiring emergency orthopaedic surgery, there is some evidence to support the recommendation to correct the INR to ≤ 1.5 in patients on VKA who requires emergency surgery.


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