Acquired FVIII deficiency in the setting of prior mechanical mitral valve replacement: A delicate balance of competing hemorrhagic and thrombotic risks Free

Introduction:

Acquired Factor VIII (FVIII) deficiency, also known as acquired hemophilia A, is a rare and lethal bleeding disorder caused by the development of autoantibodies (inhibitors) against FVIII, typically resulting in spontaneous, life-threatening hemorrhages. It is associated with a high all-cause mortality rate of up to 21%. While immunosuppressive therapy (IS) is the cornerstone of therapy, its application becomes especially problematic in those who require long-term anticoagulation (AC). One such category of patients is those with MVR, for whom lifelong warfarin therapy is conventional in order to prevent valve thrombosis and systemic embolism.

We were presented with the rare and complicated case of acquired FVIII deficiency in a patient with a history of MVR on long-term warfarin complicated by recent life-threatening bleeding. This resulted in a systematic review of the literature to establish current evidence in managing IS balance, anticoagulation, and control of bleeding in such complex patients.

Methods:

We conducted a systematic literature review in accordance with the PRISMA 2020 guidelines. Databases searched included PubMed, Embase, Cochrane, and ClinicalTrials.gov. The search strategy utilized a combination of MeSH terms and free-text keywords. The inclusion criteria required that the studies give evidence of both a diagnosis of acquired FVIII deficiency and concurrent indications for therapeutic anticoagulation. The exclusion criteria were congenital hemophilia without inhibitor development.

Results:

Our search yielded 80 potentially relevant publications. After abstract and title screening, 29 articles underwent full-text review, of which 19 met the inclusion criteria. Notably, there is a profound paucity of evidence specifically addressing the management of anticoagulation in acquired FVIII deficiency with concurrent mechanical valve replacement. To our knowledge, only two case reports describe congenital hemophilia patients with MVR, both navigating long-term AC; however, neither discusses the acquired form or a structured approach to managing thrombotic and bleeding risk simultaneously.

Most included cases involved management strategies where immunosuppression with corticosteroids (e.g., prednisone 1 mg/kg/day) combined with cyclophosphamide (1–2 mg/kg/day) or rituximab was initiated promptly to eradicate the inhibitor. FVIII activity typically begins to recover within 2 - 4 weeks of IS initiation. In our case and select others, a threshold FVIII activity level of >50% was used to resume warfarin therapy safely, with a target INR between 2.5 and 3.5 for mitral valves. Therapeutic maneuvers such as tapering IS following optimal FVIII recovery and individualized bridging with mechanical or pharmacologic prophylaxis were essential to minimize both bleeding and thrombosis.

Discussion:

Our analysis highlights the profound clinical dilemma offered by acquired hemophilia in the patient with substantial thrombotic risk from MVR. The patients require emergent removal of FVIII inhibitors and an end to bleeding, but are also at risk of valve thrombosis if anticoagulation is delayed for too long. Our findings support a stepwise approach: (1) Initiation of IS immediately upon diagnosis; (2) strict monitoring of FVIII levels to determine timing of anticoagulation resumption; (3) considering mechanical prophylaxis and low-dose pharmacologic bridging strategies in the interim; and (4) use of shared decision-making and interdisciplinary case conferencing for individualized risk stratification.

This systemic approach combines the immediacy of hemorrhagic risk with the reality of thromboembolic complications on late long-term AC.

Conclusion:

Acquired FVIII deficiency in patients with prior MVR is a rare but critical clinical challenge. It is a condition that mandates prompt initiation of immunosuppression while necessitating cautious deliberation of the timing and degree of anticoagulation. Our literature review and experience suggest that FVIII activity >50% may serve as a reasonable threshold to cautiously resume warfarin in these patients. A multidisciplinary, patient-centered approach and stepwise escalation of anticoagulation intensity based on bleeding control and FVIII recovery offer the safest pathway. In the absence of robust guidelines, this literature review provides a provisional algorithm for managing this unique coagulopathy.