P1658: DELAYED REVERSAL OF FACTOR V INHIBITOR ACTIVITY POST-IMMUNOSUPPRESSIVE THERAPY, FOLLOWED BY A SUCCESSFUL PREGNANCY: A CASE REPORT

Abstract

Background: Acquired factor V inhibitor (AFVI) is a very rare autoimmune hemostatic disorder that leads to hemorrhagic manifestations of variable severity. Aims: We describe a case of a 35-year-old Caucasian female patient presenting with severe AFVI with life-threatening hemorrhages. The AFVI exhibited spontaneous reversal over several years after discontinuation of ineffective combination immunosuppressive therapies and subsequently a successful pregnancy. Methods: Diagnosis of AFVI was based on a marked prolongation of prothrombin time-international normalized ratio (INR) and activated partial thromboplastin time (APTI) not corrected by the addition of normal plasma (1:1 ratio), with FV activity reduced to <1.0%. Other coagulation factor activity levels were unchanged, and the presence of an FV inhibitor was revealed by the Bethesda inhibitor assay. Results: Over the course of 2.5 years, plasmapheresis plus immunoglobulins and different combination immunosuppressive regimens were adminstered (dexamethasone+rituximab; cyclophosphamide+dexamethasone + rituximab + cyclosporine; cyclosporine + sirolimus + cyclophosphamide + dexamethasone; bortezomib+sirolimus+methylprednisolone; sirolimus+mycophenolate mofetil). Coagulation could be effectively maintained using recombinant FVIIa. The combination immunosuppressive therapies resulted in intermittent reversal of AFVI over 2.5 years, which then became therapy-resistant. After discontinuation of the unsuccessful immunosuppressive therapies, the patient exhibited partial spontaneous remission: her FV activity gradually increased from ~1% to ~33% over the course of 5 years. The patient became pregnant and during her pregnancy, FV activity increased to 54%, and her coagulation parameters were normalized. She gave birth to a healthy child by Caesarean section without any bleeding complications. Summary/Conclusion: Patients with AFVI presenting with hemorrhagic manifestations should be treated aiming for hemostatic control as well as inhibitor eradication. The use of an activated bypassing agent for hemostatic control is effective in AFVI. The presented case is unique because the treatment regimens used included combinations of multiple immunosuppressive agents and also suggest that patients with AFVI resistant to combination immunosuppressive protocols receiving no therapy may undergo spontaneous remission. Long-term monitoring of the coagulation status and the anti-FV inhibitor levels is warranted.