Acquired factor v inhibitor and granulomatosis with polyangiitis: Diagnostic challenges and therapeutic implications Free

A 61-year-old man with hypertension and cervical disc herniation presented with four months of bilateral lower-extremity cramping pain and swelling. He denied recent surgery, immobilization, or travel. Physical examination revealed bilateral pitting edema. Duplex ultrasound demonstrated bilateral gastrocnemius vein thrombosis.

Initial labs showed WBC 7.88 × 10⁹/L (normal differential), hemoglobin 10.4 g/dL (MCV 81 fL), platelets 261 × 10⁹/L, and creatinine 1.4 mg/dL (eGFR 60 mL/min/1.73 m²). Coagulation studies revealed markedly prolonged PT > 40 s (INR 4.25) and APTT 135 s. Fibrinogen and dilute thrombin time were normal. Mixing studies failed to correct clotting times. Factor assays showed factor V activity <1%, with inhibitor titer 7.5 Bethesda units; factors II and X were moderately reduced (48% and 71%, respectively). Anticoagulation was initially withheld due to the abnormal coagulation profile.

The patient reported an “Allogen” jaw engraftment 6–8 months prior; the dentist confirmed no use of bovine thrombin glue. On further questioning, he reported mild numbness in hands and feet, recent right-ear hearing loss, and worsening chronic bilateral shoulder and knee pain. During hospitalization, renal function deteriorated with creatinine rising to 3.3 mg/dL, prompting evaluation for vasculitis. Inflammatory markers were elevated (CRP 116 mg/L, ESR 67 mm/h). Serology revealed c-ANCA > 1:1280 and proteinase-3 antibody > 8 U/mL. Rheumatology diagnosed him with granulomatosis with polyangiitis (GPA).

Prednisone was initiated inpatient, leading to improvement in his coagulation profile. Repeat duplex showed stable DVT. He was discharged for outpatient follow-up. Rituximab (375 mg/m² weekly ×4) was administered, resulting in normalization of factor V activity and disappearance of the inhibitor after the third dose. Vasculitis symptoms improved and repeat c-ANCA was negative. A follow-up duplex revealed a new tibial vein thrombosis; apixaban was started. He remains on a prednisone taper.

Factor V (FV) is a procoagulant cofactor in the common coagulation pathway, facilitating the activation of prothrombin to thrombin by factor Xa and catalyzing factor X to factor Xa. FV inhibitors prolong both PT and APTT.

Acquired FV inhibitors are rare, usually occurring after exposure to bovine thrombin used as a topical hemostatic during surgery. The incidence has declined with recombinant or purified bovine thrombin use. FV inhibitors have also been reported with malignancy (especially solid tumors), major surgery, infections, and autoimmune disorders including Sjögren's syndrome, lupus, Hashimoto's thyroiditis, bullous pemphigoid, and type 1 diabetes mellitus. To our knowledge, this case is the first to associate FV inhibition with GPA.

Bleeding,mainly mucosal is the typical clinical manifestation; intracranial hemorrhage occurs less frequently but can be fatal. Thrombotic presentations are uncommon. Our patient uniquely presented with venous thrombosis without bleeding.

Unlike other acquired coagulation inhibitors, hemostasis in FV inhibitor patients may be supported by platelet transfusions, as platelet α-granules contain FV partially protected from circulating antibodies. Management follows two steps: control active bleeding if present (usually with platelet concentrates), and eradicate the inhibitor with immunosuppression. Treatments include corticosteroids alone or combined with cyclophosphamide, rituximab, IV immunoglobulin, or plasmapheresis. However,there are no clear guidelines on management for patients presenting primarily with thrombosis.

In our patient, prednisone induced early clotting parameter improvement; four weekly rituximab doses achieved complete normalization of FV activity and inhibitor disappearance. Following new tibial vein thrombosis, anticoagulation with apixaban was started safely under close monitoring. His vasculitis markers also improved.

Only one prior report described FV inhibitor in microscopic polyangiitis treated with steroids and azathioprine. Our case expands the vasculitis spectrum associated with this rare autoantibody and underscores that thrombosis, though rare, can be a presenting feature. Early recognition, laboratory monitoring, and prompt immunosuppression are critical to prevent catastrophic hemorrhage and enable safe anticoagulation when warranted.