PO076 | ACQUIRED FACTOR V INHIBITOR WITH CONCOMITANT LUPUS ANTICOAGULANT: DIAGNOSTIC PITFALLS AND THERAPEUTIC CHALLENGES

G. Gazzelli¹, Y. Azzanelli¹, C. Vernarecci¹, F. Marotta¹, F. Giacopelli¹, E. Cenni², V. Agostini², L. Banov¹, AC Molinari¹ | ¹IRCCS Istituto Giannina Gaslini, Italy; ²IRCSS AOM S. Martino Genova, Italy

Background. Acquired Factor V (FV) inhibitors are rare, with an estimated incidence of 0.09 to 0.29 cases per million person-years. Associated with infections, malignancies, or medications, they typically present with unexplained prolongation of Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT), while the Thrombin Time (TT) remains normal. Presentation varies from asymptomatic laboratory findings to life-threatening haemorrhage or, paradoxically, thrombosis.
Case report. An 80-year-old male was recently discharged following severe pneumonia. His medical history included hypertension, aortic stenosis, previous myocardial infarction, and peripheral obstructive arterial disease (external iliac artery) treated with clopidogrel. He presented to the Emergency Department with pain and a large ecchymosis on his upper arm. Initial screening showed extreme PT/aPTT prolongation with normal platelets, TT, fibrinogen, and Factor XIII. To investigate the coagulopathy, dRVVT assays revealed a strong lupus anticoagulant (LA) effect (ratio 2.8). To distinguish a "pseudo-deficiency" from a true inhibitor, serial plasma dilutions were performed: all factors normalised at 1:16 except for Factor V, which normalised only at 1:512, confirming a specific high-titre FV inhibitor (initially 445 BU). Basing on the patient's high thrombotic risk and a stable clinical phenotype, initial therapy consisted of prednisone (1 mg/kg/day) without bypassing agents. However, after 7 days, despite a decrease in the inhibitor titre to 177 BU, the patient developed acute abdominal pain. A CT scan revealed an 8 X 6 X 10 cm rectus abdominis haematoma associated with a haemoglobin drop of 2 g/dL. Haemostatic treatment with recombinant activated Factor VII (rFVIIa) at 90 µg/kg was initiated but yielded no clinical benefit or improvement in ROTEM (EXTEM) parameters. Tragically, following rFVIIa administration, the patient suffered a cerebellar stroke, highlighting the severe thrombotic risk in this population. Since FV inhibitors interfere with the prothrombinase complex, often making bypassing agents ineffective, and FV stored in platelet alpha-granules is partially activated and relatively resistant to circulating inhibitors, one unit of platelet concentrate was transfused to allow for urgent embolisation of the inferior epigastric artery. This led to the normalisation of EXTEM, and the procedure was completed without further bleeding. Besides, a pulsed immunosuppressive protocol with a lower cumulative dose of cyclophosphamide, rituximab and steroids (CyDRi) was started. After two weeks of this treatment, the FV inhibitor decreased to 16 BU and the coagulation factors, previously extremely reduced, rose to 40 UI/dl in undiluted plasma.
Conclusions. In cases of unexplained PT/aPTT prolongation with normal TT, FV inhibitors must be considered. When initial assays suggest a multiple factor deficiency, serial plasma dilutions are essential to unmask the specific inhibitor. Clinicians must carefully balance haemorrhagic control with the high risk of thrombosis, particularly when using bypassing agents in vasculopathic patients. Platelet transfusion represents a critical haemostatic bridge when traditional agents fail, enabling high-risk interventional procedures. Finally, this case demonstrates that point-of-care viscoelastic testing (ROTEM) is an invaluable tool in this setting, as it can objectively demonstrate and monitor the immediate haemostatic effect of platelet transfusion, providing real-time guidance for high-risk invasive procedures.