PO122 | SUCCESSFUL MANAGEMENT OF THERAPEUTIC ANTICOAGULATION FOR PROVOKED VENOUS THROMBOEMBOLISM IN A PATIENT WITH FACTOR VII DEFICIENCY AND SEPTIC SHOCK

S. Birocchi¹, F.M. Monda¹, B. Clerici^1|2, M. Scavone², R. Cabiddu¹, E. Pontisso¹, C. Ortelli¹, M.L.G. Perego¹, E. Fiorini¹, L. Catarini¹, A. Bortoli¹, M. Manzoni¹, F.M. Casanova¹, A. Tripodi^2|3, F. Peyvandi^2|3, G.M. Podda^1|2 | ¹S.C. Medicina Generale 2, Ospedale San Paolo, ASST Santi Paolo e Carlo, Milano, Italy; ²Dipartimento di Scienze della Salute, Università degli Studi di Milano, Italy; ³Centro di riferimento emofilia e trombosi "Emilio Bianchi"; ⁴S. Birocchi and F.M. Monda contributed equally as co-first authors

Background. Venous and arterial thrombotic events have occasionally been reported in patients with inherited factor VII (FVII) deficiency. Here, we describe the management of provoked venous thromboembolism (VTE) in a patient with severe FVII deficiency.
Case Report. An 82-year-old woman presented to the Emergency Department because of worsening right lower limb pain and edema following a fall. Her medical history was notable for inherited FVII deficiency (basal FVII activity of 6%), managed with on-demand replacement therapy only. On admission, she was stable but tachypneic on low-flow oxygen. Initial laboratory tests showed increased inflammatory markers, acute kidney injury and a prolonged prothrombin time ratio of 2.18. Shortly after admission, she developed septic shock, for which norepinephrine and empiric antibiotics were started. A chest-abdomen contrast-enhanced computed tomography (CT) ruled out pneumonia and other uncontrolled infectious sources, but revealed multiple thromboembolic filling defects in the main, segmental, and subsegmental pulmonary arteries. CT angiography of the right lower limb showed a filling defect in the popliteal vein with surrounding soft tissue edema. Troponin and NT-proBNP were increased, whereas transthoracic echocardiography showed no signs of acute right ventricular dysfunction. To allow for the start of therapeutic anticoagulation with unfractionated heparin, plasma-derived FVII concentrate was started (Provertinum 20 IU/kg every 12 hours). FVII activity increased from 27% pre-infusion to 84% post-infusion. Following improvement of the kidney function, the patient was switched to intermediate-dose enoxaparin (6000 IU twice daily). An attempt to reduce Provertinum to once daily while maintaining enoxaparin was followed by hemoptysis and epistaxis, prompting the restoration of the twice-daily regimen. After one month of full-dose anticoagulation, compression ultrasonography and repeat chest CT angiography showed complete resolution of both the deep vein thrombosis and pulmonary embolism. Provertinum was then discontinued and apixaban was reduced to 2.5 mg twice daily. No further bleeding or thrombotic events occurred during the following 30 days. Thrombin generation assay (TGA) results are summarized in Table 1. During the acute phase, TGA showed prolonged lag time (min) and time to peak (min), consistent with severe FVII deficiency, but markedly increased peak-thrombin (nM/L) and endogenous thrombin potential (ETP, nM x min). The ETP ratio with/without thrombomodulin was high, suggesting reduced sensitivity to thrombomodulin-mediated anticoagulant activity. Of note, this assessment was performed close to the episode of mucosal bleeding occurred during anticoagulation, although the assay did not clearly capture this bleeding tendency. At follow-up, lag time and time to peak remained prolonged, whereas ETP and peak-thrombin normalized or decreased. However, the ETP ratio with/without thrombomodulin remained high. Overall, these findings point towards a hypercoagulable state despite severe FVII deficiency, particularly pronounced during the acute phase of disease.
Conclusions. We described a case of successful anticoagulation obtained with careful dosing of replacement therapy in a FVII deficiency patient with provoked VTE. TGA may provide useful information beyond standard clotting tests in this context, although its clinical interpretation should remain closely integrated with clinical data.