PO150 | FACTOR XII DEFICIENCY IN THE SETTING OF RECURRENT THROMBOSIS AND EXTENDED VENOUS OBSTRUCTION: A CASE ANALYSIS

L. Leoni¹, G. Pata¹, A. Domenighini¹, L. Crippa², T. D'aliberti¹, G. Galimberti¹, F. Paciullo¹, P. Rovere Querini¹ | ¹Internal Medicine Unit; ²Coagulation Service Thrombosis Research Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy

Background. Factor XII (FXII), also known as Hageman factor, is a plasma serine protease that plays a key role in the initiation of the intrinsic pathway of coagulation and in the kallikrein–kinin system. [1] Congenital FXII deficiency is a rare autosomal recessive disorder characterized by a prolonged activated partial thromboplastin time (aPTT) in the absence of a bleeding tendency. [2] Despite its apparent importance in vitro, FXII deficiency is paradoxically not associated with clinical hemorrhage, and its physiological role in hemostasis remains controversial. Emerging evidence has suggested a potential link between FXII deficiency and thromboembolic risk, although this association remains debated. [3;4]. We report a clinical case in which FXII deficiency emerged during the evaluation of recurrent venous thrombosis.
Case Report. A 46-year-old woman with a history of end-stage chronic kidney disease on hemodialysis due a congenital kidney, and a previous total splenopancreatectomy for pancreatic neuroendocrine tumor complicated by secondary diabetes mellitus, was evaluated. The patient also has a history of multiple thrombotic and hemorrhagic events. Her thrombosis history included recurrent catheter-related thrombosis, chronic superior vena cava (SVC) with extensive collateral circulation, pulmonary embolism, portal vein thrombosis, and inferior vena cava thrombosis (IVC). A history of lupus anticoagulant (LAC) positivity was reported, although the details were unclear. Despite the high thrombotic burden, anticoagulation had previously been avoided due to recurrent severe hemorrhagic events, including gastrointestinal bleeding from angiodysplasias and esophageal varices. The patient was admitted for acute respiratory failure requiring high-flow oxygen therapy. Computed tomography (CT) scan revealed extensive thrombosis involving the azygos vein and the SVC, extending to the right atrium, without evidence of pulmonary embolism. Pulmonary scintigraphy was non-diagnostic due to impaired tracer flow caused by SVC thrombosis. Multidisciplinary evaluation, including hematology and vascular surgery consultation, found no indication for surgical intervention and recommended anticoagulation therapy. Interventional radiology assessment excluded the feasibility of SVC stenting due to the extent of thrombosis. Anticoagulation with unfractionated heparin was initiated. Given the history of recurrent thrombosis with a reported prior positivity for LAC, antiphospholipid antibody testing was performed. LAC, anti-cardiolipin, and anti-β2 glycoprotein I antibodies were negative; however, low-titer positivity for anti-phosphatidylserine/prothrombin IgM antibodies was detected (42.5 U; normal value <30).In light of the prolonged aPTT, a mixing test was performed and showed normal results, suggesting the absence of circulating inhibitors. Coagulation factor assays were requested, revealing mild deficiencies in factors VII, IX, and XI (42%, 61%, and 49%, respectively) and a moderate deficiency of factor XII (25%). Long-term anticoagulation with warfarin was initiated, but the patient continued to have unexplained respiratory failure. Repeat CT showed unchanged thrombotic burden and suggested a systemic-to-pulmonary shunt. Phlebography confirmed occlusion of the intrahepatic IVC and SVC, with patent subclavian and hemiazygos veins; recanalization was unsuccessful.The patient was discharged on high-flow oxygen therapy, maintained on anticoagulation, with continuation of thrice-weekly hemodialysis sessions. Approximately two weeks later, she was referred to the Emergency Department for progressively worsening dyspnea, hypotension, and tachycardia. Diagnostic evaluation demonstrated cardiac tamponade, so she subsequently underwent emergent pericardiocentesis, which yielded a hemorrhagic pericardial effusion.
Conclusions. This case highlights the diagnostic complexity of thrombosis in patients with multiple risk factors, including malignancy, chronic central venous catheters, and vascular abnormalities. Although Factor XII deficiency is classically regarded as non-hemorrhagic, emerging evidence suggests it may paradoxically contributing to inflammatory and prothrombotic processes implicated in a wide range of pathological conditions across multiple medical disciplines. [4]
References. [1]Schmaier, A.H.; Stavrou, E.X. Factor XII—What’s important but not commonly thought about. Res. Pract. Thromb. Haemost. 2019, 3, 599–606. [2] Gailani D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R et al., eds. Hematology: Basic Principles and Practice. 7th ed. Elsevier; 2018 [3]Renné T, Schmaier AH, Nickel KF, Blombäck M, Maas C. In vivo roles of factor XII. Blood. 2012;120(22):4296–4303. [4]Girolami A, Ruzzon E, Lombardi AM, Cabrio L, Randi ML. Thrombophilia and FXII deficiency: fact or fiction? Hematology. 2004;9(4):259–261. [4]Krajewska, K.; Pawlus, J.; Ptaszynska, K.; Lisowska, A. Factor XII—A New Therapeutic Target? A Systematic Review. Int. J. Mol. Sci. 2026, 27, 1331. https://doi.org/10.3390/ijms27031331