Anticoagulant Therapy in Patients with Severe Factor XI Deficiency

Introduction:

Severe factor XI (FXI) deficiency is a rare autosomal coagulation factor deficiency defined as an activity level of less than 15-20IU/dL, that is usually associated with bleeding only in the setting of invasive procedures or trauma. It´s prevalence is approximately 1 in a million in the general population, although we found a higher prevalence among Ashkenazi and Iraqi Jewish population.

Bleeding tendency does not consistently correlate with FXI levels or genotypes (Lewandowska MD et al. Hematol Oncol Clin North Am 2021 Dec;35(6):1157-1169)].

As FXI has both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may protect subjects with FXI deficiency because they may have reduced risk of ischemic stroke (cerebral vascular events and deep vein thrombosis). Nevertheless, patients with severe coagulopathies sometimes require anticoagulants or antiplatelet therapy due to various cardiovascular events. Experience regarding the prescription of these treatments in severe FXI deficiency is limited.

Here we describe the experience of prophylactic and therapeutic anticoagulation in 2 patients with severe Factor XI deficiency.

Results:

The first case is a 66-year-old male patient diagnosed with severe FXI (plasma levels 1.5%) deficiency following a haemorrhagic complication after a tonsillectomy performed at the age of 11. The patient reported a history of recurrent epistaxis, which he has always controlled with nasal packing without the need of additional treatment. No gingival bleeding or spontaneous bruising. From a surgical perspective, he has undergone a dental extraction, experiencing bleeding 24 hours after the procedure.

He was referred to Haemostasis consultations on April 24, 2024, due to a recent diagnosis of atrial fibrillation with a CHADSVASC score of 2. We started him on dabigatran 110mg every 12 hours. He was referred to cardiology for left atrial appendage closure.

Since the start of the treatment, there has been one episode of rectal bleeding due to haemorrhoid treated with tranexamic acid and requiring the suspension of anticoagulation for 3 weeks. There was no anaemia or need for replacement therapy with factor.

The second case is a 77- year old patient with a history of stage IV sigmoid adenocarcinoma treated with chemotherapy and subsequently sigmoidoscopy in July2023 without haemorrhagic complications. Later he was diagnosed with IgG Lambda multiple myeloma ISS-2 and began treatment with chemotherapy (Daratunumab, Lenalidomide and dexamethasone) in January 2024 as well as thromboprophylaxis with rivaroxaban 10mg/day.

He was then, referred to Haemostasis consultations due to prolongued aTTP in February 2024. Assessing intrinsic pathway factors revealed a severe deficiency ofF XI (1.5%). During follow-up (7 months), the patient did not experience any haemorrhagic complications while on prophylactic anticoagulation. He underwent surgery for inguinal hernia in March 2024 receiving prior replacement treatment with recombinant FXI concentrations (Hemoleven, LFB) at 20UI/kg without any haemorrhagic complications after surgery.

Conclusions:

None of our cases showed major bleeding complications during follow-up while on therapeutic and prophylactic anticoagulant therapy, but further studies are needed.

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