Observational cohort study of long-term outcomes of liver transplantation in haemophilia.

INTRODUCTION: Gene therapy is now a reality for individuals with haemophilia, yet little is known regarding the quality-of-life impact of factor correction. As few data exist, and recognizing the analogy to liver transplantation (OLTX), we identified OLTX+ and OLTX- men in the ATHNdataset to compare post-OLTX factor VIII and IX on quality of life (QoL) by Haem-A-QoL and PROMIS-29. METHODS: OLTX- were matched to OLTX+ by age, race, and haemophilia type and severity. Deidentified demographic data, including post-transplant factor levels, genotype and target joint disease were analysed by descriptive statistics. Haem-A-Qol and PROMIS-29 were compared in OLTX+ and OLTX- by student's t-test and univariate regression models. RESULTS: Of 86 people with haemophilia A (HA) or haemophilia B (HB) cared for at 10 haemophilia treatment centers (HTCs), 21 (24.4%) OLTX+ and 65 (75.6%) OLTX- were identified. OLTX+ and OLTX- had a similar frequency of target joint disease (p = .806), HA genotypes, null versus non-null (p = .696), and HIV infection (p = .316). At a median 9.2 years post-OLTX, median FVIII, .63 IU/mL [IQR 0.52-0.97] and FIX, .91 IU/mL [IQR .63-1.32], Haem-A-QoL, PROMIS-29, and HOT scores were comparable. Severe HA/HB had lower post-OLTX 'dealing with haemophilia' scores (p = .022) and higher 'sports and leisure' (p = .010) and 'view of yourself' scores (p = .024) than OLTX+ non-severe participants. Non-caucasian OLTX+ had significantly lower scores in sports and leisure (p = .042), future expectations (p = .021) and total score (p = .010). CONCLUSION: Nine years after OLTX, QoL is comparable to OLTX-, but significantly better in OLTX+ with severe than non-severe disease and in caucasians than non-caucasians.

Hereditary Antithrombin Deficiency Pilot Project Registry from the American Thrombosis and Hemostasis Network (ATHN).

BACKGROUND: Patients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). ATHN 12: HAD Pilot Project established a registry to collect data on patients with HAD to inform current practice and serve as a platform to design a multicenter global registry for patients with HAD. METHODS: The HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and AT concentrate administration were recorded. RESULTS: Ninety-four (94) patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD18); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% patients: (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low molecular weight heparin was administered in 33% and AT concentrate in 19% and 11% prior and post-delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular, respectively. Overall, 35% participants received AT concentrate without adverse events. CONCLUSIONS: In ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend towards using DOACs. LMWH was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients.