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Transplant
OP26 Predicting thrombotic complications after liver transplantation in patients with Budd Chiari syndrome
  1. R Westbrook,
  2. R Westbrook,
  3. D Orr,
  4. N Heaton,
  5. J O'Grady,
  6. R Patel,
  7. N Lea,
  8. A Quaglia,
  9. A Pagliuca,
  10. R Arya,
  11. G Mufti,
  12. M Heneghan
  1. King's College Hospital, London, UK

Abstract

Introduction Myeloproliferative disorders (MPD) are the commonest cause of Budd Chiari syndrome (BCS). A somatic mutation of the tyrosine kinase JAK2 gene (JAK2V617F) is present in a large proportion of patients with MPD and is used as a screening tool to detect occult MPD. Recently a germline 46/1 haplotype block and mutations in the TET2 gene have also been implicated in the pathogenesis of MPD. We evaluate whether these underlying genetic abnormalities are relevant to the occurrence of thrombotic complications post liver transplantation (LT).

Method Samples of DNA were extracted from total blood or bone marrow. Real-time PCR was performed to screen for JAK2 mutations. TET2 mutations were analysed by next generation high throughput DNA sequencing (Roche 454). DNA was analysed by pyrosequencing for two SNP's which tag the 46/1 haplotype. Histology of liver biopsies performed for graft dysfunction were reviewed for evidence of veno-occlusive disease (VOD). The INR post LT and patient outcomes were recorded.

Results 36 patients underwent LT for BCS between 1995 and 2008. Median duration of follow-up after LT was 40 months (1–195 months) and 1-year survival was 84%. Pro-coagulant conditions were identified in 22 patients (MPD n=17, Protein C Deficiency n=2, Behcet's n=2 and lupus anti-coagulant n=1). The remaining 14 patients were classed as idiopathic. Overall, 22/36 (61%) were positive for the JAK2 mutation, 6/27 (22%) for the TET2 mutation and 19/26 (73%) for the 46/1 haplotype. In the idiopathic cohort, 8/13 (63%) tested positive for JAK2 suggesting latent MPD. All patients were treated with warfarin following LT. Thrombotic complications occurred in 12/36 (33%) and included hepatic artery thrombosis (n=3, 2/3 being late), VOD (n=7), splenic vein thrombosis (n=1) and portal vein thrombosis (n=1), at a median time of 40 months post LT (range 1–164 months). Re-transplantation was more common in those with thrombotic complications (7/12 (58%) vs 1/24 (4%), (p=0.0006)) and mortality was higher (4/12, (25%) vs 3/24, (13%)), but this did not reach statistical significance (p=0.2). The presence of a JAK2 mutation was associated with the development of a thrombotic complication post LT (11/12 vs 1/24, p=0.01). Neither the 46/1 haplotype nor the TET2 mutation was associated with an increase in post LT thrombotic complications or morbidity. Mean INR was not significantly different in those patients who developed a thrombotic complication (2.73 vs 2.70, p=NS).

Conclusion A JAK2 mutation appears to be associated with an increased risk of recurrent BCS and other thrombotic complications post LT. Thrombotic complications following LT are associated with an increase in morbidity and mortality. In patients with a JAK2 mutation, the role of additional anticoagulation or JAK2 inhibitor therapy needs to be investigated to try and prevent thrombotic complications.

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