Heterozygosity for the Factor v Leiden (G1691a) Mutation Predisposes Renal Transplant Recipients to Thrombotic Complications and Graft Loss1

Wüthrich, Rudolf P.; Cicvara-Muzar, Snjezana; Booy, Christa; Maly, Friedrich E.

doi:10.1097/00007890-200108150-00037

Cited by 50 publications

(44 citation statements)

References 8 publications

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“…Other explanations from previous reports point to the increased risk of renal transplant loss due to perfusion defects in the initial ischemia-reperfusion phase (11).…”

Section: Discussionmentioning

confidence: 97%

“…As major reasons the occurrence of acute rejections, probably mostly vascular rejections, has been described (6,8,10). Furthermore, rates of early graft loss due to venous thromboembolism and graft perfusion defects were significantly elevated in patient groups tainted with thrombophilia (11). Other groups have recently observed that the prothrombin (PT) G20210A mutation similarly predisposed to early transplant failure (12).…”

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confidence: 99%

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Outcome of Kidney Transplantation in Patients with Inherited Thrombophilia

Heidenreich

Junker²,

Lang³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Inherited prothrombotic risk factors predispose patients to thromboembolic events. In kidney transplant recipients, thrombophilia may manifest itself with venous thrombosis, microvascular occlusion, or acute rejection with major consequences for allograft survival. This is a prospective study on 165 renal allograft recipients to evaluate the contribution of genetic thrombophilic risk factors to transplant outcome. Besides antithrombin, protein C, and protein S deficiencies, none of which was found in our patient group, factor V G1691A (FV G1691A), prothrombin G20210A (PT G20210A) mutations, and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms were studied. The primary endpoint of the study was occurrence of an acute rejection within the first 90 d and transplant loss within 1 yr. Heterozygous FV G1691A and PT G20210A mutations and the MTHFR T677T variant were significantly associated with acute rejections with rejection rates of 68%, 67%, and 71%, respectively, as compared with 35% in patients not carrying these genotypes. Many rejections that were histologically proven were acute vascular ones. Transplant loss was significantly associated exclusively with the PT G20210A group (50% 1-yr graft survival; odds ratio, 10.0; 95% confidence interval, 1.8 to 56.1). PT G20210A patients exerted the highest prothrombotic activity pretransplant, as determined by prothrombin 1.2 fragments (PT F1.2), which may be the background for minor outcome. In conclusion, common prothrombotic mutations are significantly associated with acute rejections, especially vascular rejections, and for PT G20210A also with early transplant failure. Screening for hypercoagulable states pretransplant is recommended to intensify anticoagulatory treatment posttransplant. heidenr@uni-muenster.de

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“…Other explanations from previous reports point to the increased risk of renal transplant loss due to perfusion defects in the initial ischemia-reperfusion phase (11).…”

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Outcome of Kidney Transplantation in Patients with Inherited Thrombophilia

Heidenreich

Junker²,

Lang³

et al. 2003

Journal of the American Society of Nephrology

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“…6 Studies have shown that recipients with hypercoagulable disorders have a significantly higher risk of early graft failure apart from thromboembolic events and acute rejection. 16 Long-term graft survival is higher when anticoagulants are administered prophylactically. 17 Genetic analysis has shown that single nucleotide polymorphisms seem to have no statistically significant association with acute rejections, except from factor V mutation Q506.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Florou

Koukoulaki²,

Theodoros³

et al. 2017

Exp Clin Transplant

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Thrombophilia due to activated protein C resistance (Leiden mutation) is the most common inherited thrombophilic disorder with 5% incidence in whites. Renal transplant of these patients entails a risk of vascular thrombosis soon after the transplant; and acute rejection episodes and graft loss within the first year. We present a case of a successful living-related renal transplant in man with a recent history of repeat episodes of vascular access thrombosis attributed to inherited thrombophilia (heterozygosity for factor V mutation Q506 and homozygosity for mutation T677 for methylenetetrahydrofolate reductase). Transplant recipient was administered anticoagulation therapy with low molecular weight heparin pre-and postoperatively. No thrombotic or hemorrhagic events occurred posttransplant. A high suspicion of thrombophilic disorders in patients with end-stage renal disease with vascular access thrombotic events should be screened further to prevent failure of a subsequent renal transplant. Inherited thrombophilic disorders may not exclude living-related kidney transplant provided that anticoagulation therapy is administered perioperatively.

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“…1 A prevalência da mutação FV G1691A na população de receptores renais equivale à da população não transplantada, com pequenas variações de acordo com o grupo étnico estudado. 4,[23][24][25] No presente estudo, a prevalência desta mutação foi de 1,5%, o que é equivalente à observada na população brasileira de não transplantados. 28 Após o transplante renal, existe significativo declínio da atividade fibrinolítica 29 e da ativação da proteína C, 30 além de ativação de trombina, plaquetas e da via intrínseca da coagulação quando os pacientes estão imunossuprimidos com ciclosporina.…”

Section: Discussionunclassified

“…2,3 O número de condições associadas à trombofilia aumentou proporcionalmente ao desenvolvimento de novas metodologias que permitiram a identificação de maior número de polimorfismos em genes relacionados com o sistema de coagulação e de anticoagulação. A mutação G1691A no gene do fator V (FV) do sistema de coagulação (Fator V de Leiden), 4 a mutação G20210A no gene da protrombina (PT) 5 e a presença de anticorpos anticardiolipina (aCL) 6,7 circulantes no sangue periférico são importantes condições associadas à trombofilia e podem influenciar o risco de perda do enxerto renal atribuída a eventos trombóticos. Estudos populacionais indicam, entretanto, que a prevalência de trombofilia não é uniforme.…”

Section: Introductionunclassified