Hypercoagulability in Kidney Transplant Recipients

Parajuli, Sandesh; Lockridge, Joseph B.; Langewisch, Eric; Norman, Douglas J.; Kujovich, Jody L.

doi:10.1097/tp.0000000000000887

Cited by 41 publications

(45 citation statements)

References 84 publications

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“…anti‐phospholipid antibodies, protein C & S deficiencies, etc.). This may be a protective strategy in the first 24 h posttransplant that avoids the management difficulties of postoperative anticoagulation.…”

Section: Discussionmentioning

confidence: 99%

Thrombalexin: Use of a Cytotopic Anticoagulant to Reduce Thrombotic Microangiopathy in a Highly Sensitized Model of Kidney Transplantation

Manook

Kwun

Burghuber

et al. 2017

American Journal of Transplantation

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Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anti-coagulation is difficult due to bleeding. A novel ‘cytotopic’ agent, ‘Thrombalexin’, (TLN) combines a cell-membrane bound (mirystoyl tail) anti-thrombin (HLL peptide) which can be perfused directly to the donor organ or cells. Thromboelastography (TEG) was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN vs. HLL (without cytotopic tail) vs. negative-control. Both TLN and HLL treated rhesus or human whole blood result in significantly prolonged r-time compared to kaolin controls. Only TLN-treated human endothelial cells (EC) and neonatal porcine islets (NPI) prolonged time to clot formation. Detection of membrane-bound TLN was confirmed by immunohistochemistry and FACS. In vivo, perfusion of a NHP kidney TLN-supplemented preservation solution in a sensitized model of transplantation demonstrated no evidence of TLN systemically. Histologically, TLN was shown to be present up to four days after transplantation. There was no platelet deposition and TMA severity, as well as microvascular injury scores (glomerulitis + peritubular capillaritis) were less in the TLN treated animals. Despite promising evidence of localized efficacy, no survival benefit was demonstrated.

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Section: Discussionmentioning

confidence: 99%

Thrombalexin: Use of a Cytotopic Anticoagulant to Reduce Thrombotic Microangiopathy in a Highly Sensitized Model of Kidney Transplantation

Manook

Kwun

Burghuber

et al. 2017

American Journal of Transplantation

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“…In that larger cohort, seasonal mortality remained significant after adjustment for other laboratory and clinical variables . Season‐related hypercoagulability may be an even more important element in kidney transplant recipients than in the general population . Long‐term kidney transplant recipients have a chronic prothrombotic and persistent inflammatory state, with significantly elevated levels of fibrinogen, d‐dimer, prothrombin activation fragments F1 + 2, and IL−6 .…”

Section: Discussionmentioning

confidence: 89%

“…Overall p < 0.001 population [18]. Long-term kidney transplant recipients have a chronic prothrombotic and persistent inflammatory state, with significantly elevated levels of fibrinogen, d-dimer, prothrombin activation fragments F1 + 2, and ILÀ6 [19].…”

Section: Discussionmentioning

confidence: 97%

Seasonality of mortality and graft failure among kidney transplant recipients in the US - a retrospective study

et al. 2017

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Mortality in the general population and in patients on chronic hemodialysis is significantly higher in winter than summer. It is unknown whether such a seasonal difference exists for mortality or graft failure among kidney transplant recipients. We analyzed United Network for Organ Sharing (UNOS) data to assess whether the annual distribution of deaths and graft failures differed significantly from expected. There was significant annual variation in both deaths (n = 52 523) and graft failures (n = 50 301; both P < 0.001). The number of observed deaths exceeded the number expected by 8.9% in winter (P < 0.001), whereas the number of deaths was 4.8% lower than expected in summer (P < 0.01). The pattern was strongest for deaths attributable to cardiovascular disease (n = 11 509; 21.9%). Similarly, there was an excess of graft failures in winter (3.6%; P < 0.01) and a deficit in other seasons (all P ≤ 0.02). This pattern was observed for graft failures due to chronic rejection (P < 0.001) and other causes (P < 0.001), but not for acute rejection (P = 0.28) or recurrent disease (P = 0.27). Potential explanations for this variation include changes in physiologic parameters, changes in medication adherence and other behaviors, or changes in insurance coverage or clinical care. Further studies are necessary to identify specific mechanisms.

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“…[1–3,10] Sofue [2] successfully performed living donor kidney transplantation in a patient with secondary APS following a combination of prophylactic plasmapheresis and anticoagulation therapy. The plasmapheresis reduced the LA, aCL, and anti-β2GPI levels to the normal ranges.…”

Section: Discussionmentioning

confidence: 99%

Living donor renal transplantation in patients with antiphospholipid syndrome

Choi

Jung²,

Shin³

et al. 2016

Medicine

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Introduction:Antiphospholipid syndrome (APS), autoantibodies directed against phospholipid-binding proteins are associated with cause vascular thrombosis. Patients with APS requiring renal transplantation are at risk of early graft loss due to arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Here, we report 3 cases of successful renal transplantation in patients with APS.Clinical Findings:A 53-year-old man with end-stage renal disease (ESRD) had experienced bilateral deep venous thrombosis (DVT) in the lower extremities 16 years ago and was administered warfarin. However, he frequently experienced recurrent DVT despite of anticoagulation therapy. Before the surgery, APS was confirmed based on positive results lupus anticoagulant in serological tests. A 40-year-old man with polycystic kidney disease and a history recurrent DVT tested positive for lupus anticoagulant and anticardiolipin antibodies. Lastly, a 42-year-old woman with ESRD was diagnosed with APS 7 years ago. She also developed DVT and tested positive for lupus anticoagulant and anti-B2-glycoprotein 1.The anticoagulation protocol was as follows in all cases:Warfarin was stopped 5 days before living donor renal transplantation and intravenous heparin therapy was started. During surgery, bolus heparin injections (3000 U) were administered to prevent arterial or venous thrombosis. Heparin was substituted with warfarin on postoperative day 4. The third patient (42/F) developed clinical rejection indicated by increased serum creatinine levels and donor-specific antibodies (DSA) and received steroid pulse therapy, plasmapheresis, and rituximab. This treatment restored graft function to within the normal range. The latest graft function in all patients was maintained at normal levels in the outpatient clinic.Conclusions:Living donor renal transplantation may be successful in patients with APS following perioperative anticoagulation therapy. However, because of the high risk of TMA or vascular thrombosis in the early postoperative period, close monitoring for hypercoagulability and continuous anticoagulation is essential for maintaining graft function.

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Hypercoagulability in Kidney Transplant Recipients

Cited by 41 publications

References 84 publications

Thrombalexin: Use of a Cytotopic Anticoagulant to Reduce Thrombotic Microangiopathy in a Highly Sensitized Model of Kidney Transplantation

Thrombalexin: Use of a Cytotopic Anticoagulant to Reduce Thrombotic Microangiopathy in a Highly Sensitized Model of Kidney Transplantation

Seasonality of mortality and graft failure among kidney transplant recipients in the US - a retrospective study

Living donor renal transplantation in patients with antiphospholipid syndrome

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