Significance of microvascular thrombosis in renal allografts: role of ex vivo thrombolytic therapy

Abstract

Back table flush with activase rapidly lyses severe intraglomerular microthrombi making them successfully transplantable. Pre-treatment with activase seems to be an effective therapeutic intervention for kidneys with massive intraglomerular thrombosis.

Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi‐blinded prospective randomized trial

“…In two retrospective studies, Nghiem et al report the use of tPA in HTK for DCD kidneys with significant glomerular microthrombi burden. In the first study, tPA was added to a second ex vivo flush prior to engraftment for 12 kidney transplants, resulting in one graft loss (8%) and three patients (25%) with DGF . In the second study, tPA in HTK was utilized during MPP for similar kidneys with significant thrombosed glomeruli, but otherwise favorable findings, on biopsy.…”

“…Despite acceptable long‐term outcome data, DCD kidneys are at increased risk for delayed graft function (DGF), probably due to microthrombi and additional warm ischemia related to the withdrawal process . Typically, heparin is given before or at withdrawal of support, with a wait period of two to five min following cardiac death before organ recovery commences .…”

“…In some locations, pre‐mortem heparin is not allowed or strongly discouraged , which further increases the likelihood of microthrombi formation in the donated kidney. Enzymatic thrombolysis following DCD organ recovery may potentially help address microthrombi‐induced organ injury . With the hypothesis that microthrombi result in DGF and increased vascular resistance, we initiated an organ procurement organization (OPO)‐wide trial utilizing the thrombolytic tissue plasminogen activator (tPA) as a component of the post‐procurement perfusate during machine pulsatile perfusion (MPP), prospectively randomizing one kidney from each enrolled donor to receive the thrombolytic intervention with the other kidney assigned to the control group.…”

Thrombolytic Therapy During ex-vivo Normothermic Machine Perfusion of Human Livers Reduces Peribiliary Vascular Plexus Injury

“…A potential option to reduce biliary injury and ITBS incidence is administering tissue plasminogen activator (tPA) into the HA to lyse microthrombi. Several studies have demonstrated this effect clinically, showing that tPA administration prior to liver reperfusion mitigates the risk of developing ITBS in DCD LT (11,(13)(14)(15)(16) and reduces intraglomerular microthrombi in renal allografts (17). However, a major concern with this approach in LT is transferring tPA activity from the donor liver to recipients, who are often already experiencing coagulopathy, Abbreviations: BE, biliary epithelium; BDI, bile duct injury; CBD, common bile duct; CIT, cold ischemic time; dPBG, deep peribiliary glands; DCD, donation after circulatory death; EVLP, ex-vivo liver perfusion; HA, hepatic artery; H&E, hematoxylin and eosin; IMB, intramural bleeding; ITBS, ischemic-type biliary strictures; LT, liver transplant; MS, mural stroma; NEDS, New England Donor Services; NMP, normothermic machine perfusion; pPBG, periluminal peribiliary glands; PV, portal vein; PVP, peribiliary vascular plexus; tPA, tissue plasminogen activator; tWIT, total warm ischemic time; fWIT, functional warm ischemic time; UW, University of Wisconsin; WIT, warm ischemic time.…”