Manifestation of tranexamic acid toxicity in chronic kidney disease and kidney transplant patients: A report of four cases and review of literature

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Excerpt

Uraemic bleeding is a well‐known complication in patients with chronic kidney disease (CKD).1 The pathophysiology of uraemic bleeding is complex, including platelet dysfunction, abnormal platelet‐vessel wall interactions and anaemia.1 In uraemic patients, disturbance of platelet α‐granules, impaired synthesis and/or release of thromboxane A2, abnormal calcium metabolism, oxidative stress, and systemic inflammation all contribute to platelet dysfunction.3 Circulating fibrinogen fragments (fibrinogen degradation products) in uraemia also inhibit platelet aggregation by competitively binding to glycoprotein IIb/IIIa receptors.4 Tranexamic acid (TXA) is a synthetic lysine derivative, which exerts its anti‐fibrinolytic effect by competitively inhibiting activation of plasminogen, thereby reducing conversion of plasminogen to plasmin. TXA, at higher doses, also directly inhibits plasmin. Plasmin is the enzyme responsible for degradation of fibrin clots and fibrinogen. In uraemic patients, TXA was shown to inhibit fibrinolysis, shorten bleeding time and improve platelet function.5
Tranexamic acid was reported to be beneficial as adjunctive therapy in the treatment of recurrent acute gastrointestinal bleeding from colonic angiodysplasia in a haemodialysis (HD) patient,8 subdural and intracerebral haemorrhage in a HD patient,9 and major upper gastrointestinal bleeding in 20 HD patients.10 No side‐effects were observed in these patients. TXA had also been used successfully in treating haematuria in 10 polycystic kidney disease patients with or without CKD.11 TXA was generally well tolerated, except one patient who developed acute bilateral ureteric obstruction due to blood clots which necessitated insertion of double J‐shaped catheters.11 Renal excretion is the major route of TXA elimination and over 95% of TXA is excreted in the urine as unchanged form. Dosage adjustment of TXA in dialysis patients remains controversial and there are no data regarding drug clearance by dialysis.14 TXA can also cross the blood–brain barrier. Therefore, dialysis patients are particularly prone to TXA‐induced neurotoxicity.
From 2005 to 2014, we encountered three peritoneal dialysis (PD) patients and one kidney transplant recipient (KTR) who developed severe complications after TXA use. There were two PD patients who developed neurotoxicity after intravenous TXA, one PD patient who developed neurotoxicity after oral TXA, and a rare case of acute obstructive uropathy secondary to acute blood clot retention after oral TXA use for menorrhagia in a KTR. We also performed a qualitative literature review of published cases of TXA toxicity in CKD patients in the PubMed database.
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