We agree with Mezzano and colleagues about the potential role of fibrinolysis in the bleeding complications associated with chronic renal failure. Fibrinolysis might also contribute to 'complications' in a more general sense; the focus of our Review was primarily factors contributing to platelet dysfunction, an area in which we believe the majority of data regarding pathophysiology exist. This is consistent with other reviews on uremic bleeding published recently.1,2 As in our Review, those articles do not mention the potential therapeutic role of drugs, such as tranexamic acid, that interrupt fibrinolysis.1,2
We respectfully disagree that the available evidence shows tranexamic acid to be more effective than the commonly used approaches that we reviewed and proposed in our algorithm. Some reports of the few cases or studies of tranexamic acid did not indicate the route of administration. When details of the regimen were provided, intravenous tranexamic acid was administered initially followed by several weeks of oral tranexamic acid, or oral tranexamic acid was used alone for several weeks or months.3,4,5,6,7 Oral tranexamic acid is not available in the US (and possibly in other places in the world) and, therefore, is not an intervention that is commonly considered by physicians in these areas. Intravenous tranexamic acid might, however, be useful in the acute setting, especially if other options do not elicit the desired response.
As pointed out by Mezzano et al., most of the studies used bleeding time as an end point to assess bleeding risk. We agree that this parameter has limitations, which is why we did not directly promote its use or incorporate it into our decision-making algorithm.
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Mezzano D et al. (1999) Tranexamic acid inhibits fibrinolysis, shortens the bleeding time and improves platelet function in patients with chronic renal failure. Thromb Haemost 82: 1250–1254
Vujkovac B et al. (1998) Successful treatment of bleeding from colonic angiodysplasias with tranexamic acid in a hemodialysis patient. Am J Kidney Dis 31: 536–538
Vujkovac B et al. (2000) Treatment of subdural and intracerebral haematoma in a haemodialysis patient with tranexamic acid. Nephrol Dial Transplant 15: 107–109
Sabovic M et al. (2003) Tranexamic acid is beneficial as adjunctive therapy in treating major upper gastrointestinal bleeding in dialysis patients. Nephrol Dial Transplant 18: 1388–1391
Sabovic M et al. (2005) The effect of long term, low-dose tranexamic acid treatment on platelet dysfunction and haemoglobin levels in haemodialysis patients. Thromb Haemost 94: 1245–1250
The authors declare no competing financial interests.
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Hedges, S., Dehoney, S., Hooper, J. et al. Authors’ response to “Tranexamic acid and uremic bleeding: evidence-based treatment recommendations”. Nat Rev Nephrol 3, E3 (2007). https://doi.org/10.1038/ncpneph0529