Transdermal estradiol for the management of refractory uremic bleeding

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The efficacy and thrombogenicity of transdermal estradiol in the management of refractory uremic bleeding in adults are examined.


Platelet dysfunction from chronic kidney disease may induce uremic bleeding. This type of bleeding may involve the skin, oral and nasal mucosa, gingivae, respiratory system, and gastrointestinal or urinary tract. While the mainstay of treatment for uremic bleeding primarily involves dialysis and use of prohemostatic agents such as desmopressin and erythropoiesis-stimulating agents, certain patients may experience bleeding refractory to these interventions. In this clinical scenario, a weak conditional recommendation (grade 2C) supporting transdermal estradiol as a therapy of last resort exists. Limited data suggest that transdermal estradiol may reduce bleeding time and transfusion requirements in dialysis patients with recurrent episodes of hematochezia, gastrointestinal telangiectasia, and hematomas. The management of uremic bleeding will require long-term therapy, and case reports have documented the safe use of transdermal estradiol for up to 25 months. Oral conjugated estrogens increase the risk of deep vein thrombosis in women; however, the transdermal route of administration has been associated with a lower incidence of venous thromboembolism and stroke relative to oral estrogen and, in some studies, its associated risk of thrombosis is not significantly different when compared with placebo.


Patients who are refractory to routine interventions for uremic bleeding may benefit from transdermal estrogen despite the limited data. Extended therapy with low-dose transdermal estrogen (≤50 μg daily) may provide a hemostatic benefit that outweighs thrombotic risk.

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