Monday, December 13, 2010

Q: 54 year old male with ESRD (End Stage Renal Disease) admitted to ICU post-operatively. Patient has significant "oozing" from surgical site. Surgeon ruled out surgical bleed. You corrected coagulopathy and gave one dose of DDAVP (Desmopressin) with only partial response. Hematology recommends IV Estrogen. What is the dose?


Answer: Estrogens improve bleeding time and decrease clinical bleeding significantly particularly in uremic patients. The dose is 0.6 mg/kg IV over 30 minutes per day. It can be repeated upto 5 days.The time to onset of action is about 6 hours. Estrogens have also been successfully used in patients with GI bleed in patients with uremic platelet dysfunction.

Mechanism of action: It has been postulated that the hormones decrease production of L-arginine, which is a precursor of NO. By decreasing NO concentrations, which seem to be higher in uremia, there is less guanylyl cyclase stimulation and less production of cGMP. This potentially leads to increased production of TxA2 and ADP, which are crucial contributors to formation of platelet plugs. Also estrogen decrease antithrombin III and protein S levels, and increase factor VII concentrations, might contribute to the therapeutic effect in this clinical situation.

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