NCT01382134

Effect of Aspirin, Hemodilution and Desmopressin on Platelet Dysfunction

Effect of Aspirin, in Vitro Hemodilution and Desmopressin on Platelet Dysfunction Associated With Mild Hypothermia in Healthy Volunteers

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Study hypothesis: Desmopressin (DDAVP) can improve platelet function under influence of aspirin, hemodilution and mild hypothermia Mild hypothermia (34-35oC) is known to cause platelet dysfunction. This could lead to increased surgical bleeding and increased transfusion requirement during surgery. Although this hypothermia-induced platelet dysfunction seems to be reversible with warming, this is not always possible or desirable. Desmopressin (DDAVP) is a drug which has proven efficacy in improving platelet function in uraemic and cirrhosis patients, and in reducing blood loss in selected surgeries. In a recent study, we have found that subcutaneous injection of 1.5 mcg (1/10th the usual dose) is already sufficient to fully reverse the platelet dysfunction seen at 32oC. We have demonstrated in another study that prolongation of the bleeding time in a 20% hemodiluted sample predicts increased postoperative bleeding after total knee replacement. We have therefore designed this study as a follow up to our last two studies on DDAVP and hypothermia, to investigate whether hemodilution affects hypothermia induced platelet dysfunction and the response to DDAVP. In addition, another common cause of perioperative platelet dysfunction is the intake of COX inhibitors, particularly aspirin by patients. Therefor the effect of aspirin on hypothermia induced platelet dysfunction and the response to DDAVP, will also be investigated.

Detailed description

Mild hypothermia (34-35oC) is known to cause platelet dysfunction. Increased surgical bleeding and increased transfusion requirement at this temperature range has been reported in both cardiac and noncardiac surgeries. This degree of hypothermia is common during any general anaesthesia, particularly during surgeries which invlove major fluid shift and large area exposure of patients, e.g. trauma and burn patients. Although this hypothermia-induced platelet dysfunction seems to be reversible with warming, warming is not always possible or desirable. During major trauma or burn surgery, surface warming of patient is practically difficult. During surgeries with major blood loss and fluid shift, heat loss usually occurs at a rate that is more rapid than any warming device can catch up with. During neurosurgery, cooling may be beneficial to neurological outcome. Desmopressin (DDAVP) is a drug which has proven efficacy in improving platelet function in uraemic and cirrhosis patients, and in reducing blood loss in selected surgeries. In a previous in vitro study, we have found that desmopressin significantly improves platelet function at 32oC. The improvement is seen with a very low concentration of desmopressin in vitro, which suggests that probably doses much smaller than the "standard dose" (15 mcg slow iv or subcutaneous) may be useful. In keeping with this in vitro study, in a more recent study, we have found that subcutaneous injection of 1.5 mcg (1/10th the usual dose) is already sufficient to fully reverse the platelet dysfunction seen at 32oC. One of the limitations of our previous two studies is that the degree of platelet dysfuction observed at 32oC is relatively mild, with only around 20% prolongation of the closure times on the PFA-100® platelet function analyser. The clinical significance of such prolongation remains uncertain. However, we have demonstrated previously in another study that prolongation of the closure time to \>188 sec in a 20% hemodiluted sample predicts increased postoperative bleeding after total knee replacement. We have therefore designed this study as a follow up to our last two studies on DDAVP and hypothermia, to investigate whether hemodilution affects hypothermia induced platelet dysfunction and the response to DDAVP. In addition, another common cause of perioperative platelet dysfunction is the intake of COX inhibitors, particularly aspirin by patients. Therefor the effect of aspirin on hypothermia induced platelet dysfunction and the response to DDAVP, will also be investigated.

Conditions

• Platelet Dysfunction
• Hemodilution
• Mild Hypothermia
• NSAID
• Desmopressin

Interventions

Type	Name	Description
DRUG	Aspirin, desmopressin	Aspirin 100mg daily for 3 days Desmopressin 15 microgram subcutaneously once only
DRUG	Placebo, desmopressin	Placebo 1 tab daily for 3 days Desmopressin 15 microgram subcutaneously once only

Timeline

• Start date: 2011-07-01
• Primary completion: 2012-07-01
• Completion: 2013-09-01
• First posted: 2011-06-27
• Last updated: 2013-11-15

Locations

1 site across 1 country: China