Effect of Aspirin, Hemodilution and Desmopressin on Platelet Dysfunction
Condition: Platelet Dysfunction; Hemodilution; Mild Hypothermia; NSAID; Desmopressin
MeSH terms: Blood Platelet Disorders; Hypothermia
Study type: Interventional

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.
    

Intervention name(s): Aspirin, desmopressin; Placebo, desmopressin
Intervention type(s): Drug; Drug
Intervention description(s): Aspirin 100mg daily for 3 days Desmopressin 15 microgram subcutaneously once only; Placebo 1 tab daily for 3 days Desmopressin 15 microgram subcutaneously once only
Intervention MeSH terms: Aspirin; Deamino Arginine Vasopressin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Platelet dysfunction; Hemodilution; Mild hypothermia; NSAID; Desmopressin