The effectiveness of low-dose desmopressin in improving hypothermia-induced impairment of primary haemostasis under influence of aspirin - a randomized controlled trial

Pui Yee Tsui, Chi Wai Cheung, Yvonne Lee, Susan Wai Sum Leung, Kwok Fu Jacobus Ng, Pui Yee Tsui, Chi Wai Cheung, Yvonne Lee, Susan Wai Sum Leung, Kwok Fu Jacobus Ng

Abstract

Background: Mild hypothermia (34-35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers.

Methods: Sixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively.

Results: Collagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34-39.74 %, p = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5-20.85 %, p < 0.001) and 8.0 % (95 %CI 6.38-10.04 %, p = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32-36.49 %, p = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C (p = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram (p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only (p = 0.011).

Conclusion: It was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period.

Trial registration: ClinicalTrials.gov: NCT01382134.

Figures

Fig. 1
Fig. 1
Flow diagram of patient recruitment
Fig. 2
Fig. 2
Levels of 11-dehydro thromboxane B2 in aspirin group and placebo group. () represents aspirin group and () represents placebo group. p < 0.001
Fig. 3
Fig. 3
Effects of desmopressin on PFA-100® closure times ADPCT (a) and EPICT (b) of aspirin group at 37 °C. Bars represent control (normal saline) (), desmopressin 1.5 microgram () and 5 microgram () respectively. * indicates p < 0.05. Error bars indicate SD. ADPCT: Collagen/adenosine diphosphate closure time. EPICT: Collagen/adrenaline closure time
Fig. 4
Fig. 4
Effects of desmopressin on PFA-100® closure times ADPCT (a) and EPICT (b) of aspirin group at 32 °C. Bars represent control (normal saline) (), desmopressin 1.5 microgram () and 5 microgram () respectively. * indicates p < 0.05. Error bars indicate SD. ADPCT: Collagen/adenosine diphosphate closure time. EPICT: Collagen/adrenaline closure time
Fig. 5
Fig. 5
Effect of different doses of desmopressin on PFA-100® on ADP closure time (ADPCT (a)) at 32 °C (∎) and 37 °C (▽), as well as adrenaline closure time (EPICT (b)) at 32 °C (●) and 37 °C (△) respectively. * indicates p < 0.05. Error bars indicate SD

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