Low‐dose desmopressin improves hypothermia‐induced impairment of primary haemostasis in healthy volunteers*

Abstract

SummaryMild hypothermia (34-35°C) increases peri-operative blood loss. We have previously demonstrated the beneficial effect of in vitro desmopressin on impairment of primary haemostasis associated with hypothermia. This study evaluated subcutaneous desmopressin in 52 healthy volunteers, randomly assigned to receive either normal saline or desmopressin 1.5, 5 or 15 lg (with 13 in each group). Blood samples were collected before and 2 h after drug administration and incubated at 32 and 37°C. Platelet function analyser PFA-100 Ò closure times were measured. Hypothermia at 32°C prolonged mean (95% CI) closure times (for adenosine diphosphate ⁄ collagen by 11.3% (7.5-15.2%) and for adrenaline ⁄ collagen by 16.2% (11.3-21.2%); these changes were reversed by desmopressin. A very small dose was found to be effective (1.5 lg); this dose did not significantly change closure times at 37°C, but fully prevented its prolongation at 32°C. Subcutaneous desmopressin prevents the development of hypothermia-induced impairment of primary haemostasis.

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

“…Our data showed that at the doses used in this study, there was no significant increase in vWF release. This is in concordance with our previous studies where low dose desmopressin corrects primary haemostasis impairment without causing an increase in vWF levels [17]. In an in vitro setting, the absence of endothelial cells means that there will not be vWF release accounting for the improvement in primary haemostasis.…”

“…The design of this study was based on our previous studies on evaluation of hypothermia-induced primary haemostasis impairment and the effect of desmopressin on such impairment [14, 17]. In this study, it was shown once again the baseline ADPCT and EPICT were significantly prolonged in presence of hypothermia.…”

“…In our previous studies, we have shown that low dose subcutaneous desmopressin could improve hypothermia-induced impairment in primary haemostasis [17]. It was shown that the dosage required could be as low as 1.5 microgram, much lower than the standard dose of 15 microgram used in treating platelet dysfunction associated with uraemia or cirrhosis.…”

Management of bleeding and coagulopathy following major trauma: an updated European guideline

“…Nevertheless, desmopressin has been recommended in patients treated with platelet inhibitors, suffering from intracerebral bleeding [438,453] and in trauma patients with von Willebrand disease [466]. Interestingly, desmopressin prevents the development of hypothermia-induced impairment of primary haemostasis [467] and significantly increases platelet aggregation during hypothermia and acidosis [468]. …”

Correction of hypothermic and dilutional coagulopathy with concentrates of fibrinogen and factor XIII: an in vitro study with ROTEM

“…A study from 1994 measuring activated partial thromboplastin time found additional but not synergistic effects of hypothermia and haemodilution with a crystalloid [ 5 ]. Possible explanations for the observed synergy between hypothermia and HES, may be that both hypothermia [ 2 , 26 ] and HES [ 27 , 28 ] have direct effects on platelets, and that also plasma coagulation activity is decreased during both hypothermia [ 2 ] and haemodilution [ 29 ]. Platelet activation is very important for the thrombin burst associated with propagation of coagulation, which may explain why the ROTEM parameters CFT and AA were particularly affected by the combination of HES-haemodilution and hypothermia.…”