Marked Temperature Dependence of the Platelet Calcium Signal Induced by Human von Willebrand Factor

Abstract

Interaction of von Willebrand factor (vWF) with the platelet is essential to hemostasis when vascular injury occurs. This interaction elevates the intracellular free calcium concentration ([Ca2+]i) and promotes platelet activation. The present study investigated the temperature dependence of vWF-induced [Ca2+]i signaling in human platelets. The influence of temperature can provide invaluable insight into the underlying mechanism. Platelet [Ca2+]i was monitored with Fura-PE3. Ristocetin-mediated binding of vWF induced a transient platelet [Ca2+]i increase at 37°C, but no response at lower temperatures (20°C to 25°C). This temperature dependence could not be attributed to a reduction in vWF binding, as ristocetin-mediated platelet aggregation and agglutination were essentially unaffected by temperature. Most other platelet agonists (U-46619, -thrombin, and adenosine 5′-diphosphate [ADP]) induced a [Ca2+]isignal whose amplitude did not diminish at lower temperatures. The [Ca2+]i signal in response to arachidonic acid, however, showed similar temperature dependence to that seen with vWF. Assessment of thromboxane A2 production showed a strong temperature dependence for metabolism of arachidonic acid by the cyclo-oxygenase pathway. vWF induced thromboxane A2production in the platelet. Aspirin treatment abolished the vWF-induced [Ca2+]i signal. These observations suggest that release of arachidonic acid and its conversion to thromboxane A2 play a central role in vWF-mediated [Ca2+]i signaling in the platelet at physiological temperatures.

Contemporary perioperative care strategies

“…Mild hypothermia (34–36°) occurs in about 30–70 per cent of surgical patients145, 146, accounting for increased morbidity, hospital length of stay and costs147. Coagulopathy induced by hypothermia leads to impairment of thrombocyte activity148 and inactivation of coagulation factors149, all of which increase blood loss and thus the requirement for allogeneic blood transfusion (ABT)150. Of note, most routine coagulation tests obtained during surgery are performed at 37 °C, irrespective of the patient's actual core temperature; their results may thus not reflect the ongoing coagulopathy.…”

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

“…Mild hypothermia (34–35 °C) is known to cause platelet dysfunction [1–3]. Increased surgical bleeding and increased transfusion requirements have been reported in both cardiac and non‐cardiac surgery at this temperature range [4–7].…”

Relationship Between Hypothermia and Blood Loss in Adult Patients Undergoing Open Lumbar Spine Surgery

“…The mechanism by which hypothermia increases blood loss may be related to a multifactoral coagulopathy precipitated by subphysiologic body temperature. [9][10][11][12][13][14][15][16][17][18] Hypothermia has been shown to strongly inhibit multiple steps in the coagulation cascade, progressively prolonging the prothrombin and partial thromboplastin times with increasing hypothermia. [9][10][11] Hypothermia also appears to disrupt thrombin and fibrinogen synthesis.…”

“…12 Furthermore, there seems to be an inhibition of platelet activation through multiple mediators that is reversible with increases in temperature. [13][14][15] Although hypothermia has been shown to disrupt platelet function, 11,16 coagulation protease activity is inhibited 16 and platelet aggregation is increased 17 Therefore, total blood loss may have been artificially decreased in these patients as a result of the lack of suction continuing to pull blood from the surgical site, potentially confounding their select results.…”

“…The authors of the study also noted a lack of quality evidence supporting minimization of intraoperative hypothermia as a means of decreasing intraoperative blood loss and its related complications. 3 Clinical 4-8 and basic science [9][10][11][12][13][14][15][16][17][18][19][20] research supports the association between core hypothermia and increased surgical blood loss. Mild hypothermia, defined as core body temperature between 34°C and 36°C, has been shown to increase blood loss and transfusion requirements in patients undergoing total hip replacement.…”