The Effects of Hypothermia and Acidosis on Coagulation During Treatment With Rivaroxaban Measured With Rotational Thromboelastometry (ROTEM)

Non-vitamin K oral anticoagulants (NOACs) are widely used as prophylaxis against ischaemic stroke in patients with atrial fibrillation and have replaced vitamin K antagonists (VKA) in many case. Compared to the latter they have demonstrated reduced incidence of stroke, all-cause mortality, and a reduced risk of bleeding, except for gastrointestinal bleeding. According to guidelines from the European Society of Cardiology it is recommended that patients with atrial fibrillation (AF) and adequate CHA¬2DS2-VASc score (2 for men and 3 for women) preferentially are treated with NOAC rather than VKA, except in cases with significant mitral stenosis or mechanical heart valves. Both the prevalence of patients with AF and of patients treated with NOAC have increased in the last decade.

The NOACs available in clinical practice include one thrombin inhibitor (dabigatran) and three factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) [3]. These drugs drive a patient's blood further from clotting toward bleeding, and managing this tendency is important for clinicians during haemorrhage or coagulopathy, which both occur e.g., in the setting of trauma.

Trauma is a significant cause of mortality worldwide and among patients suffering from traumatic injuries the leading cause of preventable death is uncontrolled bleeding. Coagulopathy has been shown to contribute to bleeding in as many as one third of trauma cases, predicting organ failure and mortality. This trauma induced coagulopathy (TIC) is associated with hypothermia and acidosis. To prevent further coagulopathy current trauma guidelines recommend that both body temperature and pH are kept within normal reference range. Coagulopathy, hypothermia, and acidosis have collectively come to be known as the 'lethal triad'.

For trauma patients, hypothermia is associated with larger usage of blood products and increased mortality/morbidity. How hypothermia affects haemostasis and blood loss has been investigated in several studies. Hypothermia has been shown to worsen the function of secondary haemostasis through temporary reduction of fibrinogen synthesis and inhibition of the initiation phase of thrombin generation.

Hypothermia and acidosis often coexist and body temperatures of less than 35 degrees Celsius have been shown to correlate with acidosis. The effects of hypothermia and acidosis on whole blood coagulation in vitro, have previously been studied using Rotational thromboelastometry (ROTEM). For hypothermia, a significant increase in coagulation time (CT) and clot formation time (CFT) was observed, while acidosis alone did not produce these significant effects. Interestingly however, combining acidosis with hypothermia worsened the effects of the latter, providing increases in CT and CFT at higher temperatures, and a synergistic effect between acidosis and hypothermia could be demonstrated.