Effects of Remote Ischemic Preconditioning on the Coagulation Profile of Patients With Aneurysmal Subarachnoid Hemorrhage

Abstract

Animal studies suggest that ischemic preconditioning prolongs coagulation times. Because coagulation changes could hinder the translation of preconditioning into clinical settings where hemorrhage may be an issue, such as ischemic or hemorrhagic stroke, we evaluated the effects of remote ischemic preconditioning (RIPC) on coagulation in patients undergoing RIPC after aneurysmal subarachnoid hemorrhage (SAH). Twenty-one patients with SAH (mean age, 56.3 years) underwent 137 RIPC sessions 2 to 12 days after SAH, each consisting of 3 to 4 cycles of 5 to 10 minutes of lower limb ischemia followed by reperfusion. Partial thromboplastin time (PTT), prothrombin time (PT), and international normalized ratio (INR) were analyzed before and after sessions. Patients were followed for hemorrhagic complications. No immediate effect was identified on PTT (mean pre-RIPC, 27.62 s; post-RIPC, 27.54 s; P = .82), PT (pre-RIPC, 10.77 s; post-RIPC, 10.81 s; P = .59), or INR (pre-RIPC, 1.030; post-RIPC, 1.034; P = .57) after each session. However, statistically significant increases in PT and INR were identified after exposure to at least 4 sessions (mean PT pre-RIPC, 11.33 s; post-RIPC, 12.1 s; P = .01; INR pre-RIPC, 1.02; post-RIPC, 1.09; P = .014, PTT pre-RIPC, 27.4 s; post-RIPC, 27.85 s; P = .092) with a direct correlation between the number of sessions and the degree of increase in PT (Pearson correlation coefficient = 0.59, P = .007) and INR (Pearson correlation coefficient = 0.57, P = .010). Prolonged coagulation times were not observed in controls. No hemorrhagic complications were associated with the procedure. RIPC by limb ischemia appears to prolong the PT and INR in human subjects with SAH after at least 4 sessions, correlating with the number of sessions. However, values remained within normal range and there were no hemorrhagic complications.