Abstract
Background:
Several animal studies have suggested that ischemic preconditioning (IP) may prolong the coagulation times of the subjects treated. This presents a potential challenge for the translation of the technique into clinical settings as abnormal coagulation profiles may negatively affect the outcomes of IP in patients with ischemic stroke or intracerebral hemorrhage. This study evaluates the immediate and late effects of remote ischemic preconditioning (RIPC) on coagulation in patients enrolled in two trials of RIPC after aneurysmal subarachnoid hemorrhage (SAH).
Methods:
21 patients with SAH (mean age 56, range 38-81) underwent 137 RIPC sessions, 2-12 days following SAH. RIPC was induced by 3-4 cycles of 5-10 minutes of lower limb ischemia followed by reperfusion using a blood pressure cuff inflated to a pressure of 200 mmHg or 30 mm Hg above the systolic blood pressure. Vascular occlusion was confirmed with Doppler. Blood samples for partial thromboplastin time (PTT), prothrombin time (PT), and INR were collected before and after each session. Patients were followed for potential hemorrhagic complications.
Results:
The coagulation profile was analyzed in 47 samples. No significant immediate effect was identified on PTT (mean pre RIPC 27.6 sec vs. post RIPC 27.5 sec, p=0.8), PT (mean pre RIPC 10.8 sec vs. post RIPC 10.8 sec, p=0.6) or INR (mean pre RIPC 1.03 vs. post RIPC 1.034, p=0.6) after each session. However, a significant increase of PT and INR but not PTT was identified after exposure to the complete series of at least 4 sessions (mean PT pre RIPC 11.3 sec vs. post RIPC 12.1, p=0.01; mean INR pre RIPC 1.02 vs. post RIPC 1.09, p=0.014, mean PTT pre RIPC 27.4 sec vs. post 27.85, p=0.092). There was also a significant direct correlation between the number of sessions and the increase in PT (Pearson=0.59, p=0.007) and INR (Pearson=0.57, p=0.01). Average follow up of 26 days demonstrated no hemorrhagic complications associated with RIPC.
Conclusions:
RIPC by limb ischemia appears to prolong the PT and affect INR in human subjects with subarachnoid hemorrhage after at least 4 sessions, a change that correlates with the number of sessions. However, PT and INR values remained within normal range and there were no hemorrhagic complications.