Lower Coated-platelet Potential is Associated with Major Hemorrhagic Complications After Discharge in Patients with Non-lacunar Brain Infarction
Estevao Ribeiro1, Angelia Kirkpatrick2, Philion Gatchoff1, Chao Xu3, Andrea Vincent4, Eleanor Mathews1, Leslie Guthery1, George Dale2, Calin Prodan1
1Neurology, 2Medicine, 3Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, 4Cognitive Research Center, University of Oklahoma
Objective:
To examine the relationship between coated-platelet levels and the occurrence of major hemorrhagic complications following discharge in non-lacunar ischemic stroke. 
Background:
Coated-platelets, a subset of highly procoagulant platelets observed upon dual-agonist stimulation with collagen and thrombin, represent approximately 30% of the entire platelet population in healthy controls. Coated-platelet levels are elevated in patients with non-lacunar ischemic stroke; among these patients, those with lower levels are at increased risk for major hemorrhagic complications during the acute stroke period. We now investigate the relationship between coated-platelets and major bleeding complications following acute stroke.
Design/Methods:
Coated-platelet levels were assayed within 96 hours in 271 consecutive patients with non-lacunar stroke. Major hemorrhagic complication was defined as ICH or major extracranial bleeding (drop in hemoglobin of ≥2 points), occurring within 12 months. Individuals performing the coated-platelet assays were not aware of clinical diagnoses. Optimal cut-points for coated-platelets were identified using recursive partitioning.
Results:
Coated-platelet levels (mean±SD) for all patients were 41.9±13.7%. Major bleeding complications were present in 20 (7%) cases.  Coated-platelet platelet levels were lower in patients with as compared to those without hemorrhagic complications (27.6±9.4% vs 43.0±13.5%, p<0.001). A 10% (absolute) increase in coated-platelet levels was associated with a 60% decrease in the odds of hemorrhagic complications (95% CI: 40-73%). The optimal split in coated-platelets for predicting hemorrhagic complications was 36.5%.  Hemorrhagic complications were present in 1/173 patients (0.6%) with coated-platelets ≥36.5%, and in 19/98 patients (19%) with coated-platelets <36.5%. ROC analysis showed an AUC of 0.83 for coated-platelets to predict hemorrhagic complication, with sensitivity of 95% and specificity of 68%. Comorbidities and discharge medications did not confound the association between coated-platelets and hemorrhagic complications.
Conclusions:

Lower platelet procoagulant potential is associated with major hemorrhagic complications following the acute stroke. These findings support a role for procoagulant platelets as a potential risk stratification tool in stroke.

10.1212/WNL.0000000000206008