Acute hemorrhagic complications are associated with lower coated‐platelet levels in non‐lacunar brain infarction

Abstract

To cite this article: Prodan CI, Stoner JA, Dale GL. Acute hemorrhagic complications are associated with lower coated-platelet levels in nonlacunar brain infarction. J Thromb Haemost 2015; 13: 2233-9.Summary. Background: Coated platelets are procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. Objective: To investigate whether acute hemorrhagic complications occurring during the initial hospital admission for non-lacunar ischemic stroke are associated with lower coated-platelet levels. Patients/ methods: Coated-platelet levels were determined in 385 consecutive patients with non-lacunar stroke. Hemorrhagic complications were defined as either intracranial hemorrhage or significant extracranial bleeding (drop in hemoglobin of ≥ 2 g dL À1). The rate of acute hemorrhagic complication was compared among subjects categorized into tertiles of coated-platelet levels using an exact Cochrane-Armitage trend test. Logistic regression was used to estimate the adjusted odds of hemorrhagic complication associated with coated-platelet levels. Results: Hemorrhagic complications were present in 15 (3.9%) cases. Of these, four had intracranial hemorrhage and 11 had extracranial hemorrhage. The occurrence of hemorrhagic complications differed among the coatedplatelet tertiles: 10.2% for the first tertile (coated-platelet levels < 35.5%), 1.5% for the second tertile and 0% for the third tertile (coated-platelet levels ≥ 47.5%, trend test). Logistic regression showed that the odds of hemorrhagic complication in those with levels < 35.5% were 14.59 times the odds for patients with levels ≥ 35.5% (95% CI: 3.24-65.7). Conclusions: Lower levels of procoagulant platelets are associated with acute hemorrhagic complications following non-lacunar ischemic stroke. These results suggest a role for coated-platelets in risk/ benefit assessment in the early stages of stroke.

Increased platelet procoagulant potential predicts recurrent stroke and TIA after lacunar infarction

“…Specifically, coated‐platelet levels are increased in patients with non‐lacunar stroke, in particular in those with large‐artery atherosclerosis, and elevated levels (>40%) are associated with recurrent cerebral infarction . However, lower coated‐platelet levels were observed in non‐lacunar stroke patients with imaging evidence of early hemorrhagic transformation within the infarction area (mean 29.1%) and in those with the highest incidence of acute hemorrhagic complications occurring during their initial admission for stroke (<35.5%) …”

“…17,19 However, lower coated-platelet levels were observed in non-lacunar stroke patients with imaging evidence of early hemorrhagic transformation within the infarction area (mean 29.1%) 32 and in those with the highest incidence of acute hemorrhagic complications occurring during their initial admission for stroke (<35.5%). 39 In sharp contrast to ischemic stroke, lower levels of coated-platelets were reported in intracerebral hemorrhage, including an increased risk for mortality noted at levels < 27.5%, 40 in severe hemophilia patients with increased bleeding phenotype, 41 and in human and animal studies focused on bleeding diatheses. 37,42 Commonly obtained platelet data, including platelet count, MPV, and aggregation studies were not abnormal in patients or animals with bleeding diatheses, 37,42 suggesting a differential involvement of the procoagulant and aggregation properties of platelets.…”

Levels of procoagulant microparticles expressing phosphatidylserine contribute to bleeding phenotype in patients with inherited thrombocytopenia

“…In our study, we observed a distinct independent platelet population in response to collagen stimulation, defined as our procoagulant platelet population. As mentioned, procoagulant platelets such as coated platelets have been investigated mainly in brain infarction and intracranial haemorrhage, in which low CP levels are associated with microbleeds and acute haemorrhagic complications in nonlacunar stroke [12,33] and bleeding volume in patients with spontaneous intracerebral haemorrhage [13]. In patients with essential thrombocythemia, nontreated patients have lower coated platelet levels than hydroxyurea-treated patients and controls, which could be a contributing factor in essential thrombocythemia platelet dysfunction [14].…”

“…It has been suggested that all these different subpopulations form a spectrum of a single procoagulant platelet type [10,11] and it is recognized that collagen is the single most important agonist in the formation of procoagulant platelets [10]. Clinical investigations of procoagulant platelets pertain almost exclusively to coated platelets, which have been investigated in conditions such as stroke, spontaneous intracerebral haemorrhage, essential thrombocythemia, diabetes mellitus, Alzheimer's disease, haemophilia and bleeding diathesis [12][13][14][15][16][17][18]; however, for other procoagulant platelet subpopulations, clinical data are very limited and more data are needed to establish the clinical importance of procoagulant platelets.…”

Procoagulant Platelets

“…In recent years, however, after the demonstration of a procoagulant platelet being predictive of bleeding or ischemic complications in patients with coronary artery disease, brain hemorrhage, traumatic brain injury, stroke, etc. [35][36][37][38][39][40][41][42] it is gaining more and more recognition. The importance of this subpopulation is further highlighted on a novel ex vivo model (which integrates all the core components of hemostasis [43]), where pharmacologic inhibition of platelet transition to a procoagulant state without affecting pro-aggregatory phenotype results in a decreased thrombus stability [44].…”