Change of microparticle procoagulant activity in patients with acute intracerebral hemorrhage

Abstract

Objective To study the procoagulant activity of microparticles (MP) in patients with acute in-tracerebral hemorrhage (ICH) and to evaluate the correlation between procoagulant activity of MPs and disease out-come. Method From August 2006 through August 2008, 83 consecutive patients with history of hypertension ad-mitted for spontaneous basal ganglia hemorrhage including 54 male and 29 female, aged (60.9±9.7) years ranged from 41 to 79 years, were enrolled into this study. The control group was consisted of 30 age- and sex-matched (P= 0.429; P = 0.415) patients admitted for mild soft tissue injury. Patients with history of head trauma or previ-ous stroke, under the antiplatelet or anticoagulant medication, severe infection, or presence of previous cerebrovas-cttlar disease were excluded. Venous blood sample was kaken within the first 24 hours after disease onset. The MPs procoaulant potential was measured with a prothrombinase assay, and the levels of IL-6,TNF-α, D-dimer (DD)and thrombin-antithrombin Ⅲ complex (TAT) in plasma were measured with enzyme-linked immunosorbent assay. The multivariate analysis was made with forward stepwise logistic regression to determined the predictors of one. month mortality. The plasma levels of MPs were compared between ICH group and control group, between patients with intraventricular hemorrhage (IVH) and those without IVH,and between survivors and non-survivors with the Mann-Whitney U-test. The Spearman' s rank correlation coefficient was used to analyze the correlations between the plasma levels of MPs and ICH volume, Glasgow coma scale (GCS), and plasma levels of IL-6, TNF-α, DD and TAT. A receiver operating characteristic curve (ROC curve) identified the plasma MPs cutoff levels that predicted one-month mortality of patients. Under ROC curve, z statistic analysis was used to compare the area under curves (AUCs) between plasma IMPs and Glasgow coma scale, ICH volumes, and plasma levels of IL-6, TNF-α, DD and TAT for one-month mortality. Results Thirty-six patients (43.4%) died of ICH in a month. The multivariate analyses sorted out the GCS (odds ratio = 0.558, 95%CI:0.367-0.850, P = 0.007), Hematoma volume (odds ratio= 1.061, 95%C1:1.012- 1.113, P = 0.015) and IVH (odds ratio= 5.537, 95%CI:1.035-29.629, P = 0.045) as the independent pcedictors for one-week mortality. The MPs procoagulant activity in the ICH group (6.72±3.26 U/mL) was significantly higher than that in control group (1.84±0.82) U/mL (P = 0.000). The IMPs procoagulant activity in the non-survival group (8.51±3.45) U/mL was significantly higher than that in the survival group (5.35±2.33) U/mL (P = 0.000). The MPs procoagulant activity in the IVH group (7.66±3.39) U/mL was significantly higher than that in the non-lVH group (5.36±2.53) U/mL (P = 0.001). The MPs procoagulant activity was highly associated with GCS scores (r = -0.690, P = 0.000), ICH volumes (r =0.590, P = 0.000), and plasma IL-6 (r = 0.465, P = 0.015), TNF-α (r = 0.464, P = 0.016), DD(r= 0.567, P = 0.001) and TAT(r = 0.469, P = 0.014) in ICH. The ROC curve identified cutoff levels of MPs procoagulant activity to be 7.47 U/mL that predicted one-month mortality of patients with high sensitivity (77.8%) and specificity values (76.6%). Areas under curves (AUCs) of MPs procoagulant activity (AUC =0.825±0.048) were significantly larger than those of plasma IL-6 (AUC = 0.685±0.060, P = 0.042), TNF-α(AUC = 0.681±0.060, P =0.036) and TAT (AUC = 0.644±0.062, P =0.008).The AUCs ofMPs procoag-ulant activity were larger than those of plasma DD (AUC = 0.743±0.056), but this difference was not statistical significance (p = 0.226). Conclusions The procoagulant activity of MPs may contribute to the pathophysiology of ICH. The propcoagulant activity of MPs after spontaneous onset of ICH seems to correlate with clinical outcome in these patients. Its procoagulant activity can be used as an useful clinical marker for evaluating the prognosis of ICH. Key words: Microparticles; Intracerebral hemorrhage; Prognosis; Pathogenesis; Apoptosis