A Stroke Registry Data on the Use of Intravenous Recombinant Tissue Plasminogen Activator in Stroke of Unknown Time of Onset.

BACKGROUND: Stroke of unknown time of onset (SUTO) constitutes one fifth of all ischemic stroke admissions, and routine use of intravenous recombinant tissue plasminogen activator (IV rtPA) is recommended only in patients with a symptom onset time of less than 4.5 hours. There are limited data on clinical outcome in patients with SUTO versus patients with symptoms onset less than 4.5 hours from onset time. We hypothesized that efficacy and safety outcomes of IV rtPA therapy in selected SUTO patients are comparable to those with known onset time. METHODS: We compared 90 days' modified Rankin Scale (mRS), rates of symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, and death due to sICH between 3 groups treated with IV rtPA: SUTO, 3 hours or less, and 3.0-4.5 hours from prospective patient admissions between April 1, 2012, and July 31, 2013. RESULTS: There were 65 participants in the SUTO group, 186 in the 3 hours or less group, and 51 in the 3.0-4.5 hours group. In-hospital mortality rates were 14.5%, 13.5%, and 11.8%, respectively. sICH risks were 1.5%, 1.6%, and 5.8%, and death rates due to sICH were 0%, 1.1%, and 1.9%, respectively. Ninety days' odds of excellent clinical outcome (mRS score 0-1) were not different between the SUTO group (odds ratio [OR] 1.14, 95% confidence interval [CI]: .63-2.10), the 3 hours or less group (OR .87, 95% CI: .48-1.60), and the 3.0-4.5 hours group (OR .79, 95% CI: .48-1.60) (P = .82). CONCLUSION: Thrombolytic therapy outcome in SUTO is not different from in-license use in our patient population. There is an urgent need to include this patient group in ongoing randomized multicenter trials.

Clinical and laboratory predictors of deep vein thrombosis after acute stroke.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication of acute stroke, but the new incidence in the era of improved specialist input in stroke care is yet unknown. The models for VTE diagnosis is well established, but prediction models to target at-risk patients for pharmacological prophylaxis is lacking and requires further research, particularly in the aftermath of acute stroke. OBJECTIVES: To predict DVT after acute stroke using markers of haemostatic activation and stroke severity scores. METHODS: We examined the clinical utility of laboratory factors such as thrombin generation, D-dimer, fibrinogen alongside clinical factors (National Institute of Health Stroke Scale and Barthel Index) in the prediction of asymptomatic DVT, among 92 consecutively admitted patients. RESULTS: One in five patients (19.6%) had objectively confirmed DVT (6 proximal, 12 distal). Thrombolytic therapy did not protect against DVT, with 21% (6/29) of patients treated with r-tPA went on to develop DVT. Thrombin generation and fibrinogen had no clinical utility, but D-dimer at baseline and week 2 had high clinical potential in the prediction of asymptomatic DVT (2425ng/mL versus 1010ng/mL; p=0.001) and (2240 Vs 970ng/mL; p<0.001) respectively. Patients with DVT had worse stroke severity, and are functionally less able, with lower Barthel index (p=0.05), and high National Institute of Health Stroke Score (p=0.07). CONCLUSION: Thrombolytic therapy and specialist stroke intervention does not protect against DVT risk. D-dimer concentration within 48h of acute stroke is independently associated with development of DVT. This observation would require confirmation in a large study.

Thrombin Generation in Acute Ischaemic Stroke.

Introduction. Stroke remains a global leading cause of death and disability. Traditional description of plasma biology in the aftermath of acute ischaemic stroke favours development of hypercoagulability, resulting from complex interplay between plasma and endothelial factors. However, no single assay measures the overall global coagulation process. We postulate that thrombin generation would assist in identifying coagulation abnormalities after acute stroke. Aim. To investigate the coagulation abnormalities after acute ischaemic stroke using thrombin generation. Methods. We evaluated thrombin generation, measured with calibrated automated thrombography in stroke of different aetiological types (n = 170) within 48 hours of symptoms onset (baseline) and in the second week (time 2) and in normal healthy volunteers (n = 71). Results. Two-point thrombin generation assays showed prolonged lag time and time to peak at baseline (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7); p = 0.005) and (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7); p = 0.002), respectively, and at time 2 (3.5 (2.9, 4.2) versus 4.0 (3.1, 4.9); p = 0.004) and (5.9 (5.3, 6.6) versus 6.8 (5.8, 7.7) p = 0.05), respectively, in cardioembolic stroke (n = 39), when compared to noncardioembolic stroke (n = 117). The result was reproduced in multiple comparisons between acute ischaemic stroke subgroups and normal healthy volunteers. Endogenous thrombin potential and peak thrombin did not indicate hypercoagulability after acute ischaemic stroke, and thrombolytic therapy did not affect thrombin generation assays. Conclusion. Our findings suggest that thrombin generation in platelet poor plasma is not useful in defining hypercoagulability in acute ischaemic stroke. This is similar to observed trend in coronary artery disease and contrary to other hypercoagulable states.