Sami Tetri

Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study.

Background and Purpose— Warfarin use has rapidly increased with the aging of the population. We investigated the temporal trends in the incidence and outcome of warfarin-related intracerebral hemorrhages (ICHs) in a defined population. Methods— We identified all subjects with first-ever primary ICH during 1993 to 2008 among the population of Northern Ostrobothnia, Finland. The number of warfarin users was obtained from the national register of prescribed medicines kept by the Social Insurance Institution of Finland. We calculated the annual incidence of warfarin-related ICHs, 28-day case fatality, and deaths from the primary bleed. Results— The proportion of warfarin users among the population increased 3.6-fold from 0.68% in 1993 to 2.28% in 2008. Of a total of 982 patients with ICH, 182 (18.5%) had warfarin-related ICH. One-year survival rate after onset of stroke was 35.2% among warfarin users and 67.9% among nonusers. The annual incidence (P=0.062) and 28-day case fatality of warfarin-related ICHs (P=0.002) decreased during the observation period. Warfarin users were older (mean difference 6.6; 95% CI, 5.0 to 8.1; P<0.001) than nonusers. Admission international normalized ratio values above the therapeutic range (2.0 to 3.0) decreased through the observation period, suggesting improved control of anticoagulant therapy over time. Conclusions— The annual incidence and case fatality of warfarin-related ICHs decreased, although the proportion of warfarin users almost quadrupled in our population.

Hypertension and diabetes as predictors of early death after spontaneous intracerebral hemorrhage

OBJECT Previous investigators have suggested that a high mean arterial blood pressure (MABP) and an elevated plasma glucose level at admission are associated with a poor outcome after hemorrhagic stroke. It remains unclear, however, whether hypertension and diabetes are responsible for this effect. High admission MABP and plasma glucose levels may also be markers of other factors such as stroke severity. METHODS The authors retrospectively investigated the role of a high admission MABP and plasma glucose level together with other predictors of early death among 379 nonsurgical patients with spontaneous intracerebral hemorrhages (ICHs) who were admitted to the stroke unit of Oulu University Hospital. RESULTS The 3-month mortality rate was 28%. The patients who died within 3 months of ICH had significantly higher plasma glucose levels and MABPs at admission (p < 0.001). After adjustments for patient sex, age, size and location of hematoma, Glasgow Coma Scale score at admission, presence of intraventricular hemorrhage, history of cardiac disease, and previous use of warfarin, history of diabetes (relative risk 1.61, 95% CI 1.03-2.53, p < 0.05) and high MABP at admission (relative risk 1.01 per mm Hg, 95% CI 1.00-1.02, p < 0.05) remained independent predictors of death 3 months after ICH. A high admission plasma glucose level and history of hypertension were not independent predictors of death. CONCLUSIONS A high MABP at admission was found to be an independent predictor of early death in patients with ICH. History of hypertension was not responsible for the effect. Admission hyperglycemia appeared to be a stress response to the severity of the bleeding, whereas diabetes predicted early death.

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA‐ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies.

Safety of low-dose subcutaneous enoxaparin for the prevention of venous thromboembolism after primary intracerebral haemorrhage

BACKGROUND The risks and benefits of low molecular weight heparins (LMWH) for the prevention of deep-vein thrombosis (DVT) and pulmonary embolism (PE) after intracerebral haemorrhage (ICH) have not been assessed. The few studies on this subject have revealed conflicting results. METHODS We retrospectively evaluated whether subcutaneous enoxaparin (20 mg daily) reduced symptomatic venous complications or caused increased 3-month death rate. We included 407 patients who were admitted to a stroke unit and survived the first two days after onset of ICH. There were 232 patients who received anticoagulant treatment for the prevention of DVT and PE and 175 who did not. RESULTS Despite the fact that the treated patients were in worse clinical condition at the start of the treatment, 3-month death rate was 19% among them compared to 21% among those not receiving anticoagulant therapy. Low-dose subcutaneous enoxaparin (20 mg once daily) induced a significant plasma anti-factor Xa activity 2-3 hours after administration (p=0.018). Haematoma enlargements (33%) occurred in 9% and 7% of the treated and untreated patients, whereas symptomatic venous thromboembolic complications were observed in 3% and 2%, respectively. CONCLUSIONS We did not observe any increased mortality among ICH patients who survived the first 2 days after the onset of ICH and were thereafter treated with enoxaparin 20 mg daily relative to patients remaining untreated. A randomized trial of the effect of LMWH with a higher dose in prevention of venous thromboembolic complications would be indicated.

Head trauma sustained under the influence of alcohol is a predictor for future traumatic brain injury: A long-term follow-up study

Hazardous drinking may result in recurrent head trauma. It was investigated whether head trauma sustained under the influence of alcohol is a predictor of future traumatic brain injury (TBI).

Predictors for Recurrent Primary Intracerebral Hemorrhage A Retrospective Population-based Study

Background and Purpose— Underlying comorbidities, previous strokes, and medication may increase the risk for primary intracerebral hemorrhage (PICH) and its recurrence. The aim of this study was to determine the independent predictors for recurrent PICH. Methods— We identified 961 subjects with first-ever PICH from 1993 to 2008 among the population of Northern Ostrobothnia, Finland. Hospital and death records were reviewed and data on drug use were obtained from the national register of prescribed medicines. Kaplan–Meier survival curves and Cox proportional hazards models were used to demonstrate predictors for recurrence of PICH. Results— Total follow-up time of the 961 patients was 3481 person-years. During the follow-up time, 58 subjects had altogether 68 recurrent PICHs. The annual average incidence of first recurrence was 1.67%. Cumulative 5- and 10-year incidence rates were 9.6% and 14.2%, respectively. In univariable analysis, history of ischemic stroke, diabetes mellitus, and aspirin use were associated with a higher recurrence rate. In multivariable analysis, only previous ischemic stroke (adjusted hazard ratio, 2.22; 95% confidence interval, 1.22–4.05; P=0.009) independently predicted PICH recurrence. Diabetes mellitus tended to increase (adjusted hazard ratio, 2.38; 95% confidence interval, 0.98–5.80; P=0.056), whereas treated hypertension tended to decrease (0.45, 0.20–1.01; P=0.054) the risk for fatal recurrent PICH. Conclusions— Previous ischemic stroke independent of confounding factors may increase the risk for PICH recurrence.

Improved survival of patients with warfarin-associated intracerebral haemorrhage: a retrospective longitudinal population-based study

Background Warfarin-associated intracerebral haemorrhage carries poor outcome due to rapid haemorrhage growth. Reversal of warfarin anticoagulation with prothrombin complex concentrate has been implemented as an acute treatment option for these subjects. Aim We investigated whether survival of subjects with warfarin-associated intracerebral haemorrhage had improved after implementation of reversal of warfarin anticoagulation with prothrombin complex concentrate. Methods We identified all subjects with warfarin-associated intracerebral haemorrhage during 1993–2008 among the population of Northern Ostrobothnia, Finland. From 2004 onwards, prothrombin complex concentrate was used in Oulu University Hospital, the only hospital treating intracerebral haemorrhage subjects in the region, to counteract the effect of warfarin in subjects with warfarin-associated intracerebral haemorrhage. We compared the outcomes of subjects admitted during 1993–2003 and 2004–2008 and those treated and not treated with prothrombin complex concentrate. We also explored the predictors for one-year survival of the warfarin-associated intracerebral haemorrhage subjects. Results We identified altogether 181 subjects who had intracerebral haemorrhage while on warfarin. One-year survival was significantly (P = 0·031) higher for the 60 subjects admitted during 2004–2008 (43·3%) than for the 121 admitted before 2004 (30·6%). In multivariable analysis, prothrombin complex concentrate treatment reduced one-year case fatality (hazard ratio 0·52, 95% confidence interval 0·29–0·93). Thromboembolic complications did not occur more frequently among those treated with prothrombin complex concentrate. Conclusion The survival of warfarin-associated intracerebral haemorrhage subjects among the population of Northern Ostrobothnia has improved likely because of introduction of prothrombin complex concentrate.

Predictive value of C-reactive protein for the outcome after primary intracerebral hemorrhage

OBJECT Primary intracerebral hemorrhage (ICH) carries high morbidity and mortality rates. Several factors have been suggested as predicting the outcome. The value of C-reactive protein (CRP) levels in predicting a poor outcome is unclear, and findings have been contradictory. In their population-based cohort, the authors tested whether, independent of confounding factors, elevated CRP levels on admission (< 24 hours after ictus) are associated with an unfavorable outcome. METHODS The authors identified all patients who suffered primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland, and from the laboratory records they extracted the CRP values at admission. Independent predictors of an unfavorable outcome (moderate disability or worse according to the Glasgow Outcome Scale at 3 months) were tested by unconditional logistic regression in a model including all the well-established confounding factors and CRP on admission. RESULTS Of 961 patients, 807 (84%) had CRP values available within 24 hours of admission, and multivariable analysis showed elevated CRP at that point to be associated with an unfavorable outcome (OR 1.41 per 10 mg/L [95% CI 1.09-1.81], p < 0.01), together with diabetes mellitus (OR 1.99 [95% CI 1.09-3.64], p < 0.05), age (1.06 per year [95% CI 1.04-1.08], p < 0.001), low Glasgow Coma Scale score (0.75 per unit [95% CI 0.67-0.84], p < 0.001), hematoma size (1.05 per ml [95% CI 1.03-1.07], p < 0.001), and the presence of an intraventricular hemorrhage (2.70 [95% CI 1.66-4.38], p < 0.001). Subcortical location predicted a favorable outcome (0.33 [95% CI 0.20-0.54], p < 0.001). CONCLUSIONS Elevated CRP on admission is an independent predictor of an unfavorable outcome and is only slightly associated with the clinical and radiological severity of the bleeding.

Impact of ischemic heart disease and atrial fibrillation on survival after spontaneous intracerebral hemorrhage

OBJECT The well-known predictors for increased early deaths after spontaneous intracerebral hemorrhage (ICH) include the clinical and radiological severity of bleeding as well as being on a warfarin regimen at the onset of stroke. Ischemic heart disease and atrial fibrillation may also increase early deaths. In the present study the authors aimed to elucidate the role of the last 2 factors. METHODS The authors assessed the 3-month mortality rate in patients with spontaneous ICH (453 individuals) who were admitted to the stroke unit of Oulu University Hospital within a period of 11 years (1993-2004). RESULTS The 3-month mortality rate for the 453 patients was 28%. The corresponding mortality rates were 42% for the patients who had ischemic heart disease and 61% for those with atrial fibrillation on admission. The following independent predictors of death emerged after adjustment for sex and the use of warfarin or aspirin at the onset of ICH: 1) ischemic heart disease (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48, p < 0.02); 2) atrial fibrillation on admission (HR 1.79, 95% CI 1.12-2.86, p < 0.02); 3) the Glasgow Coma Scale score on admission (HR 0.82 per unit, 95% CI 0.79-0.87, p < 0.01); 4) size of hematoma (HR 1.11 per 10 ml, 95% CI 1.07-1.16, p < 0.01); 5) intraventricular hemorrhage (HR 2.62, 95% CI 1.71-4.02, p < 0.01); 6) age (HR 1.04 per year, 95% CI 1.02-1.06, p < 0.01); and 7) infratentorial location of the hematoma (HR 1.93, 95% CI 1.26-2.97, p < 0.01). CONCLUSIONS Both ischemic heart disease and atrial fibrillation independently and significantly impaired the 3-month survival of patients with ICH.

Better than expected survival after primary intracerebral hemorrhage in patients with untreated hypertension despite high admission blood pressures

Background:  Hypertension is the most important modifiable risk factor for primary intracerebral hemorrhage (ICH), but little is known of the effect of preceding hypertension on outcome. Because high mean arterial blood pressure (MABP) at admission is an independent predictor of early death in patients with ICH, we explored its role on survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension.