The influence of fluid intake on stroke recurrence--a prospective study

PurposeA nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF).MethodsA questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes.ResultsA total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone.ConclusionA large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician's decision.     

Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP

To identify hematoma progression in patients with warfarin-associated intracerebral hemorrhage (ICH) despite international normalized ratio (INR) normalization with fresh-frozen plasma (FFP), we reviewed 45 patients with warfarin-associated ICH given FFP. The median time for door to INR normalization was 30 hours (14 to 49.5), with 4 patients' hematomas enlarging after INR normalization. FFP is associated with substantial time delay to actual administration and pulmonary edema and may not prevent progression of ICH despite INR normalization.     

Obesity increases risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage

Background: Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC. Methods: Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR ≥ 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure. Results: Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m²) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 ± 1.4 vs. 2.0 ± 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure. Conclusions: Obesity and elevated initial INR are independently associated with anticoagulation reversal failure using the weight-based PCC protocol in patients with warfarin-related acute ICH. Further studies are needed to determine more effective dosing protocols and individualized strategies for anticoagulation reversal after acute ICH, especially among obese patients.     

A prospective and randomized comparison of the safety and effects of therapeutic levels of enoxaparin versus unfractionated heparin in chronically anticoagulated patients undergoing elective cardiac catheterization

Consecutive patients with atrial fibrillation and/or prosthetic heart valves, receiving chronic anticoagulation with phenprocoumon and scheduled to undergo cardiac catheterization, were randomized to subcutaneous enoxaparin twice daily (n = 32) or intravenous UFH (n = 36). Cardiac catheterization was performed at an international normalized ratio <1.5. Activated partial thromboplastin times and levels of anti-Factor Xa activity were measured daily. The time until effective anticoagulation (primary endpoint) was significantly shorter for enoxaparin than for UFH (1.1 +/- 0.4 days versus 3.7 +/- 2.5 days, p<0.0001). The percentage of days of effective anticoagulation was significantly higher in the enoxaparin group than in the UFH group (93.3 +/- 9.5% versus 53.7 +/- 26.6%, p <0.0001). In conclusion, enoxaparin achieves therapeutic levels of anticoagulation more rapidly and consistently than UFH in chronically anticoagulated patients with prosthetic heart valves and/or atrial fibrillation undergoing cardiac catheterization.     

Intracerebral hemorrhage in stroke patients anticoagulated with heparin

To characterize the clinical features of patients with acute cerebral infarction who sustained intracerebral hemorrhage related to heparin anticoagulation, we describe 10 patients and review reports of 16 cases. Cardiac-source embolism was identified in seven (70%) of the 10 patients and consisted of atrial fibrillation in six of the seven. The middle cerebral artery territory was affected in nine patients (90%), with moderate-sized or large infarcts by clinical and computed tomographic criteria. The interval between stroke onset and intracerebral hemorrhage was less than 72 hours in 80% of the patients. Intracerebral hemorrhage occurred less than or equal to 24 hours after the time heparin was started in 80% of the patients. The activated partial thromboplastin time closest to the time of intracerebral hemorrhage was greater than 2 x control in seven patients. Our findings in the 10 patients are similar to those of the 16 cases previously reported and suggest that heparin-related intracerebral hemorrhage occurs early after stroke onset, usually with moderate-sized or large infarcts, and with excessive anticoagulation in some patients.     

Anticoagulant-associated intracerebral hemorrhage

The incidence of anticoagulant-associated intracerebral hemorrhage (AAICH) quintupled during the 1990 s, probably due to increased warfarin use for the treatment of atrial fibrillation. Anticoagulant-associated intracerebral hemorrhage now accounts for nearly 20% of all intracranial hemorrhage (ICH). Among patients using warfarin for atrial fibrillation, the annual risk of ICH in trials is 0.3 to 1.0%. Predictors of potential anticoagulant-associated hemorrhage are increasing age, prior ischemic stroke, hypertension, leukoaraiosis, the early period of warfarin use, higher intensity anticoagulation, and antiplatelet use in addition to anticoagulation. Compared with other intracranial hemorrhage patients, anticoagulated patients have a greater risk of hematoma expansion, subsequent clinical deterioration and death, necessitating vigorous reversal of their coagulopathy. Recommended methods of warfarin reversal are administration of intravenous vitamin K and either prothrombin complex concentrates or fresh frozen plasma. Reversal of unfractionated heparin is accomplished with intravenous protamine sulfate. Surgical treatment of intracranial hemorrhage may be life saving in select cases, but has not reduced morbidity or mortality in large randomized trials.     

Evaluation of the yield of 24-h close observation in patients with mild traumatic brain injury on anticoagulation therapy: a retrospective multicenter study and meta-analysis

Background/aims

Patients with mild traumatic brain injury (mTBI) on anticoagulants have an increased risk of intracranial hemorrhage (ICH). However, consensus is lacking on whether to admit them after normal initial cranial CT. We evaluated the yield of 24-h neurological observation.

Methods

Retrospective multicenter study including adult patients admitted over a 5-year period with mTBI on anticoagulation [therapeutic dose heparin, direct oral anticoagulant, or vitamin K antagonist (VKA) with international normalized ratio (INR) ≥ 1.7] and reportedly normal cranial CT obtained within 24 h after trauma. Primary endpoint was symptomatic ICH within 24 h of injury. Literature on delayed ICH in patients with mTBI and anticoagulation use was reviewed.

Results

Of 17.643 mTBI patients, 905 met the inclusion criteria (median age 82 years). 97% used VKA (median INR 2.9). None developed delayed ICH within 24 h. Nine patients deteriorated neurologically due to ICH, four within 24 h (0.4%, 95% CI 0.1–1.2) and five on day 2, 18, 22, 36 and 52, respectively. In six patients, including all four that developed symptoms within 24 h, ICH was found upon reevaluation of initial imaging. The meta-analysis comprised of 9 studies with data from 2885 patients. The estimated pooled proportion of symptomatic delayed ICH or delayed diagnosis of ICH within 24 h was 0.2% (95% CI 0.0–0.5).

Conclusions

Delayed (diagnosis of) ICH within 24 h is very rare in mTBI patients on anticoagulants after reportedly normal initial CT. Routine hospitalization of these patients seems unwarranted when the initial cranial CT is scrupulously evaluated.

     

Treatment and management of acute venous thromboembolic disease

Venous thromboembolic (VTE) disease consists of deep vein thrombosis and/or pulmonary embolism. Either low molecular weight heparin given subcutaneously or unfractionated heparin administered intravenously are used for the initial treatment. Simultaneously, warfarin therapy is initiated. Thrombolytic therapy plays a limited role. Following the initial heparin treatment, anticoagulation clinics provide an excellent means of monitoring the oral anticoagulation. Patient education is important and patients should be well versed in the basic features of oral anticoagulation. The duration of oral anticoagulation is dependent on a number of factors including the presence of inherited risk factors, bleeding risk and patient reliability. Residual thrombus in the affected vein may indicate the need for prolonged anticoagulation. The low intensity oral anticoagulation (INR 1.5-2.0) is useful in preventing recurrent thrombosis following the initial treatment period with full intensity oral anticoagulation.     

Intracerebral hemorrhage following intravenous thrombolysis in Thai patients with acute ischemic stroke

In Asia, there is limited information regarding symptomatic intracerebral hemorrhage (ICH) in patients treated with intravenous (iv) recombinant tissue plasminogen activator (rtPA). The aim of this study was to identify independent factors associated with symptomatic ICH following iv rtPA. The study included 192 patients with acute ischemic stroke who were treated with iv rtPA. Baseline characteristics were compared between patients with or without ICH. Symptomatic ICH occurred in 5.7% of patients and asymptomatic ICH in 13.0% of patients. An international normalized ratio (INR) ≥1.0 (odds ratio [OR]=4.89, p=0.036), atrial fibrillation (OR=7.21, p=0.009) and blood glucose concentration >8.325 mmol/L (OR=9.00, p=0.004), were independent risk factors for symptomatic ICH. Atrial fibrillation (OR=3.56, p=0.012) and severe stroke (National Institutes of Health Stroke Scale ≥15; OR=8.94, p<0.001) were independent risk factors for asymptomatic ICH. The prevalence of symptomatic ICH following iv rtPA in Thai patients was comparable to previous studies.     

Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal

INTRODUCTION: Patients with nonvalvular atrial fibrillation are at increased risk for systemic embolism, predominantly disabling stroke. To study how stroke and mortality rates vary with different degrees of anticoagulation reflected by the international normalised ratio (INR) we critically assess information from different sources. MATERIALS AND METHODS: 1. Computerized search of the medical literature published between 1980 and July 2004 was performed using MEDLINE applied to various combinations of the search terms of atrial fibrillation, warfarin, anticoagulation, anticoagulation intensity, and INR, not restricted by language. 2. We performed a record linkage analysis with death hazard estimated as a continuous function of INR based on 21,967 patients. Similarly the risk of admission to hospital or death due to diseases of the vessels of the brain was estimated. 3. Re-analysis of data earlier published by Hylek et al. from year 2003.RESULTS AND CONCLUSIONS: 1. One randomised study showed a significantly lower risk of stroke for mean INR 2.4 compared to mean INR 1.3 combined with aspirin. Remaining studies found INRs of 2-2.5 to be as efficacious as higher anticoagulation intensities.2. Mortality as well as risk of admission to hospital or death due to diseases of the vessels of the brain followed U-shaped curves with minimum at INR 2.2 and 2.4, respectively. At high INR the risk increased 2.3 times per 1 unit increase of INR for death and 1.7 times for events in the vessels of the brain.3. The re-analysing of data of Hylek et al. indicated that there might be a substantial increase of the risk of intracranial hemorrhage when INR is increased from 2.5 to 4.We conclude that INRs in the interval 2.0--2.5 give the lowest risk of stroke and death in patients with nonvalvular atrial fibrillation.     

Anticoagulation in ischemic stroke: opportunities in arterial disease

In the acute phase of ischemic stroke, there is no evidence that anticoagulants provide any benefit in terms of death or dependency. A small reduction in the incidence of recurrent stroke is offset by an equally small increase in intracranial hemorrhage (ICH). In the secondary prevention of stroke, in patients with transient ischemic attacks (TIAs) and moderately disabling ischemic stroke, the relative risk reduction of major vascular events by aspirin is rather modest: 13% (or 19% in a systematic review of arterial disease in general). Anticoagulants might well offer stronger protection, since they provide a 35-50% risk reduction after myocardial infarction or in patients with TIAs or nondisabling ischemic stroke in the presence of atrial fibrillation. Meanwhile, it has become clear that anticoagulation with high intensity (INR 3.0-4.5) is associated with a high risk of ICH in patients with cerebral ischemia who are in sinus rhythm, while INR values around 1.9 do not offer protection against major vascular events. An international clinical trial of anticoagulation with INR values between 2.0 and 3.0 (ESPRIT) is still in progress. In cerebral venous sinus thrombosis, anticoagulant treatment is associated with a nonsignificant reduction of the risk of death or dependence, but the treatment has nevertheless become widely adopted because it seems safe: no increase in the proportion of patients with hemorrhagic transformation of infarction has so far been demonstrated.     

Characteristics of anticoagulant therapy and comorbidity related to overanticoagulation

The risk of hemorrhage when using coumarin anticoagulants sharply increases when the International Normalised Ratio (INR) is > or =6.0. We performed a prospective cohort study with a nested case-control design among 17,056 outpatients of an anticoagulation clinic to determine the incidence of overanticoagulation and to study the association between overanticoagulation and characteristics of anticoagulant therapy and comorbidity. The incidence rate of an INR > or =6.0 was 7.8 per 10,000 treatment days in prevalent users on the starting date and 22.5 per 10,000 treatment days in incident users during the study period. 300 cases with an INR > or =6.0 were compared with 302 randomly selected matched controls with an INR within the target zone. Patients on acenocoumarol had an increased risk of an INR > or =6.0 compared to patients on phenprocoumon. Regarding comorbidity, impaired liver function, congestive heart failure, diarrhea and fever were risk factors for overanticoagulation. Increased monitoring of INR values if risk factors are present or avoidance of risk factors could prevent excess anticoagulation and potential bleeding complications.     

Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage

Introduction: Warfarin-associated intracranial hemorrhage (ICH) requires rapid normalization of clotting function. Current therapies are associated with significant complications and/or prolonged time to correction of coagulopathy. Recombinant factor VIIa (FVIIa) might allow faster and safer correction of coagulopathy. Methods: This article presents a retrospective chart review of all patients with warfarin-associated ICH treated in a neurology/neurosurgery intensive care unit over an 11-month period. Results: All patients were treated to rapidly reverse the warfarin effect. Fifteen patients received vitamin K and fresh frozen plasma (FFP) alone (FFP group). Twelve patients also received FVIIa (FVIIa group). The median times from presentation to an international normalization ratio (INR) of less than 1.3 were 32.2 and 8.8 hours in the FFP the FVIIa groups, respectively (p=0.016). INR normalized slowly (at 110 and 130 hours, respectively) in two patients with end-stage renal failure who were given FVIIa, one of whom developed disseminated intravascular coagulation after three doses of FVIIa. No other complications occurred from FVIIa administration. One patient in the FFP group developed severe pulmonary edema. Conclusion: FVIIa may be an effective adjunct to FFP in warfarin-related ICH, facilitating faster correction of INR and decreasing FFP requirements. A prospective, randomized trial is needed to confirm these preliminary findings and to determine whether there is a clinical benefit. Dr. Diringer receives financial compensation for consulting and speaking for Novo Nordisk.     

抗凝治疗中颅内出血相关因素分析

目的 探讨应用抗凝药物治疗中有关颅内出血的危险因素,总结应用抗凝药过程中颅内出血救治的经验教训.方法 回顾性分析5例在应用抗凝药物过程中发生颅内出血的临床特征,治疗经过和结果.结果 5例颅内出血患者均合并基础疾病,GOS评分1分者(死亡)3例,3分者(重残)1例,5分者(良好)1例.颅内出血巾3例为硬膜下血肿,2例为脑内血肿.3例患者分别在意识改变后4h、3d、6d死亡.结论 抗凝治疗中发生颅内出血的病情变化快、死亡率高,对患者的危险性认识往往不足.高龄、高INR、外伤史、合并基础疾病是预后不良的主要危险因素.     

The lowest effective intensity of prophylactic anticoagulation for patients with atrial fibrillation

BACKGROUND: Stroke prevention trials in patients with atrial fibrillation (AF) mainly studied the use of warfarin in Caucasians, and the international normalized ratio (INR) was targeted in the range of 2-4. The result may not necessarily be applicable to other ethnic groups. This study aimed to determine the optimal intensity of anticoagulation for stroke prevention in Chinese patients. METHODS: We performed a retrospective study on all Chinese patients with AF taking warfarin for stroke prevention in our hospital from January 1, 2000, to June 30, 2002. Patients with a mechanical heart valve were excluded. We systematically studied their indication of using warfarin, duration of therapy and all INR results. Only those patients whose indications of using warfarin were consistent with the ACC/AHA/ESC Executive Summary were included. Thrombo-embolic episodes, sudden death, major bleeding, intracranial haemorrhage and the INR at the time of the event were recorded. The INR range was divided into six categories: <1.5, 1.5-1.9, 2.0-2.5, 2.6-3.0, 3.1-3.5, >3.5. The number of events was recorded for each category, and this formed the numerator. The denominator was the summation of time each patient stayed in each category of INR. The event rate was then calculated for each INR category. RESULTS: 555 patients were included in the analysis, they constituted 893 patient-years. The INR was kept below 2.6 in 84.9% of the time and between 1.5 and 1.9 in 35% of the time. The overall event rate in our patients was 6.0%, of which 3.9% were due to thrombo-embolic events and 2.1% were due to serious bleeding. The overall event rate was lowest in the INR range from 1.5 to 1.9. which is not significantly different from that of INR 2.0-2.5 and 2.6-3.0. The overall event rate was 3.6% in INR 1.5-3.0 which was significantly lower than 15.1% in INR <1.5 and 20.5% in INR >3.0 (p < 0.01). CONCLUSIONS: Our retrospective cohort showed that a lower INR range of 1.5-3.0 was safe and effective for stroke prevention in Chinese patients treated in a single hospital.     

Antithrombotic therapy and predilection for cerebellar hemorrhage

BACKGROUND: With the recent increase in the use of antithrombotic therapy, intracerebral hemorrhage (ICH) has been found to be a common complication. We determined whether the use of oral antithrombotic therapy and the patients' preexisting comorbidities were predictive of cerebellar hemorrhage (CH; previously reported to be associated with anticoagulants) as compared to other ICH, and whether antithrombotic therapy affected the clinical severity of CH. METHODS: A study of 327 consecutive patients hospitalized in our institute within 3 days after the onset of ICH, including 38 patients with a CH. RESULTS: CH accounted for 12% of all ICH, 75% of which occurred in patients on warfarin therapy with an international normalized ratio (INR) for prothrombin time >2.5 (p < 0.0001), and 33% of which occurred in patients on ticlopidine therapy (p = 0.017). Warfarin therapy with an INR >2.5 and high blood glucose on admission were independently predictive of CH as compared to other ICH. In addition, previous ischemic stroke (p = 0.002) and heart diseases (p = 0.018) were more prevalent in patients with CH than in those with other ICH. The number of major arteriosclerotic comorbidities and risk factors was also independently predictive of CH risk. CONCLUSIONS: We confirmed that warfarin therapy with an INR >2.5 is associated with CH. Patients with CH frequently had arteriosclerotic comorbidities requiring antithrombotic therapy that can complicate their acute management.     

Oral anticoagulation for cerebral ischemia of arterial origin: high initial bleeding risk.

BACKGROUND: The use of oral anticoagulant therapy for the prevention of arterial thromboembolism in patients who have had ischemic stroke is controversial. Coumarins may increase the bleeding risk in patients with cerebral ischemia of arterial origin. OBJECTIVES: 1) To calculate incidence rates of bleeding and thromboembolic events in patients with noncardiac cerebral ischemia who were treated routinely in an anticoagulation clinic. 2) To assess which factors contribute to the occurrence of events. 3) To determine the optimal intensity of oral anticoagulant therapy in these patients. METHODS: The authors studied all patients treated for noncardiac cerebral ischemia at the Leiden anticoagulation clinic between 1993 and 1998. Outcome events were major hemorrhage, major arterial thromboembolism, and death. RESULTS: The authors observed 356 patients for 644 patient-years. The incidence of major hemorrhage was 3.9 per 100 patient-years (95% CI, 2.5 to 5.7) and that of thromboembolism was 3.0 per 100 patient-years (95% CI, 1.8 to 4.6). The incidence of hemorrhage varied with the duration of treatment (relative risk [RR] of the first versus the second half-year, 3.8; 95% CI, 1.9 to 7.6), age (RR for age >65 years, 3.7; 95% CI, 1.1 to 12.3), and the intensity of oral anticoagulation (RR, 1.8 for each 0.5 international normalized ratio [INR] unit increase; 95% CI, 1.5 to 2.3). The optimal intensity of oral anticoagulant therapy was 2.5 to 3.5 INR; the best target value was 3.0 INR. CONCLUSION: The risk of hemorrhage with anticoagulant therapy is high in patients with ischemic stroke of arterial origin but is mainly confined to early use and elderly patients.     

Intracranial Hemorrhage Sparing Meningioma in an Anticoagulated Patient

BACKGROUND AND PURPOSE: The risk of intracerebral hemorrhage (ICH) in patients receiving antithrombotic therapy is well known. However, there is sparse literature regarding the risk of intracerebral hemorrhage in patients receiving warfarin, who have an intracranial meningioma. METHODS AND RESULTS: We report a case of a 66-year-old man who developed multifocal ICHs in the context of supratherapeutic anticoagulation. There was sparing of the intracranial meningioma despite the development and growth of multiple intraparenchymal hemorrhages that resulted in death. We also review the literature evaluating the risk of ICH in anticoagulated patients with an intracranial meningioma. CONCLUSIONS: The findings of this case lend further support to the gradually developing notion of relative safety of anticoagulation in patients with meningioma. They also underscore the importance of close monitoring of the INR.     

Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon

Variability in the control of oral anticoagulant therapy has been associated with a heightened risk of complications. We compared control of anticoagulation between two commonly used coumarins, phenprocoumon and acenocoumarol, and among anticoagulation clinics. All qualifying patients were managed at six regional anticoagulation clinics in the Netherlands. This retrospective cohort study compiled data during a three-year period from a computerised dosing and management system. Anticoagulation control was expressed as the percent of time within the therapeutic range and stability expressed as the time-weighted variance in the international normalised ratio (INR). Data were available for 22,178 patients of whom 72% were treated with acenocoumarol. INRs of patients who received phenprocoumon were within the therapeutic range 50% of the time compared with 43% for acenocoumarol (OR 1.32, 95% CI 1.24-1.41). Moreover, patients on phenprocoumon required 15% fewer monitoring visits and had more stable INR values. These observations were consistent for all six clinics. There were also sizable differences between the clinics with respect to control and stability of anticoagulation that were stable from year-to-year and were unrelated to the drug used. With its longer half-life of three to five days, phenprocoumon produces more stable anticoagulation than acenocoumarol and should generally be the drug of choice when these are the available choices. The differences observed among clinics suggest that certain clinics employ policies and practices resulting in better control of anticoagulation.     

Warfarin related intracranial haemorrhage: A case-controlled study of anticoagulation monitoring prior to spontaneous subdural or intracerebral haemorrhage

We present a retrospective, case-controlled study of the degree of over-warfarinisation and the frequency of International Normalized Ratio (INR) monitoring in patients with spontaneous intracranial haemorrhage (ICH) compared with a control group without ICH. A higher proportion of patients with ICH were taking warfarin than patients in the control group (33/221 [15%] versus 16/201 [8%], p < 0.05). There was no significant difference between the ICH group and the controls in the mean INR of warfarinised patients on presentation, the mean INR when last measured prior to presentation, or in the number of days since the INR was last tested. There was no correlation between the time since the INR was last measured and the INR on presentation. Only 2 (6%) of patients were excessively anticoagulated at the time of ICH. Thus, in this study, warfarin use was associated with an increased risk of ICH despite appropriate community INR monitoring and therapeutic anticoagulation.