ORIGINAL CONTRIBUTION Safety of Discontinuation of Anticoagulation in Patients With Intracranial Hemorrhage at High Thromboembolic Risk Thanh G. Phan, FRACP; Merian Koh, MB,BS; Eelco F. M. Wijdicks, MD Background: Limited data are available to guide the patients. The median time not taking warfarin in this co- management of anticoagulation in patients with intra- hort was 10 days. Three patients had an ischemic stroke cranial hemorrhage (ICH) at high thromboembolic risk. within 30 days of warfarin therapy discontinuation. Us- ing Kaplan-Meier survival estimates, the probability of Objective: To review the management of anticoagula- having an ischemic stroke at 30 days following warfarin tion in patients with ICH at high thromboembolic risk. therapy cessation in groups 1, 2, and 3 was 2.9% (95% confidence interval, 0%-8.0%), 2.6% (95% confidence in- Patients and Methods: We reviewed the manage- terval, 0%-7.6%), and 4.8% (95% confidence interval, 0%- ment of anticoagulation in 141 patients who have a high 13.6%), respectively. In the 35 patients who had warfa- risk of ischemic stroke and have ICH while taking war- rin therapy restarted, none had recurrence of ICH during farin. The 30-day risk of ischemic stroke while not tak- the same hospitalization. ing anticoagulation treatment was determined using Kaplan-Meier survival estimates. Conclusions: Discontinuation of warfarin therapy for 1 to 2 weeks has a comparatively low probability of em- Results: The indications for anticoagulation were a pros- bolic events in patients at high embolic risk. This should thetic heart valve (52 patients [group 1]), atrial fibrilla- be taken into consideration when deciding whether to tion and cardioembolic stroke (53 patients [group 2]), continue or discontinue anticoagulation in these pa- and a recurrent transient ischemic attack or an ischemic tients at high embolic risk. Early recurrence of ICH is ex- stroke (36 patients [group 3]). A prior ischemic stroke ceedingly uncommon. occurred in 14 (27%) of group 1 patients and in 23 (43%) of group 2 patients. Death occurred in 43% of the 141 Arch Neurol. 2000;57:1710-1713 NNUALLY, intracranial hem- hemorrhage is not known. Discontinua- orrhage (ICH) causes com- tion of warfarin seems safe, but lack of plications in 1% to 2% of strong scientific underpinnings contin- patients with a prosthetic ues to disconcert physicians confronted heart valve or atrial fibril- with these complex patients. Data have lation who are taking warfarin for throm- only come from small retrospective se- A 1,2 3-7 boembolic prophylaxis. Rapid reversal ries. To assess the risk of discontinua- tion and resumption of warfarin treat- For editorial comment ment in patients with ICH, we conducted see 1682 a hospital-based study in a large cohort of patients. of anticoagulation in the presence of ICH is needed to prevent enlargement of the RESULTS hematoma, resulting in brain herniation. While not taking warfarin, the immedi- CLINICAL FEATURES ate concern in an unprotected patient is ischemic stroke and systemic emboliza- We studied 141 patients with 146 epi- From the Department tion. In addition, the interval to resump- sodes of ICH while taking warfarin. The of Neurology, Mayo Clinic and tion of anticoagulation and its associated median patient age was 74 years (range, Foundation, Rochester, Minn. potential risk of recurrence of cerebral 23-98 years). Sixty percent of the pa- (REPRINTED) ARCH NEUROL / VOL 57, DEC 2000 WWW.ARCHNEUROL.COM 1710 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 1. Baseline Demographic Characteristics PATIENTS AND METHODS in 141 Patients With a Cerebral Hemorrhage* Prosthetic Atrial Fibrillation Recurrent TIA We retrospectively reviewed the medical records of Heart Valve and Cardioembolic or Stroke 141 patients undergoing anticoagulation who had ICH Group Stroke Group Group between January 1, 1976, and December 31, 1999. Characteristic (n = 52) (n = 53) (n = 36) This study was approved by the Institutional Re- Age, y view Board. Twenty-six patients with a metallic valve Mean 67.9 76.5 70.5 and ICH have been described previously.7 Patients Median 73 78 72 with ICH who were taking anticoagulation treat- Range 23-88 54-98 47-90 ment for deep venous thrombosis or pulmonary em- Prior TIA or stroke 14 (27) 23 (43) 36 (100) bolus were considered to be at low risk of embolic Atrial fibrillation 18 (35.6) 49 (92.5) 0 stroke and were excluded from the analysis. The hos- and cardioembolic pital course and 30-day follow-up were reviewed un- stroke til the first defining event, any embolic complica- Abnormal 30 (65.2) 20 (55.5) 3 (21.4) echocardiographic tion, ICH, or death. Abnormal transthoracic or results transesophageal echocardiographic results were de- Echocardiography 6 (11.5) 17 (32.1) 23 (62.2) fined as a left atrial size greater than 40 mm, an ejec- not done tion fraction of less than 40%, hypokinesis, a septal Hypertension 18 (34.6) 32 (60.4) 23 (62.2) 8,9 defect, and thrombus. If patent foramen ovale was Smoking 25 (48.1) 22 (41.5) 23 (62.2) the only abnormality on echocardiography, then it Diabetes 9 (17.3) 7 (13.2) 4 (10.8) was coded as a normal echocardiographic study be- IHD or CCF 20 (38.5) 29 (54.7) 13 (35.1) cause of controversy over its significance as an in- Duration taking dependent risk factor for ischemic stroke.9,10 In ad- warfarin, y dition, none of the patients in our series were taking Mean 6.9 3.9 3.5 warfarin because of patent foramen ovale. Either in- Median 5.5 3.0 1.0 travenous heparin or oral warfarin treatment was then Range 0.42-14.70 0.006-5.70 0.008-12.10 restarted, depending on the treating physicians. Prothrombin time Intracranial hemorrhage was divided into intra- on admission, s cerebral hemorrhage (including cerebellar hemor- Mean 31.3 22.5 25.0 Median 22.7 19.6 21.2 rhage, brainstem hemorrhage, lobar hemorrhage, and Range 11.5-240.0 9.7-60.5 13.9-74.8 basal ganglia hemorrhage), subarachnoid hemor- rhage (SAH), subdural hematoma (SDH), and pri- *Data are given as the number (percentage) of patients unless otherwise mary intraventricular hemorrhage (IVH). Patients indicated. TIA indicates transient ischemic attack; IHD, ischemic heart disease; with a hemorrhagic infarct were excluded from the and CCF, congestive cardiac failure. analysis. Patients were divided into 3 groups accord- ing to the indications for long-term anticoagulation. Group 1 consisted of 52 patients with prosthetic heart mean prothrombin times were 26.4 and 21.3 seconds valves. Group 2 consisted of 53 patients with atrial (range, 9.7-240.0 seconds) on admission for the 3 groups. fibrillation and cardioembolic stroke.11 Group 3 con- In group 1, 14 patients had mitral metallic valves, 31 had sisted of 36 patients with recurrent transient ische- aortic metallic valves, and 7 had combined mitral and aor- mic attacks or ischemic stroke despite therapy with tic metallic valves. In this group, 14 patients had Björk- aspirin, ticlopidine hydrochloride, or clopidogrel. Shiley (single-tilting disk) valves, 17 had Starr-Edwards Statistical analysis using the log-rank test was (caged-ball) valves, and 11 had St Jude (bileaflet–tilting used to compare the likelihood of mortality among disk) valves. Seventeen patients had various types of the various types of ICH. The 30-day risk of ische- valves, including 3 Medtronic-Hall (single–tilting disk) mic stroke while not taking anticoagulation treat- ment was determined using Kaplan-Meier survival es- valves, 3 Braunwald-Cutter (caged-ball) valves, and 2 Car- timates (censored for when heparin or warfarin bomedic (bileaflet-tilting disk) valves; 9 had biopros- therapy was restarted). thetic valves. HOSPITALIZATION AND FOLLOW-UP tients were men. The demographic characteristics are The median time not taking warfarin was 10 days (range, shown in Table 1. The type of hemorrhage was intra- 0-30 days). There were 3 patients with ischemic events cerebral hemorrhage in 87 patients (61.7%), SDH in 43 within 30 days: 1 in the posterior cerebral artery region, (30.5%), SAH in 8 (5.7%), and IVH in 3 (2.1%). The me- 1 lacunar stroke, and 1 vertebrobasilar transient ische- dian duration of anticoagulation for the cohort taken from mic attack (Table 2). Using Kaplan-Meier survival es- the start of warfarin therapy to admission with ICH was timates, the probability of having ischemic events at 7 5 years (range, 2 months to 14.7 years). A prior tran- days following warfarin treatment cessation in groups 1, sient ischemic attack or ischemic stroke occurred in group 2, and 3 was 2.9% (95% confidence interval [CI], 0%- 1 in 27% and in group 2 in 43% of the patients. The me- 8.0%), 2.6% (95% CI, 0%-7.6%), and 4.8% (95% CI, 0%- dian admission Glasgow Coma Scale score was 14. An- 13.6%), respectively. This remained unchanged at 14 and ticoagulation was reversed with fresh frozen plasma and 30 days after ictus. By 7 day, 18 (35%) of the patients in vitamin K on admission in all patients. The median and group 1 died, 16 (30%) in group 2 died, and 18 (50%) (REPRINTED) ARCH NEUROL / VOL 57, DEC 2000 WWW.ARCHNEUROL.COM 1711 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 2. Characteristics of the Patients With Ischemic Events After Discontinuation of Warfarin Therapy for Intracerebral Hematoma* Type of Indication for Carotid US or Echocardiographic Time to Stroke Patient Age, y Hemorrhage Anticoagulation Angiographic Results Results Recurrence, d Stroke Syndrome 83 ICH AF ND ND 5 Occipital infarct 43 SAH Aortic metallic Normal Normal 5 Lacunar infarct valve (BJ) 73 SDH TIA High-grade stenosis Normal 4 Vertebrobasilar TIA of the BA *All 3 patients were men.