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An Observational Cohort Study Sini Saarinen1*†, Jyrki Puolakka1†, James Boyd1†, Taneli Väyrynen2†, Harri Luurila3† and Markku Kuisma1†

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An Observational Cohort Study Sini Saarinen1*†, Jyrki Puolakka1†, James Boyd1†, Taneli Väyrynen2†, Harri Luurila3† and Markku Kuisma1† Saarinen et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:21 http://www.sjtrem.com/content/19/1/21 ORIGINALRESEARCH Open Access Warfarin and fibrinolysis - a challenging combination: an observational cohort study Sini Saarinen1*†, Jyrki Puolakka1†, James Boyd1†, Taneli Väyrynen2†, Harri Luurila3† and Markku Kuisma1† Abstract Background: Patients presenting with ST-segment elevation myocardial infarction (STEMI) frequently use warfarin. Fibrinolytic agents and warfarin both increase bleeding risk, but only a few studies have been published concerning the bleeding risk of warfarin-prescribed patients receiving fibrinolysis. The objective of this study was to define the prevalence for intracranial haemorrhage (ICH) or major bleeding in patients on warfarin treatment receiving pre-hospital fibrinolysis. Methods: This was an observational cohort study. Data for this retrospective case series were collected in Helsinki Emergency Medical Service catchment area from 1.1.1997 to 30.6.2010. All warfarin patients with suspected ST- segment elevation myocardial infarction (STEMI), who received pre-hospital fibrinolysis, were included. Bleeding complications were detected from Medical Records and classified as ICH, major or minor bleeding. Results: Thirty-six warfarin patients received fibrinolysis during the study period. Fourteen patients had bleeding complications. One (3%, 95% CI 0-15%) patient had ICH, six (17%, 95% CI 7-32%) had major and seven (19%, 95% CI 9-35%) had minor bleeding. The only fatal bleeding occurred in a patient with ICH. Patients’ age, fibrinolytic agent used or aspirin use did not predispose to bleeding complications. High International Normalized Ratio (INR) seemed to predispose to bleedings with values over 3, but no statistically significant difference was found. Conclusions: Bleedings occur frequently in warfarin patients treated with fibrinolysis in the real world setting, but they are rarely fatal. Background can be fatal. These patients are frequently transported Pre-hospital fibrinolysis is an effective alternative in the directly to primary percutaneous coronary intervention treatment of acute ST-segment elevation myocardial (PCI). According to the guidelines, fibrinolysis should, infarction (STEMI). Reduced time delay from the onset however, be considered if PCI cannot be performed of symptoms to fibrinolysis is related to reduced mortal- within 90-120 minutes when emergency medical service ity [1,2]. Many patients presenting with STEMI also have (EMS) meets the patient [3-5]. Additionally, the informa- other diseases, such as atrial fibrillation or severe heart tion on prior warfarin usage is not always available, failure, requiring oral anticoagulants for the prevention especially in patients who are resuscitated from sudden of thromboembolic complications. Guidelines of Eur- out-of-hospital cardiac arrest. opean Society of Cardiology, American College of Cardi- Even though bleeding associated with fibrinolysis has ology (ACC) and American Heart Association (AHA) been carefully investigated, only a few studies have been consider the use of oral anticoagulants as a relative con- done concerning patients on oral anticoagulants receiv- traindication for fibrinolysis [3-5]. The most threatening ing fibrinolysis. The aim of this study was to report the complication associated with both warfarin and fibrinoly- prevalence of serious haemorrhages with patients on tic agents is an intracranial or a major bleeding, which oral anticoagulants receiving pre-hospital fibrinolysis for suspected STEMI. * Correspondence: [email protected] † Contributed equally Methods 1Helsinki Emergency Medical Service System, Helsinki University Central This was an observational cohort study approved by Insti- Hospital, PL 112, 00099 Helsinki City, Helsinki, Finland Full list of author information is available at the end of the article tutional Review Board of Helsinki University Central © 2011 Saarinen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Saarinen et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:21 Page 2 of 6 http://www.sjtrem.com/content/19/1/21 Hospital. The study plan was retrospective, but data was major bleeding groups were compared to minor and no- collected prospectively for Fibrinolysis Registry in Helsinki bleeding groups. These two groups were chosen to be EMS area during 1.1.1997-30.6.2010. Helsinki is the capital compared on the basis of clinical relevance. city of Finland with 584 000 inhabitants. The EMS consists of seven to eight basic life support (BLS) -units, four Results advanced life support (ALS) -units, a medical supervisor Study population unit and a physician staffed mobile intensive care unit Altogether 1322 pre-hospital fibrinolysis for suspected (MICU). The medical supervisor unit and the MICU are STEMI were given during the study period. The study provided with fibrinolytic agents. population consisted of 36 warfarin treated patients, All patients on warfarin were included, if they received whose baseline characteristics are shown in Table 1. out-of-hospital fibrinolysis for suspected STEMI during Eighty three percent (95% CI 68-93%) of study patients the study period. Unlike many other studies concerning were treated with fibrinolysis before year 2005. Chest bleeding complications, this was a “real world setting” pain was the most common presenting symptom (n = study including all patients despite their age, bleeding 24; 67%, 95% CI 50-80%). The main location of ST- risk or clinical condition. The decision to initiate fibri- segment elevation was anterior wall in 18 (50%, 95% nolysis for suspected STEMI was made by an emergency CI 34-66%), inferior wall in 15 (42%, 95% CI 27-58%) physician, either on scene or after consultation with 12- and lateral wall in 3 (8%, 95% CI 2-23%) patients. lead electrocardiogram (ECG) transmission. Emergency Median time from the onset of the symptoms to fibri- physicians in Helsinki EMS filled a detailed documenta- nolysis was 68 min (IQR 49-113 min), while median tion form for Fibrinolysis Registry after each pre-hospi- time from emergency call to fibrinolysis was 51 min tal fibrinolysis. All patients receiving fibrinolysis for (IQR 36-60 min). Other contraindications for fibrinoly- suspected STEMI or pulmonary embolism are included sis than warfarin existed with four (11%, 95% CI 4- in the Fibrinolysis registry of Helsinki EMS, as well as 26%) patients. Those were malignancy, hypertension patients with suspected STEMI receiving other treat- and previous ICH. ment than fibrinolysis (i.e. primary PCI). Only patients receiving fibrinolysis for suspected STEMI were included in the study. STEMI diagnose was not con- Table 1 Baseline characteristics of study patients (n = 36) firmed from Hospital Medical Records. Therefore it is n (%, 95% CI) possible some patients received fibrinolysis inappropri- Age (years)* 70 (62-78) ately not actually suffering from STEMI. However, a Sex; men 28 (78%, 62-89%) physician responsible for maintaining the registry Previous medical history checked correctness of indications for fibrinolysis and ischaemic heart disease 21 (58%, 42-73%) ECG diagnostics in all cases. hypertension 24 (67%, 50-80%) One of the authors (J.P) investigated the Medical diabetes 11 (31%, 18-47%) Records of receiving hospitals to detect possible compli- myocardial infarction 17 (47%, 32-63%) cations after fibrinolysis. Reported laboratory tests were thrombolysis 9 (25%, 14-41%) drawn on arrival to hospital. Bleeding complications PCI or CABG 5 (14%, 6-29%) were classified as intracranial haemorrhage (ICH), major use of aspirin 2 (6%, 1-19%) and minor bleeding. ICH was diagnosed by computer Signs before fibrinolysis tomography (CT) scan or as an autopsy finding. Major cardiac arrest 10 (28%, 16-44%) bleeding was defined as a haemorrhage causing a need pulmonary oedema 1 (3%, 0-15%) for a blood-transfusion, all other bleedings reported in cardiogenic shock 5 (14%, 6-29%) Medical Records were defined as minor. Time from Warfarin fibrinolysis to bleeding, blood units transfused and treat- prior use known before fibrinolysis 34 (94%, 81-99%) ment of bleeding were also registered. indication Statistical analysis was performed using SPSS for Win- atrial fibrillation 20 (55.5%, 40-70%) dows V18.0 Software (SPSS Inc, Chicago, IL, USA). Chi- cerebrovascular disease 6 (17%, 7-32%) Square test (Fisher’s Exact Test) was used for categorical pulmonary embolism 1 (3%, 0-15%) variables and Mann-Whitney U test for continuous vari- deep vein thrombosis 2 (5.5%, 1-19%) ables with non-normal distribution. Median values were heart valve disease 3 (8%, 2-23%) reported with 25th-75th percentiles and proportions cardiomyopathy 4 (11%, 4-26%) with 95% confidence intervals (95% CI) according to the * = median (IQR). PCI = Percutaneous Coronary Intervention, CABG = Coronary Agresti-Coull method. For statistical analysis ICH and Artery Bypass Graft Surgery. Saarinen et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:21 Page 3 of 6 http://www.sjtrem.com/content/19/1/21 Medication before hospital admission. Median time from fibrino- Four fibrinolytic agents were used: streptokinase 1997- lysis to bleeding was 22 h (IQR
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