International Normalized Ratio Monitoring Research Articles

Pharmacometabonomics Technique to Identify Warfarin Response Using Nuclear Magnetic Resonance Spectroscopy.

Warfarin, an anticoagulant medication, is prescribed regularly despite of its bleeding tendency for the prevention and/or treatment of various thromboembolic conditions, such as deep vein thrombosis, and complications associated with atrial fibrillation, and myocardial infarction, but because of its narrow therapeutic window, it has a lot of interactions with drugs and diet. Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment. Pharmacometabonomics is a novel scientific field which deals with identification and quantification of the metabolites present in the metabolome using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR). Pharmacometabonomics helps to indicate perturbation in the levels of metabolites in the cells and tissues due to drug or ingestion of any substance. NMR is one of the most widely-used spectroscopic techniques in metabolomics because of its reproducibility and speed. There are many factors that influence the metabolism of warfarin, making changes in drug dosage common, and clinical factors like drug-drug interactions, dietary interactions and age explain for the most part the variability in warfarin dosing. Some studies have showed that pharmacogenetic testing for warfarin dosing does not improve health outcomes, and around 26% of the variation in warfarin dose requirements remains unexplained yet. Many recent pharmacometabonomics studies have been conducted to identify novel biomarkers of drug therapies such as paracetamol, aspirin and simvastatin. Thus, a technique such as NMR based pharmacometabonomics to find novel biomarkers in plasma and urine might be useful to predict warfarin outcome.

Patients' preferences for new versus old anticoagulants: a mixed-method vignette-based study.

For both patients and clinicians, differences between older and new anticoagulants have major implications for treatment selection, day-to-day management of therapy and adherence. To explore patients' preferences for warfarin versus direct oral anticoagulant (DOAC) therapy. Mixed-method study involving anticoagulated older patients admitted to hospital. Part A comprised a vignette-based questionnaire; patients were asked whether they preferred Medicine A (warfarin) or Medicine B (DOAC). Part B interviews explored patients' satisfaction with their current anticoagulant. Responses were thematically analysed. Forty patients participated: 23 warfarin-treated, 17 DOAC-treated. Collectively, Parts A and B identified that most patients were satisfied with their current therapy (warfarin or DOAC), expressing reluctance to change to alternatives. Among patients who were able to numerically rate their satisfaction with therapy, most were 'satisfied' with their current anticoagulant, although warfarin-treated patients were slightly less 'satisfied' (median score 3.5) than those on DOACs (median score 5.0). Despite this, warfarin-treated patients still preferred their current therapy (over DOACs) due to familiarity and the security of regular international normalised ratio (INR) monitoring; those who preferred DOACs cited previous warfarin-related bleeding and unstable INRs as key reasons. DOAC-treated patients who preferred warfarin perceived regular monitoring as a major advantage; only those having had negative experiences with warfarin clearly preferred DOACs. Most patients accepted their currently prescribed anticoagulant, be it warfarin or DOACs. Features of specific anticoagulants, such as regular monitoring with warfarin, were perceived variably - some patients cited them as advantages and others as disadvantages. The clearest preference identified was for the agent already being taken.

Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: a retrospective cross-sectional study

BackgroundWarfarin is the most widely used anticoagulant in the world. The difficulty of managing warfarin contributes to great potential for patient harm, both from excessive anticoagulation and insufficient anticoagulation. This study assessed the International Normalized Ratio (INR) control outcome measures and warfarin dose adjustment practices at cardiology and hematology outpatient clinics at a teaching hospital in Addis Ababa, Ethiopia.MethodsThe study was based on a cross - sectional study design involving 360 retrospective patients’ chart review among outpatients who received warfarin for its various indications.ResultsThe mean frequency of INR monitoring per patient was 62.9 days (17.2–143.7 days).Patients spent 52.2%, 29.0% and 18.8% of the time in sub-therapeutic, therapeutic and supra-therapeutic ranges, respectively. The daily warfarin dose was increased 50.9% and 36.9% and decreased in 52.8% and 60.9% of the time for occurrences of sub-therapeutic and supra-therapeutic INRs to achieve target ranges of 2.0–3.0 and 2.5–3.5, respectively.ConclusionThe quality of anticoagulation management with warfarin among outpatients in Tikur Anbessa Specialized Hospital was sub-optimal. This was reflected by low Time in Therapeutic Range (TTR), longer than recommended INR monitoring frequency, and minimal actions taken to adjust warfarin dose after occurrences of non-therapeutic INRs.

Warfarin Management and Outcomes in Patients with Nonvalvular Atrial Fibrillation Within an Integrated Health Care System.

Warfarin is a common treatment option to manage patients with nonvalvular atrial fibrillation (NVAF) in clinical practice. Understanding current pharmacist-led anticoagulation clinic management patterns and associated outcomes is important for quality improvement; however, currently little evidence associating outcomes with management patterns exists. To (a) describe warfarin management patterns and (b) evaluate associations between warfarin treatment and clinical outcomes for patients with NVAF in an integrated health care system. A retrospective cohort study was conducted among NVAF patients with warfarin therapy between January 1, 2006, and December 31, 2011, using Kaiser Permanente Southern California data, and followed until December 31, 2013. Management patterns related to international normalized ratio (INR) monitoring, anticoagulation clinic pharmacist intervention (consultation), and warfarin dose adjustments were investigated along with yearly attrition rates, time-in-therapeutic ranges (TTRs), and clinical outcomes (stroke or systemic embolism and major bleeding). Descriptive statistics and multivariable Cox proportional hazard models were used to determine associations between TTR and clinical outcomes. A total of 32,074 NVAF patients on warfarin treatment were identified and followed for a median of 3.8 years. About half (49%) of the patients were newly initiating warfarin therapy. INR monitoring and pharmacist interventions were conducted roughly every 3 weeks after 6 months of warfarin treatment. Sixty-three percent of the study population had ≥ 1 warfarin dose adjustments with a mean (SD) of 6.7 (6.3) annual dose adjustments. Warfarin dose adjustments occurred at a median of 1 day (interquartile ranges [IQR] 1-3) after the INR measurement. Yearly attrition rate was from 3.3% to 6.3% during the follow-up, and median (IQR) TTR was 61% (46%-73%). Patients who received frequent INR monitoring (≥ 27 times per year), pharmacist interventions (≥ 24 times per year), or frequently adjusted warfarin dose (≥ 11 times per year) consistently showed poor TTRs (mean TTR for the highest quartiles was 45.3%-48.3%). A higher TTR was associated with a lower risk of clinical outcomes regardless of frequency of INR monitoring, pharmacist interventions, or number of dose adjustments. Patients whose TTRs were < 65%, even with frequent pharmacist interventions, had similar stroke or systemic embolism event rates, as compared with patients with TTRs < 65% and less frequent interventions (1.88 vs. 1.54 stroke or systemic embolism rates per 100 person-years, respectively, P = 0.78). The lowest TTR quartile (< 46%) was associated with a 3 times higher risk of stroke or systemic embolism (hazard ratio [HR] = 3.19, 95% CI = 2.71-3.77) and a 2 times higher risk of major bleeding (HR = 2.10, 95% CI = 1.96-2.24) compared with the highest TTR quartile (≥ 73%). Despite close monitoring with timely warfarin dose adjustments, there were still a substantial number of challenging patients whose TTRs were suboptimal despite a higher number of pharmacist interventions. These patients eventually experienced more stroke or systemic embolism and bleeding events among NVAF patients managed by anticoagulation clinics. New individualized treatment or management strategies for patients who are not able to reach optimal therapeutic ranges are necessary to improve outcomes. This research and manuscript were funded by Bristol-Myers Squibb Company and Pfizer. Authors from Bristol-Myers Squibb Company and Pfizer participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An received a grant for research support from Bristol-Myers Squibb/Pfizer. Niu, Rashid, and Zheng received a grant from Bristol-Myers Squibb/Pfizer to their institutions for salary reimbursement. Vo, Singh, and Aranda are employed by Bristol-Myers Squibb; Bruno was employed by Bristol-Myers Squibb at the time of this study. Mendes and Dills are employed by Pfizer, and Mendes was a member of the Pfizer Cardiovascular and Metabolic Field Medical Team during the time of this study. Lang, Jazdzewski, and Le have no known conflicts of interest to report. Study concept and design were contributed primarily by An and Rashid, along with the other authors. Niu took the lead in data collection, along with Zheng, and data interpretation was performed by An, along with Mendes and Dills, with assistance from the other authors. The manuscript was written by An and revised by Mendes, Dills, Vo, Singh, Bruno, and Aranda, along with Lang, Le, and Jazdezewski. Part of this study's findings was presented at the CHEST 2015 Annual Meeting in Montreal, Canada, on October 28, 2015.

Incidence of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS) according to its severity and temporal grading classification.

To evaluate hepatic encephalopathy (HE) incidence after transjugular intrahepatic portosystemic shunt (TIPS) and classify by gravity and frequency. This is a retrospective study of 75 patients with no previous episodes of HE who underwent TIPS between 2008 and 2014 with clinical follow-up after 6 and 12months. Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). HE was reported using two classifications: (1) gravity divided in moderate (West-Haven grades I-II) and severe (III-IV); (2) frequency divided in episodic and recurrent/persistent. Overall HE incidence was 36% at 6months, with 12month incidence significantly decreased to 27% (p=0.02). 13/75 (17%) patients had one episode of moderate HE, while 3/75 (4%) patients had severe recurrent/persistent HE. Age was the only pre-TIPS risk predictor. Post-TIPS bilirubin and INR showed variations from basal values only in the presence of diagnosed HE. Bilirubin significantly increased (p=0.03) in correlation to HE severity, whereas INR changes correlated with temporal frequency (p=0.04). HE distribution classified for severity is similar at 6 and 12months, whereas when classified for frequency shows significant differences (p=0.04). A classification by gravity and frequency attests post-TIPS HE as a manageable risk. Monitoring of bilirubin and INR may help on clinical management risk stratification.

Awareness and Impact of International Normalized Ratio Monitoring in Ongoing Anticoagulation Therapy in Cardiac Patients

Awareness and Impact of International Normalized Ratio Monitoring in Ongoing Anticoagulation Therapy in Cardiac Patients

Effect of International Normalized Ratio monitoring at home versus the clinic on monitoring adherence in adults taking oral anticoagulant medications: a systematic review protocol

The objective of this review is to compare International Normalized Ratio (INR) monitoring adherence in two different settings: the outpatient INR clinic and the patient's home or residence. The review seeks to identify non-adherence trends in both settings to help providers determine which setting is best for patients on warfarin to improve INR monitoring adherence. Improved INR monitoring adherence correlates with maintaining routine INR testing.Specifically, the review question is what is the effect of home point-of-care INR monitoring compared to clinic monitoring on INR monitoring adherence in adults taking oral anticoagulant medications?

PORTALS: design of an innovative approach to anticoagulation management through eHealth

BackgroundFor the monitoring of International Normalized Ratio (INR) values, venous thromboembolism (VTE) and atrial fibrillation (AF) patients can visit anticoagulation clinics, laboratories, or physicians for venous puncture. Point-of-care testing (POCT) made it possible for patients to monitor INR themselves (self-monitoring) and even self-adjust their medication dosage (self-dosage). Both skills are accepted as forms of self-management. eHealth applications can improve this self-management, resulting in better clinical outcomes.MethodsOur study, called PORTALS, aims at identifying the optimal implementation strategy of training to improve self-management and explore factors that enhance good self-management skills. In addition, the relationship between the implementation strategy of training, clinical outcomes, and individual characteristics will be investigated. Of the 247 recruited participants, 110 chose to continue with regular care. 137 patients have been randomly divided in subgroups and compared using a parallel cohort design: one group will be trained and educated by e-learning, and the other group will receive face-to-face group training.DiscussionMore insight in factors that enhance good self-management will help to improve clinical outcomes and patient satisfaction on anticoagulation therapy. Our study will provide practical insights and knowledge of eHealth in daily practice and of the importance of education on the adoption of self-management. We expect the self-management program including training to help patients to better manage their own INR values and medication use, thereby increasing health status and diminishing thromboembolic events and hospitalisation.Trial registrationThe Netherlands National Trial Register, number NTR3947.

The Time in Therapeutic Range and Bleeding Complications of Warfarin in Different Geographic Regions of Turkey: A Subgroup Analysis of WARFARIN-TR Study.

Background: The time in therapeutic range values may vary between different geographical regions of Turkey in patients vitamin K antagonist therapy.Aims: To evaluate the time in therapeutic range percentages, efficacy, safety and awareness of warfarin according to the different geographical regions in patients who participated in the WARFARIN-TR study (The Awareness, Efficacy, Safety and Time in Therapeutic Range of Warfarin in the Turkish population) in Turkey.Study Design: Cross-sectional study.Methods: The WARFARIN-TR study includes 4987 patients using warfarin and involved regular international normalized ratio monitoring between January 1, 2014 and December 31, 2014. Patients attended follow-ups for 12 months. The sample size calculations were analysed according to the density of the regional population and according to Turkish Statistical Institute data. The time in therapeutic range was calculated according to F.R. Roosendaal’s algorithm. Awareness was evaluated based on the patients’ knowledge of the effect of warfarin and food-drug interactions with simple questions developed based on a literature review. Results: The Turkey-wide time in therapeutic range was reported as 49.5%±22.9 in the WARFARIN-TR study. There were statistically significant differences between regions in terms of time in therapeutic range (p<0.001). The highest rate was reported in the Marmara region (54.99%±20.91) and the lowest was in the South-eastern Anatolia region (41.95±24.15) (p<0.001). Bleeding events were most frequently seen in Eastern Anatolia (41.6%), with major bleeding in the Aegean region (5.11%) and South-eastern Anatolia (5.36%). There were statistically significant differences between the regions in terms of awareness (p<0.001).Conclusion: Statistically significant differences were observed in terms of the efficacy, safety and awareness of warfarin therapy according to different geographical regions in Turkey.

The effect of amiodarone on warfarin anticoagulation: a register‐based nationwide cohort study involving the Swedish population

Background Data indicate that the interaction between warfarin and amiodarone results in an increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as co-medication to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more scarce. Objectives An investigation of how initiation of amiodarone affects the anticoagulant effect and dosing of warfarin, using data from three nationwide registries. Patients/Methods In a retrospective cohort study including 754 patients, warfarin doses were compared between two 4-week periods, before and 18-21 weeks after initiating co-treatment with amiodarone. In addition, warfarin doses and international normalized ratio (INR) values were calculated week-by-week after the initiation of amiodarone. Results The initiation of amiodarone increased the mean INR from 2.6 to 3.1. The proportion of patients with a supratherapeutic INR over 3.0 and 4.0 increased from 12% to 37% and 0.9% to 5.5%, respectively. The subsequent mean decrease in warfarin dose was 24.6% (95% confidence interval [CI], 23.5, 25.6). The frequency of INR monitoring within 1 and 2 weeks after initiation of amiodarone was 67% and 90%. Conclusions Although warfarin doses in most patients were within the therapeutic range, more than one in three patients initiating co-treatment with amiodarone were exposed to a supratherapeutic anticoagulative effect within 3 weeks. In order to further avoid severe unnecessary bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring, anticipating an average dose reduction of 25%.

Reducing International Normalized Ratio (INR) Related After-Hours Calls: A Performance Improvement (PI) Project

Many skilled nursing facility (SNF) residents require International Normalized Ratio (INR) monitoring. Nurses often report INRs after-hours, congesting phone lines with non-urgent calls, preventing urgent calls from being addressed expediently. This project was done in conjunction with Optum and Gonzaga University, and included 60 SNFs and 30 Nurse Practitioners (NPs). December 2014 call logs were used for baseline trends. 56% of SNFs used lab based monitoring despite evidence of more time spent at therapeutic INR with point-of-care (POC) monitoring. Labs create lag time as SNFs receive results late, leaving little time to communicate with NPs before the close of business. At baseline 15.34% of calls were for INRs, with disproportionate volumes on weekends. 25 SNFs called regarding INR results.

Pharmacogenetic dosing of warfarin in the Han-Chinese population: a randomized trial.

This study aimed to determine clinical utility of genotype-guided dosing for warfarin in Han-Chinese. A total of 320 patients were randomly assigned International Warfarin Pharmacogenetic Consortium algorithm, Taiwan algorithm and optimal clinical care arms. The primary outcome of the study was the percentage of time in the therapeutic range during the first 90 days of treatment. The percentage of time in the therapeutic range of the clinical care group in the first 2 weeks was significantly higher than the algorithm groups. This difference was no longer observed after 4 weeks. No difference in excessive anticoagulation (international normalized ratio ≥4.0) and adverse events was observed. Genotype-guided dosing did not provide significant benefit. Loading dose with frequent international normalized ratio monitoring could provide sufficient control of anticoagulation.

Warfarin utilisation and anticoagulation control in patients with atrial fibrillation and chronic kidney disease

ObjectiveTo evaluate warfarin prescription, quality of international normalised ratio (INR) monitoring and of INR control in patients with atrial fibrillation (AF) and chronic kidney disease (CKD).MethodsWe performed a retrospective cohort...

Hepatitis C virus transmission in a skilled nursing facility, North Dakota, 2013.

From March-May 2013, 3 cases of acute hepatitis C virus (HCV) infection were diagnosed among elderly patients residing at the same skilled nursing facility (facility A) and who received health care at hospital X during their likely exposure period. We performed HCV testing of at-risk populations; quasispecies analysis was performed to determine relatedness of HCV in persons with current infection. Infection control practice assessments were conducted at facility A and hospital X. Persons residing in facility A on September 9, 2013, were enrolled in a case-control study to identify risk factors for HCV infection. Forty-five outbreak-associated infections were identified. Thirty cases and 62 controls were enrolled in the case-control study. Only podiatry (odds ratio, 11.6; 95% confidence interval, 2.4-57.2) and international normalized ratio monitoring by phlebotomy (odds ratio, 6.7; 95% confidence interval, 1.7-26.6) at facility A were significantly associated with case status. Infection control lapses during podiatry and point-of-care testing procedures at facility A were identified. HCV transmission was confirmed among residents of facility A. The exact mode of transmission was not able to be identified, but infection control lapses were likely responsible. This outbreak highlights the importance of prompt reporting and investigation of incident HCV infection and the need for adherence to basic infection control procedures by health care personnel.

Impact of Baseline Stroke Risk and Bleeding Risk on Warfarin International Normalized Ratio Control in Atrial Fibrillation (from the TREAT-AF Study)

Warfarin prevents stroke and prolongs survival in patients with atrial fibrillation and flutter (AF, collectively) but can cause hemorrhage. The time in international normalized ratio (INR) therapeutic range (TTR) mediates stroke reduction and bleeding risk. This study sought to determine the relation between baseline stroke, bleeding risk, and TTR. Using data from The Retrospective Evaluation and Assessment of Therapies in Atrial Fibrillation (TREAT-AF) retrospective cohort study, national Veterans Health Administration records were used to identify patients with newly diagnosed AF from 2003 to 2012 and subsequent initiation of warfarin. Baseline stroke and bleeding risk was determined by calculating CHA2DS2-VASc and HAS-BLED scores, respectively. Main outcomes were first-year and long-term TTR and INR monitoring rate. In 167,190 patients, the proportion of patients with TTR (>65%) decreased across increasing strata of CHA2DS2-VASc and HAS-BLED. After covariate adjustment, odds of achieving TTR >65% were significantly associated with high CHA2DS2-VASc or HAS-BLED score. INR monitoring rate was similar across risk strata. In conclusion, increased baseline stroke and bleeding risk is associated with poor INR control, despite similar rates of INR monitoring. These findings may paradoxically limit warfarin's efficacy and safety in high-risk patients and may explain observed increased bleeding and stroke rates in this cohort.

Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism

The present study aimed to investigate the factors affecting the first therapeutic-target-achieving (TTA) time of warfarin therapy in patients with acute pulmonary embolism (PTE). Between January 2008 and June 2013, patients with PTE confirmed by transpulmonary arterial enhanced computed tomographic pulmonary angiography or pulmonary ventilation perfusion scanning were included in the present study. Data collected included demographic information, history of tobacco and alcohol intake, basic diseases (stable and unstable hypertension, diabetes, heart failure, cancer/cerebral infarction, old myocardial infarction and atrial fibrillation), liver and kidney function, the haemoglobin and platelet count of the blood, international normalized ratio monitoring, warfarin dosage adjustment and medication combinations. Dynamic changes in international normalized ratio, anticoagulant efficacy, and adverse events within 90 days were monitored and analyzed. Univariate analysis demonstrated that the following factors affect the first TTA time: Initial dose, body mass index (BMI), liver function, heart failure, and the administration of levofloxacin, cephalosporins, and blood circulation-activating drugs. Logistic regression analysis revealed that the following were independent factors of the first TTA time: Initial dose, BMI, liver function, heart failure and levofloxacin. Therefore, the results of the present study demonstrated that various factors may affect the first TTA time of warfarin therapy, including the initial dose, BMI, liver function, heart function and concomitant medication.

Impact of age on long-term anticoagulation and how gender and monitoring setting affect it: implications for decision making and patient management.

Stabilization of anticoagulation control is seminal to reducing the risk of adverse effects of vitamin K antagonists. Reliable information on how ageing influences this is lacking. We set out to assess the true age-related changes in anticoagulation control, how gender and patient setting influence this, and the possible implications of these for patient outcomes and management. In atrial fibrillation (AF) patients of a unified anticoagulant service monitoring patients in general practice or hospital-based clinics and housebound patients at home, international normalized ratio (INR) and warfarin dose data between 2000 and 2013 were extracted via the DAWN dosing program. Anticoagulation control was assessed by calculating percentage time spent within target INR (TTR). A total of 2094 AF patients [938 (44.8%) in general practice (GP) and 531 (25.4%) in hospital (H)-based clinics and 625 (29.8%) through the domiciliary service (D)] were evaluated. The frequency of warfarin dose changes and INR monitoring events declined until about age 67, then increased as patients got older. The TTR according to age was significantly lower and the probability of having a TTR≤65% according to age was higher for D than for H and GP, and females had a greater probability of having a TTR ≤65% than age-matched males. Identification of factors underlying poorer anticoagulation control in older housebound patients and the introduction of effective modifications to improve the clinical effectiveness of anticoagulation in such patients is needed.

Renal Dysfunction, CHADS2 Score, and Adherence to the Anticoagulant Treatment in Nonvalvular Atrial Fibrillation.

We investigated the risk of stroke associated with renal dysfunction and the impact of warfarin therapies in Chinese patients with nonvalvular atrial fibrillation (NVAF). Information was collected on age, sex, height, weight, type of atrial fibrillation, and serum creatinine within the previous 6 months, together with the variables needed to calculate the CHADS2 score. For patients not taking warfarin, reasons why not were recorded. Three thousand seventeen eligible patients with NVAF, mean (1 standard deviation [SD]) age of 67.7 (13.0) years, from 50 Chinese hospitals were included from May 2012 to October 2012, with a mean (1SD) CHADS2 score of 2.0 (1.5). Of these, 58.3% were male and 86.2% were at high risk of stroke with a CHADS2 score ≥1. Only 42.6% were on warfarin, and 22.5% of the patients had moderate or severe renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2). After adjustment for the CHADS2 score, renal dysfunction remained moderately but significantly associated with the risk of stroke/TIA (odds ratio = 1.005, 95% confidence interval: 1.002-1.009, P = .002). There was, however, no significant difference in anticoagulant usage between patients with or without impaired renal dysfunction. The most common anticoagulant concerns were the low proportion of patients with regular international normalized ratio monitoring (43.0%) and the risk of bleeding (33.3%). Renal impairment was common and independently associated with the risk of cerebrovascular embolism in Chinese patients with NVAF but not independently related to underuse of anticoagulant treatment.

Reversing the trend: interventions to treat intracranial haemorrhage associated with anticoagulation.

Spontaneous intracranial haemorrhage (ICH) is less common as a cause of stroke than ischaemia, but it has significantly worse morbidity and mortality. To some extent this reflects, the different demographics of the populations affected, but a lack of effective therapeutic options is also a contributory factor. Whilst ICH as a result of underlying vascular malformations or other structural lesions offers certain neuroradiological and/or neurosurgical possibilities to prevent recurrence, interventions to reverse damage caused by the index event remain limited regardless of aetiology. As a result, current management is mainly supportive and includes reversal of anticoagulation where appropriate, blood pressure control, prevention of hyperglycaemia and pyrexia, and the treatment of emergent complications, such as seizures. Anticoagulant and antiplatelet medications are often associated with ICH and adversely affect outcome. Patients are treated with these agents for a variety of reasons, including primary or secondary prevention of cardiac and cerebral ischaemic events. Historically, there has been a choice been between aspirin (or other antiplatelet agents) or a coumarin. However, recently a number of new agents have been developed (novel oral anticoagulants—NOACs), and have potential advantages over Warfarin, including a lower risk of haemorrhagic complications for an equivalent level of thrombo-embolic risk reduction and the lack of requirement for international normalised ratio (INR) monitoring. However, none of the NOACs has a specific agent to reverse their action in the event of haemorrhagic complications. This month, journal club focuses on reversal of drugs which contribute to or have the potential to worsen ICH. The first paper reports a randomised-controlled trial of platelet infusion versus the standard care in patients with ICH on antiplatelet agents. The second paper is a randomised-controlled trial of fresh frozen plasma versus prothrombin complex concentrate in the reversal of warfarin-associated ICH. Finally, we review an observational study of ICH associated with NOACs, focussing on prognostic factors and effectiveness of haemostatic treatments.

A male patient with myocardial infarction as a first manifestation of antiphospholipid syndrome — treatment with rivaroxaban

Data on the efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) in the antiphospholipid syndrome (APS) are not clear. We present a case of a male patient aged 34 years with a history of myocardial infarction at the age of 25 treated conservatively, at that time associated with the risk factors including arterial hypertension, cigarette smoking, hypercholesterolaemia, and overweight. The notable laboratory finding observed for the first time was prolonged activated partial thromboplastin time (aPTT). At the age of 32 the patient experienced left-sided distal thrombosis of the lower limb and ischaemic stroke. The prolonged aPTT was further evaluated. APS testing was performed revealing the positive lupus anticoagulant, elevated anticardiolipin IgG antibodies and b-2-glicoprotein I IgG antibodies. Anticoagulant therapy with warfarin was initiated. Due to the disadvantages of the need for international normalised ratio monitoring, the treatment with rivaroxaban 20 mg daily was implemented according to the patient’s preferences. The patient has been taking the rivaroxaban for 15 months and has not experienced the recurrent venous and arterial thromboembolism. This case confirms that patients with APS who experienced arterial thrombosis may benefit from treatment with NOAC. Moreover, it emphasises the need for thrombophilia screening in patients aged 50 years and younger following the myocardial infarction, especially below 30 years even in the presence of cardiovascular risk factors. Recurrent thrombotic events following myocardial infarction, especially in the absence of coronary artery stenosis, should prompt search for acquired thrombophilia, especially APS, which predisposes to venous thromboembolism and ischaemic stroke.