The Experts below are selected from a list of 9132 Experts worldwide ranked by ideXlab platform
Valentin Fuster - One of the best experts on this subject based on the ideXlab platform.
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Antiplatelet Drug resistance part 2 laboratory resistance to Antiplatelet Drugs fact or artifact
Nature Reviews Cardiology, 2009Co-Authors: Diana A. Gorog, Joseph Sweeny, Valentin FusterAbstract:Many patients experience recurrent ischemic events despite optimal Antiplatelet therapy. This has generated much interest in finding a laboratory test of platelet function to identify such patients, who have been termed 'nonresponders' or Antiplatelet 'resistant'. Laboratory tests of platelet function have identified 'resistance' in 5-60% of patients taking aspirin and 4-30% of those taking clopidogrel. However, these tests of 'resistance' have not correlated closely with subsequent recurrent events, and have not reliably identified nonresponders to Antiplatelet therapy. Here, we identify and discuss three major limitations common to all these tests. Firstly, they are performed on citrate-anticoagulated blood, secondly, blood is stored for a variable period of time, and thirdly, the assessment of thrombotic status on the basis of platelet response to only one or two agonists ignores the complexity of the mechanism of platelet thrombus formation in vivo. In this Review we discuss the significance of these important limitations, and the applicability of such in vitro platelet function tests to the prediction of in vivo events. We conclude that such tests are so unphysiological that they cannot reliably predict the true thrombotic status of patients. Identification of 'resistance' on the basis of these tests lacks sensitivity and specificity for identifying thrombotic risk, and is likely to be artifactual.
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Antiplatelet Drug resistance part 2 laboratory resistance to Antiplatelet Drugs fact or artifact
Nature Reviews Cardiology, 2009Co-Authors: Diana A. Gorog, Joseph Sweeny, Valentin FusterAbstract:In the second part of their Review on resistance to Antiplatelet medication, the authors discuss the various laboratory tests of platelet function and highlight the limitations of these methods for determining the true thrombotic status of the patient.
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Antiplatelet Drug 'resistance'. Part 1: mechanisms and clinical measurements
Nature reviews. Cardiology, 2009Co-Authors: Joseph Sweeny, Diana A. Gorog, Valentin FusterAbstract:Antiplatelet Drug therapy has become one of the cornerstones of treatment for patients with cardiovascular disease. Large clinical trials have shown that Antiplatelet medications have important clinical benefits and prevent adverse outcomes in patients with coronary artery disease. Recurrent adverse cardiovascular events still occur in a substantial proportion of patients on standard dual Antiplatelet therapy, however, which has been attributed to nonresponsiveness to this treatment. Both pharmacological and pharmacokinetic mechanisms are involved in variability in responsiveness to Antiplatelet agents, and include Drug bioavailability, medication noncompliance, Drug-Drug interactions, cytochrome P450 activity, and genetic polymorphisms. Numerous observational studies have consistently shown an association between Antiplatelet Drug nonresponsiveness and adverse clinical outcomes. However, these studies are limited by varying Antiplatelet Drug dosing regimens, heterogeneous laboratory assessments for ex vivo platelet function, and wide interindividual variation in platelet responses. Only within the last 2 years have randomized clinical trials indicated that increased dosing with Antiplatelet Drugs could reduce adverse clinical outcomes. Nonetheless, large clinical trials with standardized laboratory methods and well-defined protocols are needed that will definitively determine the association between Antiplatelet Drug nonresponsiveness and clinical events, and establish therapeutic strategies to overcome blunted Antiplatelet effects.
Alan D. Michelson - One of the best experts on this subject based on the ideXlab platform.
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Antiplatelet Drugs in the management of thrombotic ischemic events in children
2019Co-Authors: Alan D. MichelsonAbstract:Abstract There is a paucity of data on Antiplatelet therapy in the management of thrombotic/ischemic events in children, with very few randomized controlled trials. Because of this lack of rigorous evidence, no Antiplatelet Drug is approved for use in children by the U.S. Food and Drug Administration—although aspirin (a cyclooxygenase 1 inhibitor), clopidogrel (a P2Y12 antagonist) and dipyridamole (a phosphodiesterase inhibitor) are routinely used off-label in children. In addition, the P2Y12 antagonists ticagrelor and cangrelor are under active investigation as Antiplatelet agents in children. Pediatric guidelines for Antiplatelet therapy are mostly weak recommendations based on low quality of evidence.
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gls 409 an antagonist of both p2y 1 and p2y 12 potently inhibits canine coronary artery thrombosis and reversibly inhibits human platelet activation
Scientific Reports, 2018Co-Authors: Elena Smolensky Koganov, Ivan B. Yanachkov, Milka Yanachkova, George E. Wright, Alan D. Michelson, Karin Przyklenk, Andrew L. FrelingerAbstract:Dual Antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y12 receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y1 and P2Y12 ADP receptors, may be a novel and promising Antiplatelet Drug candidate. However, the salutary Antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding. The goals of this study were to: 1) provide proof-of-concept that the efficacy of GLS-409 may be maintained at lower dose(s), not accompanied by an increased propensity to bleeding; and 2) establish the extent and kinetics of the reversibility of human platelet inhibition by the agent. Lower doses of GLS-409 were identified that inhibited in vivo recurrent coronary thrombosis with no increase in bleeding time. Human platelet inhibition by GLS-409 was reversible, with rapid recovery of platelet reactivity to ADP, as measured by platelet surface activated GPIIb-IIIa and platelet surface P-selectin. These data support the concept that GLS-409 warrants further, larger-scale investigation as a novel, potential therapy in acute coronary syndromes.
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Novel aspects of Antiplatelet therapy in cardiovascular disease.
Research and practice in thrombosis and haemostasis, 2018Co-Authors: Thomas Gremmel, Alan D. Michelson, Andrew L. Frelinger, Deepak L. BhattAbstract:Antiplatelet therapy is a cornerstone in the secondary prophylaxis of adverse cardiovascular events such as myocardial infarction and stroke. The cyclooxygenase inhibitor aspirin remains the most frequently prescribed Antiplatelet Drug, followed by adenosine diphosphate P2Y12 receptor blockers. Glycoprotein IIb-IIIa antagonists are intravenously available Antiplatelet agents preventing platelet-to-platelet aggregation via the fibrinogen receptor. The thrombin receptor inhibitor vorapaxar allows the targeting of yet a third pathway of platelet activation. Despite the advent of novel agents and major advances in Antiplatelet treatment over the last decade, atherothrombotic events still impair the prognosis of many patients with cardiovascular disease. Consequently, Antiplatelet therapy remains a field of intense research and a large number of studies on its various aspects are published each year. This review article summarizes recent developments in Antiplatelet therapy in cardiovascular disease focusing particularly on the duration of dual Antiplatelet therapy, new treatment regimens, the role of platelet function testing, and potential future targets of Antiplatelet agents.
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GLS-409, an Antagonist of Both P2Y1 and P2Y12, Potently Inhibits Canine Coronary Artery Thrombosis and Reversibly Inhibits Human Platelet Activation
Nature Publishing Group, 2018Co-Authors: Elena Smolensky Koganov, Ivan B. Yanachkov, Milka Yanachkova, George E. Wright, Alan D. Michelson, Karin Przyklenk, Andrew L. FrelingerAbstract:Abstract Dual Antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y12 receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y1 and P2Y12 ADP receptors, may be a novel and promising Antiplatelet Drug candidate. However, the salutary Antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding. The goals of this study were to: 1) provide proof-of-concept that the efficacy of GLS-409 may be maintained at lower dose(s), not accompanied by an increased propensity to bleeding; and 2) establish the extent and kinetics of the reversibility of human platelet inhibition by the agent. Lower doses of GLS-409 were identified that inhibited in vivo recurrent coronary thrombosis with no increase in bleeding time. Human platelet inhibition by GLS-409 was reversible, with rapid recovery of platelet reactivity to ADP, as measured by platelet surface activated GPIIb-IIIa and platelet surface P-selectin. These data support the concept that GLS-409 warrants further, larger-scale investigation as a novel, potential therapy in acute coronary syndromes
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Synergistic Inhibition of Both P2Y1 and P2Y12 Adenosine Diphosphate Receptors As Novel Approach to Rapidly Attenuate Platelet-Mediated Thrombosis
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Thomas Gremmel, Ivan B. Yanachkov, Milka Yanachkova, George E. Wright, Joseph M. Wider, Vishnu V. Undyala, Alan D. Michelson, Andrew L. Frelinger, Karin PrzyklenkAbstract:Objective—Unlike currently approved adenosine diphosphate receptor antagonists, the new diadenosine tetraphosphate derivative GLS-409 targets not only P2Y12 but also the second human platelet adenosine diphosphate receptor P2Y1 and may, therefore, be a promising Antiplatelet Drug candidate. The current study is the first to investigate the in vivo antithrombotic effects of GLS-409. Approach and Results—We studied (1) the in vivo effects of GLS-409 on agonist-stimulated platelet aggregation in anesthetized rats, (2) the antithrombotic activity of GLS-409 and the associated effect on the bleeding time in a canine model of platelet-mediated coronary artery thrombosis, and (3) the inhibition of agonist-stimulated platelet aggregation by GLS-409 versus selective P2Y1 and P2Y12 inhibition in vitro in samples from healthy human subjects before and 2 hours after aspirin intake. In vivo treatment with GLS-409 significantly inhibited adenosine diphosphate- and collagen-stimulated platelet aggregation in rats. Furth...
Diana A. Gorog - One of the best experts on this subject based on the ideXlab platform.
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Antiplatelet Drug resistance part 2 laboratory resistance to Antiplatelet Drugs fact or artifact
Nature Reviews Cardiology, 2009Co-Authors: Diana A. Gorog, Joseph Sweeny, Valentin FusterAbstract:Many patients experience recurrent ischemic events despite optimal Antiplatelet therapy. This has generated much interest in finding a laboratory test of platelet function to identify such patients, who have been termed 'nonresponders' or Antiplatelet 'resistant'. Laboratory tests of platelet function have identified 'resistance' in 5-60% of patients taking aspirin and 4-30% of those taking clopidogrel. However, these tests of 'resistance' have not correlated closely with subsequent recurrent events, and have not reliably identified nonresponders to Antiplatelet therapy. Here, we identify and discuss three major limitations common to all these tests. Firstly, they are performed on citrate-anticoagulated blood, secondly, blood is stored for a variable period of time, and thirdly, the assessment of thrombotic status on the basis of platelet response to only one or two agonists ignores the complexity of the mechanism of platelet thrombus formation in vivo. In this Review we discuss the significance of these important limitations, and the applicability of such in vitro platelet function tests to the prediction of in vivo events. We conclude that such tests are so unphysiological that they cannot reliably predict the true thrombotic status of patients. Identification of 'resistance' on the basis of these tests lacks sensitivity and specificity for identifying thrombotic risk, and is likely to be artifactual.
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Antiplatelet Drug resistance part 2 laboratory resistance to Antiplatelet Drugs fact or artifact
Nature Reviews Cardiology, 2009Co-Authors: Diana A. Gorog, Joseph Sweeny, Valentin FusterAbstract:In the second part of their Review on resistance to Antiplatelet medication, the authors discuss the various laboratory tests of platelet function and highlight the limitations of these methods for determining the true thrombotic status of the patient.
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Antiplatelet Drug 'resistance'. Part 1: mechanisms and clinical measurements
Nature reviews. Cardiology, 2009Co-Authors: Joseph Sweeny, Diana A. Gorog, Valentin FusterAbstract:Antiplatelet Drug therapy has become one of the cornerstones of treatment for patients with cardiovascular disease. Large clinical trials have shown that Antiplatelet medications have important clinical benefits and prevent adverse outcomes in patients with coronary artery disease. Recurrent adverse cardiovascular events still occur in a substantial proportion of patients on standard dual Antiplatelet therapy, however, which has been attributed to nonresponsiveness to this treatment. Both pharmacological and pharmacokinetic mechanisms are involved in variability in responsiveness to Antiplatelet agents, and include Drug bioavailability, medication noncompliance, Drug-Drug interactions, cytochrome P450 activity, and genetic polymorphisms. Numerous observational studies have consistently shown an association between Antiplatelet Drug nonresponsiveness and adverse clinical outcomes. However, these studies are limited by varying Antiplatelet Drug dosing regimens, heterogeneous laboratory assessments for ex vivo platelet function, and wide interindividual variation in platelet responses. Only within the last 2 years have randomized clinical trials indicated that increased dosing with Antiplatelet Drugs could reduce adverse clinical outcomes. Nonetheless, large clinical trials with standardized laboratory methods and well-defined protocols are needed that will definitively determine the association between Antiplatelet Drug nonresponsiveness and clinical events, and establish therapeutic strategies to overcome blunted Antiplatelet effects.
Andrew L. Frelinger - One of the best experts on this subject based on the ideXlab platform.
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gls 409 an antagonist of both p2y 1 and p2y 12 potently inhibits canine coronary artery thrombosis and reversibly inhibits human platelet activation
Scientific Reports, 2018Co-Authors: Elena Smolensky Koganov, Ivan B. Yanachkov, Milka Yanachkova, George E. Wright, Alan D. Michelson, Karin Przyklenk, Andrew L. FrelingerAbstract:Dual Antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y12 receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y1 and P2Y12 ADP receptors, may be a novel and promising Antiplatelet Drug candidate. However, the salutary Antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding. The goals of this study were to: 1) provide proof-of-concept that the efficacy of GLS-409 may be maintained at lower dose(s), not accompanied by an increased propensity to bleeding; and 2) establish the extent and kinetics of the reversibility of human platelet inhibition by the agent. Lower doses of GLS-409 were identified that inhibited in vivo recurrent coronary thrombosis with no increase in bleeding time. Human platelet inhibition by GLS-409 was reversible, with rapid recovery of platelet reactivity to ADP, as measured by platelet surface activated GPIIb-IIIa and platelet surface P-selectin. These data support the concept that GLS-409 warrants further, larger-scale investigation as a novel, potential therapy in acute coronary syndromes.
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Novel aspects of Antiplatelet therapy in cardiovascular disease.
Research and practice in thrombosis and haemostasis, 2018Co-Authors: Thomas Gremmel, Alan D. Michelson, Andrew L. Frelinger, Deepak L. BhattAbstract:Antiplatelet therapy is a cornerstone in the secondary prophylaxis of adverse cardiovascular events such as myocardial infarction and stroke. The cyclooxygenase inhibitor aspirin remains the most frequently prescribed Antiplatelet Drug, followed by adenosine diphosphate P2Y12 receptor blockers. Glycoprotein IIb-IIIa antagonists are intravenously available Antiplatelet agents preventing platelet-to-platelet aggregation via the fibrinogen receptor. The thrombin receptor inhibitor vorapaxar allows the targeting of yet a third pathway of platelet activation. Despite the advent of novel agents and major advances in Antiplatelet treatment over the last decade, atherothrombotic events still impair the prognosis of many patients with cardiovascular disease. Consequently, Antiplatelet therapy remains a field of intense research and a large number of studies on its various aspects are published each year. This review article summarizes recent developments in Antiplatelet therapy in cardiovascular disease focusing particularly on the duration of dual Antiplatelet therapy, new treatment regimens, the role of platelet function testing, and potential future targets of Antiplatelet agents.
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GLS-409, an Antagonist of Both P2Y1 and P2Y12, Potently Inhibits Canine Coronary Artery Thrombosis and Reversibly Inhibits Human Platelet Activation
Nature Publishing Group, 2018Co-Authors: Elena Smolensky Koganov, Ivan B. Yanachkov, Milka Yanachkova, George E. Wright, Alan D. Michelson, Karin Przyklenk, Andrew L. FrelingerAbstract:Abstract Dual Antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y12 receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y1 and P2Y12 ADP receptors, may be a novel and promising Antiplatelet Drug candidate. However, the salutary Antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding. The goals of this study were to: 1) provide proof-of-concept that the efficacy of GLS-409 may be maintained at lower dose(s), not accompanied by an increased propensity to bleeding; and 2) establish the extent and kinetics of the reversibility of human platelet inhibition by the agent. Lower doses of GLS-409 were identified that inhibited in vivo recurrent coronary thrombosis with no increase in bleeding time. Human platelet inhibition by GLS-409 was reversible, with rapid recovery of platelet reactivity to ADP, as measured by platelet surface activated GPIIb-IIIa and platelet surface P-selectin. These data support the concept that GLS-409 warrants further, larger-scale investigation as a novel, potential therapy in acute coronary syndromes
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Synergistic Inhibition of Both P2Y1 and P2Y12 Adenosine Diphosphate Receptors As Novel Approach to Rapidly Attenuate Platelet-Mediated Thrombosis
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Thomas Gremmel, Ivan B. Yanachkov, Milka Yanachkova, George E. Wright, Joseph M. Wider, Vishnu V. Undyala, Alan D. Michelson, Andrew L. Frelinger, Karin PrzyklenkAbstract:Objective—Unlike currently approved adenosine diphosphate receptor antagonists, the new diadenosine tetraphosphate derivative GLS-409 targets not only P2Y12 but also the second human platelet adenosine diphosphate receptor P2Y1 and may, therefore, be a promising Antiplatelet Drug candidate. The current study is the first to investigate the in vivo antithrombotic effects of GLS-409. Approach and Results—We studied (1) the in vivo effects of GLS-409 on agonist-stimulated platelet aggregation in anesthetized rats, (2) the antithrombotic activity of GLS-409 and the associated effect on the bleeding time in a canine model of platelet-mediated coronary artery thrombosis, and (3) the inhibition of agonist-stimulated platelet aggregation by GLS-409 versus selective P2Y1 and P2Y12 inhibition in vitro in samples from healthy human subjects before and 2 hours after aspirin intake. In vivo treatment with GLS-409 significantly inhibited adenosine diphosphate- and collagen-stimulated platelet aggregation in rats. Furth...
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Measuring Antiplatelet Drug effects in the laboratory
Thrombosis research, 2007Co-Authors: Paul J. Harrison, Andrew L. Frelinger, Mark I. Furman, Alan D. MichelsonAbstract:This review discusses the advantages and disadvantages of currently available tests for the monitoring of Antiplatelet therapy (especially aspirin and clopidogrel). Many tests of platelet function are now available for clinical use, and some of these tests have been shown to predict clinical outcomes after Antiplatelet therapy. However, in most of these studies, the number of major adverse clinical events was low. No published studies address the clinical effectiveness of altering therapy based on the results of monitoring Antiplatelet therapy. Therefore, the correct treatment, if any, of "resistance" to Antiplatelet therapy is unknown and, other than in research trials, monitoring of Antiplatelet therapy in patients is not generally recommended. A clinically meaningful definition of "resistance" to Antiplatelet Drugs needs to be developed, based on data linking Drug-dependent laboratory tests to clinical outcomes in patients.
Philip M W Bath - One of the best experts on this subject based on the ideXlab platform.
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desmopressin for reversal of Antiplatelet Drugs in stroke due to haemorrhage dash protocol for a phase ii double blind randomised controlled feasibility trial
BMJ Open, 2020Co-Authors: Michael J R Desborough, Rustam Alshahi Salman, Simon J Stanworth, Diane Havard, Paul Brennan, Robert A Dineen, Timothy J Coats, Trish Hepburn, Philip M W BathAbstract:Introduction Intracerebral haemorrhage (ICH) can be devastating and is a common cause of death and disability worldwide. Pre-ICH Antiplatelet Drug use is associated with a 27% relative increase in 1 month case fatality compared with patients not using antithrombotic Drugs. We aim to assess the feasibility of conducting a randomised controlled testing the safety and efficacy of desmopressin for patients with Antiplatelet-associated ICH. Methods and analysis We aim to include 50 patients within 24 hours of spontaneous ICH onset, associated with oral Antiplatelet Drug(s) use in at least the preceding 7 days. Patients will be randomised (1:1) to receive intravenous desmopressin 20 µg in 50 mL sodium chloride 0.9% infused over 20 min or matching placebo. We will mask participants, relatives and outcome assessors to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, number of patients receiving allocated treatment, rate of recruitment and adherence to treatment and follow-up. Secondary outcomes include change in ICH volume at 24 hours; hyponatraemia at 24 hours, length of hospital stay, discharge destination, early death less than 28 days, death or dependency at day 90, death up to day 90, serious adverse events (including thromboembolic events) up to day 90; disability (Barthel index, day 90), quality of life (EuroQol 5D (EQ-5D), day 90), cognition (telephone mini-mental state examination day 90) and health economic assessment (EQ-5D). Ethics and dissemination The Desmopressin for reversal of Antiplatelet Drugs in Stroke due to Haemorrhage (DASH) trial received ethical approval from the East Midlands—Nottingham 2 research ethics committee (18/EM/0184). The DASH trial is funded by National Institute for Health and Care Research RfPB grant: PB-PG-0816-20011. Trial results will be published in a peer reviewed academic journal and disseminated through academic conferences and through patient stroke support groups. Reporting will be in compliance with Consolidated Standards of Reporting Trials recommendations. Trial registration numbers NCT03696121; ISRCTN67038373; EudraCT 2018-001904-12.
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desmopressin for reversal of Antiplatelet Drugs in stroke due to haemorrhage dash rationale and design of a phase ii double blind randomised controlled trial
British Journal of Haematology, 2019Co-Authors: Michael J R Desborough, Simon J Stanworth, Diane Havard, Paul Brennan, Robert A Dineen, Timothy J Coats, Trish Hepburn, Alshahi R Salman, P Johnson, Philip M W BathAbstract:RationaleIntracerebral haemorrhage caused ˜3 million deaths worldwide in 2015. Two‐thirds of survivors are left dependent on others. Roughly one third of patients are taking Antiplatelet Drugs at the time of intracerebral haemorrhage in high‐income countries, and this proportion has been increasing over time. Pre‐stroke Antiplatelet Drug use is associated with a 27% relative increase in one‐month case fatality compared to patients not using antithrombotic Drugs. Platelet transfusion, tranexamic acid, and recombinant activated factor VII do not seem to improve outcome after Antiplatelet‐associated intracerebral haemorrhage, but desmopressin has seemed promising in non‐randomised pilot studies.ObjectivesWe aim to assess the feasibility of screening, checking the eligibility, approaching, randomising, administering desmopressin or placebo, and completing follow‐up for patients with Antiplatelet‐associated intracerebral haemorrhage. DesignWe aim to include 50 patients within 12 hours of spontaneous intracerebral haemorrhage onset, associated with oral Antiplatelet Drug(s) use in the preceding seven days. Exclusion criteria are: known secondary cause for intracerebral haemorrhage; risk of fluid retention associated with desmopressin; significant hypotension (SBP < 90 mmHg); known Drug‐eluting coronary artery stent in previous three months; allergy to desmopressin; pre‐stroke dependency; Glasgow coma scale < 5; pre‐morbid life expectancy < 3 months; and pregnant or breastfeeding at randomisation. Patients will be randomised (1:1) to receive intravenous desmopressin 20 μg in 50 mls Sodium Chloride 0.9% infused over 20 minutes or matching placebo. We will mask participants, relatives, researchers and outcome assessors to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, number of patients receiving allocated treatment, rate of recruitment, and adherence to treatment and follow up. Secondary outcomes include change in intracerebral haemorrhage volume at 24 hours; hyponatraemia at 24 hours, length of hospital stay, discharge destination, early mortality < 28 days, death or dependency at day 90, mortality up to day 90, serious adverse events (including thromboembolic events) up to day 90; disability (Barthel index, day 90), quality of life (EuroQol, day 90), cognition (telephone MMSE day 90), and health economic assessment (EQ‐5D). Baseline platelet dysfunction will be measured and correlated with response to desmopressin; and change in factor VIII, VWF antigen and VWF activity will be assessed one hour after administration of desmopressin.ConclusionThis is a feasibility trial, which will inform the design of a definitive trial.