anticoagulant reversal
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2022 ◽  
Vol 12 ◽  
Author(s):  
Igor Sibon ◽  
Mikael Mazighi ◽  
Didier Smadja

Background: The occurrence of both ischaemic (IS) and haemorrhagic stroke in patients on anticoagulation is a major issue due to the frequency of their prescriptions in westernised countries and the expected impact of anticoagulant activity on recanalization during an IS or on the outcomes associated with intracerebral haemorrhage (ICH). Several guidelines are available but sometimes differ in their conclusions or regarding specific issues, and their application in routine emergency settings may be limited by particular individual issues or heterogeneous local specificities.Methods: Based on the current guidelines and additional published data, the algorithms proposed in this paper aim to help the decision-making process regarding stroke management in the setting of concurrent anticoagulants by addressing specific clinical situations based on clinical variables commonly encountered in real-world practise.Results: For patients on non–vitamin K oral anticoagulants, reversion can be achieved with specific antidotes, but only idarucizumab, the specific dabigatran antidote, is indicated in both IS and ICH. Due to the low risk of a prothrombotic effect, idarucizumab can be immediately used in IS patients eligible for thrombolysis before the dabigatran concentration is known. To optimise ICH management, the time since symptom onset, with thresholds proposed at 6 and 9 hours based on the expected timing of haematoma expansion, could also to be taken into account.Conclusions: Anticoagulant reversal in patients presenting with a stroke remains a major issue, and algorithms based on a step-by-step approach may be useful for clinical practise. Real-life studies strongly support the benefits of idarucizumab availability in stroke units and emergency departments.


Nursing ◽  
2021 ◽  
Vol 51 (6) ◽  
pp. 54-64
Author(s):  
Andrea Hafer ◽  
Lindsay McCann

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alessandro Prior ◽  
Pietro Fiaschi ◽  
Corrado Iaccarino ◽  
Roberto Stefini ◽  
Denise Battaglini ◽  
...  

Abstract Background Anticoagulant assumption is a concern in neurosurgical patient that implies a delicate balance between the risk of thromboembolism versus the risk of peri- and postoperative hemorrhage. Methods We performed a survey among 129 different neurosurgical departments in Italy to evaluate practice patterns regarding the management of neurosurgical patients taking anticoagulant drugs. Furthermore, we reviewed the available literature, with the aim of providing a comprehensive but practical summary of current recommendations. Results Our survey revealed that there is a lack of knowledge, mostly regarding the indication and the strategies of anticoagulant reversal in neurosurgical clinical practice. This may be due a lack of national and international guidelines for the care of anticoagulated neurosurgical patients, along with the fact that coagulation and hemostasis are not simple topics for a neurosurgeon. Conclusions To overcome this issue, establishment of hospital-wide policy concerning management of anticoagulated patients and developed in an interdisciplinary manner are strongly recommended.


2020 ◽  
Vol 49 (1) ◽  
pp. 456-456
Author(s):  
Liza Vo ◽  
Anne Rain Brown ◽  
Reagan Collins

Blood ◽  
2020 ◽  
Author(s):  
Jack Ansell ◽  
Bryan Laulicht ◽  
Sasha H Bakhru ◽  
Allison Burnett ◽  
Xuan Jiang ◽  
...  

Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind non-covalently by charge-charge interaction to unfractionated heparin (UFH) and low molecular weight heparin (LMWH). It shows similar binding characteristics to the direct oral anticoagulants (DOAC). Dynamic light scattering methodology was used to demonstrate ciraparantag binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and to commonly used drugs. Ciraparantag reaches maximum concentration within minutes following intravenous (IV) administration with a half-life of 12 - 19 minutes. It is primarily hydrolyzed by serum peptidases into two metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration) a single IV dose of ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduces the amount of blood loss. Ciraparantag given after the bleeding injury also significantly reduces blood loss. Ciraparantag appears to have substantial ability to reduce blood loss in animal models given a variety of anticoagulants and has potential as a useful DOAC reversal agent.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-24
Author(s):  
Jack Ansell ◽  
Bryan Laulicht ◽  
Sasha Bakhru ◽  
Xiaohui Luo ◽  
Stephen Villano

Introduction: There is an unmet need for safe and effective anticoagulant reversal agents, with rapid onset of effects, for use in cases such as serious or life-threating bleeding, prior to urgent or emergency surgery, after major trauma, or in cases of anticoagulant overdose. Ciraparantag, an anticoagulant reversal agent with broad activity, binds directly to anticoagulant molecules including direct oral anticoagulants (DOACs), enoxaparin, and unfractionated heparin, without binding to endogenous coagulation factors or other plasma proteins. Two Phase 2 studies evaluated the safety and efficacy of ciraparantag for reversal of anticoagulation induced by apixaban or rivaroxaban in healthy adults. Methods: Two randomized, placebo-controlled, dose-ranging studies were conducted in healthy subjects 50-75 years of age. Subjects received apixaban or rivaroxaban until steady state. Study 1 subjects received apixaban 10 mg orally twice daily for 3.5 days. Study 2 subjects received rivaroxaban 20 mg orally once daily for 3 days. At steady-state anticoagulation subjects were randomized 3:1 to a single intravenous (IV) dose of ciraparantag (Study 1: 30, 60, or 120 mg; Study 2: 30, 60, 120 or 180 mg) or placebo. Efficacy was based on manual whole blood clotting time (WBCT) at multiple timepoints over 24 hours beginning at 15 minutes after dosing. Subjects and technicians performing the WBCT testing were blinded to treatment. WBCT measures were performed in triplicate (simultaneous testing by 3 different evaluators) at 3 separate timepoints to analyze inter-observer variability using an analysis of variance (ANOVA) model with effects for observer and subject. Results: In Study 1 (apixaban), 49 subjects were randomized to receive study drug (36 ciraparantag, 13 placebo) and completed the study as planned. In Study 2 (rivaroxaban), 64 subjects were randomized to receive study drug (48 ciraparantag, 16 placebo) and all but one subject completed the study as planned. Ciraparantag demonstrated a rapid and dose-dependent reversal of apixaban and rivaroxaban anticoagulation as measured by the proportion of subjects whose WBCT decreased to within 10% above baseline at 15 minutes after study drug infusion. A lower dose of ciraparantag was required to achieve reversal of apixaban in a large fraction of subjects compared to the dose required for reversal of rivaroxaban (Figure). Reversal of anticoagulation was sustained in these subjects throughout the 24-hour measurement period. In both studies, there was good agreement among the triplicate manual WBCT measurements; all inter-observer coefficient of variance values were <5%. Ciraparantag was well tolerated; the most frequent adverse events were mild, transient sensations of warmth during or soon after infusion. Conclusions: In healthy subjects at steady-state levels of anticoagulation, ciraparantag single IV doses were well tolerated and produced rapid reversal of anticoagulation in high proportions of subjects within 15 minutes of administration (the first timepoint assessed) at doses ≥60 mg for apixaban and at a dose of 180 mg for rivaroxaban which were maintained throughout the 24-hour measurement period. Figure. Proportion of subjects with WBCT reversed to within 10% above baseline at 15 minutes and 30 minutes after dosing Disclosures Ansell: Amag Pharmaceuticals, Inc.: Consultancy. Bakhru:Pherosphere Technologies, Inc.: Current Employment. Luo:Amag Pharmaceuticals, Inc.: Current Employment. Villano:Amag Pharmaceuticals, Inc.: Consultancy. OffLabel Disclosure: Ciraparantag is an investigational drug being evaluated for the reversal of anticoagulation induced by direct oral anticoagulant (DOAC) therapies.


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