Thrombolysis for Acute Ischemic Stroke After Protamine Reversal of Heparin

Danoun, Omar A.; Sachar, Pawani; Rajamani, Kumar

doi:10.1097/mjt.0000000000000634

Cited by 8 publications

(6 citation statements)

References 5 publications

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“…So far, the safety and efficacy of IVT after heparin antagonization with protamine has not been evaluated in large studies. In our case series and systematic review of the published cases of IVT in heparin-/protamine-treated AIS patients published from 2011 until the end of September 2021, 12,[31][32][33][34][35][36] the main findings were as follows.…”

Section: Discussionmentioning

confidence: 79%

“…Furthermore, no adverse events due to protamine were reported. In the systematic literature review, a total of 34 articles were identified and 7 articles including five case reports (Fontaine et al, 31 Bereczki et al, 32 Safouris et al, 33 Danoun et al, 34 and Warner et al 12 ) and two case series of three patients each (Guevara et al, 35 Ranasinghe et al 36 ) were retained (see Figure 1).…”

Section: Resultsmentioning

confidence: 99%

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Intravenous thrombolysis in acute ischemic stroke after antagonization of unfractionated heparin with protamine: case series and systematic review of literature

Kneer

Adeyemi

Sartor-Pfeiffer

et al. 2023

Ther Adv Neurol Disord

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Background and aims: Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin. Objectives: The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine. Methods: Patients from our stroke center (between January 2015 and September 2021) treated with IVT after heparin antagonization with protamine were analyzed. National Institutes of Health Stroke Scale (NIHSS) was used for stroke severity and modified Rankin Scale (mRS) for outcome assessment. Substantial neurological improvement was defined as the difference between admission and discharge NIHSS of ⩾8 or discharge NIHSS of ⩽1. Good outcome at follow-up after 3 months was defined as mRS 0–2. Safety data were obtained for mortality, symptomatic intracerebral hemorrhage (sICH), and for adverse events due to protamine. Second, a systematic review was performed searching PubMed and Scopus for studies and case reviews presenting AIS patients treated with IVT after heparin antagonization with protamine. The search was limited from January 1, 2011 to September 29, 2021. Furthermore, we conducted a propensity score matching comparing protamine-treated patients to a control IVT group without protamine (ratio 2:1, match tolerance 0.2). Results: A total of 16 patients, 5 treated in our hospital and 11 from literature, [65.2 ± 13.1 years, 37.5% female, median premorbid mRS (pmRS) 1 (IQR 1, 4)] treated with IVT after heparin antagonization using protamine were included and compared to 31 IVT patients [76.2 ± 10.9 years, 45% female, median pmRS 1 (IQR 0, 2)]. Substantial neurological improvement was evident in 68.8% of protamine-treated patients versus 38.7% of control patients ( p = 0.028). Good clinical outcome at follow-up was observed in 56.3% versus 58.1% of patients ( p = 0.576). No adverse events due to protamine were reported, one patient suffered sICH after secondary endovascular thrombectomy of large vessel occlusion. Mortality was 6.3% versus 22.6% ( p = 0.236). Conclusion: IVT after heparin antagonization with protamine seems to be safe and, prospectively, may extend the number of AIS patients who can benefit from reperfusion treatment using IVT. Further prospective registry trials would be helpful to further investigate the clinical applicability of heparin antagonization.

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Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Intravenous thrombolysis in acute ischemic stroke after antagonization of unfractionated heparin with protamine: case series and systematic review of literature

Kneer

Adeyemi

Sartor-Pfeiffer

et al. 2023

Ther Adv Neurol Disord

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“…It is used at a dose of 0.9 mg/kg of body weight. The frequency of r-tPA treatment has been increasing over the past 15 years [4][5][6].…”

Section: Recombinant Tissue-type Plasminogen Activatormentioning

confidence: 99%

“…Requirements of using rt-Pa: -diagnosis of ischemic stroke with a significant neurological deficit by a doctor experienced in the treatment of stroke; -determining the exact time of onset of symptoms based on reliable and credible medical history from the patient or witness of the event; -exclusion of intracranial bleeding by computed tomography or magnetic resonance imaging; -determination of basic life parameters [4][5][6]. Intravenous thrombolysis is the basis for the AIS treatment in any patient with a disability causing deficits within 4.6 hours of the onset of symptoms.…”

Section: Recombinant Tissue-type Plasminogen Activatormentioning

confidence: 99%

Thrombolysis and Mechanical Thrombectomy as Leading Treatments for Acute Ischemic Stroke

Filipska

Wiśniewski

Ślusarz

2019

PNIN

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Brain vascular diseases, especially strokes, are still a very serious public health and medicine problem. The world is still facing an epidemic of stroke. With the impact load increasing all over the world, there is a continuing need to understand the characteristics of this disease and its impact in different countries. Despite significant improvements in primary prevention and treatment efficacy over the past decades, stroke is still a debilitating disease. Early treatment is the key to successful recovery of patients with ischemic stroke. The aim of the study is to show the most effective methods of treating patients in the acute phase of ischemic stroke. (JNNN 2019;8(4):177–181) Key Words: ischemic stroke, treatment, thrombolysis, thrombectomy

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“…Thus, we do not recommend IVT after emergent reversal of prolonged INR using the concentrates at this time, although a few case reports supported the feasibility of this strategy [ 57 , 58 ]. Similarly, we do not recommend IVT after emergent reversal of prolonged aPTT using protamine sulfate, though a few case reports supported its feasibility [ 59 , 60 ].…”

Section: Revised Clinical Guides On Stroke Thrombolysis For Anticoagumentioning

confidence: 99%

Consensus Guides on Stroke Thrombolysis for Anticoagulated Patients from Japan: Application to Other Populations

2018

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Development of direct oral anticoagulants and their antidotes has led to the need to reconsider the eligibility of acute stroke patients who have been taking oral anticoagulants for intravenous thrombolysis. Officially authorized Japanese guidelines on this issue were revised twice at the time of approval for clinical use of direct oral anticoagulants and idarucizumab, a specific reversal agent for dabigatran. A unique recommendation in the latest Japanese clinical guides was that thrombolysis can be recommended if the time of the last dose of direct oral anticoagulants exceeds 4 hours and if commonly available anticoagulation markers are normal or subnormal, i.e., international normalized ratio of prothrombin time <1.7 and activated partial thromboplastin time <1.5 times the baseline value (≤40 seconds only as a guide). These criteria are partly supported by the findings of domestic multicenter and single-center surveys that symptomatic or asymptomatic intracranial hemorrhage following thrombolysis was rare under the conditions of the criteria. Even for dabigatran users, stroke thrombolysis can be considered without pretreatment by idarucizumab if patients meet the above criteria. If not, direct mechanical thrombectomy can be considered without pretreatment by idarucizumab or thrombolysis, and use of idarucizumab, followed immediately by thrombolysis, can be considered only when thrombectomy cannot be quickly performed. These clinical guides are practical and to some extent economical, but they have some limitations, including lack of corroborating information from sufficient numbers of relevant cases. The guides will be further modified based on the results of future research.

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Thrombolysis for Acute Ischemic Stroke After Protamine Reversal of Heparin

Cited by 8 publications

References 5 publications

Intravenous thrombolysis in acute ischemic stroke after antagonization of unfractionated heparin with protamine: case series and systematic review of literature

Intravenous thrombolysis in acute ischemic stroke after antagonization of unfractionated heparin with protamine: case series and systematic review of literature

Thrombolysis and Mechanical Thrombectomy as Leading Treatments for Acute Ischemic Stroke

Consensus Guides on Stroke Thrombolysis for Anticoagulated Patients from Japan: Application to Other Populations

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