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Unfractionated Heparin in SARS-CoV-2 Pneumonia: Ischemic Stroke Case Report.

ABSTRACT: Thromboembolism is a known phenomenon in patients with Coronavirus disease 2019 (COVID-19). Recent investigations have revealed that a significant proportion of those hospitalized with severe COVID-19 demonstrate clinical and laboratory markers compatible with hypercoagulability, which is differentiated from disseminated intravascular coagulation (DIC), termed COVID-associated coagulopathy. Additionally, there is increasing concern for development of acute ischemic stroke because of this hypercoagulable state. We present a patient with COVID-19 pneumonia who was managed with unfractionated heparin (UFH) infusion and developed a large ischemic infarct shortly after cessation of the infusion. In retrospect, the patient's coagulation parameters were consistent with overt DIC, although some of these parameters are easily masked by the effects of UFH. These findings emphasize the importance of anticoagulation as well as its careful discontinuation, as failure to do so may result in a significant thromboembolic event.

SUBMITTER: Efendizade A

PROVIDER: S-EPMC7545009 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Unfractionated Heparin in SARS-CoV-2 Pneumonia: Ischemic Stroke Case Report.

Efendizade Aslan A Dmytriw Adam A AA Hewitt Kevin K Davies Gwynivere A GA

Frontiers in neurology 20200925

Thromboembolism is a known phenomenon in patients with Coronavirus disease 2019 (COVID-19). Recent investigations have revealed that a significant proportion of those hospitalized with severe COVID-19 demonstrate clinical and laboratory markers compatible with hypercoagulability, which is differentiated from disseminated intravascular coagulation (DIC), termed COVID-associated coagulopathy. Additionally, there is increasing concern for development of acute ischemic stroke because of this hyperco ...[more]

PMID: 33101181

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Project description:Coronaviruses such as SARS-CoV-2, which is responsible for COVID-19, depend on virus spike protein binding to host cell receptors to cause infection. The SARS-CoV-2 spike protein binds primarily to ACE2 on target cells and is then processed by membrane proteases, including TMPRSS2, leading to viral internalisation or fusion with the plasma membrane. It has been suggested, however, that receptors other than ACE2 may be involved in virus binding. We have investigated the interactions of recombinant versions of the spike protein with human epithelial cell lines that express low/very low levels of ACE2 and TMPRSS2 in a proxy assay for interaction with host cells. A tagged form of the spike protein containing the S1 and S2 regions bound in a temperature-dependent manner to all cell lines, whereas the S1 region alone and the receptor-binding domain (RBD) interacted only weakly. Spike protein associated with cells independently of ACE2 and TMPRSS2, while RBD required the presence of high levels of ACE2 for interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we tested the effects of various heparins on ACE2-independent spike protein interaction with cells. Unfractionated heparin inhibited spike protein interaction with an IC50 value of <0.05 U/mL, whereas two low-molecular-weight heparins were less effective. A mutant form of the spike protein, lacking the arginine-rich putative furin cleavage site, interacted only weakly with cells and had a lower affinity for unfractionated and low-molecular-weight heparin than the wild-type spike protein. This suggests that the furin cleavage site might also be a heparin-binding site and potentially important for interactions with host cells. The glycosaminoglycans heparan sulphate and dermatan sulphate, but not chondroitin sulphate, also inhibited the binding of spike protein, indicating that it might bind to one or both of these glycosaminoglycans on the surface of target cells.

Project description:BackgroundLow-molecular-weight heparins (LMWHs) and heparinoids are anticoagulants that may have more powerful antithrombotic effects than standard unfractionated heparin (UFH) but a lower risk of bleeding complications. This is an update of the original Cochrane Review of these agents, first published in 2001 and last updated in 2008.ObjectivesTo determine whether antithrombotic therapy with LMWHs or heparinoids is associated with a reduction in the proportion of people who are dead or dependent for activities in daily living compared with UFH.Search methodsWe searched the Cochrane Stroke Group Trials Register (last searched February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library Issue 1, 2017), MEDLINE (1966 to February 2017), and Embase (1980 to February 2017). We also searched trials registers to February 2017: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform.Selection criteriaUnconfounded randomised trials comparing LMWH or heparinoids with standard UFH in people with acute ischaemic stroke, in which participants were recruited within 14 days of stroke onset.Data collection and analysisTwo review authors independently chose studies for inclusion, assessed risk of bias and trial quality, extracted and analysed the data. Differences were resolved by discussion.Main resultsWe included nine trials involving 3137 participants. We did not identify any new trials for inclusion in this updated review. None of the studies reported data on the primary outcome in sufficient detail to enable analysis for the review. Overall, there was a moderate risk of bias in the included studies. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (96/1616 allocated LMWH/heparinoid versus 78/1486 allocated UFH; odds ratio (OR) 1.06, 95% CI 0.78 to 1.47; 8 trials, 3102 participants, low quality evidence). LMWH or heparinoid were associated with a significant reduction in deep vein thrombosis (DVT) compared with UFH (OR 0.55, 95% CI 0.44 to 0.70, 7 trials, 2585 participants, low quality evidence). However, the number of the major clinical events such as pulmonary embolism (PE) and intracranial haemorrhage was too small to provide a reliable estimate of the effects.Authors' conclusionsTreatment with a LMWH or heparinoid after acute ischaemic stroke appears to decrease the occurrence of DVT compared with standard UFH, but there are too few data to provide reliable information on their effects on other important outcomes, including functional outcome, death and intracranial haemorrhage.

Project description:IntroductionInjection laryngoplasty is a common procedure for patients with vocal fold dysfunction, but the literature on its benefits has been mainly focused on those related to structural lesions or laryngeal nerve involvement. Stroke patients may be at increased risk of aspiration due to insufficient vocal fold motion. However, how injection laryngoplasty can be of benefit in stroke patients has not been reported yet.Patient concernsSix chronic stroke patients with long-standing swallowing difficulties and who showed severe aspiration despite long-term swallowing rehabilitation.DiagnosisLaryngoscope evaluation revealed insufficient glottic closure as the cause of aspiration.InterventionsInjection laryngoplasty was done per-orally under local anaesthesia with calcium hydroxylapatite (Radiesse Voice, 1-1.5 mL) in an office setting. Respiratory pressures and peak cough flows were assessed at baseline and at 2 weeks follow-up.OutcomesAt 2 weeks, the mean peak cough flow (Δ = +95.09 L/min) increased significantly after the procedure. The maximal expiratory (Δ = +18.40 cm H2O) and inspiratory (Δ = +20.20 cm H2O) pressures also improved, indicating that injection laryngoplasty was effective in augmenting respiratory and cough parameters. All cases showed improvement in the Functional Oral Intake Scale (Δ = +4). Feeding tubes were successfully removed.ConclusionInjection laryngoplasty proved to be both successful and safe in improving glottic closure with immediate results in those who had failed to show a positive response after long-term swallowing rehabilitation. The positive and dramatic clinical outcomes were observed through changes in the coughing force. Our case series support the use of injection larygnoplasty as a powerful adjunctive treatment method to prevent aspiration pneumonia in post-stroke patients with vocal fold insufficiency. Pre- and post-injection peak cough flow changes may reflect improvement in glottic closure and indicate the safety of swallowing with reduced risk of aspiration.

Dataset Information

Unfractionated Heparin in SARS-CoV-2 Pneumonia: Ischemic Stroke Case Report.

Publications

Unfractionated Heparin in SARS-CoV-2 Pneumonia: Ischemic Stroke Case Report.

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