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1.
JAMA ; 327(9): 826-835, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1750256

ABSTRACT

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.


Subject(s)
Cerebral Arteries , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Thrombectomy , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , Arterial Occlusive Diseases/complications , Combined Modality Therapy , Double-Blind Method , Female , Humans , Ischemic Stroke/complications , Male , Middle Aged , Treatment Outcome
2.
J Stroke Cerebrovasc Dis ; 31(1): 106179, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525870

ABSTRACT

OBJECTIVES: This study aims to evaluate shortening door-to-needle time of intravenous recombinant tissue plasminogen activator of acute ischemic stroke patients by multidisciplinary collaboration and workflow optimization based on our hospital resources. MATERIALS AND METHODS: We included patients undergoing thrombolysis with intravenous recombinant tissue plasminogen activator from January 1, 2018, to September 30, 2020. Patients were divided into pre- (January 1, 2018, to December 31, 2019) and post-intervention groups (January 1, 2020, to September 31, 2020). We conducted multi-department collaboration and process optimization by implementing 16 different measures in prehospital, in-hospital, and post-acute feedback stages for acute ischemic stroke patients treated with intravenous thrombolysis. A comparison of outcomes between both groups was analyzed. RESULTS: Two hundred and sixty-three patients received intravenous recombinant tissue plasminogen activator in our hospital during the study period, with 128 and 135 patients receiving treatment in the pre-intervention and post-intervention groups, respectively. The median (interquartile range) door-to-needle time decreased significantly from 57.0 (45.3-77.8) min to 37.0 (29.0-49.0) min. Door-to-needle time was shortened to 32 min in the post-intervention period in the 3rd quarter of 2020. The door-to-needle times at the metrics of ≤ 30 min, ≤ 45 min, ≤ 60 min improved considerably, and the DNT> 60 min metric exhibited a significant reduction. CONCLUSIONS: A multidisciplinary collaboration and continuous process optimization can result in overall shortened door-to-needle despite the challenges incurred by the COVID-19 pandemic.


Subject(s)
Brain Ischemia/drug therapy , COVID-19/complications , Cooperative Behavior , Ischemic Stroke/drug therapy , Patient Care Team , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Early Medical Intervention , Emergency Medical Services , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Male , Pandemics , SARS-CoV-2 , Time Management , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Workflow
3.
Chest ; 161(3): 710-727, 2022 03.
Article in English | MEDLINE | ID: covidwho-1491838

ABSTRACT

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19/complications , Pandemics , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Thrombosis/complications , Tissue Plasminogen Activator/administration & dosage , Adolescent , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , Cross-Sectional Studies , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Partial Thromboplastin Time , Respiratory Insufficiency/blood , Respiratory Insufficiency/etiology , Retrospective Studies , Thrombosis/blood , Thrombosis/drug therapy , Treatment Outcome , Young Adult
4.
J Stroke Cerebrovasc Dis ; 30(12): 106121, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415617

ABSTRACT

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Thrombolytic Therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Disability Evaluation , Europe , Female , Fibrinolytic Agents/adverse effects , Hospital Mortality , Humans , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Iran , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Male , Middle Aged , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome
5.
J Stroke Cerebrovasc Dis ; 30(10): 106035, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1347731

ABSTRACT

OBJECTIVES: Most data on telestroke utilization come from single academic hub-and-spoke telestroke networks. Our objective was to describe characteristics of telestroke consultations among a national sample of telestroke sites on one of the most commonly used common vendor platforms, prior to the COVID-19 public health emergency. MATERIALS AND METHODS: A commercial telestroke vendor provided data on all telestroke consultations by two specialist provider groups from 2013-2019. Kendall's τ ß nonparametric test was utilized to assess time trends. Generalized linear models were used to assess the association between hospital consult utilization and alteplase use adjusting for hospital characteristics. RESULTS: Among 67,736 telestroke consultations to 132 spoke sites over the study period, most occurred in the emergency department (90%) and for stroke indications (final clinical diagnoses: TIA 13%, ischemic stroke 39%, hemorrhagic stroke 2%, stroke mimics 46%). Stroke severity was low (median NIHSS 2, IQR 0-6). Alteplase was recommended for 23% of ischemic stroke patients. From 2013 to 2019, times from ED arrival to NIHSS, CT scan, imaging review, consult, and alteplase administration all decreased (p<0.05 for all), while times from consult start to alteplase recommendation and bolus increased (p<0.01 for both). Transfer was recommended for 8% of ischemic stroke patients. Number of patients treated with alteplase per hospital increased with increasing number of consults and hospital size and was also associated with US region in unadjusted and adjusted analyses. Longer duration of hospital participation in the network was associated with shorter hospital median door-to-needle time for alteplase delivery (39 min shorter per year, p=0.04). CONCLUSIONS: Among spoke sites using a commercial telestroke platform over a seven-year time horizon, times to consult start and alteplase bolus decreased over time. Similar to academic networks, duration of telestroke participation in this commercial network was associated with faster alteplase delivery, suggesting practice improves performance.


Subject(s)
COVID-19 , Fibrinolytic Agents/administration & dosage , Practice Patterns, Physicians'/trends , Remote Consultation/trends , Stroke/surgery , Thrombolytic Therapy/trends , Time-to-Treatment/trends , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , Databases, Factual , Female , Humans , Male , Middle Aged , Quality Improvement/trends , Quality Indicators, Health Care/trends , Stroke/diagnosis , Time Factors , Treatment Outcome , United States
7.
J Thromb Haemost ; 18(7): 1747-1751, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317985

ABSTRACT

BACKGROUND: Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES: Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS: Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS: At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 µg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2  = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). CONCLUSION: The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation Disorders/blood , Blood Coagulation , Coronavirus Infections/blood , Pneumonia, Viral/blood , Aged , Anticoagulants/administration & dosage , Biomarkers/blood , Blood Coagulation/drug effects , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/virology , Blood Coagulation Tests , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Fibrinolytic Agents/administration & dosage , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Treatment Outcome
8.
J Thromb Haemost ; 18(7): 1752-1755, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317980

ABSTRACT

A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low-compliance in ARDS. The COVID-19 pandemic is overwhelming the world's medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID-19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation Disorders/drug therapy , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/virology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Fatal Outcome , Female , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Recovery of Function , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
9.
Pharmacol Res ; 159: 104965, 2020 09.
Article in English | MEDLINE | ID: covidwho-1279676

ABSTRACT

Little is still known about the clinical features associated with the occurrence of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus disease 2019 (COVID-19). The aim of the present study was to describe the prevalence of pre-admission antithrombotic therapies in patients with COVID-19 and to investigate the potential association between antithrombotic therapy and ARDS, as disease clinical presentation, or in-hospital mortality. We enrolled 192 consecutive patients with laboratory-confirmed COVID-19 admitted to emergency department of five Italian hospitals. The study population was divided in two groups according to the evidence of ARDS at chest computed tomography at admission. Propensity score weighting adjusted regression analysis was performed to assess the risk ARDS at admission, and death during hospitalization, in patients treated or not with antiplatelet and anticoagulant agents. ARDS was reported in 73 cases (38 %), who showed more likely hypertension compared to those without ARDS (57.8 % vs 49.6 %; P = 0.005). Thirty-five patients (18.5 %) died during the hospitalization. Not survived COVID-19 patients showed a statistically significant increased age (77 ± 8.31 vs 65.57 ± 8.31; P = 0.001), hypertension (77.1 % vs 53.5 %; P = 0.018) and coronary artery disease prevalence (28.6 % vs 10.2 %; P = 0.009). Both unadjusted and adjusted regression analyses showed no difference in the risk of ARDS at admission, or death during hospitalization, between patients treated or not with antiplatelets or anticoagulants. Pre-admission antithrombotic therapy, both antiplatelet and anticoagulant, does not seem to show a protective effect in severe forms of COVID-19 with ARDS at presentation and rapidly evolving toward death.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Fibrinolytic Agents/therapeutic use , Pneumonia, Viral/drug therapy , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/mortality , Drug Administration Schedule , Female , Fibrinolytic Agents/administration & dosage , Hospital Mortality , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Patient Admission , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/prevention & control , SARS-CoV-2
10.
Pan Afr Med J ; 38: 185, 2021.
Article in English | MEDLINE | ID: covidwho-1190640

ABSTRACT

Since the onset of the COVID-19 pandemic, several small cohorts have reported the recurrent occurrence of venous thromboembolic disease (VTE), particulary pulmonary embolism, in serious patients hospitalized in intensive care units. We report the case of a patient who presented a minor COVID-19 infection treated on an outpatient basis with good clinical resolution. She developed a pulmonary embolism three weeks after the onset of symptoms. When she was admitted to the emergency room, the two real time reverse transcription polymerase chain reactions (RT-PCRs) performed were negative, moreover the anti-SARS-CoV-2 Immunoglobulin Gs (IgGs) serological test was positive and the chest scanner without and with injection of contrast product showed specific images of COVID-19 with intermediate pulmonary embolism according to the classification of the European society of cardiology (ESC). This observation is interesting since there are not many studies which address the question of the occurrence of late pulmonary embolism in patients with non-severe COVID-19 and raises the discussion on the criteria for the initiation of thromboembolic prophylaxis treatment at the first diagnosis of the disease and duration of that treatment.


Subject(s)
COVID-19/complications , Pulmonary Embolism/diagnosis , Adult , Female , Fibrinolytic Agents/administration & dosage , Humans , Pulmonary Embolism/virology , Real-Time Polymerase Chain Reaction , Serologic Tests , Severity of Illness Index , Time Factors
11.
Int J Mol Sci ; 22(5)2021 Feb 27.
Article in English | MEDLINE | ID: covidwho-1120857

ABSTRACT

The beneficial effects of long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFAs) in cardioprotection are widely known and generally accepted. In this literature review, we have focused on the known and postulated mechanisms of action of omega-3 PUFAs and their metabolites on various components of the haemostatic system, in particular on blood platelets and endothelium. We have also made an attempt to provide a comprehensive review of epidemiological studies with particular regard to clinical trials. Notably, the results of these studies are contradictory, and some of them failed to report the beneficial effects of taking or supplementing omega-3 PUFAs in the diet. A potential explanation, in our opinion, could be the need to use higher doses of omega-3 PUFAs and a proper ratio of omega-3 and omega-6 PUFAs. An additional problem which is difficult to solve is the use of a proper neutral placebo for interventional studies. Despite some controversies regarding the beneficial effects of supplementation of omega-3 PUFAs in cardiovascular disease, our review suggests that a promising aspect of future studies and applications is to focus on the anti-thrombotic properties of these compounds. An argument supporting this assumption is the recent use of omega-3 PUFAs as a supporting tool for the treatment of COVID-19 complications.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/drug therapy , Fatty Acids, Omega-3/administration & dosage , Blood Platelets/drug effects , Blood Platelets/metabolism , COVID-19/blood , COVID-19/drug therapy , Cardiovascular Diseases/blood , Cardiovascular Diseases/metabolism , Diet , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-6/administration & dosage , Fibrinolytic Agents/administration & dosage , Hemostasis/drug effects , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2/isolation & purification , Thrombosis/drug therapy
12.
Eur Rev Med Pharmacol Sci ; 25(4): 2123-2130, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1116633

ABSTRACT

OBJECTIVE: Diffuse thrombosis represents one of the most predominant causes of death by COVID-19 and SARS-CoV-2 infection seems to increase the risk of developing venous thromboembolic diseases (VTE). Aim of this study is to analyze the relationship between validated predictive scores for VTE such as IMPROVE and IMPROVEDD and: (1) Intensification of Care (IoC, admission to Pulmonology Department or Intensive Care Unit) (2) in-hospital mortality rate 3) 30-days mortality rate. PATIENTS AND METHODS: We retrospectively evaluated 51 adult patients with laboratory diagnosis of SARS-CoV-2 infection and calculated IMPROVE and IMPROVEDD scores. All patients underwent venous color-Doppler ultrasound of the lower limbs to assess the presence of superficial vein thrombosis (SVT) and/or deep vein thrombosis (DVT). Patients with normal values of D-dimer did not receive heparin therapy (LMWH); patients with ≥ 4 ULN values of D-dimer or with a diagnosis of DVT were treated with therapeutic LMWH dosage, while the remaining patients were treated with prophylactic LMWH dosages. RESULTS: We found strong relations between IMPROVE score and the need for IoC and with the in-hospital mortality rate and between the IMPROVEDD score and the need for IoC. We defined that an IMPROVE score greater than 4 points was significantly associated to in-hospital mortality rate (p = 0.05), while an IMPROVEDD score greater than 3 points was associated with the need for IoC (p = 0.04). Multivariate logistic analysis showed how IMPROVE score was significantly associated to in-hospital and 30-days mortality rates. CONCLUSIONS: IMPROVE score can be considered an independent predictor of in-hospital and 30-days mortality.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , SARS-CoV-2 , Venous Thrombosis/prevention & control , Adult , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/mortality , Critical Care/statistics & numerical data , Disease-Free Survival , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolytic Agents/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Italy , Logistic Models , Lower Extremity/diagnostic imaging , Multivariate Analysis , Retrospective Studies , Risk Assessment , Risk Factors , Ultrasonography, Doppler, Duplex , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Venous Thrombosis/mortality
13.
Ann Clin Transl Neurol ; 8(4): 929-937, 2021 04.
Article in English | MEDLINE | ID: covidwho-1092495

ABSTRACT

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Patient Admission/trends , Stroke/epidemiology , Stroke/therapy , Brain Ischemia/epidemiology , Brain Ischemia/therapy , Fibrinolytic Agents/administration & dosage , Humans , Pandemics , Texas/epidemiology , Thrombectomy/trends , Thrombolytic Therapy/trends
15.
Medicina (Kaunas) ; 57(2)2021 Jan 26.
Article in English | MEDLINE | ID: covidwho-1061108

ABSTRACT

Traditionally, the management of patients with pulmonary embolism has been accomplished with anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although the administration of heparins and oral vitamin K antagonists still plays a role in pulmonary embolism management, the use of these therapies are limited due to other options now available. This is due to their toxicity profile, clearance limitations, and many interactions with other medications and nutrients. The emergence of direct oral anticoagulation therapies has led to more options now being available to manage pulmonary embolism in inpatient and outpatient settings conveniently. These oral therapeutic options have opened up opportunities for safe and effective pulmonary embolism management, as more evidence and research is now available about reversal agents and monitoring parameters. The evolution of the pharmacological management of pulmonary embolism has provided us with better understanding regarding the selection of anticoagulants. There is also a better understanding and employment of anticoagulants in pulmonary embolism in special populations, such as patients with liver failure, renal failure, malignancy, and COVID-19.


Subject(s)
Anticoagulants/therapeutic use , Fibrinolytic Agents/therapeutic use , Pulmonary Embolism/drug therapy , Administration, Oral , Anticoagulants/administration & dosage , COVID-19/complications , Fibrinolytic Agents/administration & dosage , Humans , Liver Failure/complications , Neoplasms/complications , Renal Insufficiency/complications , Risk Factors , SARS-CoV-2
17.
J Thromb Thrombolysis ; 52(2): 468-470, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1002138

ABSTRACT

Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease that can be triggered by different events, including viral infections. It presents as thrombotic microangiopathy and can lead to severe complications that often require management in the intensive care unit (ICU). We report a patient who presented with acquired TTP following COVID-19 infection. A 44-year-old woman presented to the emergency department with severe anemia, acute kidney injury and respiratory failure due to COVID-19. Clinical and laboratory findings were suggestive for thrombotic microangiopathy. On day 8 laboratory tests confirmed the diagnosis of acquired TTP. The patient needed 14 plasma exchanges, treatment with steroids, rituximab and caplacizumab and 18 days of mechanical ventilation. She completely recovered and was discharged home on day 51. Acquired TTP can be triggered by different events leading to immune stimulation. COVID-19 has been associated with different inflammatory and auto-immune diseases. Considering the temporal sequence and the lack of other possible causes, we suggest that COVID-19 infection could have been the triggering factor in the development of TTP. Since other similar cases have already been described, possible association between COVID and TTP deserves further investigation.


Subject(s)
COVID-19 , Plasma Exchange/methods , Purpura, Thrombotic Thrombocytopenic , Respiration, Artificial/methods , Respiratory Insufficiency , Rituximab/administration & dosage , Single-Domain Antibodies/administration & dosage , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Adult , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , COVID-19/therapy , Female , Fibrinolytic Agents/administration & dosage , Humans , Immunologic Factors/administration & dosage , Male , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/etiology , Purpura, Thrombotic Thrombocytopenic/physiopathology , Purpura, Thrombotic Thrombocytopenic/therapy , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiology , Treatment Outcome
18.
J Cardiovasc Pharmacol Ther ; 26(3): 203-216, 2021 05.
Article in English | MEDLINE | ID: covidwho-983818

ABSTRACT

Although COVID-19 is viewed primarily as a respiratory disease, cardiovascular risk factors and disease are prevalent among infected patients and are associated with worse outcomes. In addition, among multiple extra-pulmonary manifestations, there has been an increasing recognition of specific cardiovascular complications of COVID-19. Despite this, in the initial stages of the pandemic there was evidence of a reduction in patients presenting to acute cardiovascular services. In this masterclass review, with the aid of 2 exemplar cases, we will focus on the important therapeutic implications of COVID-19 for interventional cardiologists. We summarize the existing evidence base regarding the varied cardiovascular presentations seen in COVID-19 positive patients and the prognostic importance and potential mechanisms of acute myocardial injury in this setting. Importantly, through the use of a systematic review of the literature, we focus our discussion on the observed higher rates of coronary thrombus burden in patients with COVID-19 and acute coronary syndromes.


Subject(s)
COVID-19/physiopathology , Coronary Thrombosis , Fibrinolytic Agents/administration & dosage , Humans , Inflammation Mediators/metabolism , Pandemics , Percutaneous Coronary Intervention/methods , SARS-CoV-2 , ST Elevation Myocardial Infarction/pathology , Thrombosis/pathology , Troponin/biosynthesis
19.
Eur J Neurol ; 27(12): 2641-2645, 2020 12.
Article in English | MEDLINE | ID: covidwho-877180

ABSTRACT

BACKGROUND AND PURPOSE: Comorbidity of acute ischaemic stroke with Covid-19 is a challenging condition, potentially influencing the decision of whether to administer intravenous thrombolysis (IVT). We aimed to assess the 1-month outcome in ischaemic stroke patients with Covid-19 infection who received IVT alone or before thrombectomy (bridging therapy). METHODS: As a collaboration initiative promoted by the Italian Stroke Organization, all Italian stroke units (n = 190) were contacted and invited to participate in data collection on stroke patients with Covid-19 who received IVT. RESULTS: Seventy-five invited centers agreed to participate. Thirty patients received IVT alone and 17 received bridging therapy between 21 February 2020 and 30 April 2020 in 20 centers (n = 18, Northern Italy; n = 2, Central Italy). At 1 month, 14 (30.4%) patients died and 20 (62.5%) survivors had a modified Rankin Scale (mRS) score of 3 to 5. At 24 to 36 hours, asymptomatic intracerebral hemorrhage (ICH) was reported in eight (17.4%) patients and symptomatic ICH (sICH) in two (4.3%) patients. Causes of death were severe ischaemic stroke (n = 8), a new ischaemic stroke (n = 2), acute respiratory failure (n = 1), acute renal failure (n = 1), acute myocardial infarction (n = 1), and endocarditis (n = 1). In survivors with a 1-month mRS score of 3 to 5, baseline glucose level was higher, whereas endovascular procedure time in cases of bridging therapy was longer. Baseline National Institutes of Health Stroke Scale glucose and creatinine levels were higher in patients who died. CONCLUSIONS: Intravenous thrombolysis for patients with stroke and Covid-19 was not a rare event in the most affected areas by pandemic, and rates of 1-month unfavorable outcomes were high compared to previous data from the pre-Covid-19 literature. However, risk of sICH was not increased.


Subject(s)
COVID-19/complications , COVID-19/therapy , Ischemic Stroke/complications , Ischemic Stroke/therapy , Thrombolytic Therapy/methods , Aged , Aged, 80 and over , Blood Glucose/analysis , COVID-19/mortality , Cause of Death , Creatinine/blood , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Injections, Intravenous , Ischemic Stroke/mortality , Italy/epidemiology , Male , Pandemics , Survival Analysis , Thrombectomy , Treatment Outcome
20.
BMC Pregnancy Childbirth ; 20(1): 587, 2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-818079

ABSTRACT

BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. We do not just face new and unknown manifestations, but also how different patient groups are affected by SARS-COV-2 infection, such as pregnant women. Coronavirus Disease 2019 (COVID-19), preeclampsia, eclampsia and posterior reversible leukoencephalopathy share endothelium damage and similar pathophysiology. CASE PRESENTATION: A 35-year-old pregnant woman was admitted for tonic-clonic seizures and SARS-COV-2 infection. She had a normal pregnancy control and no other symptoms before tonic-clonic seizures development. After a Caesarean section (C-section) she developed high blood pressure, and we initiated antihypertensive treatment with labetalol, amlodipine and captopril. Few hours later she developed symptoms of cortical blindness that resolved in 72 h with normal brain computed tomography (CT) angiography. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy.


Subject(s)
Antihypertensive Agents/administration & dosage , Betacoronavirus/isolation & purification , Blindness, Cortical , Cesarean Section/methods , Coronavirus Infections , Eclampsia , Fibrinolytic Agents/administration & dosage , Pandemics , Pneumonia, Viral , Pregnancy Complications, Infectious , Seizures , Adult , Blindness, Cortical/diagnosis , Blindness, Cortical/virology , Brain/diagnostic imaging , COVID-19 , Computed Tomography Angiography/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Diagnosis, Differential , Eclampsia/diagnosis , Eclampsia/therapy , Eclampsia/virology , Female , Humans , Neurologic Examination/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/etiology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Outcome , SARS-CoV-2 , Seizures/diagnosis , Seizures/etiology , Seizures/therapy , Tomography, X-Ray Computed/methods , Treatment Outcome
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