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1.
Sci Rep ; 12(1): 17408, 2022 Oct 18.
Статья в английский | MEDLINE | ID: covidwho-2077099

Реферат

Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.


Тема - темы
Acute Kidney Injury , COVID-19 , Thrombosis , Humans , Nadroparin/adverse effects , Critical Illness , Prospective Studies , COVID-19/complications , Anticoagulants/therapeutic use , Thrombosis/prevention & control
2.
S Afr Med J ; 112(7): 472-477, 2022 07 01.
Статья в английский | MEDLINE | ID: covidwho-2073605

Реферат

BACKGROUND: An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. OBJECTIVES: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. METHODS: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. RESULTS: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7). CONCLUSION: The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/adverse effects , Cross-Sectional Studies , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Humans , South Africa/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
3.
Surg Infect (Larchmt) ; 23(8): 705-711, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2017669

Реферат

Background: Thrombosis (T) is common in coronavirus disease 2019 (COVID-19) patients, and d-dimer concentrations correlate with outcomes. Controversy exists with regards to anticoagulation (AC) for patients. We implemented a full-heparinization AC protocol from the onset of the pandemic and hypothesized that a safety signal would be undetectable. Patients and Methods: Prospective evaluation of 111 patients with COVID-19 critical illness hospitalized from March to June 2020. All patients received therapeutic heparinoid-based AC from admission. Incidences of T, bleeding (B), or both (BT) were noted. The primary outcome was mortality. Kruskal-Wallis test and logistic regression were performed. Results are expressed as n (%), median (interquartile range) and odds ratios with 95% confidence intervals. Alpha was set at 0.05. Results: Thirty-two patients (28%) had T, 23 (20%) had B, and 14 (12%) had BT; 42 (40%) patients were unaffected. Two logistic regression models (outcome = mortality) evaluated BT as T, or BT as B. For BT as T, neither T, B, nor male gender predicted mortality; similarly, for BT as B, neither T, B, nor male gender predicted mortality. Factors associated with higher odds of death included higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; p = 0.0045), higher d-dimer concentration (OR, 1.00; 95% CI, 1.00-1.01; p = 0.043), and higher activated partial thromboplastin time (aPTT; OR, 1.09; 95% CI, 1.02-1.16; p = 0.010). Conclusions: Neither T nor B predicted mortality in this prospective cohort of anticoagulated patients with COVID-19 critical illness. These data support continued full-dose heparinoid prophylaxis.


Тема - темы
COVID-19 , Heparinoids , Thrombosis , Anticoagulants/adverse effects , COVID-19/complications , Critical Illness , Humans , Male , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control
4.
Nat Commun ; 13(1): 5206, 2022 09 05.
Статья в английский | MEDLINE | ID: covidwho-2008281

Реферат

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet serious adverse effect of the adenoviral vector vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen) against COVID-19. The mechanisms involved in clot formation and thrombocytopenia in VITT are yet to be fully determined. Here we show neutrophils undergoing NETosis and confirm expression markers of NETs in VITT patients. VITT antibodies directly stimulate neutrophils to release NETs and induce thrombus formation containing abundant platelets, neutrophils, fibrin, extracellular DNA and citrullinated histone H3 in a flow microfluidics system and in vivo. Inhibition of NETosis prevents VITT-induced thrombosis in mice but not thrombocytopenia. In contrast, in vivo blockage of FcγRIIa abrogates both thrombosis and thrombocytopenia suggesting these are distinct processes. Our findings indicate that anti-PF4 antibodies activate blood cells via FcγRIIa and are responsible for thrombosis and thrombocytopenia in VITT. Future development of NETosis and FcγRIIa inhibitors are needed to treat VITT and similar immune thrombotic thrombocytopenia conditions more effectively, leading to better patient outcomes.


Тема - темы
COVID-19 , Extracellular Traps , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , Ad26COVS1 , Animals , ChAdOx1 nCoV-19 , Extracellular Traps/metabolism , Humans , Mice , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Thrombocytopenia/chemically induced , Thrombosis/prevention & control , Vaccines/metabolism
5.
Am J Cardiol ; 181: 38-44, 2022 Oct 15.
Статья в английский | MEDLINE | ID: covidwho-1982506

Реферат

Atrial fibrillation/flutter (AF) and COVID-19 are associated with an elevated risk of arterial and venous thrombosis. Whether preadmission oral anticoagulation (OAC) for AF reduces the incidence of in-hospital death or thrombotic events among patients with COVID-19 is unknown. We identified 630 patients with pre-existing AF and a hospitalization diagnosis of COVID-19 and stratified them according to preadmission OAC use. Multivariable logistic regression was employed to relate preadmission OAC to composite in-hospital mortality or thrombotic events. Unadjusted composite in-hospital mortality or thrombotic complications occurred less often in those on than not on preadmission OAC (27.1% vs 46.8%, p <0.001). After adjustment, the incidence of composite in-hospital all-cause mortality or thrombotic complications remained lower with preadmission OAC (odds ratio 0.37, confidence interval 0.25 to 0.53, p <0.0001). Secondary outcomes including all-cause mortality (16.3% vs 24.9%, p = 0.007), intensive care unit admission (14.7% vs 29.0%, p <0.001), intubation (6.4% vs 18.6%, p <0.001), and noninvasive ventilation (18.6% vs 27.5%, p = 0.007) occurred less frequently, and length of stay was shorter (6 vs 7 days, p <0.001) in patients on than those not on preadmission OAC. A higher CHA2DS2-VASc score was associated with an increased risk of thrombotic events. In conclusion, among patients with baseline AF who were hospitalized with COVID-19, those on preadmission OAC had lower rates of death, arterial and venous thrombotic events, and less severe COVID-19.


Тема - темы
Atrial Fibrillation , Atrial Flutter , COVID-19 , Stroke , Thrombosis , Administration, Oral , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Atrial Flutter/drug therapy , COVID-19/complications , COVID-19/epidemiology , Hospital Mortality , Hospitalization , Humans , Risk Assessment , Risk Factors , Stroke/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
6.
J Thromb Thrombolysis ; 54(3): 420-430, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-1971785

Реферат

Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25-0.62; p˂0.01; I2 = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85-3.03; p = 0.15; I2 = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33-1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/adverse effects , COVID-19/drug therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Thrombosis/prevention & control
7.
ASAIO J ; 68(7): 920-924, 2022 07 01.
Статья в английский | MEDLINE | ID: covidwho-1967929

Реферат

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.


Тема - темы
Extracorporeal Membrane Oxygenation , Thrombosis , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Antithrombins/therapeutic use , Extracorporeal Membrane Oxygenation/adverse effects , Fibrinolytic Agents/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/complications , Hemorrhage/prevention & control , Heparin/adverse effects , Heparin/therapeutic use , Hirudin Therapy , Hirudins/adverse effects , Humans , Peptide Fragments/adverse effects , Peptide Fragments/therapeutic use , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Retrospective Studies , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Treatment Outcome
8.
R I Med J (2013) ; 105(6): 36-40, 2022 08 01.
Статья в английский | MEDLINE | ID: covidwho-1958239

Реферат

Early in the pandemic, it was recognized that infection with COVID-19 was associated with an increased incidence in both venous and arterial thrombotic events leading to poor patient outcomes. Given the rapid rise of the pandemic, anticoagulation strategies were initially based upon retrospective and observational data with few high-quality randomized control trials to help direct strategies regarding the use of thromboprophylaxis during hospitalization, empiric therapeutic anticoagulation, and extended-duration thromboprophylaxis after discharge. Over the past year, several randomized control trials have now been published evaluating these strategies. In this article, we hope to review the current literature surrounding the use of intermediate-dose thromboprophylaxis, empiric therapeutic anticoagulation, and the use of extended-duration thromboprophylaxis for patients hospitalized with COVID-19.


Тема - темы
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , Humans , Inpatients , Retrospective Studies , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
9.
Saudi Med J ; 43(7): 715-722, 2022 Jul.
Статья в английский | MEDLINE | ID: covidwho-1955133

Реферат

OBJECTIVES: To assess the effect of different thromboprophylaxis regimens on clinical outcomes and mortality of critical ill patients with coronavirus disease -19 (COVID-19). METHODS: We investigated the medical records of patients with positive COVID-19 (using polymerase chain reaction test) who were admitted to the intensive care unit (ICU) at Sakarya University Hospital, Sakarya, Turkey, from March 2020 to January 2021. We included patients under anticoagulant therapy in the clinical course. The patients were allocated to 3 groups: Group A - low-dose (prophylactic) low-molecular-weight-heparin (LMWH) therapy, Group B - high-dose (therapeutic) LMWH therapy, and patients that received aspirin additional to the high-dose (therapeutic) LMWH as Group C. Primary outcomes were overall mortality rates and length of stay (LOS) in ICU. Secondary outcomes were rates of major hemorrhagic and thrombotic events. RESULTS: Records of 475 patients were reviewed and 164 patients were included. No significant difference was detected in mortality rates between groups (p=0.135). Intensive care unit stay was 13 (9-24.5) days in Group A, 11 (8.75-23) days in Group B, and 13 (9-17) days in Group C without a significant difference (p=0.547). No significant difference was detected between groups in terms of thrombotic (p=0.565) and hemorrhagic events (p=0.615). CONCLUSION: A high-dose anticoagulation therapy and addition of aspirin to LMWH therapy did not decrease the mortality rates and LOS in ICU in critical ill COVID-19 patients. In addition, it did not increase the incidence of major hemorrhage and major thrombotic events.


Тема - темы
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Aspirin/therapeutic use , Critical Illness/therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Retrospective Studies , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control
10.
Anticancer Res ; 42(7): 3261-3274, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1924868

Реферат

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.


Тема - темы
COVID-19 , Neoplasms , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Endothelial Cells , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Neoplasms/complications , Neoplasms/drug therapy , Prospective Studies , RNA, Viral , Risk Factors , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
11.
J Thromb Haemost ; 20(10): 2226-2236, 2022 10.
Статья в английский | MEDLINE | ID: covidwho-1916260

Реферат

Despite the emergence of high quality randomized trial data with the use of antithrombotic agents to reduce the risk of thromboembolism, end-organ failure, and possibly mortality in patients with coronavirus disease 2019 (COVID-19), questions still remain as to optimal patient selection for these strategies, the use of antithrombotics in outpatient settings and in-hospital settings (including critical care units), thromboprophylaxis in special patient populations, and the management of acute thrombosis in hospitalized COVID-19 patients. In October 2021, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary and international panel of content experts, two patient representatives, and a methodologist to develop recommendations on treatment with anticoagulants and antiplatelet agents for COVID-19 patients. The ISTH Guideline panel discussed additional topics to be well suited to a non-Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for Good Practice Statements (GPS) to support good clinical care in the antithrombotic management of COVID-19 patients in various clinical settings. The GPS panel agreed on 17 GPS: 3 in the outpatient (pre-hospital) setting, 12 in the hospital setting both in non-critical care (ward) as well as intensive care unit settings, and 2 in the immediate post-hospital discharge setting based on limited evidence or expert opinion that supports net clinical benefit in enacting the statements provided. The antithrombotic therapies discussed in these GPS should be available in low- and middle-income countries.


Тема - темы
COVID-19 , Fibrinolytic Agents , Anticoagulants/therapeutic use , COVID-19/drug therapy , Fibrinolytic Agents/therapeutic use , Hemostasis , Humans , Platelet Aggregation Inhibitors/therapeutic use , Thrombosis/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control
13.
Expert Rev Hematol ; 15(7): 635-643, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1908641

Реферат

OBJECTIVES: The present paper aimed to study the available literature on the hypercoagulability state of pediatric patients affected by COVID-19, and the current management of thrombosis in these patients, considering that no guidelines have been published since now in this age group. METHODS: N 244 titles were screened using the selected MESH words, 180 abstracts and 120 full texts were read, 12 articles were included, and four were analyzed by meta-analysis. RESULTS: Over 1128 COVID-19 positive patients, nearly half of them developed inflammatory sequelae, and 7.35% (40 patients over 544 who developed MIS-C) had thrombotic events. Less than 50% of patients with inflammatory disease were under anticoagulant prophylactic treatment, and doses of anticoagulant protocols vary from different centers. Thrombotic events prevented after the start of unfractionated heparin (UFH) therapy, even if 1.06% (4 patients) died. Only two patients presented complications after anticoagulant treatment, with non-fatal bleeding after UFH treatment. No other complications were reported. No difference in the incidence of thrombotic events between patients under prophylactic low molecular weight heparin (LMWH) and those without was found in meta-analysis (p = 0.32). CONCLUSIONS: Little is known on the incidence and management of hyper coagulopathy in pediatric COVID-19 infection. Further studies have to clarify this topic.


Тема - темы
COVID-19 , Thrombosis , Adolescent , Anticoagulants , COVID-19/complications , COVID-19/epidemiology , Child , Heparin , Heparin, Low-Molecular-Weight , Humans , Incidence , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
14.
J Vasc Surg Venous Lymphat Disord ; 10(5): 1128-1136, 2022 09.
Статья в английский | MEDLINE | ID: covidwho-1895298

Реферат

BACKGROUND: Thrombosis in COVID-19 worsens mortality. In our study, we sought to investigate how the dose and type of anticoagulation (AC) can influence patient outcomes. METHODS: This is a single-center retrospective analysis of critically ill intubated patients with COVID-19, comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) at therapeutic and prophylactic doses. Of 218 patients, 135 received LMWH (70 prophylactic, 65 therapeutic) and 83 UFH (11 prophylactic, 72 therapeutic). The primary outcome was mortality. Secondary outcomes were thromboembolic complications confirmed on imaging and major bleeding complications. Cox proportional-hazards regression models were used to determine whether the type and dose of AC were independent predictors of survival. We performed Kaplan-Meier survival analysis to compare the cumulative survivals. RESULTS: Overall, therapeutic AC, with either LMWH (65% vs 79%, P = .09) or UFH (32% vs 46%, P = .73), conveyed no survival benefit over prophylactic AC. UFH was associated with a higher mortality rate than LMWH (66% vs 28%, P = .001), which was also evident in the multivariable analysis (LMWH vs UFH mortality, hazard ratio: 0.47, P = .001) and in the Kaplan-Meier survival analysis. Thrombotic and bleeding complications did not depend on the AC type (prophylactic LMWH vs UFH: thrombosis P = .49, bleeding P = .075; therapeutic LMWH vs UFH: thrombosis P = .5, bleeding P = .17). When comparing prophylactic with therapeutic AC, the rate of both thrombotic and bleeding complications was higher with the use of LMWH compared with UFH. In addition, transfusion requirements were significantly higher with both therapeutic LMWH and UFH. CONCLUSIONS: Among intubated critically ill COVID-19 intensive care unit patients, therapeutic AC, with either LMWH or UFH, conveyed no survival benefit over prophylactic AC. AC with LMWH was associated with higher cumulative survival compared with AC with UFH.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/adverse effects , COVID-19/complications , Critical Illness , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Humans , Retrospective Studies , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/prevention & control
15.
Blood Coagul Fibrinolysis ; 33(5): 239-256, 2022 Jul 01.
Статья в английский | MEDLINE | ID: covidwho-1891118

Реферат

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.


Тема - темы
COVID-19 , Sepsis , Thrombocytopenia , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Arginine/analogs & derivatives , Critical Illness , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pipecolic Acids , Sepsis/drug therapy , Sulfonamides , Thrombocytopenia/chemically induced , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/drug therapy
16.
J Vasc Surg ; 76(5): 1374-1382.e1, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-1885970

Реферат

OBJECTIVE: Hypercoagulability and thrombotic complications seen in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the associated pathophysiology, have been reported extensively. However, there is limited information regarding the factors related to this phenomenon and its association with the Coronavirus disease 2019 (COVID-19) Delta variant. METHODS: A retrospective review including patients admitted to a tertiary center with a COVID-19 positive test and at least one acute thrombotic event confirmed by imaging between June 2020 and August 2021 was performed. We compared the rates of thrombotic events in patients with COVID-19 before and during the Delta peak. We also analyzed the association of the thrombotic complications with demographic characteristics, comorbidities, anticoagulation strategies, and prothrombotic markers while describing other complications secondary to COVID-19 infection. RESULTS: Of 964 patients admitted with COVID-19 diagnosis, 26.5% (n = 256) had a thrombotic event evidenced by ultrasound or computed tomography scan. Venous thromboembolism was found in 60% (n = 153), arterial thrombosis in 23% (n = 60), and both venous and arterial thromboses in 17% (n = 17) of the study cohort. Of all patients, 94% were not vaccinated. Delta variant wave (DW) patients had thrombotic episodes in 34.7% (n = 50/144) of cases compared with 25% (n = 206/820) of non-Delta wave (NDW) patients, posing an estimated risk 1.36 times higher in patients infected with COVID-19 during the DW than NDW. Overall, DW subjects were significantly younger (P < .001) with lower body mass index (P = .021) compared with NDW patients. Statistical analyses showed African American patients were more likely to have arterial thrombosis compared with the other groups when testing positive for COVID-19 (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.04-3.05; P = .035, whereas immunosuppressed patients had less risk of arterial thrombosis (OR, 0.38; 95% CI, 0.15-0.96; P = .042). Female gender (OR, 2.15; 95% CI, 1.20-3.85; P = .009) and patients with active malignancy (OR, 5.99; 95% CI, 2.14-16.78; P = .001) had an increased risk of having multiple thrombotic events at different locations secondary to COVID-19. CONCLUSIONS: COVID-19 infection is associated with elevated rates of thrombotic complications and an especially higher risk in patients infected during the Delta variant peak. We highlight the importance of vaccination and the development of new anticoagulation strategies for patients with COVID-19 with additional hypercoagulable risk factors to prevent thrombotic complications caused by this disease.


Тема - темы
COVID-19 , Thrombophilia , Thrombosis , Humans , Female , COVID-19/complications , SARS-CoV-2 , COVID-19 Testing , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control , Thrombophilia/complications , Anticoagulants/therapeutic use
17.
Rinsho Ketsueki ; 63(5): 471-480, 2022.
Статья в Японский | MEDLINE | ID: covidwho-1879649

Реферат

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and is known to have thrombotic complications. Various-sized thrombosis occurs in the arteries and veins, especially in lung tissue. The prevention and treatment of thrombosis is an important issue that is directly linked to its prognosis. Additionally, the drastic fibrinolytic enhancement and lethal bleeding in some severe COVID-19 are important issues. The efficacy of antiplatelet for COVID-19 is controversial. Thus, warfarin or tranexamic acid alone should be avoided. Heparin is effective for mild to moderate COVID-19 but is ineffective in severe cases since the anticoagulant activity of heparin is insufficient or heparin increases major bleeding. In severe COVID-19 cases with drastic fibrinolytic enhancement, heparin and nafamostat combination therapy may avoid lethal bleeding. In COVID-19 clinical practice, not only the coagulation activation was evaluated but also the fibrinolytic activation to consider treatment strategies.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , COVID-19/complications , Fibrinolytic Agents/therapeutic use , Hemorrhage/drug therapy , Heparin , Humans , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control
18.
Circ J ; 86(7): 1137-1142, 2022 06 24.
Статья в английский | MEDLINE | ID: covidwho-1879294

Реферат

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , Blood Coagulation , Critical Illness/therapy , Humans , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control
19.
Curr Opin Pediatr ; 34(3): 261-267, 2022 06 01.
Статья в английский | MEDLINE | ID: covidwho-1874057

Реферат

PURPOSE OF REVIEW: To provide an update regarding what is known about thrombotic events and thromboprophylaxis in critically ill children with SARS-CoV-2 infection. RECENT FINDINGS: Pediatric patients with SARS-CoV-2 generally have mild illness; however, intensive care is required in about 20-30% of hospitalized children with COVID-19 and an even higher proportion in those with MIS-C. Increased rates of thrombosis have been observed in adults hospitalized with COVID-19, and clinical trials have attempted to optimize thromboprophylaxis. There is significant variability in the estimated incidence of thrombosis in pediatric patients (0-27%) because of variation in patient populations and study design. Multiple studies demonstrate an increased rate of thrombosis compared with baseline in hospitalized pediatric patients. Few studies have evaluated risk factors for thrombosis, but critical illness, older age, and other known thrombosis risk factors appear to increase the risk. Thromboprophylaxis strategies are inconsistent, with little evidence of efficacy but few reports of major bleeding. SUMMARY: Critically ill children with SARS-CoV-2-related illnesses are at increased risk of thrombosis. Thromboprophylaxis should be considered in select patients with COVID-19 or MIS-C, though the optimal strategy is not yet known. More data is required to guide practice to prevent thrombosis in this population.


Тема - темы
COVID-19 , Thrombosis , Venous Thromboembolism , Adult , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Child , Critical Illness/therapy , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
20.
Eur Heart J Cardiovasc Pharmacother ; 8(4): 402-405, 2022 06 08.
Статья в английский | MEDLINE | ID: covidwho-1853023

Реферат

Coronavirus disease 2019 (COVID-19) is characterized by striking dysregulation of the immune system, with evidence of hyperinflammation, an impaired induction of interferons, and delayed adaptive immune responses. In addition to dysfunctional immune responses, thrombosis is a hallmark of severe COVID-19. Because traditional anticoagulation strategies are associated with increased bleeding, novel strategies that address both the immune and thrombotic dysfunction associated with COVID-19 would be of tremendous benefit. In this commentary, we discuss the unique properties of low dose naltrexone (LDN) which could be leveraged to reduce the immune-mediated thrombotic complications in COVID-19. Mechanistically, LDN can blunt innate immune responses and Toll-like receptor (TLR) signaling, reducing interleukin1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferon (IFN) levels. Because of the immune-mediated thrombotic mechanisms that underlie COVID-19, we hypothesize that the immune-modulating and known pharmacologic properties of LDN could be leveraged as a novel therapeutic strategy in COVID-19.


Тема - темы
COVID-19 , Thrombosis , Humans , Immunity, Innate , Naltrexone/pharmacology , Thromboinflammation , Thrombosis/prevention & control
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