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1.
Eur J Intern Med ; 105: 1-7, 2022 11.
Статья в английский | MEDLINE | ID: covidwho-2086143

Реферат

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia and arterial and venous thrombosis in unusual sites, as cerebral venous sinuses and splanchnic veins. VITT has been described to occur almost exclusively after administration of ChAdOx1 nCoV-19 and Ad26.COV2.S adenovirus vector- based COVID-19 vaccines. Clinical and laboratory features of VITT resemble those of heparin-induced thrombocytopenia (HIT). It has been hypothesized that negatively charged polyadenylated hexone proteins of the AdV vectors could act as heparin to induce the conformational changes of PF4 molecule that lead to the formation of anti-PF4/polyanion antibodies. The anti-PF4 immune response in VITT is fostered by the presence of a proinflammatory milieu, elicited by some impurities found in ChAdOx1 nCoV-19 vaccine, as well as by soluble spike protein resulting from alternative splice events. Anti-PF4 antibodies bind PF4, forming immune complexes which activate platelets, monocytes and granulocytes, resulting in the VITT's immunothrombosis. The reason why only a tiny minority of patents receiving AdV-based COVID-19 vaccines develop VITT is still unknown. It has been hypothesized that individual intrinsic factors, either acquired (i.e., pre-priming of B cells to produce anti-PF4 antibodies by previous contacts with bacteria or viruses) or inherited (i.e., differences in platelet T-cell ubiquitin ligand-2 [TULA-2] expression) can predispose a few subjects to develop VITT. A better knowledge of the mechanistic basis of VITT is essential to improve the safety and the effectiveness of future vaccines and gene therapies using adenovirus vectors.


Тема - темы
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , Humans , Antigen-Antibody Complex , COVID-19 Vaccines/adverse effects , Ad26COVS1 , ChAdOx1 nCoV-19 , Ligands , Spike Glycoprotein, Coronavirus , COVID-19/prevention & control , Platelet Factor 4/genetics , Platelet Factor 4/metabolism , Heparin/adverse effects , Thrombocytopenia/chemically induced , Vaccines/adverse effects , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Ubiquitins
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.
Rinsho Ketsueki ; 63(9): 1233-1241, 2022.
Статья в Японский | MEDLINE | ID: covidwho-2056364

Реферат

The levels of anti-platelet factor 4 (PF4) antibodies, also known as anti-PF4 or heparin complex antibodies, are used to diagnose heparin-induced thrombocytopenia (HIT). In HIT, anti-PF4 antibodies induced by heparin exposure cause thrombocytopenia and thrombosis. However, anti-PF4 antibodies were recently reported to be associated with the development of fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination for coronavirus disease 2019. HIT and VITT are caused by anti-PF4 antibodies and have similar pathological conditions. However, the severity of these conditions differs and the detection sensitivity of their antibodies varies depending on the assays used. Herein, we review HIT and VITT associated with anti-PF4 antibodies.


Тема - темы
COVID-19 , Heparin , Platelet Factor 4 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Antibodies , Anticoagulants/adverse effects , COVID-19/prevention & control , Heparin/adverse effects , Humans , Immunologic Factors , Purpura, Thrombocytopenic, Idiopathic/complications , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/etiology , Thrombosis/pathology , Vaccines/adverse effects
4.
Rev Neurol ; 75(7): 199-202, 2022 10 01.
Статья в английский, испанский | MEDLINE | ID: covidwho-2057053

Реферат

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient's neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.


TITLE: Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.Introducción. La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico. Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones. El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.


Тема - темы
COVID-19 Vaccines , COVID-19 , Thrombocytopenia , Thrombosis , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cerebral Hemorrhage/etiology , ChAdOx1 nCoV-19 , Female , Heparin/adverse effects , Humans , Middle Aged , Pandemics , Platelet Factor 4 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thrombocytopenia/etiology
5.
J Thromb Haemost ; 20(12): 2896-2908, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2052857

Реферат

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology. OBJECTIVES: To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset. PATIENTS/METHODS: Asserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78-179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate; n = 476), and rapid immunological chemiluminescence anti-PF4 assay (n = 460), in a multicenter study. RESULTS: For first episode presentations, 190/1284 (14.8%) ELISA tests were positive. Conversely, most (445/460; 96.7%) chemiluminescence anti-PF4 test results were negative. All functional assays showed associations of higher median ELISA optical density with functional positivity and with high rates of ELISA positivity (64.0% to 85.2%). Data also identified functional positivity in 14.8%-36.0% of ELISA negative samples, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases. CONCLUSION: To our knowledge, this is the largest multicenter evaluation of anti-PF4 testing for investigation of VITT. Discrepancies in test results (ELISA vs. ELISA or ELISA vs. functional assay) in some patients highlighted limitations in relying on single methods (ELISA and functional) for PF4 antibody detection in VITT, and also highlights the variability in phenotypic test presentation and pathomechanism of VITT.


Тема - темы
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Humans , Platelet Factor 4 , Heparin/adverse effects , Australia , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/diagnosis , Immunologic Factors/adverse effects , Immunoglobulin G
6.
Semin Thromb Hemost ; 48(7): 850-857, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2050627

Реферат

Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008-0-012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH-anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.


Тема - темы
COVID-19 , Hemostatics , Humans , Heparin, Low-Molecular-Weight/therapeutic use , Enoxaparin/therapeutic use , COVID-19/drug therapy , Critical Illness , C-Reactive Protein , Anticoagulants/therapeutic use , Heparin/adverse effects , Viper Venoms , Antithrombins , Factor Xa Inhibitors
7.
Intern Med ; 61(18): 2797-2801, 2022 Sep 15.
Статья в английский | MEDLINE | ID: covidwho-2029870

Реферат

A 53-year-old woman with severe coronavirus disease 2019 (COVID-19) pneumonia was admitted and treated with intravenous unfractionated heparin for thromboprophylaxis under general anesthesia with mechanical ventilation. She developed right hemiparesis after hospitalization due to a large hemorrhagic infarction. Her platelet count decreased from 243,000/µL at administration to 121,000/µL. Anti-platelet factor 4-heparin antibody testing was positive according to a latex immunoturbidimetric assay. She was therefore diagnosed with heparin-induced thrombocytopenia. We immediately stopped the heparin and started argatroban; the platelet count recovered, and thrombosis did not relapse. Physicians should consider heparin-induced thrombocytopenia as a cause of ischemic stroke in patients with COVID-19 infection.


Тема - темы
COVID-19 , Ischemic Stroke , Thrombocytopenia , Venous Thromboembolism , Anticoagulants/adverse effects , COVID-19/complications , Female , Heparin/adverse effects , Humans , Ischemic Stroke/etiology , Middle Aged , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy , Venous Thromboembolism/drug therapy
8.
Trials ; 23(1): 774, 2022 Sep 14.
Статья в английский | MEDLINE | ID: covidwho-2029729

Реферат

BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS, hastens recovery and is safe in non-COVID ARDS. Unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. Based on these findings, we designed the CHARTER-Ireland Study, a phase 1b/2a randomised controlled study of nebulised heparin in patients requiring advanced respiratory support for COVID-19 pneumonia. METHODS: This is a multi-centre, phase 1b/IIa, randomised, parallel-group, open-label study. The study will randomise 40 SARs-CoV-2-positive patients receiving advanced respiratory support in a critical care area. Randomisation will be via 1:1 allocation to usual care plus nebulised unfractionated heparin 6 hourly to day 10 while receiving advanced respiratory support or usual care only. The study aims to evaluate whether unfractionated heparin will decrease the procoagulant response associated with ARDS up to day 10. The study will also assess safety and tolerability of nebulised heparin as defined by number of severe adverse events; oxygen index and respiratory oxygenation index of intubated and unintubated, respectively; ventilatory ratio; and plasma concentration of interleukin (IL)-1ß, IL6, IL-8, IL-10 and soluble tumour necrosis factor receptor 1, C-reactive protein, procalcitonin, ferritin, fibrinogen and lactate dehydrogenase as well as the ratios of IL-1ß/IL-10 and IL-6/IL-10. These parameters will be assessed on days 1, 3, 5 and 10; time to separation from advanced respiratory support, time to discharge from the intensive care unit and number tracheostomised to day 28; and survival to days 28 and 60 and to hospital discharge, censored at day 60. Some clinical outcome data from our study will be included in the international meta-trials, CHARTER and INHALE-HEP. DISCUSSION: This trial aims to provide evidence of potential therapeutic benefit while establishing safety of nebulised heparin in the management of ARDS associated with SARs-CoV-2 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04511923 . Registered on 13 August 2020. Protocol version 8, 22/12/2021 Protocol identifier: NUIG-2020-003 EudraCT registration number: 2020-003349-12 9 October 2020.


Тема - темы
Acute Lung Injury , COVID-19 , Respiratory Distress Syndrome , Acute Lung Injury/diagnosis , Acute Lung Injury/etiology , Animals , Fibrin , Heparin/adverse effects , Humans , Interleukin-10 , Ireland , Mammals , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2
9.
J Thromb Haemost ; 20(11): 2579-2586, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2019525

Реферат

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic, heparin-induced thrombocytopenia (HIT)-mimicking, adverse reaction caused by platelet-activating anti-platelet factor 4 (PF4) antibodies that occurs rarely after adenovirus vector-based COVID-19 vaccination. Strength of PF4-dependent enzyme immunoassay (EIA) reactivity-judged by optical density (OD) measurements-strongly predicts platelet-activating properties of HIT antibodies in a functional test. Whether a similar relationship holds for VITT antibodies is unknown. OBJECTIVES: To evaluate probability for positive platelet activation testing for VITT antibodies based upon EIA OD reactivity; and to investigate simple approaches to minimize false-negative platelet activation testing for VITT. METHODS: All samples referred for VITT testing were systematically evaluated by semiquantitative in-house PF4/heparin-EIA (OD readings) and PF4-induced platelet activation (PIPA) testing within a cohort study. EIA-positive sera testing PIPA-negative were retested following 1/4 to 1/10 dilution. Logistic regression was performed to predict the probability of a positive PIPA per magnitude of EIA reactivity. RESULTS: Greater EIA ODs in sera from patients with suspected VITT correlated strongly with greater likelihood of PIPA reactivity. Of 61 sera (with OD values >1.0) testing negative in the PIPA, a high proportion (27/61, 44.3%) became PIPA positive when tested at 1/4 to 1/10 dilution. CONCLUSIONS: VITT serology resembles HIT in that greater EIA OD reactivity predicts higher probability of positive testing for platelet-activating antibodies. Unlike the situation with HIT antibodies, however, diluting putative VITT serum increases probability of a positive platelet activation assay, suggesting that optimal complex formation depends on the stoichiometric ratio of PF4 and anti-PF4 VITT antibodies.


Тема - темы
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , Humans , Heparin/adverse effects , Cohort Studies , COVID-19 Vaccines , Platelet Factor 4 , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Immunoenzyme Techniques , Antibodies , Thrombosis/diagnosis , Thrombosis/chemically induced , Purpura, Thrombocytopenic, Idiopathic/chemically induced
10.
J Infect Chemother ; 28(8): 1208-1211, 2022 Aug.
Статья в английский | MEDLINE | ID: covidwho-1983457

Реферат

A 53-year-old male Japanese patient with COVID-19 was admitted to our hospital after his respiratory condition worsened on day 9 of the disease. With the diagnosis of severe COVID-19, treatment with remdesivir, dexamethasone, and unfractionated heparin was started for the prevention of thrombosis. Although the patient's respiratory status data improved after treatment, severe respiratory failure persisted. Thrombocytopenia and D-dimer elevation were observed on day 8 after heparin therapy initiation. Heparin-induced thrombocytopenia (HIT) antibody measured by immunological assay was positive, and contrast computed tomography showed pulmonary artery thrombus. The patient was diagnosed with HIT because the pre-test probability score (4Ts score) for HIT was 7 points. Heparin was changed to apixaban, a direct oral anticoagulant, which resulted in a reduction of the pulmonary thrombus and improvement of the respiratory failure. In patients with COVID-19, anticoagulant therapy with heparin requires careful monitoring of thrombocytopenia and elevated D-dimer as possible complications related to HIT. (151/250 words).


Тема - темы
COVID-19 , Pulmonary Embolism , Respiratory Insufficiency , Thrombocytopenia , Thrombosis , Anticoagulants/adverse effects , COVID-19/drug therapy , Heparin/adverse effects , Humans , Male , Middle Aged , Pulmonary Embolism/drug therapy , Respiratory Insufficiency/chemically induced , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/drug therapy , Thrombosis/drug therapy
11.
Bioconjug Chem ; 33(8): 1574-1583, 2022 08 17.
Статья в английский | MEDLINE | ID: covidwho-1977960

Реферат

The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.


Тема - темы
Thrombocytopenia , Antibodies, Monoclonal/therapeutic use , Anticoagulants/adverse effects , Fondaparinux/adverse effects , Heparin/adverse effects , Humans , Platelet Factor 4/metabolism , Platelet Factor 4/therapeutic use , Polysaccharides , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
12.
Eur Heart J Qual Care Clin Outcomes ; 8(8): 909-918, 2022 Nov 17.
Статья в английский | MEDLINE | ID: covidwho-1973139

Реферат

AIMS: This study aimed to compare the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. METHODS AND RESULTS: We systematically searched several databases and included observational studies or clinical trials that compared the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. A total of nine studies comprising 9637 patients were included. Metanalysis showed that LMWH administration was associated with a lower in-hospital mortality and 28/30-day mortality compared with UFH administration {[relative risk (RR) 0.44; 95% confidence interval (95% CI) 0.32-0.61; I2: 87.9%] and (RR 0.45; 95% CI 0.24-0.86; I2: 78.4%), respectively}. Patient with LMWH had shorter duration of hospital and ICU length of stay compared with UFH {[weighted mean difference (WMD) -2.20; 95% CI -3.01 to -1.40; I2:0%] and (WMD -1.41; 95% CI -2.20 to -0.63; I2: 0%), respectively}. The risk of ICU admission or mechanical ventilation was lower in patients who received LMWH than in those who received UFH (RR 0.67; 95% CI 0.55-0.81; I2: 67.3%). However, there was no difference in the incidence of bleeding with LMWH compared with UFH (RR 0.27; 95% CI 0.07-1.01; I2: 64.6%). CONCLUSION: Our meta-analysis showed that administration of LMWH was associated with better outcomes compared with UFH in hospitalized COVID-19 patients. Prospective cohorts and RCTs are urgently needed to explore the definitive effect of LMWH to provide direct high-certainty evidence. PROSPERO registration number: CRD42021271977.


Тема - темы
COVID-19 , Venous Thromboembolism , Humans , Heparin, Low-Molecular-Weight/therapeutic use , Heparin/adverse effects , Anticoagulants/therapeutic use , COVID-19/epidemiology , Prospective Studies , Venous Thromboembolism/drug therapy
13.
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
14.
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
15.
Am J Case Rep ; 23: e937017, 2022 Jul 21.
Статья в английский | MEDLINE | ID: covidwho-1954990

Реферат

BACKGROUND Anticoagulation with heparin infrequently causes elevated serum potassium via a reduction in the number and affinity of adrenal angiotensin II receptors, causing reversible aldosterone suppression, thereby leading to enhanced sodium excretion and hyperkalemia. CASE REPORT A 77 year-old man presented with productive cough and shortness of breath and was subsequently found to have non-ST-elevation myocardial infarction and concomitant symptomatic COVID-19 infection, for which he was started on a high-dose unfractionated heparin infusion. A gradual increase in serum potassium followed, with a subsequent return to a normal potassium level after stopping treatment with heparin. An evaluation for hemolysis was unrevealing, and the patient was not on any other medications known to cause hyperkalemia. On day 6, heparin was restarted owing to a high suspicion of pulmonary embolism. There was a subsequent increase in serum potassium level, which was followed by a return to baseline after discontinuation of heparin, thereby confirming the suspected diagnosis. CONCLUSIONS Acute increases in serum potassium levels in hospitalized patients can result in weakness, paralysis, conduction abnormalities, and cardiac arrhythmias that, if left untreated, can result in serious morbidity and potentially death in a short period of time. As this clinical entity is infrequently encountered in clinical practice, it can easily be overlooked by clinicians. The prompt exclusion of alternative causes of acutely elevated serum potassium levels and the identification of heparin administration as an easily reversible trigger is imperative and can potentially be life-saving.


Тема - темы
COVID-19 , Hyperkalemia , Aged , Aldosterone , Anticoagulants/therapeutic use , Heparin/adverse effects , Humans , Hyperkalemia/chemically induced , Hyperkalemia/drug therapy , Male , Potassium/therapeutic use
16.
Brain Nerve ; 74(7): 905-909, 2022 Jul.
Статья в Японский | MEDLINE | ID: covidwho-1954946

Реферат

Thrombosis with thrombocytopenia syndrome (TTS) induced by the coronavirus disease 2019 vaccine is characterized by thrombocytopenia and thrombosis. Positivity for the anti-platelet factor 4-antibody is related to TTS pathophysiology, similar to heparin-induced thrombocytopenia. Although TTS is very rare, with an incidence of almost 1/100,000 cases, physicians need to keep in mind this adverse reaction that can lead to serious symptoms and death. Prompt treatment should be initiated in cases of suspected TTS.


Тема - темы
COVID-19 Vaccines , COVID-19 , Thrombocytopenia , Thrombosis , Anticoagulants/adverse effects , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Heparin/adverse effects , Humans , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/chemically induced
17.
BMC Emerg Med ; 22(1): 107, 2022 06 14.
Статья в английский | MEDLINE | ID: covidwho-1951062

Реферат

BACKGROUND: The optimal prophylactic dose of heparin in patients with coronavirus-associated disease 2019 (COVID-19) in the emergency department (ED) is debated. This study aimed to analyze different thromboprophylaxis approaches in unvaccinated COVID-19 patients admitted to ED without initial venous thromboembolism. METHODS: Retrospectively, the effect of intermediate/high versus low dose heparin treatment was evaluated from December 2020 to July 2021 in a tertiary Academic Hospital in northeast Italy. The primary outcome comprised arterial or venous thromboembolism or all-cause death within 30 days. Secondary outcomes comprised each single primary outcome component or major hemorrhagic event. Cox regression was used to determine predictors of the primary outcome and propensity score weights to balance the effect of heparin treatment on all outcomes. RESULTS: Data of 144 consecutive patients (age 70 ± 13, 33% females) were included in the study. High-dose prophylactic heparin was used in 69%, intermediate in 15%, and low in 17% of patients. The primary outcome occurred in 48 patients. Independent predictors of the primary outcome were COVID-19 severity (hazards ratio (HR) 1.96, 95% confidence interval (CI) 1.05-3.65, p = 0.035) and D-dimer levels (HR each log ng/dl 1.38, 95% CI 1.04-1.84, p = 0.026). Intermediate/high dose heparin did not affect the risk of the primary outcome compared with the low dose (weighted HR 1.39, 95% CI 0.75-2.56, p = 0.292). Intermediate/high heparin increased the risk of major hemorrhagic events (weighted HR 5.92, 95% CI 1.09-32, p = 0.039). CONCLUSIONS: In unvaccinated COVID-19 patients admitted to ED, prophylaxis with heparin at the intermediate/high dose did not reduce primary outcome compared with the low dose but increased the risk of major hemorrhagic events.


Тема - темы
COVID-19 , Venous Thromboembolism , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Emergency Service, Hospital , Female , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Hemorrhage/epidemiology , Heparin/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
18.
J Med Case Rep ; 16(1): 271, 2022 Jul 11.
Статья в английский | MEDLINE | ID: covidwho-1925808

Реферат

INTRODUCTION: Recombinant adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2 have been observed to be associated with vaccine-induced immune thrombotic thrombocytopenia. Though vaccine-induced immune thrombotic thrombocytopenia is a rare complication after vaccination with recombinant adenoviral vector vaccines, it can lead to severe complications. In vaccine-induced immune thrombotic thrombocytopenia, the vector vaccine induces heparin-independent production of platelet factor 4 autoantibodies, resulting in platelet activation and aggregation. Therefore, patients suffering from vaccine-induced immune thrombotic thrombocytopenia particularly present with signs of arterial or venous thrombosis, often at atypical sites, but also signs of bleeding due to disseminated intravascular coagulation and severe thrombocytopenia. We describe herein a rare case of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia. This case report presents the diagnosis and treatment of a healthy 29-year-old male Caucasian patient suffering from an extended portomesenteric thrombosis associated with atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia after the first dose of an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 [ChAdOx1 nCoV-19 (AZD1222)]. Therapeutic management of vaccine-induced immune thrombotic thrombocytopenia initially focused on systemic anticoagulation avoiding heparin and the application of steroids and intravenous immune globulins as per the recommendations of international societies of hematology and hemostaseology. Owing to the atraumatic splenic rupture and extended portomesenteric thrombosis, successful management of this case required splenectomy with additional placement of a transjugular intrahepatic portosystemic shunt to perform local thrombaspiration, plus repeated local lysis to reconstitute hepatopetal blood flow. CONCLUSION: The complexity and wide spectrum of the clinical picture in patients suffering from vaccine-induced immune thrombotic thrombocytopenia demand an early interdisciplinary diagnostic and therapeutic approach. Severe cases of portomesenteric thrombosis in vaccine-induced immune thrombotic thrombocytopenia, refractory to conservative management, may require additional placement of a transjugular intrahepatic portosystemic shunt, thrombaspiration, thrombolysis, and surgical intervention for effective management.


Тема - темы
COVID-19 , Portasystemic Shunt, Transjugular Intrahepatic , Purpura, Thrombocytopenic, Idiopathic , Splenic Rupture , Thrombocytopenia , Thrombosis , Vaccines , Adult , ChAdOx1 nCoV-19 , Heparin/adverse effects , Humans , Male , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/methods , Purpura, Thrombocytopenic, Idiopathic/complications , Thrombocytopenia/chemically induced , Thrombosis/etiology , Thrombosis/therapy , Vaccines/adverse effects
19.
BMJ ; 378: e070022, 2022 07 04.
Статья в английский | MEDLINE | ID: covidwho-1932663

Реферат

OBJECTIVE: To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital. MAIN OUTCOME MEASURES: Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework. RESULTS: 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses. CONCLUSIONS: Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173088.


Тема - темы
Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Bayes Theorem , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Hospitals , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy
20.
J Thromb Haemost ; 20(10): 2214-2225, 2022 10.
Статья в английский | MEDLINE | ID: covidwho-1927616

Реферат

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.


Тема - темы
COVID-19 , Heparin, Low-Molecular-Weight , Aftercare , Anticoagulants/adverse effects , Fibrinolytic Agents/adverse effects , Heparin/adverse effects , Humans , Patient Discharge , Platelet Aggregation Inhibitors/adverse effects , Rivaroxaban
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