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      A critical review of the pathophysiology of thrombotic complications and clinical practice recommendations for thromboprophylaxis in pregnant patients with COVID‐19

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          Abstract

          Those who are infected with Severe Acute Respiratory Syndrome‐related CoronaVirus‐2 are theoretically at increased risk of venous thromboembolism during self‐isolation if they have reduced mobility or are dehydrated. Should patients develop coronavirus disease (COVID‐19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly. These thromboembolic events are the result of at least two distinct mechanisms – microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital‐associated venous thromboembolism. Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID‐19. To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID‐19. Nevertheless, several organizations have vigilantly issued pregnancy‐specific guidelines for thromboprophylaxis in COVID‐19. Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high‐quality evidence available to inform clinical practice. Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID‐19. However, its utility in non‐pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis. Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID‐19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities. There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID‐19. Likewise, there is no evidence to comment on the role of low‐dose aspirin in thromboprophylaxis or of anti‐cytokine and antiviral agents in preventing immunothrombosis. These unanswered questions are being studied within the context of clinical trials.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

              Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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                Author and article information

                Contributors
                Rohan.DSouza@sinaihealthsystem.ca
                Journal
                Acta Obstet Gynecol Scand
                Acta Obstet Gynecol Scand
                10.1111/(ISSN)1600-0412
                AOGS
                Acta Obstetricia et Gynecologica Scandinavica
                John Wiley and Sons Inc. (Hoboken )
                0001-6349
                1600-0412
                05 August 2020
                : 10.1111/aogs.13962
                Affiliations
                [ 1 ] Division of Maternal‐Fetal Medicine Department of Obstetrics & Gynaecology Mount Sinai Hospital University of Toronto Toronto Canada
                [ 2 ] Lunenfeld‐Tanenbaum Research Institute Toronto Canada
                [ 3 ] Division of General Internal Medicine Department of Medicine McGill University Health Centre McGill University Montreal Canada
                [ 4 ] Research Institute of the McGill University Health Centre Montreal Canada
                [ 5 ] McMaster University Hamilton Canada
                [ 6 ] Division of Obstetrics and Gynecology Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet Stockholm Sweden
                [ 7 ] Center for Fetal Medicine Department of Obstetrics and Gynecology Karolinska University Hospital Stockholm Sweden
                [ 8 ] Women’s Health and Perinatology Research Group Department of Clinical Medicine UiT The Arctic University of Norway Tromsø Norway
                [ 9 ] Thrombosis & Haemophilia Centre Guy’s and St Thomas’ Hospital NHS Foundation Trust London UK
                [ 10 ] Maternal–Fetal Medicine Service National Women’s Health Auckland City Hospital Auckland New Zealand
                Author notes
                [*] [* ] Correspondence

                Rohan D___Souza, Mount Sinai Hospital, 700 University Avenue, Room 3‐908, Toronto, Ontario M5G 1X5, Canada.

                Email: Rohan.DSouza@ 123456sinaihealthsystem.ca

                Author information
                https://orcid.org/0000-0002-4049-2017
                https://orcid.org/0000-0002-1997-3107
                Article
                AOGS13962
                10.1111/aogs.13962
                7404828
                32678949
                40c0d00d-d68d-4419-8991-2cb285819943
                © 2020 Nordic Federation of Societies of Obstetrics and Gynecology

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 13 June 2020
                : 01 July 2020
                : 09 July 2020
                Page count
                Figures: 0, Tables: 3, Pages: 11, Words: 6828
                Categories
                State‐of‐the‐art Review
                State‐of‐the‐art Review
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:05.08.2020

                Obstetrics & Gynecology
                covid‐19,pregnancy,sars‐cov‐2,thromboembolic complications,thromboprophylaxis,venous thromboembolism

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