Abstract: Thrombosis Research 198 (2021) 19–22
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Thrombosis Research
journal homepage: www.elsevier.com/locate/thromres
Letter to the Editors-in-Chief
Low molecular weight heparin and 28-day mortality among patients with coronavirus disease
2019: A cohort study in the early epidemic era
Patients with COVID-19 and preexisting diseases are likely to have
poor outcomes. Coagulopathy is a prominent clinical manifestation and
coagulation markers are recognized as haematological risk factors for
mortality. Anticoagulant use is an important supportive treatment that
may benefit patient survival. Preliminary data showed that anticoagu
lant therapy was associated with lower mortality in severe patients with
markedly elevated D-dimer [1]. However, data on anticoagulation use in
Chinese patients during the early pandemic era are limited. The asso
ciations of Low Molecular Weight Heparin (LMWH) and other available
treatments with patients’ prognoses are not well established. Therefore,
we report our initial experience in treatments for COVID-19 hospitalized
patients, particularly the use of LMWH.
A pragmatic cohort study was performed, involving adult patients
with PCR-confirmed COVID-19 consecutively admitted to the affiliated
hospital of Jianghan University between January 10th, 2020 and
February 28th, 2020. Patients were followed for 28 days after admis
sion. COVID-19 infection was diagnosed according to the Chinese
management guideline (Trial Version 5 Revised, http://www.nhc.gov.
cn/yzygj/s7653p/202002/d4b895337e19445f8d728fcaf1e3e13a.sh
tml). We obtained ethical approval from the Medical Ethics Committee
of Affiliated Hospital of Jianghan University and China-Japan Friend
ship Hospital (WHSHIRB-K-2020015) on April 21, 2020. Subcutaneous
LMWH (Low Molecular Weight Heparin Sodium for Injection, Jiangsu
Wanbang Biochemical Pharmaceutical Co. LTD, China) use was recor
ded, administered as prophylactic dosage 3000–5000 U/day or the
therapeutic dose was based on actual body weight (100 U/kg, q12h). All
patients were given intravenous methylprednisolone according to our
guideline, 40 or 80 mg/day. The primary outcome was mortality within
28 days after hospital admission. Patients discharged earlier were fol
lowed to day 28 to ascertain survival.
Data were summarized as number (percentage) for categorical var
iables and mean (SD) or median (interquartile ranges [IQR]) for
continuous variables as appropriate. t-test, Mann Whitney U test, Chisquare test or Fisher exact test were used to compare differences in
baseline characteristics, treatment and complications. To explore an
association of LMWH treatment with 28-day mortality, we fitted
multivariable Cox regression model with covariates adjusted. The pro
portional hazard assumption was tested and if the assumption was
violated, an extended Cox analysis with time-varying covariates was
performed. The violating covariates were handled by their interactions
with followed-up time. Patients alive at day 28 were regarded as rightcensored. Based on the up-to-date knowledge on COVID-19 and prior
research, we constructed a causal diagram to visually illustrate the po
tential effect of exposures on fatal outcomes (Fig.A.1). Five blocks of
factors were analyzed: typical demographic information, comorbidities,
COVID-19 severity, coagulopathy on admission, and treatments
provided in hospital. In our prior research, normal D-dimer on admis
sion and day 3 were highly..
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