Study Design and Population
The study was a single-center retrospective cohort study performed in a 28-bed neurointensive care unit (NICU) of a university hospital in China. The Ethics Committee of our hospital approved the study and waived the requirement for informed consent because of the minimal risk to participants.
Using an electronic patient data recording system, all patients admitted to our NICU from September 2019 to September 2020 were screened. The inclusion criteria comprised ABI patients transferred to the NICU within 24 h after surgery or endovascular therapy (including acute traumatic brain injury, acute hemorrhagic stroke, acute ischemic stroke and acute aneurysmal subarachnoid hemorrhage). Patients were excluded if they had any of the following characteristics: age < 18 years; pregnancy at the time of hospitalization; length of NICU stay < 3 days; therapeutic anticoagulation already in progress before transfer to the NICU; previously diagnosed DVT; active tumor; severe liver or kidney disease; long-term bedridden status; or lack of CCUS scans.
All patients were treated according to guidelines and received DVT prevention measures, including intermittent pneumatic compression and passive limb exercises, as soon as possible. The use of chemical DVT prophylaxis or treatment via low-molecular-weight heparin, heparin, etc., was determined by the attending doctor.
Patient Data Collection
A standardized sheet was used by investigators (Z. G. and R. T.) to collect information from patients’ electronic medical records. Data included baseline characteristics (age, sex, height, weight, and diagnosis); disease history (cardiovascular, pulmonary, hepatic, renal, diabetes); risk factors for DVT (current smoking, estrogen use, ambulatory status, family history of hypercoagulability); disease characteristics (disease onset time; GCS score at admission; APACHE II score at transfer in; brain herniation; comorbidities during treatment, such as shock, hepatic injury, renal injury, gastrointestinal bleeding, sepsis, or pulmonary embolus); treatment approaches (surgery or endovascular therapy; operation time; decompressive craniectomy; second surgery; mechanical ventilation; renal‑replacement therapy; transfusion, such as red blood cells, plasma, platelets, anticoagulation therapy and its onset time); and patient outcomes (fatality in the NICU, length of NICU stay, GCS score at transfer out).
CCUS procedures
All CCUS scans were performed according to the guidelines for ultrasound for lower extremity DVT [12] and were carried out by experienced sonographers (C.T., M.Y., and X.H.) who were not aware of the patients’ clinical features or coagulation test results. A color duplex ultrasound system (Vivid iq: GE Healthcare, Milwaukee, USA) with a 5 to 10 MHz transducer was used for the scans. CCUS was performed once or twice weekly during each patient’s NICU stay.
Coagulation tests
Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, thrombin time (TT) and D-dimer, based on clotting (viscosity-based detection system), chromogenic and immunologic assays were performed in all patients at The First Affiliated Hospital of USTC Central Clinical Chemistry Laboratory (The STA R Max®, Diagnostica Stago, Asnières, France). All tests were performed on the first day and at a series of later timepoints (once or twice weekly) during the NICU stay.
Statistical analysis
Normally distributed data are presented as the means ± standard deviations. Other continuous data are expressed as medians and interquartile ranges. Categorical variables were expressed as n (%). Student’s t-tests, Mann-Whitney U tests, chi-square tests or Fisher’s exact tests were used to compare variables between different groups. A multivariate analysis was performed using logistic regression models with a stepwise approach according to univariate results (P < 0.10) and clinical relevance. The results are expressed as odds ratios (ORs) and 95% CIs. Log likelihood was used to measure the goodness of fit of each model.
The effects of IDDVT and time on the measured parameters were examined by two-way repeated-measures ANOVA, followed by a Bonferroni correction for multiple comparisons. In order to simplify statistical analysis, the data from the first day in the NICU were labeled day 1, the data from the second through fourth days were labeled days 2–4, the data from the fifth through seventh days were labeled days 5–7, and the data beyond the seventh day were labeled day > 7.
For each parameter that differed between groups, a receiver operating characteristic (ROC) curve was plotted to identify optimal predictors of IDDVT and its extension by utilizing the area under the curve (AUC). The threshold values of the parameters were determined according to usual recommendations by estimating several indexes such as the Youden index.
P < 0.05 was considered statistically significant. SPSS 26.0 (SPSS, Chicago, USA) was used for statistical analysis.