D-Dimer-Driven Anticoagulation Reduces Mortality in Intubated COVID-19 Patients: A Cohort Study With a Propensity-Matched Analysis

Abstract

Objective: Examine the possible beneficial effects of early, D-dimer driven anticoagulation in preventing thrombotic complications and improving the overall outcomes of COVID-19 intubated patients. Methods: To address COVID-19 hypercoagulability, we developed a clinical protocol to escalate anticoagulation based on serum D-dimer levels. We retrospectively reviewed all our first 240 intubated patients with COVID-19. Of the 240, 195 were stratified into patients treated based on this protocol (ON-protocol, n = 91) and the control group, patients who received standard thromboprophylaxis (OFF-protocol, n = 104). All patients were admitted to the Stony Brook University Hospital intensive care units (ICUs) between February 7th, 2020 and May 17, 2020 and were otherwise treated in the same manner for all aspects of COVID-19 disease. Results: We found that the overall mortality was significantly lower ON-protocol compared to OFF-protocol (27.47 vs. 58.66%, P < 0.001). Average maximum D-dimer levels were significantly lower in the ON-protocol group (7,553 vs. 12,343 ng/mL), as was serum creatinine (2.2 vs. 2.8 mg/dL). Patients with poorly controlled D-dimer levels had higher rates of kidney dysfunction and mortality. Transfusion requirements and serious bleeding events were similar between groups. To address any possible between-group differences, we performed a propensity-matched analysis of 124 of the subjects (62 matched pairs, ON-protocol and OFF-protocol), which showed similar findings (31 vs. 57% overall mortality in the ON-protocol and OFF-protocol group, respectively). Conclusions: D-dimer-driven anticoagulation appears to be safe in patients with COVID-19 infection and is associated with improved survival. What This Paper Adds: It has been shown that hypercoagulability in patients with severe COVID-19 infection leads to thromboembolic complications and organ dysfunction. Anticoagulation has been variably administered to these patients, but it is unknown whether routine or escalated thromboprophylaxis provides a survival benefit. Our data shows that escalated D-dimer driven anticoagulation is associated with improved organ function and overall survival in intubated COVID-19 ICU patients at our institution. Importantly, we found that timely escalation of this anticoagulation is critical in preventing organ dysfunction and mortality in patients with severe COVID-19 infection.

Keywords: COVID-19; D-dimer-driven anticoagulation; anticoagulation; d-dimer; hypercoagulability; thrombotic complications.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Tassiopoulos, Mofakham, Rubano, Labropoulos, Bannazadeh, Drakos, Volteas, Cleri, Alkadaa, Asencio, Oganov, Hou, Rutigliano, Singer, Vosswinkel, Talamini, Mikell and Kaushansky.

Figures

Figure 1

Patient selection algorithm and the anticoagulation protocol.

Figure 2

Protocol-driven anticoagulation is associated with significantly lower mortality. (A) Overall mortality in intubated patients with COVID-19 infection who were admitted to the ICU. (B) Comparison of overall mortality between ON-protocol group (green line, N = 91) and OFF-protocol group (blue line, N = 104) (log-rank test, P < 0.001).

Figure 3

The ON-protocol and OFF-protocol groups were admitted at similar time periods but with drastically different outcomes in terms of mortality and discharged rates. (A) The admission and intubation timeline of both ON (green) and OFF-protocol (blue) groups are shown. (B) For both the ON- (green lines) and OFF-protocol (blue lines) groups, we plotted the accumulated percentages of the discharged and expired patients. Dashed and solid lines, respectively, represent the accumulated percentages of discharged and expired patients in each group. The overall mortality rate is 58.65% in the OFF-protocol group compared to the 27.47% in the ON-protocol group, while patients in the ON-protocol group were discharged at a much higher rate (69.23% compared to 37.5% in the OFF-protocol group).

Figure 4

Subgroup analysis of 124 patients matched from ON-protocol (n = 62) and OFF-protocol groups (n = 62) exhibits similar results as the whole group analysis. Sixty two pairs of ON and OFF-protocol patients were analyzed on age, gender, BMI, SOFA score, heart disease, diabetes, and hypertension with the distance of a PS score ≤ 0.01. The other comorbidity variables were not used because the values were ≤ 10. The mortality rates in these groups are 31% (ON-protocol) vs. 57% (OFF-protocol, P = 0.0061).

Figure 5

Escalated, D-dimer driven anticoagulation (ON-protocol group) is associated with improved critical laboratory values in multiorgan dysfunctions in COVID-19 intubated patients. The early start of AC in the ON-protocol group was associated with significant changes in the course of the disease in intubated patients. The green and blue lines represent the mean of D-dimer, creatinine and BUN for ON- and OFF-protocol groups over thirty days. Notice the elevated level of these laboratory values in the first two weeks following intubation, which is associated with many of mortalities in the OFF-protocol group. The shaded area represents the SE of the mean. These analyses are time-locked to the intubation date marked by the red dashed line.