Clot waveform of APTT has abnormal patterns in subjects with COVID-19

Abstract

In Coronavirus disease 2019 (COVID-19) subjects, recent evidence suggests the presence of unique coagulation abnormalities. In this study, we performed clot waveform analyses to investigate whether specific modulations are observed in COVID-19 subjects. We analyzed the second derivative of the absorbance in routine APTT tests performed using an ACL-TOP system. We observed high frequencies of abnormal patterns in APTT second-derivative curves that could be classified into an early shoulder type, a late shoulder type, or a biphasic type, high maximum first-derivative and second-derivative peak levels, and a low minimum second-derivative peak level in COVID-19 subjects. These modulations were not observed in subjects with disseminated intravascular coagulation. These abnormal patterns are also observed in patients with lupus anticoagulant, hemophilia, or factor IX deficiency. The plasma fibrinogen levels might also be involved in the abnormal APTT waveforms, especially the high maximum first-derivative and second-derivative peak levels. The abnormal patterns in the APTT second-derivative curves appear with highest frequency at around 2 weeks after the onset of COVID-19 and were not associated with the severity of COVID-19. These results suggest the possible presence of a specific abnormal coagulopathy in COVID-19.

Figure 1

Representative APTT clot waveforms in COVID-19 and other subjects. Representative APTT clot waveforms in COVID-19 and other subjects are shown. (A) Normal subject, (B–D) COVID-19 subjects, (E) DIC subject, and (F) subject with lupus anti-coagulant.

Figure 2

Parameters of APTT derivative curves for COVID-19 subjects. The maximum first-derivative peak (A), the maximum second-derivative peak (B), and the minimum second-derivative peak (C) for COVID-19 subjects are shown. COVID-19 (All), COVID-19 (D-dimer), COVID-19 (CRP), and COVID-19 (1st visit) represent the following data analyses: all APTT tests that were performed, APTT tests performed at time points corresponding to the maximum D-dimer or CRP level during each subject’s time course, and APTT tests performed at the time of each subject’s initial visit to the hospital, respectively. * P < 0.01 vs. normal, †P < 0.01 vs. other groups except LA, ‡P < 0.05 vs. normal, §P < 0.01 vs. other groups, ||P < 0.05 vs. other groups.

Figure 3

Differences in laboratory data related to coagulation among the patterns of APTT second-derivative curves. (A) APTT, (B) plasma fibrinogen levels, (C) D-dimer levels, and (D) CRP levels in specimens with normal, early shoulder, late shoulder, and biphasic patterns of APTT second-derivative curves. * P < 0.05 vs. normal, †P < 0.01 vs. normal.

Figure 4

Correlations between parameters of APTT derivative curves and laboratory data related to coagulation in COVID-19 subjects. Correlations between the maximum first-derivative peak (A, D, G, J), the maximum second-derivative peak (B, E, H, K), and the minimum second-derivative peak (C, F, I, L) and APTT (A–C), fibrinogen (D–F), D-dimer (G–I), and CRP (J–L).

Figure 5

Time course of the frequency of abnormal patterns and parameters of APTT derivative curves among COVID-19 subjects. (A–D) Time course of APTT clot waveforms in one COVID-19 subject. (E–H) Time course of the frequency of abnormal patterns and parameters of APTT derivative curves among COVID-19 subjects. * P < 0.05 vs. ≤ day 8, P < 0.01 vs. days 9–12 and days 13–16.