An Evaluation of the Activated Partial Thromboplastin Time Waveform

Abstract

The activated partial thromboplastin time (APTT) waveform includes several parameters that are related to various underlying diseases. The APTT waveform was examined in various diseases. Regarding the pattern of APTT waveform, a biphasic pattern of the first or second derivative curve (DC) was observed in patients with hemophilia and patients positive for antiphospholipid (aPL) antibodies or coagulation factor VIII (FVIII) inhibitors. The time of the first and second DC and fibrin formation at 1/2 height were prolonged in patients with hemophilia, patients with inhibitors, patients positive for aPL, patients treated with anti-Xa agents, and patients with disseminated intravascular coagulation (DIC). These values all tended to decrease in pregnant women (at 28-36 weeks' gestation). The height of the second derivative peak 1 was significantly lower in patients with hemophilia, patients with FVIII inhibitors, patients positive for aPL, patients treated with anti-Xa agents, and patients with DIC; these values tended to be significantly higher in pregnant women. The height of the first DC was significantly lower in patients who were positive for FVIII inhibitors and was significantly higher in patients treated with anti-Xa agents and pregnant women. The height of the first and second DC was useful for the analysis of hemophilia, FVIII inhibitor, and aPL.

Update on the Clot Waveform Analysis

“…The routine APTT-CWA ( Figure 4A-D) is automatically enlarged to visualize biphasic pattern, which allows hemostatic abnormalities to be easily recognized; however, it is not able to further differentiate among these diseases. 19 Although the FVIII activity is measured based on the peak time of FFC in APTT, better correlation with FVIII activity is observed in the peak height of the first and second DC than in the peak time of the first and second DC and FFC. 20 Other reports 6,16 have also recommended the peak height of first and second DC for evaluating hemostatic abnormalities in hemophilia.…”

“…The peak heights of the first and second DCs are significantly low in hemophilia patients with inhibitor and patients with acquired hemophilia A. [19][20][21] Monitoring for the Treatment of Hemophilia-Related Diseases by CWA Hemophilia patients with inhibitors are frequently treated with bypass therapy using agents, such as recombinant human activated FVII (rhFVIIa), activated prothrombin complex concentrate (APCC), and emicizumab. 22 In patients with FVIII inhibitor, the effect of APCC is clear on the APTT-CWA, but it is difficult to monitor other bypass therapies, especially rhFVIIa and emicizumab 23 (Figure 5A-C).…”

“…The peak heights of the first and second DCs are significantly low in hemophilia patients with inhibitor and patients with acquired hemophilia A. 19 – 21 …”

Clot Waveform of APTT Has Abnormal Patterns in Subjects with COVID-19

“…Regarding the abnormal APTT second-derivative waveforms, these patterns are sometimes observed in speci c de ciencies or inhibitions of coagulation factors, such as hemophilia, or the presence of lupus anticoagulant 15,16 . Concordantly with previous reports, we observed the presence of biphasic patterns in patients with lupus anticoagulant, hemophilia, or factor IX de ciency and in one subject who was taking warfarin (Table 1).…”

“…However, since the APTT is prolonged to a greater degree in patients with lupus anticoagulant and since the appearance of an abnormal pattern was rare among subjects taking warfarin (1/20), the presence of lupus anticoagulant or a decrease in vitamin K-dependent coagulation factors might not explain, at least not entirely, the mechanisms responsible for the biphasic pattern observed in COVID-19 subjects. One possible mechanism is the presence of an inhibitor to speci c coagulation factors or a severe consumption of these factors, possibly explaining the appearance of a biphasic pattern in APTT second-derivative curves 15 . However, the appearance of a biphasic pattern was not associated with the severity of COVID-19 (Table 2), which is not concordant with a possible mechanism in which the consumption of speci c coagulation factors results in the abnormal APTT second-derivative waveforms.…”