A correlation of thrombin generation assay and clot waveform analysis in patients on warfarin

Figures & data

Figure 1. aPTT-clot waveform analysis transmittance curve (A) and the first (B) and second derivatives (C). Trans%: Percentage of transmittance, dT/dt: the derivative of transmittance taken with respect to time, d2T/dt2: the second derivative calculated from dT/dt with respect to time Min 1: Maximum clotting velocity, Min 2: Maximum clotting acceleration, Max2: Maximum clotting deceleration

Table 1. Laboratory results, PT, aPTT and its associated CWA parameters and thrombin generation results of 54 study subjects on warfarin.

Laboratory Results	Mean ± SD	Minimum	Maximum	Reference Intervals
Coagulation Profile
INR	4.31 ± 0.31	1.33	6.89
PT (sec)	44.8 ± 3.2	13.8	71.7	9.9–11.
aPTT (sec)	51.4 ± 3.1	30.8	85.8	25.7–32.5
Thrombin Generation Parameters
Lag time (min)	13.05 ± 1.31	5.00	26.83	1.50–3.17
ETP (nM/min)	271.30 ± 43.90	116.25	940.25	971.77–1696.0
Peak Thrombin (nM)	44.52 ± 7.62	10.19	133.07	195.63–341.52
Time To Peak (min)	16.63 ± 1.63	7.50	42.33	3.78–6.50
PT-CWA Parameters (Unadjusted)
Min1 (%/s)	3.03 ± 1.48	1.17	8.32
Min2 (%/s^2)	1.76 ± 0.69	0.44	3.51
Max2 (%/s^2)	0.86 ± 0.44	0.212	2.19
aPTT-CWA Parameters (Unadjusted)
Min1 (%/s)	3.80 ± 0.25	0.86	7.24	3.11–6.8
Min2 (%/s^2)	0.37 ± 0.13	0.07	1.15	0.44–1.10
Max2 (%/s^2)	0.06 ± 0.05	0.04	0.85	0.35–0.92
aPTT-CWA Parameters (Adjusted*)
Min1 (%/s)	5.57 ± 0.37	3.10	9.67
Min2 (%/s^2)	0.81 ± 0.11	0.21	1.54
Max2 (%/s^2)	0.30 ± 0.13	0.19	1.14

* Adjusted: adjusted to the final plateau transmittance.

CWA: Clot Waveform; ETP: endogenous thrombin potential.

Figure 2. A comparison of thrombin generation curves measured by the CAT and aPTT-CWA transmittance curves of two different patients with two extremes of INR ranges of 1.94 and 4.50 r, respectively. (A) and (C) show the thrombin generation curves while (B) and (D) show the 1st and 2nd derivatives curves of the aPTT-based clot waveform transmittance curves. CAT: Calibrated automated thrombogram; CWA: Clot waveform analysis; ETP: Endogenous thrombin potential.

Table 2. Correlation between aPTT-CWA and thrombin generation parameters in 54 patients on warfarin anticoagulation*.

Thrombin Generation Parameters	aPTT-CWA (Unadjusted)			Adjusted aPTT-CWA**
	Min1	Min2	Max2	Min1	Min2	Max2
Lag Time	r = −0.140 P = 0.920	r = −0.204 P = 0.138	r = −0.180 P = 0.193	r = −0.415 P = 0.002	r = −0.472 P < 0.001	r = −0.402 P = 0.003
ETP	r = 0.235 P = 0.087	r = 0.326 P = 0.016	r = 0.437 P < 0.001	r = 0.610 P < 0.001	r = 0.563 P < 0.001	r = 0.642 P < 0.001
Peak thrombin	r = 0.435 P = 0.001	r = 0.485 P < 0.001	r = 0.578 P < 0.001	r = 0.734 P < 0.001	r = 0.693 P < 0.001	r = 0.751 P < 0.001
Time to Peak	r = −0.428 P = 0.676	r = −0.486 P < 0.001	r = −0.211 P = 0.002	r = −0.580 P = 0.001	r = −0.563 P < 0.001	r = −0.408 P < 0.001

*Bonferroni correction for multiple comparison of CWA parameters with p value < 0.017 considered as statistically significant.

**Adjusted: adjusted to the final plateau transmittance.

ETP: Endogenous thrombin potential; CWA: Clot waveform analysis.

Table 3. Correlation between unadjusted PT-CWA and INR and thrombin generation parameters respectively in 54 patients on warfarin anticoagulation*^/**.

Unadjusted PT-CWA	Thrombin Generation Parameters				Unadjusted aPTT-CWA			INR
	Lag Time	ETP	Peak Thrombin	Time to Peak	Min1	Min2	Max2
Min1	r = 0.306 P = 0.024	r = −0.035 P = 0.803	r  = −0.026 P = 0.851	r = 0.282 P = 0.039	r = 0.670 P = <0.001	r = 0.375 P = 0.005	r = 0.350 P = 0.010	r = −0.62 P = 0.655
Min2	r = 0.253 P = 0.064	r = 0.026 P = 0.854	r = 0.106 P = 0.446	r = 0.245 P = 0.074	r = 0.683 P  = <0.001	r = 0.415 P = 0.002	r = 0.243 P = 0.077	r = −0.195 P = 0.160
Max2	r = 0.077 P = 0.582	r = 0.334 P = 0.013	r = 0.354 P = 0.009	r = 0.120 P = 0.387	r = 0.545 P = <0.001	r = 0.273 P = 0.046	r = 0.498 P = <0.001	r = −0.432 P = 0.001

* Bonferroni correction for multiple comparison of CWA parameters with p value < 0.017 considered as statistically significant.

** Adjusted: adjusted to the final plateau transmittance.

ETP: Endogenous thrombin potential; CWA: Clot waveform analysis.