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Table 3 Examples of Trombin generation response to different procoagulant states

From: Global assays of hemostasis in the diagnostics of hypercoagulation and evaluation of thrombosis risk

Procoagulant state Number of patients in study group TG trigger and additional substances Data range in control group, mean ± SD unless otherwise indicated Data range in group with hypercoagulation, mean ± SD unless otherwise indicated Significance Predictive value Reference Comments
Recurrence after first unprovoked VTE 254 – with a first VTE, 34 - with recurrence 1 pM TF 1 uM PL ETP, nM∙min 1502 ± 446 ETP, nM∙min 1361 ± 499 0.122 1 tertile compared to the 3 HR = 2.54 [68] Prospective study. Analysis was performed 2-3 months after completion of anticoagulant therapy.
IIa max, nM 232 ± 82 IIa max, nM 187 ± 89 0.005 HR = 3.09
Tlag, min 12 ± 6 Tlag, min 13 ± 5 0.319 HR = 2.29
  1 pM TF 1 uM PL 4 nM TM ETP, nM∙min 986 ± 422 ETP, nM∙min 763 ± 468 0.009 HR = 3.35 [68]  
IIa max, nM 201 ± 75 IIa max, nM 148 ± 88 <0.001 HR = 4.49
Tlag, min 17 ± 7 Tlag, min 19 ± 10 0.174 HR = 2.39
Unprovoked recurrence after first VTE 188 with a first VTE, 29 – with recurrence 5 pM TF 4 uM PL     ETP > 50th percentile HR = 2.9 [69] Prospective study. Analysis was performed 2-3 months after completion of anticoagulant therapy.
  5 pM TF 4 uM PL 8nM TM     No significant predictive value [69]  
Recurrence after first unprovoked VTE 914 with a first VTE, 100 – with recurrence 72 pM TF 3.2 uM PL IIa max, nM 349 ± 108 IIa max, nM 419 ± 110 <0.001 IIa max >400 nM RR = 2.5 [70] Prospective study. Analysis was performed after completion of anticoagulant therapy.
First and recurrent VT 187 with a first unprovoked VT 404 controls 1/6 deluted plasma 2.5 pM TF 4 uM PL 1.2 nM TM Mean ETP(95% CI), nM∙min 1641 (1607 -1676) Mean ETP(95% CI), nM∙min 1695(1639–1750)   ETP > 90th percentile measured in control subjects DVT HR = 1.7 [71] Analysis was performed 3 months after completion of anticoagulant therapy.
173 with a first provoked VT 404 controls   Mean ETP(95% CI), nM∙min 1641 (1607 -1676) Mean ETP(95% CI), nM∙min 1649(1595-1703)    [71]  
59 recurrent VTE      HR of recurrence 1.1 [71]  
Recurrence after first unprovoked VTE 105 with a first VTE, 40 – with recurrence 5 pM TF 4 uM PL ETP, nM∙min 1671 ± 514 ETP, nM∙min 1491 ± 536 0.111   [72] Prospective study. Analysis was performed upon diagnosis of VTE
IIa max, nM 302 ± 91 IIa max, nM 261 ± 125 0.058
Tlag, min 7.2 ± 2.2 Tlag, min 8.7 ± 5 <0.001
Acute Ischemic Stroke (men) 42 patients 408 controls 5 pM TF 4 uM PL geometric mean and interquartile range ETP, nM∙min 1755 (1620 - 1940) geometric mean and interquartile range ETP, nM∙min 1720 (1572 - 1978)   HR = 0.88/sd [74] Prospective study.
IIa max, nM 327.0 (304.9 - 357.8) IIa max, nM 330.2 (301.8 - 361.4)   HR = 1.04/sd
Acute Ischemic Stroke (women) 45 patients 666 controls 5 pM TF 4 uM PL ETP, nM∙min 1755 (1604 - 1940) ETP, nM∙min 1863 (1636 -1998)   HR = 1.55/sd [74] Prospective study
IIa max, nM 333.6 (311.0 - 372.4) IIa max, nM 357.8 (320.5 - 391.5)   HR = 1.71/sd
Coronary Heart Disease events 186 patients 1000 controls 5 pM TF 4 uM PL ETP, nM∙min 1765 (1620 - 1940) ETP, nM∙min 1772 (1604- 1939   HR = 1.09/sd [74] Prospective study
IIa max, nM 333.0 (308.0 - 365.0) IIa max, nM 330.3 (301.9- 357.8)   HR = 1.02/sd IIa max
Prothrombin G20210A mutation 148 heterozigote, 111 - controls 6.8 pM TF 30 uM PL median and interquartile range ETP, nM∙min 1053 (946–1171) median and interquartile range ETP, nM∙min 1358 (1190–1492) the carriers as opposed to the non-carriers <0.001   [75]  
IIa max, nM 292 (267–330) IIa max, nM 349 (307–385) <0.001
Tlag, min 2.54 (2.46–2.84) Tlag, min 2.74 (2.46–3.04) 0.268
3 homozigote   ETP, nM∙min 1661 (1451–1976)    [75]  
IIa max, nM 466 (446–470)
Tlag, min 3.06 (2.14–5.08)
AT III-inherited deficiency 9 - controls 18 Type I-IIRS/PE 5 pM TF 4 uM PL ETP, nM∙min 2200 ± 320 ETP, nM∙min 3366 ± 668 Only Type I-IIRS/PE end controls ETP differs significantlly   [76]  
IIa max, nM 377.3 ± 49.1 IIa max, nM 493.4 ± 75.0
17 -IIHBS heterozygote   ETP, nM∙min 2142 ± 464
IIa max, nM 427.2 ± 98.3
8 - Cambridge II heterozygote   ETP, nM∙min 2211 ± 268
IIa max, nM 391.4 ± 46.8
VTE in cancer patients 1033 cancer patients 77 VTE cases 71.6 pM TF 3.2 uM PL median (25th to 75th percentile) ETP, nM∙min 4386 (3804-4890) median (25th to 75th percentile) ETP, nM∙min 4475 (4087-4915) 0.197 IIa max > 611 nM (75th percentile) HR = 2.1 [80] Prospective study
IIa max, nM 499 (360-603) IIa max, nM 556 (432-677) 0.014
Type 2 diabetes mellitus 52 patients, 60 controls 1 pM TF 1 uM PL Median (range) ETP, nM∙min 1844 (1,317–2592) Median (range) ETP, nM∙min 1835 (1213–2656) 0.96   [55]  
IIa max, nM 264 (97–432) IIa max, nM 303 (207–434) <0.001
Tlag, min 7.8 (4.7–18.4) Tlag, min 5.9 (4.5–11.5) <0.001
1 pM TF 1 uM PL 4 nM TM ETP, nM∙min 1301 (535–2381) ETP, nM∙min 1497 (1061–2418) 0.003   [55]  
IIa max, nM 256 (79–433) IIa max, nM 297 (216–427) 0.001
Tlag, min 10.4 (6.3–25.8) Tlag, min 7.8 (5.6–13.6) <0.001
43 patients, 60 controls Ca only ETP, nM∙min 1678 (539–2231) ETP, nM∙min 1781 (288–2598) 0.05   [55]  
IIa max, nM 151 (41–289) IIa max, nM 202 (128–350) <0.001
Tlag, min 12.6 (7.0–29.5) Tlag, min 10.8 (7.2–16.1) <0.001
Diabetes mellitus 89 patients 49 controls 5 pM TF 4 uM PL ETP, nM∙min 1566.4 ± 240.7 ETP, nM∙min 1876.5 ± 390.0 <0.001   [62]  
IIa max, nM 252.8 ± 44.6 IIa max, nM 308.9 ± 39.5 <0.001
Tlag, min 4.15 ± 0.74 Tlag, min 3.59 ± 0.62 <0.001
Normal pregnancy 19 health pregnant women  10 controls 5 pM TF 20 uM PL 0.1 mg/ml CTI ETP, nM∙min 1553 ± 567 pre-pregnancy ETP, nM∙min 1162 ± 446 Significant difference between pre-pregnancy and early/late pregnancy P < 0.001   [82]  
IIa max, nM 81 ± 41
Early ETP, nM∙min 2157 ± 466
IIa max, nM 159 ± 100 IIa max, nM 219 ± 117
Late ETP, nM∙min 2410 ± 543
IIa max, nM 336 ± 178
Normal pregnancy 1st Trimester (n = 36) 5 pM TF 4 uM PL TG on normal pooled plasma was significantly lower than TG on pregnant women. The exact parameter’s values weren’t shown ETP, nM∙min 2123 ± 335 No significant differences between trimesters   [83]  
IIa max, nM 366 ± 43
2nd Trimester (n = 42) ETP, nM∙min 2067 ± 326
IIa max, nM 374 ± 42
3rd Trimester (n = 23) ETP, nM∙min 1915 ± 261
IIa max, nM 336 ± 49