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 |