Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests
Abstract
:1. Introduction
2. Hemostasis in Healthy Pregnancies
2.1. Coagulation and Fibrinolysis
2.2. Platelets
3. Hemostasis in Pre-Eclampsia
3.1. Genetic Factors
3.2. Endothelial Dysfunction
3.3. Role of microRNAs in Endothelial Dysfunction and Hypercoagulation
3.4. Hemostatic Imbalance
3.5. Coagulation and Fibrinolysis
3.6. Platelets
4. Neonates
4.1. Neonatal Developmental Hemostasis
4.1.1. Neonatal Endothelium
4.1.2. Coagulation and Fibrinolysis
4.1.3. Platelet Function
4.2. Hemostasis in Neonates Born to Pre-Eclamptic Mothers
5. Evaluation of Hemostasis in Healthy Pregnant Women and in Women with Pre-Eclampsia
5.1. Conventional Coagulation Tests (CCTs)
5.2. Viscoelastic Tests
5.2.1. TEG/ROTEM in Healthy Pregnancies
Rotational Thromboelastometry (ROTEM) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Study | Trimester | Assay | CT (sec) | CFT (sec) | MCF (mm) | A-Angle (°) | A10 (mm) | A30 (mm) | LI30 (%) | ML (%) | Notes |
Rheenen-Flach et al., 2013 [118] | Postpartum controls >6 weeks (19 women) | INTEM | 127–262 | 44–88 | 57–69 | 71–81 | - | 56–68 | - | - | Suggested reference ranges |
EXTEM | 22–145 | 42–104 | 59–72 | 69–81 | - | 57–70 | - | - | |||
Healthy pregnant women 8–20 GW (45 women) | INTEM | 119–213 * | 40–86 | 59–72 * | 73–82 | - | 57–71 * | - | - | ||
EXTEM | 38–97 * | 45–101 | 60–75 * | 68–82 | - | 59–75 * | - | - | |||
Healthy pregnant women 20–32 GW (41 women) | INTEM | 122–215 | 41–75 * | 62–73 * | 75–82 * | - | 60–72 * | - | - | ||
EXTEM | 29–113 | 41–95 | 63–77 * | 72–81 * | - | 61–76 * | - | - | |||
Healthy pregnant women 32–42 GW (44 women) | INTEM | 107–213 | 36–70 * | 63–78 * | 76–82 * | - | 62–77 * | - | - | ||
EXTEM | 3–180 * | 31–101 | 64–79 * | 72–83 | - | 63–78 * | - | - | |||
De Lange et al., 2014 [106] | Healthy pregnant women during labor (161 women) | INTEM | 109–225 | 40–103 | 63–78 | 70–82 | 55–72 | - | - | 0–15 | Suggested reference ranges |
EXTEM | 31–63 | 41–120 | 42–78 | 67–83 | 48–74 | - | - | 0–41 | |||
FIBTEM | 1–79 | - | 13–45 | 50–83 | 12–38 | - | - | 0–6 | |||
APTEM | 33–62 | 42–118 | 61–79 | 69–82 | 54–72 | - | - | 0–15 | |||
Healthy pregnant women 1 h after delivery (161 women) | INTEM | 98–225 | 37–118 | 48–78 | 67–82 | 46–73 | - | - | 0–15 | ||
EXTEM | 34–66 | 44–154 | 55–78 | 63–81 | 44–73 | - | - | 0–44 | |||
FIBTEM | 31–59 | - | 12–42 | 65–83 | 12–44 | - | - | 0–10 | |||
APTEM | 31–71 | 47–158 | 56–78 | 60–81 | 43–72 | - | - | 0–14 | |||
Lee et al., 2020 a [104] Lee et al., 2020 b [119] | Non-pregnant controls (132 women) | INTEM | 115–245 | 42–103 | 59–76 | 70–82 | - | 59–76 | - | - | Suggested reference ranges |
EXTEM | 43–69 | 43–108 | 60–78 | 69–82 | - | 60–78 | - | - | |||
FIBTEM | 40–74 | - | 16–34 | 67–81 | - | 16–34 | - | - | |||
Healthy pregnant women Term >37 GW (121 women) | INTEM | 118–222 | 36–89 * | 61–78 * | 72–82 | 54–73 | 61–78 * | - | - | ||
EXTEM | 40–65 * | 41–93 | 63–77 * | 71–82 | 56–74 | 63–77 * | - | - | |||
FIBTEM | 41–66 | - | 16–40 * | 69–81 | 15–37 | 16–40 * | - | - | |||
Shamshirsaz et al., 2021 [102] | Non-pregnant controls (33 women) | INTEM | 131–220 | 50–93 | 57–72 | 71–79 | 57–72 | - | - | 2–13 | Suggested reference ranges |
EXTEM | 42–75 | 47–99 | 59–74 | 70–81 | 52–70 | - | - | 3–13 | |||
FIBTEM | 40–64 | - | 10–31 | 63–82 | 10–32 | - | - | 0–13 | |||
Healthy pregnant women 1st trimester (34 women) | INTEM | 152–203 | 45–91 | 57–72 | 72–81 | 52–69 | - | - | 2–13 | ||
EXTEM | 45–75 | 44–97 | 61–76 * | 71–81 | 54–72 | - | - | 3–17 * | |||
FIBTEM | 41–69 | - | 12–35 | 68–81 | 11–33 | - | - | 0–8 | |||
Healthy pregnant women 2nd trimester (34 women) | INTEM | 137–207 | 43–91 | 57–74 | 71–81 | 51–71 | - | - | 2–15 | ||
EXTEM | 44–69 | 42–100 | 60–77 * | 71–81 | 52–74 | - | - | 2–17 * | |||
FIBTEM | 38–64 | - | 12–34 | 67–81 | 12–32 | - | - | 0–3 * | |||
Healthy pregnant women 3rd trimester (41 women) | INTEM | 127–207 | 42–88 * | 61–77 * | 73–81 * | 53–72 * | - | - | 2–10 * | ||
EXTEM | 40–71 | 38–94 * | 63–79 * | 71–82 * | 54–75 * | - | - | 2–12 | |||
FIBTEM | 36–65 | - | 17–36 * | 69–82 * | 16–34 * | - | - | 0–2 * | |||
Getrajdman et al., 2021 [120] | Healthy pregnant women at term (120) | NATEM | 32–759 | 69–243 | 57–77 | 50–77 | 44–69 | - | 100–100 | - | Suggested reference ranges |
NaHEPTEM | 224–717 | 66–210 | 58–74 | 53–77 | 44–67 | - | 99–100 | - | |||
Thromboelastography (TEG) | |||||||||||
Study | Trimester | Assay | R (min) | K (min) | MA (mm) | A-angle (°) | LY30 (%) | LY60 (%) | CI | Notes | |
Polak et al., 2011 [115] | Non-pregnant controls (43 women) | Kaolin | 4–8 | 1–4 | 55–73 | 47–74 | - | 0–15 | −3–3 | Suggested reference ranges | |
Healthy pregnant women 3rd trimester (60 women) | 2–8 * | 1–3 * | 64–76 * | 60–77 * | - | 0–3 * | 0–5 * | ||||
Yang et al., 2019 [116] | Non-pregnant controls (145 women) | Kaolin | 4.1–10.6 | 1.1–5.2 | 46.3–65.2 | 38.4–76.4 | 0–10.6 | - | −7.5–1.9 | Suggested reference ranges | |
Healthy pregnant women 1st trimester (252 women) | 1.1–10.4 * | 0.9–3.1 | 46.1–69.8 * | 53.6–75.9 | 0–10.7 | - | −5.5–2.5 | ||||
Healthy pregnant women 2nd trimester (340 women) | 3.9–9.7 * | 0.8–2.4 * | 49.8–72.1 * | 56.7–78.0 * | 0–9.7 | - | −3.7–2.9 * | ||||
Healthy pregnant women 3rd trimester (161 women) | 3.8–9.0 * | 0.8–2.5 * | 49.4–75.9 * | 57.6–79.3 * | 0–8.8 | - | −3.0–2.6 * | ||||
Xie et al., 2021 [123] | Healthy pregnant women 3rd trimester (125 women) | Kaolin | 4–7.7 | 1.2–3.2 | 51.9–70.1 | 41.4–74.4 | - | - | - | Suggested reference ranges |
5.2.2. TEG/ROTEM in Pre-Eclampsia
6. Future Insights
6.1. Neonates Born to Mothers with Pre-Eclampsia May Develop Endothelial Dysfunction
6.2. Viscoelastic Tests May Be Helpful in Pre-Eclampsia Management
6.3. Viscoelastic Tests May Be Helpful in Neonates Born to Pre-Eclamptic Women
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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(A) Non-PREGNANT CONTROLS vs. HEALTHY PREGNANT WOMEN | ||||||||
---|---|---|---|---|---|---|---|---|
Study | Population | Platelets (×109/L) | PT (sec) | aPTT (sec) | Fibrinogen (mg/dL) | D-Dimers (μg/mL) | ATIII (%) | Notes |
Huissoud et al., 2009 [103] | Non-pregnant controls (20 women) | 234 (194–266) | 15 (14–15) | 32 (28–35) | 330 (310–360) | - | - | Values are “Median” (IQR) |
Healthy pregnant women 1st trimester (17 women) | 266 (233–302) | 15 (14–15) | 32 (28–35) | 400 (370–430) * | - | - | ||
Healthy pregnant women 2nd trimester (9 women) | 202 (181–222) | 14 (14–15) | 31 (28–34) | 460 (430–480) * | - | - | ||
Healthy pregnant women 3rd trimester (58 women) | 138 (119–152) * | 14 (14–15) | 30 (28–32) | 500 (440–580) * | - | - | ||
De Lange et al., 2014 [106] | Healthy pregnant women during labor (161 women) | 214 (179–257) | - | - | 490 (440–580) | 0.18 (0.11–026) * | - | Values are “Median” (IQR) |
Healthy pregnant women 1 h after delivery (161 women) | 203 (171–246) | - | - | 470 (410–540) | 0.31 (0.19–0.47) | - | ||
Shamshirsaz et al., 2021 [102] | Non-pregnant controls (33 women) | 221 (192–253) | 13.1 (12.8–13.4) | 30.6 (27.8–32.2) | 321 (279–445) | 0.26 (0.22–0.45) | - | Values are “Median” (IQR). †: Statistically significant between 1st and 2nd trimester. ‡: Statistically significant between 1st and 3rd trimester. |
Healthy pregnant women 1st trimester (34 women) | 208 (172–246) | 12.9 (12.8–13.3) | 29.2 (27.3–30.8) | 407 (369–458) * | 0.37 (0.26–0.47) * | - | ||
Healthy pregnant women 2nd trimester (34 women) | 195 (165–224) | 12.9 (12.5–13.1) | 27.6 (26.7–29.2) | 449 (385–497) | 0.53 (0.37–0.82) † | - | ||
Healthy pregnant women 3rd trimester (41 women) | 171 (137–205) ‡ | 12.9 (12.5–13.2) | 27.7 (26.5–28.9) ‡ | 470 (437–518) ‡ | 0.85 (0.65–1.24) ‡ | - | ||
(B) HEALTHY PREGNANT CONTROLS vs. WOMEN WITH PRE-ECLAMPSIA | ||||||||
Study | Population | Platelets (×109/L) | PT (sec) | aPTT (sec) | Fibrinogen (mg/dL) | D-Dimers (μg/mL) | ATIII (%) | Notes |
Orlikowski et al., 1996 [7] | Healthy pregnant controls | - | 10.2 ± 0.6 | 28.5 ± 3.1 | 530 ± 100 | - | 98 ± 10 | Values are “Mean ± SD” |
Pregnant women with PE and Eclampsia (49 women) | 199 ± 90 | 10.4 ± 0.9 | 24.9 ± 3.6 | 540 ± 140 | - | 83 ± 15 | ||
Yin et al., 1998 [107] | Healthy pregnant controls (19 women) | - | - | - | 367 ± 116 | - | 105.8 ± 14.2 | Values are “Mean ± SD” |
Pregnant women with PE (30 women) | - | - | - | 455 ± 129 * | - | 86.6 ± 15.1 * | ||
Sharma et al., 1999 [108] | Healthy pregnant controls (52 women) | 225 ± 58 | - | - | - | - | - | Values are “Mean ± SD”. †: Statistically significant between pregnant women with severe PE and platelet count < 100 × 109/L; pregnant women with mild PE; and with severe PE and platelet count ≥ 100 × 109/L. |
Pregnant women with mild PE (140 women) | 230 ± 67 | - | - | - | - | - | ||
Pregnant women with severe PE and platelet count ≥ 100 × 109/L (80 women) | 220 ± 67 | - | - | - | - | - | ||
Pregnant women with severe PE and platelet count < 100 × 109/L (34 women) | 67 ± 17 *† | - | - | - | - | - | ||
Tanjung et al., 2005 [24] | Healthy pregnant controls (27 women) | - | - | - | 499 ± 130 | 1.6 ± 0.0018 | 93.4 ± 12.1 | Values are “Mean ± SD” |
Pregnant women with PE At term (32) | - | - | - | 462 ± 150 | 2.316 ± 0.0034 | 88.5 ± 14.4 | ||
Pregnant women with PE Preterm (8) | - | - | - | 564 ± 170 | 1.283 ± 0.0018 | 84 ± 10.2 * | ||
Davies et al., 2007 [65] | Healthy pregnant controls (93 women) | 257 ± 89 | 13.2 ± 0.9 | 28.7 ± 1.3 | 440 ± 100 | - | - | Values are “Mean ± SD” |
Pregnant women with mild PE (23 women) | 230 ± 83 | 13.2 ± 0.9 | 30.2 ± 4.3 | 410 ± 100 | - | - | ||
Pregnant women with severe PE (27 women) | 177 ± 81 * | 13.3 ± 1.2 | 31.3 ± 3.4 * | 400 ± 90 | - | - | ||
Spieza et al., 2015 [105] | Healthy pregnant controls (60 women) | 228 ± 54 | - | 28 ± 3 | - | 0.491 ± 0.399 | - | Values are “Mean ± SD” |
Pregnant women with PE (30 women) | 206 ± 54 | - | 26 ± 3 * | - | 0.563 ± 0.49 | - | ||
Lidan et al., 2019 [4] | Healthy pregnant controls (59 women) | 238.63 ± 63.62 | 10.8 ± 0.75 | 26.92 ± 2.58 | 435 ± 99 | 1.43 ± 0.5 | 97.37 ± 14.6 | Values are “Mean ± SD” |
Pregnant women with mild PE (32 women) | 242.5 ± 64.81 | 10.77 ± 0.66 | 27.30 ± 3.11 | 422 ± 103 | 1.51 ± 0.46 | 90.05 ± 17.19 | ||
Pregnant women with severe PE (26 women) | 231.23 ± 53.21 | 10.57 ± 0.62 | 26.15 ± 4.4 | 396 ± 99 | 1.68 ± 0.72 | 81.85 ± 18.97 |
Description | TEG Parameter | ROTEM Parameter | Reflecting |
---|---|---|---|
Clotting time (time to 2 mm amplitude) | Reaction time (R) in minutes | Clotting time (CT) in seconds |
|
Clot kinetics (time from 2 mm to 20 mm amplitude) | Clot kinetics (K) in minutes | Clot formation time (CFT) in seconds |
|
Alpha angle (clot strengthening) | A-angle in degrees (slope between R and K) | A-angle in degrees (slope between the baseline and a tangent to the clotting curve through the 2 mm point) |
|
Maximum strength/amplitude of the clot | Maximum amplitude (MA) in mm | Maximum clot firmness (MCF) in mm |
|
Clot firmness (amplitude) at set time after clotting time | Amplitude at 10, 30 min, etc. (A 10, 30, etc.) in mm (post-MA) | Amplitude at 10, 30 min, etc. (A 10, 30, etc.) in mm (post-CT) |
|
Ratio of the amplitude and MA/MCF at set time after reaching maximum amplitude and clotting time, respectively | Lysis index or clot lysis at 10, 30, etc., minutes (LY or CL 10, 30, etc.) in percentage (post-MA) | Lysis index or clot lysis at 10, 30, etc. (LI or CL 10, 30, etc.) in percentage (minutes post-CT) |
|
Calculated through a mathematical formula considering the relative contribution of R, K, A-angle, and MA | Coagulation index (CI) | - |
|
Maximum lysis detected during the run time (difference between MCF and the lowest amplitude after MCF, described in terms of percentage of MCF) | - | Maximum lysis (ML) in percentage |
|
ROTEM assays | |||
Assay | Reagent(s) | Reflecting | |
Intrinsic thromboelastometry (INTEM) | Phospholipids Ellagic acid | Intrinsic pathway. Assessment of factors XII, XI, IX, VIII, X, V, II, I, platelets, and fibrinolysis. | |
Extrinsic thromboelastometry (EXTEM) | Tissue factor | Extrinsic pathway. Assessment of factors VII, X, V, II, I, platelets, and fibrinolysis. | |
Fibrinogen thromboelastometry (FIBTEM) | Tissue factor | Type of EXTEM. Cytochalasin D is added as a platelet inhibitor. Fibrinogen levels and fibrin polymerization can be assessed in a functional way. | |
Aprotinin thromboelastometry (APTEM) | Tissue factor | Type of EXTEM. Aprotinin or tranexamic acid are added to inhibit fibrinolysis. | |
Non-Activated thromboelastometry NATEM) | - | Theoretically, it reflects the in vivo profile of the individual. | |
TEG assays | |||
Assay | Reagent(s) | Reflecting | |
K-TEG | Kaolin | Intrinsic pathway | |
H-TEG | Kaolin/Heparinase | Compared with K-TEG to assess the heparin effect | |
R-TEG | Kaolin/Tissue factor | Extrinsic pathway. Clot is formed immediately. Rapid interpretation of amplitude. Assessment of platelets and fibrinogen | |
TEG-FF | Kaolin/Tissue factor/Abciximab (GPIIb/IIIa platelet receptor inhibitor) | Fibrin polymerization. Compared with K-TEG to assess the contribution of fibrinogen to clot strength absent of any platelet function. | |
TEG-PM | Reptilase/Factor XIIIa + kaolin or ADP or arachidonic acid | Percentage of maximal platelet contribution in the presence of ADP or arachidonic acid to assess for an antiplatelet effect. | |
Native TEG | Calcium | Tissue factor expression on monocytes. |
Rotational Thromboelastometry (ROTEM) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Study | Population | Assay | CT (sec) | CFT (sec) | MCF (mm) | A-Angle (°) | A10 (mm) | A30 (mm) | LI30 (%) | ML (%) | Notes |
Huissoud et al., 2009 [103] | Non-pregnant controls (20 women) | INTEM | 159 (138–189) | 78 (65–98) | 58 (54–62) | - | - | - | 98 (98–100) | - | Values are “Median (IQR)” |
EXTEM | 51 (45–55) | 101 (88–121) | 59 (57–62) | - | - | - | 99 (99–100) | - | |||
FIBTEM | 51 (44–53) | - | 13 (11–16) | - | - | - | - | - | |||
APTEM | 63 (56–67) | 96 (78–116) | 58 (56–62) | - | - | - | 99 (97–99) | - | |||
Healthy pregnant women 1st trimester (17 women) | INTEM | 168 (143–198) | 74 (62–82) | 62 (59–64) | - | - | - | 99 (98–99) | - | ||
EXTEM | 54 (51–61) | 82 (66–94) * | 62 (60–94) | - | - | - | 99 (99–99) | - | |||
FIBTEM | 59 (52–65) | - | 18 (15–23) | - | - | - | 100 (100–100) | - | |||
APTEM | 65 (58–83) | 84 (71–88) | 64 (60–67) | - | - | - | 99 (98–100) | - | |||
Healthy pregnant women 2nd trimester (9 women) | INTEM | 145 (131–168) | 62 (58–66) * | 66 (64–68) * | - | - | - | 100 (99–100) | - | ||
EXTEM | 54 (51–63) | 77 (70–78) * | 67 (66–71) * | - | - | - | 99 (99–100) | - | |||
FIBTEM | 61 (50–64) | - | 19 (19–22) * | - | - | - | 100 (100–100) | - | |||
APTEM | 58 (51–84) | 66 (65–68) | 67 (65–82) | - | - | - | 100 (99–100) | - | |||
Healthy pregnant women 3rd trimester (58 women) | INTEM | 155 (132–186) | 66 (58–78) * | 66 (63–69) * | - | - | - | 100 (99–100) | - | ||
EXTEM | 53 (47–62) | 74 (66–89) * | 67 (64–71) * | - | - | - | 100 (99–100) | - | |||
FIBTEM | 52 (46–65) | - | 19 (17–23) * | - | - | - | - | - | |||
APTEM | 57 (52–75) | 74 (64–96) | 67 (64–70) | - | - | - | 100 (99–100) | - | |||
Rheenen-Flach et al., 2013 [118] | Postpartum controls >6 weeks (19 women) | INTEM | 195 ± 34 | 66 ± 11 | 63 ± 3 | 77 ± 2 | - | 62 ± 3 | - | - | Values are “Mean ± SD” |
EXTEM | 83 ± 31 | 73 ± 16 | 65 ± 3 | 75 ± 3 | - | 64 ± 3 | - | - | |||
Healthy pregnant women 8–20 GW (45 women) | INTEM | 166 ± 24 * | 63 ± 12 | 65 ± 3 * | 77 ± 2 | - | 64 ± 34 * | - | - | ||
EXTEM | 67 ± 15 * | 73 ± 14 | 68 ± 3 * | 75 ± 3 | - | 67 ± 3 * | - | - | |||
Healthy pregnant women 20–32 GW (41 women) | INTEM | 168 ± 24 | 58 ± 9 * | 67 ± 3 * | 78 ± 2 * | - | 66 ± 3 * | - | - | ||
EXTEM | 71 ± 21 | 68 ± 14 | 70 ± 4 * | 77 ± 2 * | - | 69 ± 4 * | - | - | |||
Healthy pregnant women 32–42 GW (44 women) | INTEM | 160 ± 27 | 53 ± 9 * | 71 ± 4 * | 79 ± 3 * | - | 70 ± 4 * | - | - | ||
EXTEM | 92 ± 45 * | 66 ± 18 | 72 ± 4 * | 77 ± 3 | - | 71 ± 4 * | - | - | |||
De Lange, 2014 [106] | Healthy pregnant women during labor (161 women) | INTEM | 147 (138–164) | 55 (49–63) | 71 (69–74) | 79 (77–80) | 64 (62–67) | - | - | 5 (2–8) | Values are “Median (IQR)” |
EXTEM | 45 (41–50) | 69 (62–81) | 71 (69–74) | 77 (74–79) | 64 (61–68) | - | - | 7 (4–12) | |||
FIBTEM | 39 (37–44) | - | 25 (22–28) | 79 (76–80) | 22 (20–26) | - | - | 0 (0–0.5) | |||
APTEM | 43 (39–48) | 69 (59–78) | 71 (69–74) | 77 (75–79) | 64 (60–67) | - | - | 4 (2–8) | |||
Healthy pregnant women 1 h after delivery (161 women) | INTEM | 137 (127–155) | 57 (50–69) | 71 (67–74) | 78 (76–80) | 64 (60–67) | - | - | 4 (2–8) | ||
EXTEM | 45 (40–49) | 73 (63–86) | 71 (68–74) | 76 (74–79) | 64 (60–67) | - | - | 8 (3–12) | |||
FIBTEM | 39 (36–42) | - | 24 (20–28) | 78 (75–80) | 21 (18–25) | - | - | 0 (0–0) | |||
APTEM | 41 (38–45) | 72 (64–85) | 71 (67–73) | 76 (74–78) | 63 (59–66) | - | - | 5 (2–8) | |||
Lee et al., 2020 a [104] Lee et al., 2020 b [119] | Non-pregnant controls (132 women) | INTEM | 167.7 ± 32.06 | 64.2 ± 15.3 | 68.3 ± 4.43 | 77.1 ± 2.73 | - | 68.4 ± 4.55 | - | - | Values are “Mean ± SD” |
EXTEM | 53.7 ± 6.26 | 65.7 ± 15.2 | 70.2 ± 4.01 | 77.4 ± 2.65 | - | 70 ± 4.13 | - | - | |||
FIBTEM | 53.4 ± 7.85 | - | 24.1 ± 4.68 | 75.5 ± 3.81 | - | 24.1 ± 4.6 | - | ||||
Healthy pregnant women Term >37 GW (121 women) | INTEM | 162.5 ± 26.19 | 60.49 ± 12.6 * | 69.6 ± 3.77 * | 77.7 ± 2.47 | - | 69.6 ± 3.79 * | - | - | ||
EXTEM | 52.2 ± 5.91* | 62.6 ± 13.08 | 71.1 ± 3.36 * | 77.6 ± 2.64 | - | 71 ± 3.32 * | - | - | |||
FIBTEM | 51.7 ± 6.21 | - | 25.8 ± 4.86 * | 76.2 ± 2.93 | - | 25.8 ± 4.93 * | - | - | |||
Shamshirsaz et al., 2021 [102] | Non-pregnant controls (33 women) | INTEM | 173 (163–192) | 72 (63–81) | 64 (62–67) | 75 (74–77) | 59 (56–63) | - | - | 7 (5–9) | Values are “Median (IQR)” |
EXTEM | 58 (54–65) | 74 (64–84) | 67 (64–70) | 76 (73–77) | 61 (57–64) | - | - | 8 (7–10) | |||
FIBTEM | 52 (48–58) | - | 20 (16–25) | 72 (70–75) | 21 (17–26) | - | - | 5 (1–8) | |||
Healthy pregnant women 1st trimester (34 women) | INTEM | 180 (168–188) | 66 (61–75) | 64 (62–67) | 77 (75–77) | 61 (58–63) | - | - | 7 (5–9) | ||
EXTEM | 58 (53–71) | 69 (58–81) | 69 (67–71) * | 76 (74–78) | 63 (60–66) | - | - | 9 (8–13) * | |||
FIBTEM | 55 (50–60) | - | 23 (19–26) | 74 (72–77) | 21 (18–24) | - | - | 2 (1–5) | |||
Healthy pregnant women 2nd trimester (34 women) | INTEM | 173 (161–184) | 67 (59–73) | 66 (63–69) | 76 (75–78) | 60 (58–63) | - | - | 8 (7–9) | ||
EXTEM | 57 (53–61) | 68 (62–79) | 69 (66–72) * | 76 (74–78) | 63 (60–67) | - | - | 9 (7–11) * | |||
FIBTEM | 51 (47–55) | - | 23 (19–26) | 75 (72–76) | 21 (18–24) | - | - | 0 (0–1) * | |||
Healthy pregnant women 3rd trimester (41 women) | INTEM | 168 (156–178) | 64 (59–71) * | 69 (66–71) * | 77 (75–78) * | 63 (60–65) * | - | - | 6 (4–7) * | ||
EXTEM | 55 (50–61) | 68 (57–75) * | 71 (68–73) * | 78 (76–79) * | 66 (61–88) * | - | - | 7 (6–9) | |||
FIBTEM | 51 (45–56) | - | 27 (24–30) * | 77 (74–78) * | 25 (22–27) * | - | - | 0 (0–1) * | |||
Getrajdman et al., 2021 [120] | Healthy pregnant women at term (120) | NATEM | 482.5 (415–552) | 112 (97.8–133) | 66 (63–70) | 69 (64.8–71) | 56 (52–61) | - | 100 (100–100) | - | Values are “Median (IQR)” |
NaHEPTEM | 493 (421–559) | 120 (98.8–137) | 65 (62–69) | 67 (64–71) | 56 (52–60) | 100 (100–100) | |||||
Lee et al., 2022 [121] | Healthy pregnant women Term >37 GW (75 women) | EXTEM | 54.3 ± 6.1 | 62.8 ± 11.5 | 70.9 ± 3.3 | Values are “Mean ± SD” | |||||
FIBTEM | 53.9 ± 7.7 | - | 24.9 ± 4.5 | - | - | - | - | - | |||
Thromboelastography (TEG) | |||||||||||
Study | Population | Assay | R (min) | K (min) | MA (mm) | A-angle (°) | LY30 (%) | LY60 (%) | CI | Notes | |
Polak et al., 2011 [115] | Non-pregnant controls (43 women) | Kaolin | 7.81 ± 2.76 | 2.72 ± 0.94 | 63.06 ± 5.4 | 54.38 ± 11.48 | - | 4.83 ± 3.64 | −1.91 ± 3.01 | Values are “Mean ± SD” | |
Healthy pregnant women 3rd trimester (60 women) | 4.75 ± 1.74 * | 1.48 ± 0.45 * | 71.33 ± 4.45 * | 69.58 ± 5.52 * | - | 1.15 ± 1.78 * | 2.68 ± 1.79 * | ||||
Shreeve et al., 2016 [117] | Healthy pregnant women <14 GW (32 women) | Kaolin | 6.2 ± 1.3 | 1.6 ± 0.4 | 67.4 ± 3.9 | 66 ± 5.1 | 1.2 ± 1.7 | 3.6 ± 2.1 | - | Values are “Mean ± SD” * Statistically significant between healthy pregnant women 37–42 GW and controls of the above group postnatally | |
Healthy pregnant women 14–28 GW (24 women) | 6.1 ± 1.3 | 1.3 ± 0.3 | 70.4 ± 3.7 | 68.5 ± 6.7 | 1.4 ± 0.8 | 5.1 ± 1.5 | - | ||||
Healthy pregnant women 28–42 GW (33 women) | 6.1 ± 1 | 1.4 ± 0.3 | 70 ± 4 | 68 ± 6 | 0.1 ± 0.8 | 4.2 ± 1.9 | - | ||||
Healthy pregnant women 37–42 GW (23 women) | 6.2 ± 1.3 | 1.3 ± 0.3 | 72 ± 3.3 | 70.1 ± 4.6 | 0.2 ± 0.4 * | 1.8 ± 1.4 * | - | ||||
Controls of the above group postnatally | 5.8 ± 1.2 | 1.2 ± 0.6 | 72.7 ± 3.7 | 72.4 ± 7.2 | 0.6 ± 0.9 | 3.1 ± 1.9 | - |
Rotational Thromboelastometry (ROTEM) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Study | Population | Assay | CT (sec) | CFT (sec) | MCF (mm) | A-Angle (°) | A10 (mm) | A30 (mm) | LI30 (%) | ML (%) | Notes |
Spieza et al., 2015 [105] | Healthy pregnant controls (60 women) | INTEM | 153 ± 20 | 67 ± 14 | 65 ± 5 | 76 ± 3 | - | - | - | 11 ± 4 | Values are “Mean ± SD |
EXTEM | 47 ± 8 | 75 ± 14 | 66 ± 4 | 75 ± 4 | - | - | - | 11 ± 5 | |||
NATEM | 463 ± 54 | 116 ± 26 | 61 ± 4 | 67 ± 5 | - | - | - | 11 ± 4 | |||
FIBTEM | - | - | 21 ± 4 | 73 ± 4 | - | - | - | - | |||
Pregnant women with PE (30 women) | INTEM | 154 ± 27 | 64 ± 12 | 71 ± 4 * | 77 ± 2 | - | - | - | 2 ± 3 * | ||
EXTEM | 48 ± 9 | 62 ± 15 * | 72 ± 5 * | 78 ± 4 * | - | - | - | 2 ± 3 * | |||
NATEM | 432 ± 89 | 130 ± 55 | 64 ± 6 | 67 ± 9 | - | - | - | 1 ± 3 * | |||
FIBTEM | - | - | 28 ± 7 * | 76 ± 6 * | - | - | - | - | |||
Thromboelastography (TEG) | |||||||||||
Study | Population | Assay | R (min) | K (min) | MA (mm) | A-angle (°) | LY30 (%) | LY60 (%) | CI | Notes | |
Orlikowski et al., 1996 [7] | Healthy pregnant controls | Kaolin | 7.8 ± 0.9 | 3.3 ± 0.7 | 59.7 ± 3.5 | - | - | - | - | Values are “Mean ± SD” | |
Pregnant women with PE and eclampsia (49 women) | 6.8 ± 1 | 3.1 ± 0.8 | 61.7 ± 6.6 | - | - | - | - | ||||
Sharma et al., 1999 [108] | Healthy pregnant controls (52 women) | Kaolin | 26.2 ± 7.5 | 10.2 ± 3.5 | 66.5 ± 7.1 | 43.1 ± 9.1 | - | - | - | Values are “Mean ± SD”. †: Statistically significant between pregnant women with severe PE and platelet count < 100 × 109/L and pregnant women with mild PE, severe PE, and platelet count ≥ 100 × 109/L. ‡: Statistically significant between pregnant women with mild PE and severe PE and healthy pregnant controls. | |
Pregnant women with mild PE (140 women) | 29.5 ± 7.2 | 10.8 ± 3.7 | 69.3 ± 7.3 ‡ | 41.6 ± 9.8 | - | - | - | ||||
Pregnant women with severe PE and platelet count ≥ 100 × 109/L (80 women) | 29.6 ± 7.6 | 11.6 ± 4.2 | 66.1 ± 6.9 | 39.9 ± 9.4 | - | - | - | ||||
Pregnant women with severe PE and platelet count < 100 × 109/L (34 women) | 37.4 ± 9.9 *† | 20.9 ± 7.4 *† | 52.1 ± 10.6 *† | 23.6 ± 9.1 *† | - | - | - | ||||
Davies et al., 2007 [65] | Healthy pregnant controls (93 women) | Celite-activated | 4.5 ± 1.8 | 1.4 ± 0.5 | 73 ± 5 | 70 ± 9 | - | - | - | Values are “Mean ± SD” | |
Pregnant women with mild PE (23 women) | 4.9 ± 1.9 | 1.4 ± 0.4 | 73 ± 5 | 71 ± 6 | - | - | - | ||||
Pregnant women with severe PE (27 women) | 5.2 ± 2.5 | 2 ± 1.7 * | 71 ± 8 | 66 ± 11 | - | - | - | ||||
Bulbul et al., 2015 [125] | Healthy pregnant controls (31 women) | Kaolin | 7.8 ± 3.7 | 2.6 ± 1.1 | 66.1 ± 5.6 | 57.4 ± 9.2 | 1.2 ± 1.6 | 3.1 ± 3.1 | −1.7 ± 3.7 | Values are “Mean ± SD” | |
Pregnant women with PE (49 women) | 9.5 ± 3 | 2.9 ± 1.2 | 66.5 ± 6.3 | 54.6 ± 9.7 | 1.7 ± 2.3 | 3.5 ± 3.4 | −2.7 ± 3.6 | ||||
Lidan et al., 2019 [4] | Healthy pregnant controls (59 women) | Kaolin | 4.71 ± 0.97 | 1.52 ± 0.37 | - | 65.58 ± 6.08 | - | - | 1.17 ± 0.93 | Values are “Mean ± SD”. †: Statistically significant between pregnant women with mild PE and pregnant women with severe PE. | |
Pregnant women with mild PE (32 women) | 4.17 ± 0.88 * | 1.36 ± 0.38 * | - | 68.76 ± 5.27 * | - | - | 3.06 ± 0.58 * | ||||
Pregnant women with severe PE (26 women) | 3.7 ± 0.5 *† | 1.13 ± 0.19 *† | - | 71.95 ± 2.77 *† | - | - | 3.74 ± 0.92 *† |
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Kontovazainitis, C.-G.; Gialamprinou, D.; Theodoridis, T.; Mitsiakos, G. Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests. Diagnostics 2024, 14, 347. https://doi.org/10.3390/diagnostics14030347
Kontovazainitis C-G, Gialamprinou D, Theodoridis T, Mitsiakos G. Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests. Diagnostics. 2024; 14(3):347. https://doi.org/10.3390/diagnostics14030347
Chicago/Turabian StyleKontovazainitis, Christos-Georgios, Dimitra Gialamprinou, Theodoros Theodoridis, and Georgios Mitsiakos. 2024. "Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests" Diagnostics 14, no. 3: 347. https://doi.org/10.3390/diagnostics14030347