Fibrinolytic potential as a risk factor for postpartum hemorrhage

Abstract

Background: Postpartum hemorrhage (PPH) is still the leading cause of maternal morbidity and mortality worldwide. While impaired fibrin polymerization plays a crucial role in the development and progress of PPH, recent approaches using viscoelastic measurements have failed to sensitively detect early changes in fibrinolysis in PPH. This study aimed to evaluate whether women experiencing PPH show alterations in POC-VET fibrinolytic potential during childbirth and whether fibrinolytic potential offers benefits in the prediction and treatment of PPH.

Methods: Blood samples were collected at three different timepoints: T0 = hospital admission (19 h ± 18 h prepartum), T1 = 30-60 min after placental separation, and T2 = first day postpartum (19 h ± 6 h postpartum). In addition to standard laboratory tests, whole-blood impedance aggregometry (Multiplate) and viscoelastic testing (VET) were performed using the ClotPro system, which included the TPA-test lysis time, to assess the POC-VET fibrinolytic potential, and selected coagulation factors were measured. The results were correlated with blood loss and clinical outcome markers. Severe PPH was defined as a hemoglobin drop > 4g/dl and/or the occurrence of shock or the need for red blood cell transfusion.

Results: Blood samples of 217 parturient women were analyzed between June 2020 and December 2020 at Heidelberg University Women's Hospital, and 206 measurements were eligible for the final analysis. Women experiencing severe PPH showed increased fibrinolytic potential already at the time of hospital admission. When compared to non-PPH, the difference persisted 30-60 min after placental separation. A higher fibrinolytic potential was accompanied by a greater drop in fibrinogen and higher d-dimer values after placental separation. While 70% of women experiencing severe PPH showed fibrinolytic potential, 54% of those without PPH showed increased fibrinolytic potential as well.

Conclusion: We were able to show that antepartal and peripartal fibrinolytic potential was elevated in women experiencing severe PPH. However, several women showed high fibrinolytic potential but lacked clinical signs of PPH. The findings indicate that high fibrinolytic potential is a risk factor for the development of coagulopathy, but further conditions are required to cause PPH.

Keywords: ClotPro; PPH; TPA-test; VET; fibrinolytic potential; point-of-care; viscoelastic hemostatic assay.

Figure 1

(A) ClotPro viscoelastic trace including the description of parameters. (B, C) Exemplary viscoelastic traces at T0 (prepartum) obtained from two women included in the study. (B) Shows the TPA-test trace of a woman with relatively low fibrinolytic potential and blood loss outside the normal range and (C) shows the TPA-test trace of a woman presenting with relatively high fibrinolytic potential at hospital admission and developing severe PPH in the course of delivery. ClotPro® hemostasis analyzer tracing image used by permission of Haemonetics Corporation. ClotPro® is a registered trademark of Haemonetics Corporation in the US, other countries or both.

Figure 2

Data collection and inclusion. Flowchart of the data collection process and data exclusion. Definition of mild and severe PPH according to estimated blood loss, ΔHb, and shock, as described above. PPH, postpartum hemorrhage.

Figure 3

Dynamic of TPA-test lysis time peripartum. Box and whisker plot: The box indicates the Q1–Q3 inter-quartile range, the horizontal line inside the box shows the median value, the marker inside the box displays the mean, the whiskers indicate observation nearest to the fences (= 1.5 IQR), the markers below and above the fences demonstrate observations above and below the fences; T0, antepartum; T1, 30–60 min after placental separation; T2, first day postdelivery; groups: white, non-PPH; light gray, mild PPH; dark gray, severe PPH. PPH, postpartum hemorrhage.

Figure 4

Dynamic of fibrinogen (A) and d-dimers (B) peripartum. Box and whisker plot: The box indicates the Q1–Q3 inter-quartile range, the horizontal line inside the box shows the median value, the marker inside the box displays the mean, the whiskers indicate observation nearest to the fences (=1.5 IQR), the markers below and above the fences demonstrate observations above and below the fences; T0, antepartum; T1, 30–60 min after placental separation; T2, first day postdelivery; groups: white, non-PPH; light gray, mild PPH; dark gray, severe PPH. PPH, postpartum hemorrhage.