Hemostatic biomarkers associated with postpartum hemorrhage: a systematic review and meta-analysis

Abstract

Postpartum hemorrhage (PPH) is a leading cause of maternal morbi-mortality. Although obstetric risk factors are well described, the impact of predelivery hematologic and hemostatic biomarkers remains incompletely understood. In this systematic review, we aimed to summarize the available literature on the association between predelivery hemostatic biomarkers and PPH/severe PPH. Searching MEDLINE, EMBASE, and CENTRAL databases from inception to October 2022, we included observational studies on unselected pregnant women without bleeding disorder reporting on PPH and on predelivery hemostatic biomarkers. Two review authors independently performed title, abstract and full-text screening, upon which quantitative syntheses of studies reporting on the same hemostatic biomarker were conducted, calculating the mean difference (MD) between women with PPH/severe PPH and controls. A search on 18 October 2022 yielded 81 articles fitting our inclusion criteria. The heterogeneity between studies was considerable. With regard to PPH, the estimated average MD in the investigated biomarkers (platelets, fibrinogen, hemoglobin, Ddimer, activated partial thromboplastin time, and prothrombin time) were not statistically significant. Women who developed severe PPH had lower predelivery platelets than controls (MD = -26.0 109/L; 95% confidence interval, -35.8 to -16.1), whereas differences in predelivery fibrinogen concentration (MD = -0.31 g/L; 95% confidence interval, -0.75 to 0.13) and levels of factor XIII or hemoglobin were not statistically significant in women with and without severe PPH. Predelivery platelet counts were, on average, lower in women with severe PPH compared with controls, suggesting the potential usefulness of this biomarker for predicting severe PPH. This trial was registered at the International Prospective Register of Systematic Reviews as CRD42022368075.

Graphical abstract

Figure 1.

PRISMA flowchart of the study.

Figure 2.

Meta-analysis for predelivery platelet count and its association with severe PPH/PPH. (A) Forest plot of the MD with a 95% CI for predelivery platelet count between women with severe PPH and controls. (B) Forest plot of the MD with a 95% CI for predelivery platelet count between women with severe PPH (per WHO definition only) and controls. (C) Forest plot of the MD with a 95% CI for predelivery platelet count between women with PPH and controls. (D) Forest plot of the MD with a 95% CI for predelivery platelet count between women with PPH (WHO definition only) and controls.

Figure 3.

Meta-analysis for fibrinogen level and its association with severe PPH/PPH. (A) Forest plot of the MD with a 95% CI for predelivery fibrinogen concentration between women with severe PPH and controls. (B) Forest plot of the MD with a 95% CI for predelivery fibrinogen concentration between women with severe PPH (WHO definition only) and controls. (C) Forest plot of the MD with a 95% CI for predelivery fibrinogen concentration between women with PPH and controls. (D) Forest plot of the MD with a 95% CI for predelivery fibrinogen concentration between women with PPH (WHO definition only) and controls.

Figure 4.

Meta-analysis for predelivery hemoglobin level and its association with severe PPH/PPH. (A) Forest plot of the MD with a 95% CI for predelivery hemoglobin level between women with severe PPH and controls. (B) Forest plot of the MD with a 95% CI for predelivery hemoglobin level between women with PPH and controls. (C) Forest plot of the MD with a 95% CI for predelivery hemoglobin level between women with PPH (per WHO definition only) and controls.