Correlation of factor XIII subunit A with factor XIII activity in a population of parturient women

Archives of Gynecology and Obstetrics https://doi.org/10.1007/s00404-024-07799-2 MATERNAL-FETAL MEDICINE Correlation of factor XIII subunit A with factor XIII activity in a population of parturient women M. L. Frevert1 · J. Bürgi3 · R. Brun1,2 · T. Hothorn4 · M. Rösslein5 · N. Ochsenbein‑Kölble1,2 · C. Haslinger1,2 · W. Korte3 Received: 2 June 2024 / Accepted: 16 October 2024 © The Author(s) 2024 Abstract Background The role of factor XIII in acute bleeding situations is gaining more and more importance. It has previously been shown that prepartum factor XIII activity has a significant impact on postpartum blood loss. Whether factor XIII antigen behaves in a similar manner is unknown. As postpartum hemorrhage is one of the leading causes of maternal morbidity and mortality worldwide and factor XIII antigen determination might be available more readily in some centers as compared to factor XIII activity, this is an important question to answer, especially in the emergency situation of a postpartum hemorrhage. Objective To assess the correlation of prepartum factor XIII antigen with prepartum factor XIII activity and to evaluate the correlation between prepartum factor XIII antigen on measured postpartum blood loss. Methods This is a secondary analysis of a prospective cohort study which analyzed the impact of prepartum blood coagulation factor XIII activity on postpartum blood loss in 1300 women at the University Hospital Zurich, Switzerland between October 2015 and November 2016 (“PPH-1300 study”). Blood loss was quantified using a previously validated technique. The association of factor XIII activity and factor XIII antigen was assessed by means of a Spearman rank correlation and differences were displayed using Bland–Altman plot and Passing–Bablok regression. The effect of the prepartum factor XIII antigen on blood loss was estimated by continuous outcome logistic regression. Results Prepartum factor XIII activity significantly correlated with prepartum factor XIII antigen (Spearman rank correlation coefficient for prepartum values 0.89, p < 0.001 and postpartum values 0.902, p < 0.001). Elevated values of prepartum factor XIII antigen showed a trend toward lower measured postpartum blood loss. Conclusion The correlation of factor XIII activity with factor XIII antigen (subunit A) in a large real-world sample as well as an association of prepartum factor XIII antigen and postpartum blood loss is observed. Factor XIII antigen determination, a highly automatable test, could be useful in emergency situations such as a PPH (as well as other bleeding situations) if the determination of factor XIII activity is not possible. To evaluate whether FXIII replenishment reduces blood loss is the focus of ongoing studies. Keywords Postpartum hemorrhage · PPH · Postpartum blood loss · Factor XIII activity · Factor XIII antigen C. Haslinger and W. Korte contributed equally. * C. Haslinger 1 Department of Obstetrics, University Hospital Zurich, Frauenklinikstrasse 10, CH‑8091 Zurich, Switzerland 2 University of Zurich, Zurich, Switzerland 3 Center for Laboratory Medicine, Hemostasis and Hemophilia Center, St. Gallen, Switzerland 4 Epidemiology, Biostatistics and Prevention, Institute, University of Zurich, Zurich, Switzerland 5 Swiss Federal Laboratories for Materials Research and Testing, Laboratory for Particles—Biology Interactions, EMPA, Lerchenfeldstrasse 5, CH‑9014 St. Gallen, Switzerland Vol.:(0123456789) Archives of Gynecology and Obstetrics Introduction Methods Postpartum hemorrhage (PPH), defined as a blood loss of 500 ml or more within 24 h after birth, is a major cause of maternal mortality and morbidity worldwide. Several risk factors for the development of a PPH exist. Recently, hematologic factors such as platelet count as well as factor XIII activity have come into focus. Factor XIII plays a major role in cross-linking fibrinogen and fibrin and is thus important in securing clot stability and increasing fibrinolytic resistance of the clot. Hence, it has been hypothesized that changes in FXIII might impact postpartum blood loss significantly. Previously, our group observed that prepartum factor XIII activity has a strong impact on postpartum blood loss. Every 1% increase in prepartum factor XIII activity was associated with a (significantly increased) odds ratio of 1.011 to keep the measured blood loss below a given cut-off. This effect was shown to hold true across every statistical model and any clinical subgroup [1]. Similarly, other researchers found prepartum factor XIII activity to be significantly lower in women with PPH than in those with a normal peripartum blood loss [2, 3]. The prospective study carried out by our group between October 2015 and November 2016 in 1300 women allowed us not only to determine factor XIII activity, but also factor XIII subunit A (factor XIII antigen), which was measured with an immunological assay. To detect factor XIII activity, various functional factor XIII assays can be used (i.e., amine incorporation or isopeptidase assays). These are difficult to automate. However, albeit first steps toward automation having been undertaken [4]. While chromogenic ammonia release assays can readily be automated, they require a specific wavelength to be monitored [5] that is not available on all analyzers. Factor XIII (subunit A) antigen, on the other hand, can be measured via ELISA or latex agglutination immunoassays. The latter can be automated on analyzers with standard wavelength monitoring and is thus easier to include in a full laboratory automation [6], resulting in requirement for fewer personnel, which is especially important during night shifts [7]. Full automation also allows for results to be available after a shorter period of time [8, 9]. Because factor XIII activity has been shown to correlate well with factor XIII antigen in cases of factor XIII deficiency [10], we wanted to assess whether these results could be reproduced in case of potential FXIII depletion due to peripartum blood loss in our real-life population of more than 1300 women. If so, this would possibly allow for F XIII antigen assay implementation in emergency use such as in the case of postpartum hemorrhage. Study design and study oversight This is a secondary analysis of a prospective single-center cohort study [1], which was carried out at the Department of Obstetrics, University Hospital Zurich, Switzerland, from October 2015 to November 2016 after institutional review board approval (KEK-ZH 2015–0011, ClinicalTrials.gov registration NCT02604602, “PPH-1300 study”). The University Hospital Zurich, CSL Behring Switzerland, the Center for Laboratory Medicine St. Gallen and a private donor (a former patient) provided the funding for the study. CSL Behring and the private donor, as nonacademic entities, had neither an influence on the design or the execution of the study; nor on the collection, management, analysis, and interpretation of da (...truncated)