Association between Clauss fibrinogen concentration and ROTEM® FIBTEM A5 in women with postpartum haemorrhage: validation of cut-off points

Objective Point-of-care tests like FIBTEM A5 have been proposed to guide the treatment of patients who might have low fibrinogen concentrations (≤2 g/L). The aim of this study was to describe fibrinogen concentrations according to previously proposed FIBTEM A5 cut-off points in blood samples collected from women during postpartum haemorrhage. Design and setting Prospective multicentre cohort study Population 511 women sustaining postpartum haemorrhage. A total of 637 blood samples were drawn during haemorrhage. Methods Clauss fibrinogen concentrations and ROTEM® FIBTEM A5 values were studied to assess the diagnostic properties of previously proposed FIBTEM A5 cut-off points for the detection of low fibrinogen concentrations. Main outcome measures Youden index, sensitivity and specificity Results Of 511 women with a median total volume of blood loss of 1500 mL (IQR 1200 to 2000) 31 women (6%) developed Clauss fibrinogen concentrations below 2 g/L. Using FIBTEM A 5 cut-off of ≤ 7 mm: 48% of cases with Clauss fibrinogen ≤2 g/L were missed (FIBTEM A5 > 7mm), and of the 28 samples with FIBTEM A5 ≤ 7mm, 12 (43%) samples had Clauss fibrinogen >2 g/L. Using FIBTEM A5 cut-off of ≤12mm: 13% of cases with Clauss fibrinogen ≤2 g/L were missed and of the 145 samples with a FIBTEM A5 ≤12 mm, 118 had Clauss fibrinogen >2 g/L, resulting in false positive selection of 81% of women. Using FIBTEM A5 ≤ 15 mm: 97% (30/31) of the samples with Clauss fibrinogen ≤2 g/L were accurately selected; yet 89% (248/278) of samples that were selected had a fibrinogen concentration of >2 g/L. Based on the Youden index, the optimal cut-off point in our cohort was a FIBTEM A5 of 12mm with sensitivity 87% and specificity 81%. Conclusions Our findings suggest that if FIBTEM A5 lower than 12 mm would have been used to detect women with fibrinogen concentrations below 2 g/L in order to treat them with fibrinogen concentrate, 87 % of the women with fibrinogen below 2 g/L would correctly have received fibrinogen. However, most women (81%) receiving fibrinogen concentrate would not have needed it, because they had plasma fibrinogen concentrations above 2 g/L. Funding no funding was obtained to conduct this research ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02149472 ### Funding Statement no funding was obtained to conduct this research ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval for the study was obtained from the Ethical Committee of the Leiden University Medical Centre (P13.246) and from the institutional review board of each participating hospital. The study was registered at [ClinicalTrials.gov][1] ([NCT02149472][2]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][1]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02149472&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F13%2F2023.10.12.23296942.atom