Background

The activity of plasminogen activators (PAs) is regulated by a complex process that involves regulation of PA gene expression by hormones, growth factors and cytokines, interactions with fibrin, and PA activity regulation by specific PA inhibitors (PAIs). Among these, PAI-1 is the most kinetically efficient. Here, we describe a case with a SERPINE1 gene variant with possible causal relationship to intraoperative bleeding.

Methods

A 15-year-old patient underwent minimally invasive pectus excavatum (MIRPE) repair with two 11-inch rods for funnel chest correction. Intraoperatively, an unusual bleeding tendency occurred, which, however, could be controlled without blood transfusions. Global tests and procoagulant factors were measured on STA R Max3, Stago, France. Multimer analysis was performed using SDS-agarose gel electrophoresis (Hydrasys 2, Sebia, France). In vitro bleeding times were measured using the PFA-200 (Siemens, Germany). The sequencing of 55 genes (complete coding sequences and adjacent intron regions) was performed via next generation sequencing (MiSeq, Illumina). For interpretation, we used in silico evaluation tools, including PolyPhen-2 and SIFT.

Results

In this case, genetic analysis of numerous relevant genes (for details see ijms24097976) in a patient who would otherwise have been found hemostaseologically unremarkable led to the probable explanation of a bleeding tendency observed intraoperatively. Postoperative detailed coagulation examination including examination of platelet aggregation according to Born and in impedance aggregometry revealed no abnormalities. However, SERPINE1 gene sequencing identified a mutation in exon 2 (c.43G>A; p.Ala15Thr).

Conclusion

For the identified SERPINE1 variant, which leads to the amino acid exchange Ala15Thr in the PAI-1 signal peptide, only two other case reports exist to date, in which individual members of affected families also exhibited a bleeding tendency occurring exclusively intra- or postoperatively (PMIDs: 15650551 and 22993578). Further studies are needed to ensure or exclude with greater certainty any influence of this variant on the coagulation system.

Offenlegung Interessenkonflikt:

There are no conflicts of interest.