Whole-Exome Sequencing of Total Joint Arthroplasty Patients Who Have Known Pulmonary Embolism: A Pilot Study

The purpose of this study was to identify genetic mutations in exome sequences of patients who had a history of pulmonary embolism (PE) after total joint arthroplasty (TJA).

From June 2017 to August 2021, 21 patients who had a history of TJA and subsequent postoperative PE were enrolled in three academic institutions for whole-exome sequencing. Their average age was 64 years (range, 46 to 81), and 15 (71.4%) were women. The average time to PE was 1.7 months (range, zero to 8.8). There were five patients who reported a prior history of thromboembolism, and one had a history of Factor V Leiden mutation. Genomic DNA was extracted from individual frozen blood samples, and fragmented DNA was then converted to an adapter-ligated whole-genome library. Libraries from individual patients were pooled, underwent sequencing, and were compared to population-wide data through the National Center for Biotechnology Information Library, ClinVar database, which archives and aggregates information regarding the relationships between genomic variation and health conditions. Within ClinVar, the range of mutation allele frequency in genes with established roles in coagulation in the general population is reported to be 0.001 to 1.52%.

Mutations in genes with established roles in coagulation occurred at higher rates compared to population baselines identified in the ClinVar database. In our cohort, whole-exome sequencing identified at least one mutation of the 30 genes investigated with established roles in coagulation in 13 patients (61.9%). At least one mutation in 10 genes related to the coagulation cascade, platelet function, or blood type was identified.

Our results suggest that genetic mutations in exome sequences are highly prevalent among patients who experience postoperative PE after TJA. These findings should serve as preliminary data to support further investigation of potential genetic risk factors on whole-exome sequencing to allow for preoperative risk stratification by TJA surgeons.