{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:41:35Z","timestamp":1776058895358,"version":"3.50.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In young patients presenting with high-risk, idiopathic pulmonary thromboembolism (PTE), prompt identification of the underlying prothrombotic state is critical. Inherited deficiencies of protein C (PC) and protein S (PS) are predominant risk factors in Asians. However, routine functional assays for PC\/PS activity may not capture the full genetic risk. Specifically, the clinical significance of a pathogenic\n                      <jats:italic>PROC<\/jats:italic>\n                      mutation in individuals with normal PC activity remains poorly defined. We hypothesize that in such individuals, the thrombogenic potential of a \u201ccryptic\u201d\n                      <jats:italic>PROC<\/jats:italic>\n                      defect may remain latent until unmasked by a profound cofactor deficiency, such as severe PS deficiency. This synergistic mechanism, and the catastrophic thrombosis it may precipitate, has not been previously documented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A previously healthy 20-year-old male presented with sudden-onset high-risk pulmonary thromboembolism and obstructive shock. Despite systemic thrombolysis, he progressed to refractory shock and was successfully rescued with VA-ECMO bridging to percutaneous mechanical thrombectomy. Coagulation workup revealed severely reduced PS activity (28.3%); notably, protein C activity was normal at 99.7%. Genetic testing identified heterozygous pathogenic mutations in\n                      <jats:italic>PROS1<\/jats:italic>\n                      (c.1680T\u2009&amp;gt;\u2009A, p.Tyr560Ter) and\n                      <jats:italic>PROC<\/jats:italic>\n                      (c.577_579delAAG, p.Lys193del), inherited from his asymptomatic parents respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case demonstrates that severe PS deficiency can unmask the thrombogenic potential of a pathogenic\n                      <jats:italic>PROC<\/jats:italic>\n                      mutation even in the setting of normal PC activity, revealing a previously underrecognized synergistic prothrombotic mechanism. It underscores the critical importance of systematic thrombophilia screening, including genetic testing for\n                      <jats:italic>PROS1<\/jats:italic>\n                      and\n                      <jats:italic>PROC<\/jats:italic>\n                      , in young patients with high-risk PTE even when PC activity is normal.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1804812","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:43:05Z","timestamp":1776055385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Severe protein S deficiency unmasks a cryptic PROC mutation with normal activity, triggering life-threatening pulmonary thromboembolism"],"prefix":"10.3389","volume":"13","author":[{"given":"Yafei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Emergency, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]},{"name":"Department of Emergency Medicine, Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine (900th Hospital)","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binbin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Emergency, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]},{"name":"Department of Emergency Medicine, Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine (900th Hospital)","place":["Fuzhou, Fujian, 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