Tse Jonathan, Gongolli Julita, Prahlow Joseph A
Western Michigan University Homer Stryker MD School of Medicine, 300 Portage St. Kalamazoo, Kalamazoo, MI, 49007, USA.
Department of Pathology, St. Louis University School of Medicine, City of St. Louis, MO, USA.
Forensic Sci Med Pathol. 2025 Mar;21(1):260-266. doi: 10.1007/s12024-024-00879-4. Epub 2024 Sep 27.
The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection.
This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients.
The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death.
The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.
调节个体对重症 COVID-19 易感性的风险因素已有充分记录。尽管如此，高凝状态仍是 COVID-19 重症疾病中一个经常被忽视的风险因素。由于 COVID-19 感染是高凝状态的一个风险因素，一个合理的推测/假设是，遗传性血栓形成倾向患者发生与 COVID-19 感染相关的血栓并发症的风险更高。
本病例报告详细介绍了两例先前未知的遗传性血栓形成倾向可能导致 COVID-19 患者死亡的病例。
首例 COVID-19 患者的死因是由于杂合子 MTHFR C667T 和杂合子 PAI-1 4G/5G 突变导致深静脉血栓形成引起的肺血栓栓塞。第二例 COVID-19 患者的死因是在杂合子 MTHFR A1298C 和纯合子 PAI-1 4G/5G 突变情况下冠状动脉血栓形成导致的急性心肌梗死。在每例病例中，COVID-19 感染也被认为是导致死亡的一个因素。
COVID-19 合并遗传性血栓形成倾向患者发生这些致命血栓事件，引发了关于这种高凝状态血栓风险因素的组合是否可能使患者面临足够大的风险从而发生这些致命血栓并发症的疑问。因此，虽然仅凭这两例不足以证明患有遗传性血栓形成倾向的 SARS-CoV-2 患者发生血栓并发症的风险增加，但这两例表明有必要进一步研究以阐明血栓风险因素之间的关系，因为这可能识别出 COVID-19 的另一种高危医学状况，并具有重要的诊断和治疗意义。
