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. 2025 Aug 13;9(6):103012.
doi: 10.1016/j.rpth.2025.103012. eCollection 2025 Aug.

Plasminogen mutation-associated thrombotic microangiopathy and role of anticoagulation: a single institution case series

Shreya Agarwal  1 , Nicola Pozzi  2 , Senthil Sukumar  3 , Camila Masias  4 , Anuja Java  5 , Spero Cataland  6
Affiliations

Plasminogen mutation-associated thrombotic microangiopathy and role of anticoagulation: a single institution case series

Shreya Agarwal et al. Res Pract Thromb Haemost. .

Abstract

Background: Knowledge gaps exist regarding the role of coagulation pathway mutations such as those in the plasminogen (PLG) gene in the pathogenesis of thrombotic microangiopathy (TMA) and treatment outcomes.

Objectives: This study aims to describe the unique phenotypic features of patients with PLG mutations and perform structural mapping of the variants to enhance variant interpretation.

Methods: This was a single-center retrospective study of patients with TMA in whom genetic testing was performed between 2011 and 2023. Data were collected regarding demographics, clinical features at their first presentation, renal outcomes, genetic mutations, and recurrence for those who were found to have a PLG mutation. Structural mapping of the PLG variants was performed using X-ray structural data.

Results: Over the 12-year study period, we identified 6 individuals in our TMA cohort with PLG mutations. Median age at the time of first TMA event was 45.5 years (range: 5-57 years). Nearly all were female (n = 5, 83%). Half of the cohort (n = 3, 50%) had recurrent TMA, with 1 having recurrent episodes while on long-term complement blockade therapy. Three patients are now on long-term anticoagulation with no further TMA recurrences observed. Structural mapping of the variants revealed that the mutations could be categorized into 3 groups. Among these, group 2 variants (residues K38 in the PAN-apple domain and residue R523 in kringle-5) had a more severe phenotype with severe thrombocytopenia at presentation and a recurrent TMA course.

Conclusion: Patients with PLG mutation-associated TMAs appear to have a poor response to complement blockade therapy, suggesting that pathways in addition to or independent of complement dysregulation may be involved in some patients. Future studies are warranted to explore the role of anticoagulation in preventing recurrence in patients with PLG mutations.

Keywords: anticoagulation; complement blockade; eculizumab; plasminogen mutation; thrombotic microangiopathy.

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Figures

Figure 1
Figure 1
CONSORT diagram for all the patients with TMA seen at Ohio State University with their genetic results. TMA, thrombotic microangiopathy.
Figure 2
Figure 2
Structural mapping of the plasminogen variants on the closed form of type II Glu-plasminogen.
See this image and copyright information in PMC

References

    1. Moake J.L. Thrombotic microangiopathies. N Engl J Med. 2002;347:589–600. doi: 10.1056/NEJMra020528. - DOI - PubMed
    1. Khosla J., Yeh A.C., Spitzer T.R., Dey B.R. Hematopoietic stem cell transplant-associated thrombotic microangiopathy: current paradigm and novel therapies. Bone Marrow Transplant. 2018;53:129–137. doi: 10.1038/bmt.2017.207. - DOI - PubMed
    1. Kavanagh D., Goodship T. Genetics and complement in atypical HUS. Pediatr Nephrol. 2010;25:2431–2442. doi: 10.1007/s00467-010-1555-5. - DOI - PMC - PubMed
    1. Zuber J., Fakhouri F., Roumenina L.T., Loirat C., Frémeaux-Bacchi V., French Study Group for aHUS/C3G Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol. 2012;8:643–657. doi: 10.1038/nrneph.2012.214. - DOI - PubMed
    1. Fakhouri F., Frémeaux-Bacchi V., Loirat C. Atypical hemolytic uremic syndrome: from the rediscovery of complement to targeted therapy. Eur J Intern Med. 2013;24:492–495. doi: 10.1016/j.ejim.2013.05.008. - DOI - PubMed

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