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A case of a young boy with hyper-fibrinolysis associated with natural fibrin precipitates suspected to have occurred through a novel coagulation and fibrinolysis mechanism

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Abstract

An 8-year-old Japanese boy with no underlying disease presented with severe intramuscular hematoma of the hip, and was admitted for a disseminated intravascular coagulation-like state with fibrinolytic dominance. Laboratory examinations revealed severe hyper-fibrinolysis with elevated markers, markedly shortened euglobulin clot lysis time, mildly decreased prothrombin, and severely decreased fibrinogen and factor XIII. Natural fibrin precipitates rapidly appeared in citrate-treated, ethylene-diamine-tetra-acetic-treated, and heparin-treated samples, but not in argatroban-treated samples, indicating that the mechanism of thrombin and fibrin formation was Ca2+-independent. The precipitates were physically similar to thrombin-triggered plasma fibrin. A global coagulation assay revealed that thrombin generation potentials were normal throughout the clinical course, whereas plasmin generation was already detected before initiation of fibrin formation in the acute phase. This phenomenon disappeared with time. Changes in coagulation abnormalities and nature of fibrinolysis paralleled those seen in specific markers for streptococcal infections. Streptokinase was possibly involved in this disease, as SDS–polyacrylamide gel electrophoresis revealed that plasmin derived from streptokinase-plasminogen complex proteolyzed the prothrombin to approximately 35-kDa α-thrombin consisting of the A–B single chain, which was identified by NH2-terminal sequence analysis. The involvement of streptokinase–plasminogen–prothrombin caused by streptococcal infection may be one mechanism that produces marked hyper-fibrinolysis associated with natural fibrin precipitates.

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Acknowledgements

We thank Dr. Masahiro Okuda for analyses on natural fibrin precipitates (Reagent production Division, Manufacturing Technology Development, Sysmex Corporation), Ms. Mika Kataoka for her excellent special technique in laboratory tests (Nara Medical University); Dr. Takeshi Mori for the fibrinogen gene analysis (Kobe University); Drs. Yukihiro Takahashi (Nara Medical University), Osamu Matsuo, and Kiyotaka Okada (Kinki University) for their excellent helpful suggestions regarding the disease pathology; and Dr. Naoko Matsumoto (Hyogo Prefectural Kaibara Hospital) for greatly clinical supports.

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Authors and Affiliations

  1. Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Atsuko Nishiyama, Kenichi Ogiwara, Yuto Nakajima, Shoko Furukawa, Tomoko Matsumoto & Keiji Nogami

  2. Advanced Medical Science of Thrombosis and Hemostasis, Nara Medical University, Kashihara, Japan

    Yuto Nakajima

  3. Clinical Laboratory, Tenri Health Care University, Tenri, Japan

    Tomoko Matsumoto

  4. Division of Pediatric Critical Care, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Hiroki Takeda

Authors
  1. Atsuko Nishiyama
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  2. Kenichi Ogiwara
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  3. Yuto Nakajima
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  4. Shoko Furukawa
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  5. Tomoko Matsumoto
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  6. Hiroki Takeda
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  7. Keiji Nogami
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Contributions

AN supported clinically, performed the experiments, analyzed the data, and made the figures; KO supported clinically, designed the research, interpreted the data, wrote the manuscript, and approved the final version; YN performed the experiments; SF supported clinically; TM performed experiments; HT supported clinically; NM supported clinically; and KN supported clinically, designed the research, performed the experiments, made the figures, wrote the paper, and edited the manuscript.

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Correspondence to Kenichi Ogiwara.

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Nishiyama, A., Ogiwara, K., Nakajima, Y. et al. A case of a young boy with hyper-fibrinolysis associated with natural fibrin precipitates suspected to have occurred through a novel coagulation and fibrinolysis mechanism. Int J Hematol 116, 276–287 (2022). https://doi.org/10.1007/s12185-022-03339-3

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  • DOI: https://doi.org/10.1007/s12185-022-03339-3

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