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A case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation.

ABSTRACT: Thrombomodulin functions as an anticoagulant through thrombin binding and protein C activation. We herein report the first case of hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction. The patient had a homozygous substitution of glycine by aspartate at amino acid residue 412 (Gly412Asp) in the thrombin-binding domain of the thrombomodulin gene (designated thrombomodulin-Nagasaki). In vitro assays using a recombinant thrombomodulin with the same mutation as the patient showed a total lack of thrombin binding and activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Marked clinical and laboratory improvement was obtained with recombinant human soluble thrombomodulin therapy.

SUBMITTER: Okada M

PROVIDER: S-EPMC7322956 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation.

Okada Masahiko M Tominaga Norio N Honda Goichi G Nishioka Junji J Akita Nobuyuki N Hayashi Tatsuya T Suzuki Koji K Moriuchi Hiroyuki H

Blood advances 20200601 12

Thrombomodulin functions as an anticoagulant through thrombin binding and protein C activation. We herein report the first case of hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction. The patient had a homozygous substitution of glycine by aspartate at amino acid residue 412 (Gly412Asp) in the thrombin-binding domain of the thrombomodulin gene (designated thrombomodulin-Nagasaki). In vitro assays using a recombinant thromb ...[more]

PMID: 32556284

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| S-EPMC218711 | biostudies-literature

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| S-EPMC1137635 | biostudies-other

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