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A case of thrombolytic therapy with recombinant tissue plasminogen activator for mechanical valve thrombosis at 9 weeks of pregnancy in a Japanese woman.

ABSTRACT: A 29-year-old woman was admitted to our hospital due to diagnosis of pregnancy at 5 weeks and a day. She underwent valve replacement with mechanical heart valve (MHV: SJM valve) for congenital mitral valve regurgitation, when 11 years old. Warfarin 4 mg was used for anticoagulation. After admission, warfarin was replaced by unfractionated heparin (UFH). She developed exertional dyspnea at 8 weeks of pregnancy. Echocardiogram and fluoroscopy showed an immobile leaflet in the closed position. She was diagnosed with mechanical valve thrombosis. Cardiac surgery or thrombolytic therapy (TT) were treatment options. TT is not established, but is reported to be safer than cardiac surgery. Recently, low-dose, slow infusion of recombinant tissue plasminogen activator (rt-PA) therapy showed acceptable results. About 2.5 h after an intravenous injection of rt-PA, diastolic rumble improved to the normal range of leaflet. Thereafter, warfarin was restarted and there was no recurrence of symptoms and no abortion. She was readmitted for the scheduled Caesarean section (CS) at 32 weeks of pregnancy, and warfarin was replaced with UFH. At 34 weeks of pregnancy, a baby was delivered by CS. She suffered hemostasis after surgery under the anticoagulation. Postoperative day 31, both mother and a child were healthy and left the hospital. .

SUBMITTER: Komatsu T

PROVIDER: S-EPMC6342610 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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A case of thrombolytic therapy with recombinant tissue plasminogen activator for mechanical valve thrombosis at 9 weeks of pregnancy in a Japanese woman.

Komatsu Toshinori T Motoki Hirohiko H Kimura Kazuhiro K Saigusa Tatsuya T Ebisawa Soichiro S Yokokawa Yusuke Y Ando Hirofumi H Ichino Takashi T Kuwahara Koichiro K

Journal of cardiology cases 20180917 1

A 29-year-old woman was admitted to our hospital due to diagnosis of pregnancy at 5 weeks and a day. She underwent valve replacement with mechanical heart valve (MHV: SJM valve) for congenital mitral valve regurgitation, when 11 years old. Warfarin 4 mg was used for anticoagulation. After admission, warfarin was replaced by unfractionated heparin (UFH). She developed exertional dyspnea at 8 weeks of pregnancy. Echocardiogram and fluoroscopy showed an immobile leaflet in the closed position. She ...[more]

PMID: 30693052

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Project description:BACKGROUND:Thromboses is a rapidly growing medical problem worldwide. Low-cost, high-scale production of thrombotic drugs is needed to meet the demand. The production of biomolecules in transgenic animals might help address this issue. To our knowledge, the expression of recombinant human plasminogen activator (rhPA) in goat mammary glands has never been reported before. METHODS:We constructed a mammary gland-specific expression vector, BLC14/rhPA, which encodes only the essential K2 fibrin-binding and P domains of wild-type tPA (deletion mutant of tPA lacking the F, E, and K1 domains), along with the goat β-lactoglobulin gene signal peptide-coding sequence. The mammary gland-specific expression vector BLC14/rhPA was transfected into goat fetal fibroblast cells by electroporation. After selection for 3 weeks by G418, stably transfected cell colonies were obtained. PCR analysis results indicated that 24 of the resistant clones were transgenic cell lines; of these, 8 lines were selected as the donor cells. The positive cells were starved for 72 h with DMEM/F12 medium containing 0.5% FBS and were then used as do. Finally, 256 reconstructed oocytes were transferred into 26 recipients, and 7 of them became pregnant (pregnancy rate, 26.9%). Two kids were obtained (BP21 and BP22). PCR analysis confirmed that both were transgenic goats. To analyze the heredity of the rhPA expressed in BP21 F0 and F1 transgenic goats, the F0 transgenic goat BP21 was mated with a normal male goat to generate an F1 transgenic goat. Enucleated metaphase II (MII) oocytes and positive donor cells were used to reconstruct embryos, which were transplanted into the oviducts of the recipients. RESULTS:Western blot results showed a specific 39 kDa band. The rhPA expression level in transgenic goat whey was about 78.32 μg/mL by ELISA. Results of ELISA and the in vitro thrombolysis test (FAPA) showed that specific activity of the rhPA in the milk of F0 and F1 transgenic goats was 13.3 times higher than that of the reteplase reference material. CONCLUSION:Thus, we demonstrated that BLC14/rhPA was reasonably effective for expression in the mammary glands of transgenic goats, and was stably inherited by the offspring. This study provides the basis for the large-scale production of biological pharmaceuticals in transgenic animals. The expression of biopharmaceuticals by transgenic animals can be used for pharmacological research and bioactive analysis, and transgenic goats were demonstrated to be promising animals for the large-scale production of thrombolytic biopharmaceuticals.

Dataset Information

A case of thrombolytic therapy with recombinant tissue plasminogen activator for mechanical valve thrombosis at 9 weeks of pregnancy in a Japanese woman.

Publications

A case of thrombolytic therapy with recombinant tissue plasminogen activator for mechanical valve thrombosis at 9 weeks of pregnancy in a Japanese woman.

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