| Project/Area Number |
18591198
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nara Medical University |
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Principal Investigator |
TANAKA Ichiro Nara Medical University, Medical Department, Assistant Professor (00201616)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Blood coagulation / Factor VIII / Inhibitor |
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| Research Abstract |
The expression of factor VIII (FVIII) : C in the presence of and-FVIII antibodies was studied using clot waveform analysis and thrombin generation test. Seven kinds of alloantibodies and 4 kinds of monoclonal antibodies against human FVIII were used. The former contains 3 alloantibodies recognizing A2 domain in the heavy chain and 4 alloantibodies recognizing C2 domain in the light chain. The latter contains each monoclonal antibody recognizing A1 and A2 domain, and 2 monoclonal antibodies recognizing C2 domain. Ten or twenty Bethesda units (BU) /ml of inhibitor IgG diluted with FVIII deficient plasma were mixed with normal plasma. The mixture was removed after incubation with time, and then maximum coagulation acceleration (| Min2 |) and FVIII : C were measured by MDAII. Moreover, both Peak Height and Endogenous Thrombin Potential (ETP) were measured on thrombin generation assay system. In the presence of final concentration of over 5 BU/ml inhibitors, low levels of FVIII : C and | Min2 | were detected even after 120 min incubation. Especially, the low levels of FVIII : C were detected in the alloantibodies and monoclonal antibody recognizing A2 domain in the heavy chain. Similarly, in most cases, small amount of thrombin generation was detected even in the presence of 20 BU/ml of inhibitors, especially in the antibodies recognizing A2 domain rather than C2-recognized antibodies. These findings indicate the expression of low levels of FVIII : C in the presence of high titer inhibitor, and confirm the prophylactic effect during regular infusions of FVIII concentrates for patients with hemophilia and inhibitors.
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