Dataset Information

Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.

ABSTRACT:

Background

Coagulation factor VIII (FVIII) inhibitor titer quantification is vital for optimizing care in people with hemophilia A.

Objectives

This study analyzed the impact of the different kinetic profiles of four FVIII monoclonal antibodies on inhibitor titer quantification using the modified Nijmegen-Bethesda assay.

Methods

Concentration-related and time-related profiles of FVIII antibodies (4A4, BO2C11, 2-54, ESH-8) were evaluated in vitro. FVIII residual activity was measured using a one-stage clotting assay and chromogenic substrate assay. Profiles of the FVIII antibodies were compared with the theoretical kinetic model: the ideal log (residual activity)-linear (inhibitor concentration) relationship. Different theoretical kinetic model-dependent and -independent criteria to calculate FVIII inhibitor titer were compared.

Results

Factor VIII monoclonal antibodies had different concentration-related and time-related profiles, ideal for comparative analysis using the modified Nijmegen-Bethesda assay. The kinetic profile of 4A4 was similar to the theoretical kinetic model, while BO2C11 showed a steeper curve, and 2-54 and ESH-8 a flatter curve, than the model. In the modified Nijmegen-Bethesda assay, conversion of measured FVIII residual activities for different inhibitor dilutions into FVIII inhibitor titer is based on the theoretical kinetic model. Therefore, titer calculations for FVIII inhibitors that deviate from the model are prone to underestimation or overestimation. Calculating a theoretical dilution at 50% FVIII residual activity by sigmoidal regression reflecting different kinetic inhibition profiles can provide a more accurate titer result.

Conclusion

Kinetic profiles of FVIII antibodies can deviate from the theoretical kinetic model in the modified Nijmegen-Bethesda assay, leading to differences in FVIII inhibitor titer quantification.

SUBMITTER: Ketteler C

PROVIDER: S-EPMC9743337 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.

Ketteler Carolin C Hoffmann Ingrid I Davidson Simon S Chen David D Tiede Andreas A Richter Nina N

Research and practice in thrombosis and haemostasis 20221101 8

<h4>Background</h4>Coagulation factor VIII (FVIII) inhibitor titer quantification is vital for optimizing care in people with hemophilia A.<h4>Objectives</h4>This study analyzed the impact of the different kinetic profiles of four FVIII monoclonal antibodies on inhibitor titer quantification using the modified Nijmegen-Bethesda assay.<h4>Methods</h4>Concentration-related and time-related profiles of FVIII antibodies (4A4, BO2C11, 2-54, ESH-8) were evaluated in vitro. FVIII residual activity was ...[more]

PMID: 36518189

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Project description:Although previous studies have reported the use of total thoracoscopic hepatectomy (TH) for malignant liver tumors, it is technically impossible to perform intraoperative ultrasonography (IUSO) to exclude intrahepatic metastasis for the whole liver via a thoracic approach. Therefore, total TH may be inappropriate for these patients. We here report the first case of modified TH for a malignant liver tumor in China.The patient was a 26-year-old man with a 10-year HBV infection. Preoperative CT showed a 1.2 cm × 0.9 cm mass located in segment VIII. His alpha-fetal protein level was 444 ng/mL. Child-Pugh was Grade (A, 6), whereas an ICG-15 test yielded 2.7%. HCC was diagnosed preoperatively. The indications for TH were difficult tumor location, HCC, and a young patient with good resilience.The modified TH included 2 steps: (1) the patient was placed in a supine position. IUSO was used to locate the tumor in segment VIII and determine that intrahepatic metastasis had not occurred. The hepatoduodenal ligament was hanged over using a Pringle maneuver; (2) patient was then placed in the left-lateral position with single-lung ventilation. Three trocars were placed into the right thoracic cavity. The intra-thoracic space was observed using a regular 10-mm rigid scope. The diaphragm was transected and retracted. IUSO was used again to confirm the tumor location. Under the Pringle maneuver (once every 10 min), the superficial portion of the liver was transected by ultrasonic shears, whereas the deeper tissue was transected by LigaSure. Bipolar was used for hemostasis. The specimen was put into a retrieval bag and removed from the abdominal trocar. The diaphragm was repaired by running suturing. The operation time was 260 minutes and estimated blood loss was 30 mL. The patient was discharged on postoperative day 5 with normal liver function. No complications arose.Total TH may be inappropriate for malignant liver tumors due to the limitation of IUSO for the whole liver. The 2-step modified TH is technically feasible and suitable for malignant liver tumors located in segments VII or VIII.Video abstract: http://links.lww.com/MD/B6.

Dataset Information

Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.

Background

Objectives

Methods

Results

Conclusion

Publications

Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.

Similar Datasets

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