SUCCESSFUL SEQUENTIAL THERAPY USING RFVII WITH A NOVEL AGENT (PLASMA-DERIVED FACTOR FVIIA AND FACTOR FX MIXTURE) TO CONTROL PERIOPERATIVE BLEEDING IN A PATIENT WITH SEVERE HEMOPHILIA A AND INHIBITORS
(Abstract release date: 05/19/16)
EHA Library. Isobe K. 06/09/16; 134647; PB1747
Dr. Kiyotaka Isobe
Contributions
Contributions
Abstract
Abstract: PB1747
Type: Publication Only
Background
The bypass therapy is usually performed to control bleeding in patients with hemophilia and inhibitors; however, approximately 10% cases are resistant to that using a single agent in the perioperative period.The plasma-derived factor FVIIa and factor FX mixture (pd FVIIa/FX), containing human serum-derived FVII and FX in a 1: 10 ratio, was recently developed in Japan as a novel bypassing agent. The bypass effect induced by FVII is enhanced under a high concentration of FX. We hypothesized that pd FVIIa/FX would induce a stronger bypass effect than conventional sequential therapy using aPCC and rFVII.Here we report our experience of sequential therapy using pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period in a patient with severe hemophilia A and inhibitors.
Aims
To determin optimal dose of of rFVII and pd FVIIa/FX based on a preoperative PK study.
Methods
A pharmacokinetics (PK) study used by pd FVIIa/FX was performed a week before surgery. FX and FVII level was measured 15 minutes, 6 hours and 24 hours after pd FVIIa/FX (120 mcg/kg) was administered. FX level was measured at Kaketsuken Co. (Japan) by activated partial thromboplastin time assays under a high concentration of FVII. The Based on the PK study, FVII and FX activity levels were simulated to determine the optimal dose and interval of rFVII when rFVII and pd FVIIa/FX were administered. Thromboelastography (ROTEMR) was used to rapidly allow to monitor the coagulation intra-operatively.Case:A 10-year-old male was diagnosed with severe hemophilia A at 8 months old. At 13 months old, inhibitor to factor FVIII (maximum 1625 BU/ml, the most recent: 19.2 BU/ml) was detected. He received immune tolerance induction therapy using rFVIII or VWF/FVIII for 2 years but with no response. At 4 years, he was started on prophylactic aPCC as a bypass therapy. At 10 years, he experienced frequent spontaneous intra-articular hemorrhage, particularly in the left knee and right ankle. Therefore, he was transferred to our institution to receive arthroscopic synovectomy of these joint.When the surgery started, the following sequential therapy was also initiated in accordance with the simulation: pd FVIIa/FX (120 mcg/kg) was administered three times every 36 h and rFVII (60mcg/kg) every 2 h. The interval of rFVII administration was gradually extended. Six days after surgery, the sequential therapy was switched to prophylactic aPCC administration.
Results
1) CoagulationThe measured activity levels of rFVII and FX were almost the same as the simulation data. The INTEMR assay, in the ROTEMR, used to monitor the intrinsic pathway showed that coagulation was recovered by sequential therapy.2) SafetyIn accordance with the product document, pd FVIIa/FX (120 mcg/kg) every 36 h was administered and no thrombotic events were detected. 3) EfficacyLittle bleeding was observed during surgery, and no sign of intra-articular hemorrhage was observed on physical examination after surgery. 4) CostThis regimen contributed to a 45% cost reduction compared with that with single agent bypass therapy using rFVII.
Conclusion
ConclusionSequential pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period is feasible and effective for patients with severe hemophilia A and inhibitors. It is necessary to determine the optimal dose of rFVII based on a preoperative PK study.
Session topic: E-poster
Keyword(s): Hemophilia, Inhibitor
Type: Publication Only
Background
The bypass therapy is usually performed to control bleeding in patients with hemophilia and inhibitors; however, approximately 10% cases are resistant to that using a single agent in the perioperative period.The plasma-derived factor FVIIa and factor FX mixture (pd FVIIa/FX), containing human serum-derived FVII and FX in a 1: 10 ratio, was recently developed in Japan as a novel bypassing agent. The bypass effect induced by FVII is enhanced under a high concentration of FX. We hypothesized that pd FVIIa/FX would induce a stronger bypass effect than conventional sequential therapy using aPCC and rFVII.Here we report our experience of sequential therapy using pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period in a patient with severe hemophilia A and inhibitors.
Aims
To determin optimal dose of of rFVII and pd FVIIa/FX based on a preoperative PK study.
Methods
A pharmacokinetics (PK) study used by pd FVIIa/FX was performed a week before surgery. FX and FVII level was measured 15 minutes, 6 hours and 24 hours after pd FVIIa/FX (120 mcg/kg) was administered. FX level was measured at Kaketsuken Co. (Japan) by activated partial thromboplastin time assays under a high concentration of FVII. The Based on the PK study, FVII and FX activity levels were simulated to determine the optimal dose and interval of rFVII when rFVII and pd FVIIa/FX were administered. Thromboelastography (ROTEMR) was used to rapidly allow to monitor the coagulation intra-operatively.Case:A 10-year-old male was diagnosed with severe hemophilia A at 8 months old. At 13 months old, inhibitor to factor FVIII (maximum 1625 BU/ml, the most recent: 19.2 BU/ml) was detected. He received immune tolerance induction therapy using rFVIII or VWF/FVIII for 2 years but with no response. At 4 years, he was started on prophylactic aPCC as a bypass therapy. At 10 years, he experienced frequent spontaneous intra-articular hemorrhage, particularly in the left knee and right ankle. Therefore, he was transferred to our institution to receive arthroscopic synovectomy of these joint.When the surgery started, the following sequential therapy was also initiated in accordance with the simulation: pd FVIIa/FX (120 mcg/kg) was administered three times every 36 h and rFVII (60mcg/kg) every 2 h. The interval of rFVII administration was gradually extended. Six days after surgery, the sequential therapy was switched to prophylactic aPCC administration.
Results
1) CoagulationThe measured activity levels of rFVII and FX were almost the same as the simulation data. The INTEMR assay, in the ROTEMR, used to monitor the intrinsic pathway showed that coagulation was recovered by sequential therapy.2) SafetyIn accordance with the product document, pd FVIIa/FX (120 mcg/kg) every 36 h was administered and no thrombotic events were detected. 3) EfficacyLittle bleeding was observed during surgery, and no sign of intra-articular hemorrhage was observed on physical examination after surgery. 4) CostThis regimen contributed to a 45% cost reduction compared with that with single agent bypass therapy using rFVII.
Conclusion
ConclusionSequential pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period is feasible and effective for patients with severe hemophilia A and inhibitors. It is necessary to determine the optimal dose of rFVII based on a preoperative PK study.
Session topic: E-poster
Keyword(s): Hemophilia, Inhibitor
Abstract: PB1747
Type: Publication Only
Background
The bypass therapy is usually performed to control bleeding in patients with hemophilia and inhibitors; however, approximately 10% cases are resistant to that using a single agent in the perioperative period.The plasma-derived factor FVIIa and factor FX mixture (pd FVIIa/FX), containing human serum-derived FVII and FX in a 1: 10 ratio, was recently developed in Japan as a novel bypassing agent. The bypass effect induced by FVII is enhanced under a high concentration of FX. We hypothesized that pd FVIIa/FX would induce a stronger bypass effect than conventional sequential therapy using aPCC and rFVII.Here we report our experience of sequential therapy using pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period in a patient with severe hemophilia A and inhibitors.
Aims
To determin optimal dose of of rFVII and pd FVIIa/FX based on a preoperative PK study.
Methods
A pharmacokinetics (PK) study used by pd FVIIa/FX was performed a week before surgery. FX and FVII level was measured 15 minutes, 6 hours and 24 hours after pd FVIIa/FX (120 mcg/kg) was administered. FX level was measured at Kaketsuken Co. (Japan) by activated partial thromboplastin time assays under a high concentration of FVII. The Based on the PK study, FVII and FX activity levels were simulated to determine the optimal dose and interval of rFVII when rFVII and pd FVIIa/FX were administered. Thromboelastography (ROTEMR) was used to rapidly allow to monitor the coagulation intra-operatively.Case:A 10-year-old male was diagnosed with severe hemophilia A at 8 months old. At 13 months old, inhibitor to factor FVIII (maximum 1625 BU/ml, the most recent: 19.2 BU/ml) was detected. He received immune tolerance induction therapy using rFVIII or VWF/FVIII for 2 years but with no response. At 4 years, he was started on prophylactic aPCC as a bypass therapy. At 10 years, he experienced frequent spontaneous intra-articular hemorrhage, particularly in the left knee and right ankle. Therefore, he was transferred to our institution to receive arthroscopic synovectomy of these joint.When the surgery started, the following sequential therapy was also initiated in accordance with the simulation: pd FVIIa/FX (120 mcg/kg) was administered three times every 36 h and rFVII (60mcg/kg) every 2 h. The interval of rFVII administration was gradually extended. Six days after surgery, the sequential therapy was switched to prophylactic aPCC administration.
Results
1) CoagulationThe measured activity levels of rFVII and FX were almost the same as the simulation data. The INTEMR assay, in the ROTEMR, used to monitor the intrinsic pathway showed that coagulation was recovered by sequential therapy.2) SafetyIn accordance with the product document, pd FVIIa/FX (120 mcg/kg) every 36 h was administered and no thrombotic events were detected. 3) EfficacyLittle bleeding was observed during surgery, and no sign of intra-articular hemorrhage was observed on physical examination after surgery. 4) CostThis regimen contributed to a 45% cost reduction compared with that with single agent bypass therapy using rFVII.
Conclusion
ConclusionSequential pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period is feasible and effective for patients with severe hemophilia A and inhibitors. It is necessary to determine the optimal dose of rFVII based on a preoperative PK study.
Session topic: E-poster
Keyword(s): Hemophilia, Inhibitor
Type: Publication Only
Background
The bypass therapy is usually performed to control bleeding in patients with hemophilia and inhibitors; however, approximately 10% cases are resistant to that using a single agent in the perioperative period.The plasma-derived factor FVIIa and factor FX mixture (pd FVIIa/FX), containing human serum-derived FVII and FX in a 1: 10 ratio, was recently developed in Japan as a novel bypassing agent. The bypass effect induced by FVII is enhanced under a high concentration of FX. We hypothesized that pd FVIIa/FX would induce a stronger bypass effect than conventional sequential therapy using aPCC and rFVII.Here we report our experience of sequential therapy using pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period in a patient with severe hemophilia A and inhibitors.
Aims
To determin optimal dose of of rFVII and pd FVIIa/FX based on a preoperative PK study.
Methods
A pharmacokinetics (PK) study used by pd FVIIa/FX was performed a week before surgery. FX and FVII level was measured 15 minutes, 6 hours and 24 hours after pd FVIIa/FX (120 mcg/kg) was administered. FX level was measured at Kaketsuken Co. (Japan) by activated partial thromboplastin time assays under a high concentration of FVII. The Based on the PK study, FVII and FX activity levels were simulated to determine the optimal dose and interval of rFVII when rFVII and pd FVIIa/FX were administered. Thromboelastography (ROTEMR) was used to rapidly allow to monitor the coagulation intra-operatively.Case:A 10-year-old male was diagnosed with severe hemophilia A at 8 months old. At 13 months old, inhibitor to factor FVIII (maximum 1625 BU/ml, the most recent: 19.2 BU/ml) was detected. He received immune tolerance induction therapy using rFVIII or VWF/FVIII for 2 years but with no response. At 4 years, he was started on prophylactic aPCC as a bypass therapy. At 10 years, he experienced frequent spontaneous intra-articular hemorrhage, particularly in the left knee and right ankle. Therefore, he was transferred to our institution to receive arthroscopic synovectomy of these joint.When the surgery started, the following sequential therapy was also initiated in accordance with the simulation: pd FVIIa/FX (120 mcg/kg) was administered three times every 36 h and rFVII (60mcg/kg) every 2 h. The interval of rFVII administration was gradually extended. Six days after surgery, the sequential therapy was switched to prophylactic aPCC administration.
Results
1) CoagulationThe measured activity levels of rFVII and FX were almost the same as the simulation data. The INTEMR assay, in the ROTEMR, used to monitor the intrinsic pathway showed that coagulation was recovered by sequential therapy.2) SafetyIn accordance with the product document, pd FVIIa/FX (120 mcg/kg) every 36 h was administered and no thrombotic events were detected. 3) EfficacyLittle bleeding was observed during surgery, and no sign of intra-articular hemorrhage was observed on physical examination after surgery. 4) CostThis regimen contributed to a 45% cost reduction compared with that with single agent bypass therapy using rFVII.
Conclusion
ConclusionSequential pd FVIIa/FX and rFVII as a bypass therapy during the perioperative period is feasible and effective for patients with severe hemophilia A and inhibitors. It is necessary to determine the optimal dose of rFVII based on a preoperative PK study.
Session topic: E-poster
Keyword(s): Hemophilia, Inhibitor
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