Purpose: This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population. Methods: We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases. Results: The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of ruri‑ octocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small. Conclusion This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

Purpose: This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population. Methods: We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases. Results: The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of ruri‑ octocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small. Conclusion This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

Purpose: This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population. Methods: We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases. Results: The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of ruri‑ octocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small. Conclusion This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

Acquired hemophilia A (AHA) is a rare bleeding disorder, especially in adolescents and young adults (AYAs) attributable to the development of autoantibodies against coagulation factor VIII (FVIII). AHA diagnosis is difficult; patients lack any history of coagulopathy. We report here on an AYA with AHA who responded well to treatment. A 19-year-old woman visited our hospital with painful swelling of the right lower leg. She had no past or familial history of a bleeding disorder. The initial laboratory data revealed a prolonged activated partial thromboplastin time and an uncorrected mixing test result. The FVIII activity was below 1% and the FVIII antibody level 22.4 Bethesda units. She was diagnosed with AHA and treated with recombinant activated coagulation factor VII, activated prothrombin complex concentrates and an oral steroid. After 9 months, FVIII antibody level was negative and the FVIII activity was normalized. AHA is very rare especially in AYAs, but physicians must be suspicious about the disorder and plan specialized coagulation tests to diagnose the disease. An early diagnosis of acquired bleeding disorders should be done for initiating the adequate treatment immediately by both controlling the acute bleeding episode and eliminating FVIII antibodies.

von Willebrand disease (VWD) is the most common hereditary bleeding disorder. The treatment of VWD consists mainly of desmopressin and plasma-derived von Willebrand factor (pd-VWF) concentrate. We report on the first patient with VWD to be treated with recombinant VWF (rVWF) concentrate in Korea. Our patient was diagnosed with type 2 VWD at 10 months of age and suffered persistent severe epistaxis despite therapeutic levels of VWF activity and factor VIII (FVIII). At 34 months of age, rVWF was initiated and administered a total of 15 times in the following 8 months. No drug-related adverse events were observed and the patient was neither admitted nor given any transfusions during this period. Unlike pd-VWF/FVIII concentrates, rVWF did not increase FVIII to the excessively high levels that constitute a risk factor for thromboembolism, and was also preferable to pd-VWF/FVIII concentrates in that it contains ultra-large multimers of VWF. This is the first reported case in Korea in which rVWF was used to treat VWD. rVWF may be well tolerated and effective in VWD patients, especially those with refractory bleeding.

von Willebrand disease (VWD) is the most common hereditary bleeding disorder. The treatment of VWD consists mainly of desmopressin and plasma-derived von Willebrand factor (pd-VWF) concentrate. We report on the first patient with VWD to be treated with recombinant VWF (rVWF) concentrate in Korea. Our patient was diagnosed with type 2 VWD at 10 months of age and suffered persistent severe epistaxis despite therapeutic levels of VWF activity and factor VIII (FVIII). At 34 months of age, rVWF was initiated and administered a total of 15 times in the following 8 months. No drug-related adverse events were observed and the patient was neither admitted nor given any transfusions during this period. Unlike pd-VWF/FVIII concentrates, rVWF did not increase FVIII to the excessively high levels that constitute a risk factor for thromboembolism, and was also preferable to pd-VWF/FVIII concentrates in that it contains ultra-large multimers of VWF. This is the first reported case in Korea in which rVWF was used to treat VWD. rVWF may be well tolerated and effective in VWD patients, especially those with refractory bleeding.

Background: Establishing hemostasis for surgical procedures in children with hereditary bleeding disorders is challenging. We evaluated the results of surgical procedures in children with hereditary bleeding disorders at our center and reviewed the preoperative management and hemorrhagic complications. Methods: We conducted a retrospective electronic medical record review from October 2006 to September 2019. Children with hereditary bleeding disorders who had elective surgeries or emergency operations were identified by an electronic record search. The primary focus was a review of clotting factor replacement strategies and bleeding complications. Results: In total, 126 elective procedures and 4 emergency surgeries were performed on 95 children at our center. Of the 95 children, hemophilia A, hemophilia B, von Willebrand disease, and factor VII deficiency were 74, 15, 4, and 2, respectively. The main disease distribution of procedures was 99 with hemophilia A, 24 with hemophilia B, and 4 with von Willebrand disease. Procedures included various orthopedic surgeries (87/130, 66.9%), placement or revision of a central venous catheter (8/130, 6.2%), and otolaryngology procedures (7/130, 5.4%). All patients received preoperative clotting factor replacement followed by various postoperative clotting factor replacement regimens. Thirteen procedures (10.0%) in five children were performed in the presence of high titers of clotting factor inhibitors. No deaths or life-threatening bleeding occurred after any procedure. Nine of the 130 procedures (6.9%) were complicated by postoperative bleeding. Tonsillectomy and adenoidectomy were the most common procedures complicated by hemorrhage (3/5, 60%). Conclusion Surgical procedures are safe in children with hereditary bleeding disorders with adequate preparation and replacement of clotting factors. Bleeding remains a problem in a subset of patients and requires ongoing hematological involvement and oversight. Delayed bleeding following tonsillectomy was particularly common and suggests a need for close follow-up and ongoing factor administration for this group of patients.

Hemophilia, an inherited bleeding disorder, is caused by a deficiency of coagulation factor VIII or IX. Most of patients with hemophilia need vascular procedure, which can lead to complications. Even though these complications can also occur in normal people, hemophilia and coagulopathy are particular risk factors. We reviewed medical records of patients with hemophilia who underwent vascular procedures and investigated its complications. Vessel-related complications occurred in five patients. Three patients had pseudoaneurysms after radial arterial puncture. All patients underwent coagulation factor replacement or ultrasound-guided compression and showed improvement. Neuropathy developed in one patient due to a hematoma that occurred after blood sampling. The hematoma improved, but motor and sensory deficits remained and neuropathy was confirmed. One patient died of uncontrolled bleeding after angiography. Vascular procedures require more attention in patients with hemophilia. Caution and prevention of complications is essential, even before the patient is diagnosed with hemophilia.
Aneurysm, False ; Angiography ; Blood Coagulation Factors ; Factor VIII ; Hematoma ; Hemophilia A ; Hemorrhage ; Humans ; Medical Records ; Punctures ; Risk Factors

Spinal epidural hematoma (SEH) is a rare neurosurgical emergency in which pressure on the spinal cord leads to acute neurological deficits, and is a rare complication in children with hemophilia. We report three cases of SEH in severe hemophilia A. An 8-month-old boy who presented with non-traumatic acute-onset irritability was found to have SEH and was later diagnosed with hemophilia. The two other patients presented with neck pain and magnetic resonance imaging confirmed the diagnosis of SEH. Two patients who received conservative management fully recovered, however the patient who presented with progressive neurological abnormalities at the time of diagnosis, received surgery but later developed breathing difficulties and quadriplegia. Early diagnosis and immediate, aggressive, clotting factor replacement therapy are crucial when managing SEH in children with hemophilia. Immediate and aggressive factor replacement, accompanied by both neurological monitoring and early imaging, are essential for hemophiliac with suspected SEH.
Child* ; Diagnosis ; Early Diagnosis ; Emergencies ; Hematoma ; Hematoma, Epidural, Spinal* ; Hemophilia A* ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neck Pain ; Quadriplegia ; Respiration ; Spinal Cord