Central venous access devices (CVAD) provide hemophilic patients, particularly children, with prolonged reliable venous access to promote routine factor replacement therapy. However, one of the significant complications of CVAD use is infection. We report the case of a severe hemophilia B patient with an inhibitor who developed septic arthritis and infective endocarditis associated with methicillin-resistant Staphylococcus aureus infection originating from a CVAD. Our patient had an underlying condition of congenital heart disease, one of the risk factors for infective endocarditis. Unfortunately, the antibiotic therapy did not have a significant effect. An echocardiogram revealed vegetation on the right ventricular moderate band and surgery was determined to be the best course of action. Septic arthritis and endocarditis rarely occur in hemophilia patients, however, they must be taken into account in hemophiliacs with continuing bacteremia.
Adolescent* ; Arthritis, Infectious* ; Bacteremia ; Child ; Endocarditis* ; Heart Defects, Congenital ; Heart Septal Defects, Ventricular ; Hemophilia A* ; Hemophilia B* ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Risk Factors

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

Inhibitor development is one of the major adverse events associated with increased morbidity and mortality in patients with congenital hemophilia. Recent treatment for them is immune tolerance induction (ITI), which involves the administration of high doses of factor concentrates over a prolonged period, sometimes combined with immunosuppressive agents. We report a case of inhibitor elimination with Rituximab, and high-dose factor VIII concentrates in a 5-year-old boy with hemophilia A. The patient improved clinically, with fewer bleeding episodes. However, he continued to have low immunoglobulin levels, which led to recurrent infections. After an infusion of intravenous immunoglobulin, inhibitor titers increased rapidly and his ITI was deemed a failure. In conclusion, even though it failed in the present study, Rituximab may be an alternative adjuvant therapy to eliminate the inhibitor in patients with hemophilia. The appropriate schedule and long-term side effects need further investigation.
Appointments and Schedules ; Child, Preschool ; Factor VIII ; Hemophilia A ; Hemorrhage ; Humans ; Immune Tolerance ; Immunoglobulins ; Immunosuppressive Agents ; Male ; Mortality ; Rituximab

BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Surgery, even relatively minor procedures, in patients with moderate to severe qualitative and quantitative deficiencies of von Willebrand factor (VWF) can be associated with a life-threatening risk of excessive bleeding. The purpose of this study was to evaluate the safety and efficacy of VWF/FVIII in patients with von Willebrand disease before surgery and determine the efficacy of VWF/FVIII.METHODS: We reviewed the results of surgical procedures in patients with VWD at Kyung Hee University Hospital at Gangdong, between September 2009 and January 2016. VWF/FVIII concentrates were administrated preoperatively to all patients.RESULTS: Between September 2009 and January 2016 at our center, eight surgical procedures were performed successfully and no severe complications were observed in the seven patients with VWD. Four orthopedic procedures, one laparoscopic appendectomy, one ovary cystectomy, one strabotomy, and one dental extraction were performed. The median duration of hospitalization was seven days. VWF/FVIII concentrates were administered prior to all procedures, including the dental extraction. In all cases, uncontrolled bleeding and thromboembolic complications were not observed.CONCLUSION: Patients with VWD who require surgery can be treated efficiently and safely with VWF/FVIII concentrates. There is excellent tolerance, efficacy and safety in preventing excessive bleeding during surgery. When administering VWF/FVIII concentrates, treatment should be monitored with VWF Ag, VWF:RCo and FVIII plasma levels.
Appendectomy ; Cystectomy ; Female ; Hemorrhage ; Hospitalization ; Humans ; Orthopedic Procedures ; Ovary ; Plasma ; von Willebrand Diseases ; von Willebrand Factor

BACKGROUND: Inhibitory antibodies to factor VIII (FVIII) or IX (FIX) are important issues when managing patients with hemophilia A or B. Advances in bypassing agents such as recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrates (APCC) have enabled the aggressive management of hemophilia with inhibitors during emergency or elective surgery. This study provides an updated evaluation of the safety and effectiveness of bypassing agents in treating perioperative bleeding. METHODS: We reviewed the records of hemophilia patients with inhibitors who underwent surgery between May 2008 and July 2014 using bypassing agents or high-dose FVIII concentrates at a single center. RESULTS: In total, 36 surgeries (24 orthopedic, 12 other) were conducted in 18 hemophilia patients with inhibitors. The median inhibitor titer at surgery was 14 (range, 0.7-1,900) Bethesda units. Most patients had high-responding inhibitors. In total, 25 patients received APCC, 9 with rFVIIa initially. In most cases, bleeding stopped or was well controlled; however, bleeding in 6 patients was controlled using sequential bypassing therapy. Hemostatic efficacy of bypassing agents in various surgeries, based on the final patient outcome, was 94.4% (34/36). Among 5 emergency surgeries, 2 deaths occurred. CONCLUSION: Good control of hemostasis can be achieved using bypassing agents in hemophilia patients with inhibitors who are undergoing surgery. Thorough planning is needed before elective surgery and more active and aggressive management may be needed for emergency surgery. Use of bypassing agents can facilitate safe and successful surgeries in hemophilia patients with inhibitors.
Antibodies ; Emergencies ; Factor VIII ; Hemophilia A* ; Hemorrhage ; Hemostasis ; Humans ; Orthopedics ; Prothrombin