A Rare Case of Acquired Hemophilia A in Adolescents and Young Adults / 임상소아혈액종양

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.

Recombinant von Willebrand Factor for Pediatric Patient with von Willebrand Disease: First Report in Korea / 임상소아혈액종양

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.

Recombinant von Willebrand Factor for Pediatric Patient with von Willebrand Disease: First Report in Korea / 임상소아혈액종양

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.

Perioperative Management and Outcomes in Children with Hereditary Bleeding Disorder: a Retrospective Review at a Single Hemophilia Treatment Center / 임상소아혈액종양

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.

Various Complications after a Vascular Procedure in Patients with Hemophilia / 임상소아혈액종양

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.

Subgroup analysis of a phase 2/3 study of rurioctocog alfa pegol in patients with severe hemophilia A: efficacy and safety in previously treated Korean patients

BACKGROUND: The efficacy and safety of extended half-life, full-length, pegylated recombinant factor VIII rurioctocog alfa pegol [BAX 855, ADYNOVATE (USA)/ADYNOVI (Europe); Baxalta US Inc., a Takeda company, Lexington, MA, USA] was investigated in previously treated Korean patients with severe hemophilia A (HA). METHODS: A post hoc data analysis from the international, multicenter, phase 2/3 PROLONG-ATE study of rurioctocog alfa pegol in patients with severe HA (NCT01736475) determined annualized bleeding rates (ABRs) and rates of adverse events (AEs) in Korean patients treated in this study. RESULTS: All 10 enrolled Korean patients receiving rurioctocog alfa pegol (9 prophylaxis, 1 on-demand) completed the study [median (range) age, 28.0 (12–50) yr; weight, 64.8 (45–90) kg; 8 patients had ≥1 target joint at screening]. Median (range) ABR was 1.9 (0.0–14.5) for patients on prophylaxis and 62.2 for the patient receiving on-demand treatment. The hemostatic efficacy of rurioctocog alfa pegol was rated “excellent” or “good” and only single infusions were required per bleeding episode. ABRs improved in most patients compared with prestudy values. No dose adjustments were required for prophylaxis, and the dosing frequency was reduced in 8 patients, compared with their previous prophylaxis regimen. No serious AEs were reported; all 9 nonserious AEs (in 3 patients) were mild in severity and unrelated to the study treatment. CONCLUSION: This post hoc analysis of a small group of Korean patients with severe HA indicated that rurioctocog alfa pegol was effective, and no serious AEs were observed. For most patients, the dosing frequency was also reduced compared with their previous regimen.

Management of Spontaneous Spinal Epidural Hematoma Developed in Children with Hemophilia / 임상소아혈액종양

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.

Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for β-thalassemia major (TM) and sickle cell disease (SCD) in children. Graft-versus-host disease (GVHD) and treatment-related mortality (TRM) remain significant challenges to improving survival after HSCT. Here, we analyzed the outcome of TM and SCD patients, who received allogeneic HSCT with myeloablative conditioning at our institution. METHODS: Twenty-two patients (15 TM, 7 SCD), with a median age of 9 years (range, 1.6–16.9), underwent allogeneic HSCT using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin-based conditioning. Cells were derived from either the bone marrow (8 patients), or peripheral blood stem cells (14 patients). The majority of patients received HSCT from a matched sibling donor (N=18). GVHD prophylaxis included cyclosporine and short course methotrexate. RESULTS: All patients achieved donor engraftment. Two SCD patients died from TRM-related grade IV gut GVHD (N=1) or severe bronchiolitis obliterans (BO) (N=1). Cumulative incidence of acute and chronic GVHD was 36.4% and 32.7%, respectively. Veno-occlusive disease (VOD) occurred in 8 patients (36.4%), but resolved in all instances. Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disease (PTLD) occurred in 1 patient. The overall survival (OS) was 90.9% (TM 100%, SCD 71.4%), with all patients achieving transfusion independence, while 8 achieved complete donor chimerism. CONCLUSION: Busulfan, cyclophosphamide, and ATG-based conditioning for HSCT of TM and SCD patients did not result in graft failure, although modifications may be required to reduce VOD incidence. Further changes to donor type and cell source prioritization are necessary to minimize TRM and morbidity caused by GVHD.

Septic Arthritis and Infective Endocarditis in an Adolescent Hemophilia B Patient with an Inhibitor and a Central Venous Access Device / 임상소아혈액종양

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.

A Multicenter Study on Korean von Willebrand Disease Realities / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of up to 1%. However in Korea, only 126 VWD patients were registered in Korea Hemophilia Foundation (KHF). The aim of this study was to determine the status of VWD patients in Korea. We analyzed VWD patients by age, gender, blood group, family history and bleeding history.METHODS: One hundred twenty-six VWD patients registered in the KHF by December 2016, and 74 patients diagnosed at six university hospitals were enrolled in this study. We evaluated the medical records from the KHF and the questionnaires from six university hospitals retrospectively.RESULTS: Seventeen patients misdiagnosed and ten patients duplicated were excluded. One hundred nine patients registered in the KHF and 64 patients diagnosed at six university hospitals met the criteria for VWD. The blood type O accounts for 72 (51.8%). VWF mutation was detected in 30 patients (17.3%). Median age at diagnosis was 10.5 yr. The bleeding score of adults was higher than that of children (P < 0.001). The most common bleeding symptom was epistaxis (48.5%). The distribution of VWD types was: 67% of type 1, 30.1% of type 2, and 2.9% of type 3.CONCLUSION: Even though only six hospitals responded to the survey, 64 patients not registered in the KHF were diagnosed with VWD. Our results suggest the prevalence of Korean VWD might be higher than previously reported. A nationwide registration system is warranted in order to accurately identify the national prevalence of VWD.

Surgery in Patients with Von Willebrand Disease : A Single Center Experience / 임상소아혈액종양

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.

Surgery in Patients with Von Willebrand Disease : A Single Center Experience / 임상소아혈액종양

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.

A Multicenter Study on Korean von Willebrand Disease Realities / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of up to 1%. However in Korea, only 126 VWD patients were registered in Korea Hemophilia Foundation (KHF). The aim of this study was to determine the status of VWD patients in Korea. We analyzed VWD patients by age, gender, blood group, family history and bleeding history. METHODS: One hundred twenty-six VWD patients registered in the KHF by December 2016, and 74 patients diagnosed at six university hospitals were enrolled in this study. We evaluated the medical records from the KHF and the questionnaires from six university hospitals retrospectively. RESULTS: Seventeen patients misdiagnosed and ten patients duplicated were excluded. One hundred nine patients registered in the KHF and 64 patients diagnosed at six university hospitals met the criteria for VWD. The blood type O accounts for 72 (51.8%). VWF mutation was detected in 30 patients (17.3%). Median age at diagnosis was 10.5 yr. The bleeding score of adults was higher than that of children (P < 0.001). The most common bleeding symptom was epistaxis (48.5%). The distribution of VWD types was: 67% of type 1, 30.1% of type 2, and 2.9% of type 3. CONCLUSION: Even though only six hospitals responded to the survey, 64 patients not registered in the KHF were diagnosed with VWD. Our results suggest the prevalence of Korean VWD might be higher than previously reported. A nationwide registration system is warranted in order to accurately identify the national prevalence of VWD.

The Use of Rituximab with Immune Tolerance Induction Therapy for Hemophilia A with Inhibitors / 임상소아혈액종양

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.

Comparison of growth and pubertal progression in wild type female rats with different bedding types

PURPOSE: Endocrine-disrupting chemicals interfere with the endocrine system and therefore affect growth and pubertal progression. The study aim was to compare the growth and pubertal progression in wild-type female rats with different bedding types. METHODS: Twenty 5-week-old female wild-type Sprague Dawley rats were randomly assigned to two groups with different bedding types: one group received wood shaving bedding, while a second group received corncob bedding. We determined crown-rump length and body weight as anthropometric measurements and assessed the serum growth hormone (GH) and estradiol levels. The gh1 mRNA expression levels were compared using quantitative real time transcription polymerase chain reaction. The estrous cycle was evaluated by vaginal smear. RESULTS: The anthropometric measurements were not significantly different between the two groups. The mean relative expression of the gh1 gene was lower in the corncob bedding group than that in the wood shaving group (P=0.768). Meanwhile serum GH and estradiol were increased in the wood shaving bedding group; however this difference was not statistically significant. The time to first estrus and the length of the estrous cycle were increased in the corncob bedding group; the proportion of normal estrous cycles was also decreased. These findings indicate irregularities in the estrous cycle. CONCLUSION: Endocrine-disrupting chemicals in corncob bedding might be associated with time to first estrus and length of the estrous cycle. Therefore, the type of bedding should be considered as a factor affecting pubertal progression in rodents.

The Use of Rituximab with Immune Tolerance Induction Therapy for Hemophilia A with Inhibitors / 임상소아혈액종양

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.

Immune tolerance induction in patients with severe hemophilia A with inhibitors

BACKGROUND: Inhibitory antibodies to factor VIII (FVIII) are an important complication when managing patients with hemophilia A. Immune tolerance induction (ITI) has been regarded as a useful method for eradicating inhibitors. We report the results of a retrospective study in Korean patients with hemophilia A who underwent ITI. METHODS: We reviewed the records of patients with hemophilia A with inhibitors who underwent ITI from March 2004 to December 2014. ITI was started with FVIII concentrates at 100 IU/kg, 3 times per week. The dose of FVIII was reduced according to the inhibitor titer and recovery of FVIII. Inhibitor elimination was defined as the time taken to achieve a negative inhibitor assay with no anamnestic response and normal FVIII recovery and/or normal half-life. RESULTS: In total, 17 patients with severe hemophilia A were evaluated. Complete tolerance was achieved in 14 of 17 patients (83%). The mean peak inhibitor titer before ITI was 38.4 BU/mL. The mean treatment duration was 26.2 months. The mean duration between inhibitor detection and ITI was 5.1 years in the complete tolerance group and 10.8 years in the partial tolerance and failed group. CONCLUSION: This study shows that ITI can be an effective and well-tolerated method for eradicating inhibitors. Possible influencing factors for ITI success were age at the start of ITI treatment and duration after inhibitor detection. More research to provide further insight about other factors and conditions is needed.

The efficacy of bypassing agents in surgery of hemophilia patients with inhibitors

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.

Arterial Pseudoaneurysm in Neonates with Hemophilia: Successful Treatment with Noninvasive Clotting Factor Replacement and Ultrasound-guided Compression

Vascular cannulation is an invasive procedure that carries the risk of complications such as pseudoaneurysms. Hemophilia, the most common severe bleeding disorder of inheritance, increases the risk of such complications through underlying hypocoagulability. Although surgical ligation has been considered the gold standard treatment, less invasive options are currently available. Here we present 2 hemophiliac neonates for whom clotting factor replacement and ultrasound (US)-guided compression were successfully used. A 3-week-old male infant and a 4-week-old male infant presented with masses in the left antecubital area and the radial aspects of both wrists, respectively, after arterial punctures. The US confirmed the presence of pseudoaneurysms located at the left brachial artery and right radial artery. US-guided compressions with clotting factor administration initially attempted while confirming a thrombus inside the pseudoaneurysm sac indicated successful management. Arterial cannulation and other procedures in hemophiliac neonates must be attempted with caution because pseudoaneurysms or uncontrolled bleeding may occur. If laboratory analyses or invasive procedures are needed for neonates with a bleeding tendency or a suspected hemophiliac disorder, arterial or venous cannulation requires more caution or should be avoided if possible. This case report suggests that US-guided compression and clotting factor administration are suitable modalities for the treatment of small pseudoaneurysms in hemophilia patients.

Sequential therapy with activated prothrombin complex concentrates and recombinant activated factor VII to treat unresponsive bleeding in patients with hemophilia and inhibitors: a single center experience

BACKGROUND: Currently, the greatest challenge in hemophilia treatment is managing hemophilia patients with inhibitors. The two main bypassing agents that are used to treat hemophilia patients with inhibitors are activated prothrombin complex concentrates (APCC) and recombinant factor VIIa (rFVIIa). Hemophilia patients with inhibitors can develop bleeding episodes, that are refractory to monotherapy with either APCC or rFVIIa and thus are often difficult to manage. METHODS: This report describes a retrospective chart review of four hospitalized patients with severe hemophilia and inhibitors who were treated with sequential therapy of APCC and rFVIIa for refractory bleeding. Sequential therapy was defined as the administration of both rFVIIa and APCC within 12 h. RESULTS: In 5 episodes experienced by 4 patients with inhibitors, bleeding was not controlled by single bypass treatment, but it was controlled when two agents were sequentially administered. Sequential therapy was administered by alternating one APCC dose to 1 to 2 rFVIIa doses, with dosing intervals ranging from 3 to 6 h. All bleeding episodes were controlled within 12 to 24 h. Sequential therapy was discontinued after 2 to 5 days. No adverse clinical events, such as thrombosis, were observed. CONCLUSION: Sequential therapy with APCC and rFVIIa was efficacious without adverse events; however, attention on thrombosis is needed. In addition, a prospective clinical trial is needed to provide further evidence for this treatment.