Perioperative Management of Patients with Hemophilia during Spinal Surgery

Kazuyoshi Kobayashi,Shiro Imagama,Kei Ando,Kenyu Ito,Mikito Tsushima,Masayoshi Morozumi,Satoshi Tanaka,Masaaki Machino,Kyotaro Ota,Yoshihiro Nishida,Naoki Ishiguro 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.3

Study Design: Single-center retrospective study. Purpose: To optimize the perioperative management of patients with hemophilia who are undergoing spinal surgery. Overview of Literature: Hemophilia is a rare disease in which there is a tendency of bleeding because of a congenital deficiency in blood coagulation factor activity. There has been no previous report on spinal surgery in patients with hemophilia. Methods: The subjects were five patients (all males) with hemophilia who underwent spinal surgery at Nagoya University Hospital. Two patients had hemophilia A (deficiency of factor VIII) and three had hemophilia B (deficiency of factor IX). The mean age at the time of surgery was 63 years (range, 46–73 years). The following surgeries were performed: posterior lumbar interbody fusion (PLIF) in two patients, and lumbar fenestration, cervical laminoplasty and lumbar fenestration, and cervical laminoplasty and PLIF in one patient each. Results: Coagulation factor at a mean dose of 4.8 ×103 U (range, 3–6 ×103 U) was intravenously injected before surgery, and a mean dose of 5.2 ×103 U (rang, 4–6 ×103 U) was continuously administered for 24 hours after surgery. Factor activity was maintained at ≥80% until postoperative day 14 and at ≥50% thereafter. The average duration of surgery was 178 minutes (range, 133–233 minutes), the estimated blood loss was 661 mL (range, 272–1,344 mL), and a drain tube was left subfascially in place for 2 days in all patients. Reoperation due to postoperative surgical site infection was required in one patient, but there were no complications due to hemorrhagic diathesis. The total dose of coagulation factor administered during hospitalization was 102 ×103 U (range, 46–198 ×103 U). Conclusions: Coordination with a hematologist and dose adjustment of the coagulation factor preparation to maintain a target level of coagulation factor activity facilitated a smooth postoperative course with perioperative control of bleeding during spinal surgery for patients with hemophilia.

Utilization Patterns of Coagulation Factor Consumption for Patients with Hemophilia

이수옥,유수연 대한의학회 2016 Journal of Korean medical science Vol.31 No.1

Hemophilia is a serious rare disease that requires continuous management and treatment for which the medicine is costly at the annual average of 100 million KRW for an individual. The aim of this study was to investigate trends in the utilization of coagulation factor (CF) used for hemophilia treatment using the National Health Insurance database from 2010 to 2013 in Korea and compare the utilization of CF with other countries. The consumption of CF per capita (IU) in Korea was not more than other countries with similar income to Korea. However, CF usage per patient IU was higher because the prevalence rate of hemophilia in Korea was lower than in other countries while the number of serious patients was much more. Therefore, it is difficult to say that the consumption of hemophilia medicine in Korea is higher than that in other countries. The consumption and cost of hemophilia medicine in Korea is likely to increase due to the increased utilization of expensive bypassing agents and the widespread use of prophylaxis for severe hemophilia. Even during the research period, it increased slightly and other countries show a similar trend. Thus, hemophilia patient management should accompany active monitoring on the health and cost outcomes of pharmaceutical treatment in the future. This study is expected to contribute to further insight into drug policies for other countries that face similar challenges with high price pharmaceuticals.

Various Complications after a Vascular Procedure in Patients with Hemophilia

하연수,박영실 대한소아혈액종양학회 2019 Clinical Pediatric Hematology-Oncology Vol.26 No.1

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.

혈우병 환자의 임상 양상에 관한 단일기관 연구

허지혜,김형욱,김영대,이영호,김남수,설인준,김상우 인제대학교 2006 仁濟醫學 Vol.27 No.-

Objective : We analyzed and investigated clinical manifestations, laboratory tests, and inhibitor development of hemophilia that had not been thoroughly studied. Methods : We retrospectively reviewed 96 patients with hemophilia who were registered in the Hanyang University hospital from Jan, 1984 to Dec, 2003, Results : The total patients, whose median age at onset was 46.0 months, in clude 84 cases of type A (87.5%) and 12 cases of type B (12.5%). The most common chief complaint was a traumatic hemorrhage. The family histories of hemophilia were revealed in 41 cases (42.7%). The median activated partial thromboplastin time (aPTT) was 66.7 seconds. The number of severe cases was 39 (40.6%). Inhibitors were present in 13 cases (13.5%) and seven cases (53.8%) were high responders. aPTT and factor levels showed reverse correlation (r=-0.467). aPTT is more prolonged in group without family history than the group with family history (P=0.037). Conclusion : In this study, the diagnosis of hemophilia are made at the lower age and the serological positivity of the HCV is decreased. Activated partial thromboplastin time and factor levels shows reverse correlation. Activated partial thromboplastin time is more prolonged in group without family history compared with group with family history. The frequencies of family history are lower than those of other developed countries, because of concealing the family history of hemophilia. The prevalence of the development of inhibitors increased compared with those of previous studies in Korea, but was lower than those of other countries. Further studies would be necessary to decrease the inhibitor development.

The Role of Genetic Diagnosis in Hemophilia A

Lee, Ja Young Interdisciplinary Society of GeneticGenomic Medici 2022 Journal of interdisciplinary genomics Vol.4 No.1

Hemophilia A is a rare X-linked congenital deficiency of clotting factor VIII (FVIII) that is traditionally diagnosed by measuring FVIII activity. Various mutations of the FVIII gene have been reported and they influence on the FVIII protein structure. A deficiency of or reduction in FVIII protein manifests as spontaneous or induced bleeding depending on the disease severity. Mutations of the FVIII gene provide important information on the severity of disease and inhibitor development. FVIII mutations also affect the discrepant activities found using different FVIII assays. FVIII activity is affected differently depending on the mutation site. Long-range PCR is commonly used to detect intron 22 inversion, the most common mutation in severe hemophilia. However, point mutations are also common in patients with hemophilia, and direct Sanger sequencing and copy number variant analysis are being used to screen for full mutations in the FVIII gene. Advances in molecular genetic methods, such as next-generation sequencing, may enable accurate analysis of mutations in the factor VIII gene, which may be useful in the diagnosis of mild to moderate hemophilia. Genetic analysis is also useful in diagnosing carriers and managing bleeding control. This review discusses the current knowledge about mutations in hemophilia and focuses on the clinical aspects associated with these mutations and the importance of genetic analysis.

류마티스관절염 환자에서 발생한 후천성 혈우병

정경희 ( Kyoung Hee Jung ),최정혜 ( Jung Hye Choi ),이혜순 ( Hye Soon Lee ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.3

Acquired hemophilia is a rare disease caused by an autoimmune reaction to coagulation factor VIII, The mortality rate of this disease is very high (8∼22%). Clinical manifestations are different from congenital hemophilia. Various diseases are associated with acquired hemophilia, including autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis (RA), tumors, inflammatory bowel disease, psoriasis, asthma, diabetes, acute hepatitis B or C, and drug reactions. However, the underlying cause is unknown in approximately 50% of cases. A few cases of acquired hemophilia with RA have been published. However, no cases have been reported in Korea. We had a patient with longstanding RA and acquired hemophilia who was suffering from upper and lower extremity purpura with a deep intramuscular hematoma. The patient was successfully treated using cyclophosphamide combined with steroid.

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia

( In-jung Kim ),( Sunghwan Yoo ),( Eunseo Lee ),( Sukhyeon Jeong ),( Sora Kim ),( Jung Il Lee ),( Kwan Sik Lee ),( Young Youn Cho ),( Hyung Joon Kim ),( Hyun Woong Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. the management of hepatitic C virus (HCV) infection and control of various complications are emerging as important factors to increase the long term prognosis of hemophilia patients. Therefore, we assessed the long term outcome of peginterferon plus rivavirin (PEG) and direct acting antivirals (DAA) in HCV patients with hemophilia. Methods: Patients (n=205) were enrolled between March 2007 and July 2019. 141 patients were treated with PEG (genotype 1, n=98; genotype 2, n=42; genotype 3a, n=1). 64 patients were treated with DAA (genotype 1, n=44; genotype 2, n=19; genotype 4, n=1). We evaluated sustained virological response (SVR), incidence of hepatocellular carcinoma (HCC). Results: Mean follow-up periods were 9.9 and 3.4 years in PEG and DAA, respectively. In genotype 1, SVR was 66.3% (65/98) and 90.9% (40/44) in PEG and DAA groups, respectively. In genotype 2, the SVR was 73.8% (31/42) and 89.4% (17/19) in PEG and DAA groups, respectively. HCC developed in 3.5% (5/141) patients treated with PEG. Among them, the mean age was 77 (range 66-83) and 4 patients were genotype 1(genotype 1a : 1, genotype 1b : 3). 3 patients had liver cirrhosis and 2 out of 3 patients (Genotype 1a : 1, genotype 2 : 1) had SVR with PEG. 1 patient who had liver cirrhosis was treated with DAA after 4 years and achieved SVR. However, HCC occurred 2 years later. 3 patients died of brain hemorrhage, pneumonia and leukemia. Conclusions: PEG showed stable SVR and low incidence of HCC after SVR. Although the follow-up period is short, oral DAA treatment showed more stable SVR than PEG and no development of HCC after SVR in CHC patients with hemophilia.

Safety and Efficacy of B-domain Deleted Third Generation Recombinant Factor VIII (GreenGene F™) in Korean Patients with Hemophilia A: Data from a Post-marketing Surveillance Study

김순기,유기영,이건수,황태주,최용묵,최은진,박상규 대한의학회 2018 Journal of Korean medical science Vol.33 No.1

Background: New B-domain deleted third generation recombinant factor VIII (FVIII; GreenGene F™, beroctocog alfa) was launched in 2010. We determined safety and efficacy of GreenGene F™ during routine clinical practice in patients with hemophilia A over a period of 12 months. Methods: From July 2010 to July 2014, a total of 136 hemophilia A patients were enrolled in a post-marketing surveillance (PMS) study. Among them, 134 patients were assessed for drug safety and 114 patients were analyzed for drug efficacy. Patients with differing hemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. Results: Among 134 patients evaluated, 85 (63.4%) had severe hemophilia. Ninety-two received a total of 1,266,077 units for prophylaxis, and 42 received 516,491 units for bleeding episodes. Three patients developed inhibitors. In 112 previously treated patients, one patient (0.9%) developed inhibitor after intensive FVIII treatment for surgery. Among 22 previously untreated patients, inhibitors were observed in 2 infants (9.1%). Overall, there were a total of 47 adverse events (other than inhibitors) of all types in 30 patients (22.4%), 11 in 10 patients (7.5%) of which were considered showing serious adverse events (SAEs); most of which were hemorrhages at different sites. None of the SAEs were judged as product related. An excellent/good efficacy rate of 91.3% for hemostasis and 89.4% for hemorrhage prevention was recorded. Conclusion: The results of this PMS study support the use of GreenGene F™ as safe and efficacious in hemorrhage prevention and treatment of hemophilia A. These results are consistent with the findings from previously published GreenGene F™ studies

Human parvovirus B19 and parvovirus 4 among Iranian patients with hemophilia

Davod Javanmard,Masood Ziaee,Hadi Ghaffari,Mohammad Hasan Namaei,Ahmad Tavakoli,Hamidreza Mollaei,Mohsen Moghoofei,Helya Sadat Mortazavi,Seyed Hamidreza Monavari 대한혈액학회 2017 Blood Research Vol.51 No.4

Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and shows great resist-ance to most disinfectants. Therefore, it is one of the common contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4) is a newly identified parvovi-rus, which is also prevalent in parenteral transmission. In this study, we aimed to evaluate the prevalence of B19V and PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran. Methods: This was a cross-sectional epidemiological study comprising nearly all people with hemo-philia in this region. Whole blood samples were taken after patient registration and sent for plasma isolation. After nucleic acid extraction, B19V was detected with real-time poly-merase chain reaction, PARV4 DNA was then detected using sensitive semi-nested PCR. Results: In total, there were 86 patients with hemophilia, with mean age 28.5±1.5 years. Of these, 90.7% were men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11 patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4 DNA. The prevalence of B19V was higher in middle-aged groups rather than younger people, whereas PARV4 infection was more common in younger patients (P<0.05). Conclusion: There was a high prevalence of B19V and PARV4 infection in this high-risk group of pa-tients with hemophilia. Due to the clinical significance of the B19 virus, imposing more precautionary measures for serum and blood products is recommended.

Human parvovirus B19 and parvovirus 4 among Iranian patients with hemophilia

Davod Javanmard,Masood Ziaee,Hadi Ghaffari,Mohammad Hasan Namaei,Ahmad Tavakoli,Hamidreza Mollaei,Mohsen Moghoofei,Helya Sadat Mortazavi,Seyed Hamidreza Monavari 대한혈액학회 2017 Blood Research Vol.52 No.4

Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and shows great resist-ance to most disinfectants. Therefore, it is one of the common contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4) is a newly identified parvovi-rus, which is also prevalent in parenteral transmission. In this study, we aimed to evaluate the prevalence of B19V and PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran. Methods: This was a cross-sectional epidemiological study comprising nearly all people with hemo-philia in this region. Whole blood samples were taken after patient registration and sent for plasma isolation. After nucleic acid extraction, B19V was detected with real-time poly-merase chain reaction, PARV4 DNA was then detected using sensitive semi-nested PCR. Results: In total, there were 86 patients with hemophilia, with mean age 28.5±1.5 years. Of these, 90.7% were men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11 patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4 DNA. The prevalence of B19V was higher in middle-aged groups rather than younger people, whereas PARV4 infection was more common in younger patients (P<0.05). Conclusion: There was a high prevalence of B19V and PARV4 infection in this high-risk group of pa-tients with hemophilia. Due to the clinical significance of the B19 virus, imposing more precautionary measures for serum and blood products is recommended.