Extra Dural Hematoma of the Dorso-Lumbar Region in a Hemophiliac: A Rare Entity

Introduction and objective: Hemophilia is a genetic bleeding disorder inherited as a recessive train linked to the male gender. Bleeding into the central nervous system in patients with hemophilia is an extremely dangerous condition that can be directly life-threatening, if left untreated. Extradural hematoma of the dorso-lumbar region is rare but potentially deadly disease in children. This condition can result in severe neurological deficits. We aim to discuss the clinical, radiological and progressive clinical aspects of this illness. Case report: We report the case of a 5-year-old child with severe hemophilia A treated for extradural hematoma of the dorso-lumbar region resulting from trauma. A spinal magnetic resonance imaging revealed an extradural hematoma. The patient was successfully treated with intensive replacement therapy and did not require surgical intervention. Conclusion: Extradural hematoma is a rare complication of hemophilia, that needs to be looked for in children who have bleeding disorders. For the best neurological outcome, early diagnosis is crucial.

Short-term outcome of total knee replacement in a patient with hemophilia:A case report and review of literature

BACKGROUND Hemophilia A is a rare inherited bleeding disorder caused by mutations in the factor Ⅷ gene. This clotting factor plays an intrinsic role in the blood coagulation pathway. Patients with hemophilia may develop orthopedic manifestations such as hemarthrosis, but multiple malunion of fractures over the knee is rare and difficult to treat.CASE SUMMARY We report a patient with hemophilia A who developed severe knee osteoarthritis along with fracture malunion and nonunion. Total knee replacement was performed using a custom-made modular hinged knee prosthesis(cemented) equipped with extended distal and proximal stems. At 3 years’ follow-up, the patient exhibited excellent clinical function and remained satisfied with the surgical outcome. Surgical intervention was accompanied by rigorous coagulation factor replacement.CONCLUSION This case highlights various unique scenarios specific to individuals with hemophilia and fracture deformity.

Successful reconstruction of an ankle defect with free tissue transfer in a hemophilia A patient with repetitive hemoarthrosis:A case report

BACKGROUND Hemophilia, an uncommon yet consequential hereditary bleeding disorder, manifests as two clinically indistinguishable forms that hinder the normal functioning of the coagulation cascade. This impairment renders individuals more susceptible to excessive bleeding during significant surgical interventions. Moreover, individuals with severe hemophilia frequently encounter recurring hemarthrosis, resulting in progressive joint destruction and, subsequently, the need for hip and knee replacement surgeries.CASE SUMMARY The patient was a 53-year-old man with hemophilia A as the underlying disease and had self-injected factor Ⅷ twice weekly for several decades. He had undergone ankle fusion surgery for recurrent hemarthrosis at the Department of Orthopedic Surgery 1 mo prior and was referred to our department because of skin necrosis after a hematoma at the surgical site. An anterolateral thigh perforator free flap was created after three cycles of factor Ⅷ administration in addition to the concomitant administration of tranexamic acid(TXA)(Transamin 250 mg cap, 1 cap tid, q8h). After the operation, from postoperative days(PODs) 1-5, the factor Ⅷ dose and interval were maintained, and q12h administration was tapered to q24h administration after POD 6. Because the patient’s flap was stable 12 d after the operation, factor Ⅷ administration was tapered to twice a week. At 6 mo follow-up, the patient recovered well without any complications.CONCLUSION To the best of our knowledge, there are very few reports of successful free flaps in patients with hemophilia, and none have been reported in patients with hemophilia A. Moreover, there are several reports on the efficacy of TXA in free flaps in general patients;however, there are no case reports of combining factor Ⅷ and TXA in patients with hemophilia. Therefore, we report this case to contribute to future academic research.

Characterization of Bleeding and Laboratory Phenotype in Hemophilia A Carriers: A Cross-Sectional Study in Benin

Background: In Africa, hemophilia is underdiagnosed and carriers have long been considered free from bleeding symptoms. However, recent research has begun to reveal hemostatic abnormalities and bleeding manifestations in carriers of hemophilia A, particularly due to excessive inactivation of normal X chromosomes. Objective: To describe the bleeding symptoms and hemostatic abnormalities in carriers of hemophilia A (HA) in Benin. Methods: This study was conducted as a prospective cross-sectional investigation between April 2021 to March 2022. The study population consisted of identified through pedigrees of persons with hemophilia A being treated in various hospitals in Benin. Data were collected through interviews conducted by trained physician and each carrier underwent a biological workup. Results: A total of 71 hemophilia A carriers were included and 38 of whom were obligatory carriers. Thirty-one carriers (43.7%) reported abnormal bleeding symptoms. Menorrhagia has (71%) being the most important manifestation, followed by bleeding during or after childbirth (45.2%). Among the 71 carriers, 45 were of reproductive age. Of whom 22 (48.8%) had a Higham score exceeding 100. Activated partial thromboplastin time was prolonged in 7 carriers (9.9%). The mean activity factor VIII:C (FVIII:C) levels were 68.8 ± 34.9 IU/dL. The average FVIII:C level in obligatory carriers was 56.9% and among potential carriers, the average FVIII:C level was higher at 80.4%. However twelve female carriers (16.9%) had FVIII:C levels < 40%. The FVIII:C/FvWAg ratio was below 0.7 in 73.2% of female drivers. Obligatory carriers (p = 0.00003) and FVIII;C/FvWAg ratio = 0.003) were statistically associated with abnormal bleeding symptoms, while blood group O (p = 0.0002) and FVIII/FvWAg ratio = 0.0016) were associated with a higher risk of menorrhagia. Conclusion: In Benin, carriers of haemophilia A present bleeding symptoms and haemostatic abnormalities. Further studies on a larger number of carriers are needed to better characterize and manage these patients.

Orthopedic disorders of the knee in hemophilia:A current concept review

The knee is frequently affected by severe orthopedic changes known as hemophilic arthropathy(HA) in patients with deficiency of coagulation factor Ⅷ or Ⅸ and thus this manuscript seeks to present a current perspective of the role of the orthopedic surgeon in the management of these problems.Lifelong factor replacement therapy(FRT) is optimal to prevent HA,however adherence to this regerous treatment is challenging leading to breakthrough bleeding.In patients with chronic hemophilic synovitis,the prelude to HA,radiosynovectomy(RS) is the optimal to ameliorate bleeding.Surgery in people with hemophilia(PWH) is associated with a high risk of bleeding and infection,and must be performed with FRT.A coordinated effort including orthopedic surgeons,hematologists,physical medicine and rehabilitation physicians,physiotherapists and other team members is key to optimal outcomes.Ideally,orthopedic procedures should be performed in specialized hospitals with experienced teams.Until we are able to prevent orthopedic problems of the knee in PWH will have to continue performing orthopedic procedures(arthrocentesis,RS,arthroscopic synovectomy,hamstring release,arthroscopic debridement,alignment osteotomy,and total knee arthroplasty).By using the aforementioned procedures,the quality of life of PWH will be improved.

Genetic diversity of HCV among various high risk populations(IDAs,thalassemia,hemophilia,HD patients) in Iran

Objective:To determine the patterns of distribution of HCV genotypes among high risk population in north of Iran.Methods:A cross-sectional study was conducted on 135 HCV RNA-positive high risk individuals including thalassemia,hemophilia,patients under hemodialysis and intravenous drug addicts.HCV genotypes were determined based on amplification with type-specific primers methods.Results:Among the 187 anti-HCV positive samples,only 135 (72.2%)gave HCV-RNA positvity.Over all,the most identified HCV type was genotype 3a(51.1%) followed by 1a(27.4%),1b(8.2%).Sixteen(11.9%)out of 135 HCV RNA-positive participants have infected with more than one genotype or subtypes as follow:1a/1b in 11(8.2%),2/3a in 3 (2.2%),and 1a/1b/3a in 2(1.5%).Stratification of participants revealed that HCV subtype 3a was more prominent in thalassemia,hemophilia and HD patients but 1a and 1b were frequent in intravenous drug addicts.Conclusions:This study is the first report on HCV genotypes among Iranian subjects with different exposure categories resided in Mazandaran.where genotype 3a was found to be the most frequent genotype in thalassemia,hemophilia,and hemodialysis patients but not in IDAs.Since the addiction age is decreasing in Iran and a lot of addicts are IDAs.it might change the subtype pattern of HCV in general population.

A Retrospective Analysis of Intracranial Hemorrhage in Children with Hemophilia A

To investigate the incidence,risk factors,clinical manifestations and prognosis of intracranial hemorrhage (ICH)in children with hemophilia A in a center of China, we conducted a retrospective analysis of 126 children with hemophilia A at our hospital in recent 4 years.Thirty-six children with hemophilia A (including 19 severe cases,and 17 moderate cases complicated with joint diseases)received low dose factor Ⅷ (FⅧ) prophylaxis,and none of them had ICH.However,13 cases of hemophilia A not given prophylaxis were complicated with ICH (12 severe cases,and 1 moderate case)and demonstrated an incidence of 10.3%(13/126)in all patients,and 28.6%(12/42)in severe cases.Of the 13 cases,9 severe ICH cases had a definite history of head injury,accounting for 69.2%.Headache was common in children >3 years,but somnolence,irritability, gaze or convulsions in children <3 years.The most common findings of cranial CT scan included intracranial hematoma (9/13),and less commonly observed were subependymal hemorrhage and intraventricular hemorrhage.After administration of FⅧ,all patients survived.Hematoma of 6 cases was observed during CT reexamination after 1-3 months. During the follow-up period,only one case had slight activity limitation on one side of the limb,but steadily recovered.Besides the decreased concentration of FⅧ,trauma is the most common risk factor of ICH in children with hemophilia A.The active treatment can improve the prognosis of ICH in children with hemophilia A.

Value of Contrast-enhanced Ultrasound in Evaluating Synovitis and Predicting Recurrent Joint Bleeding of Hemophilia

Objective Contrast-enhanced ultrasound(CEUS)is advantageous for evaluating microcirculation,and has been applied to assess arthritis in previous studies.However,CEUS examinations have not been studied for hemophilia arthritis.Hemophilia arthritis is different from other arthritis,because it is induced by spontaneous joint bleeding.Hence,CEUS may have special value in evaluating hemophilia arthritis.The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients.Methods From August 2016 to January 2017,81 severe hemophilia A patients,who were referred to our hospital for ultrasound joint assessment with conventional ultrasound,were enrolled.Among these 81 patients,46 patients consented for CEUS examinations on the same day.Results Compared to color Doppler flow imaging(CDFI),four more joints presented with a blood flow signal under CEUS mode.In addition,the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound.The ultrasound scores(including the total grey-scale ultrasound score,joint effusion/hemarthrosis,synovial hypertrophy,CDFI semi-quantitative score,and CEUS semi-quantitative score)were significantly higher in the joint bleeding group than in the no joint bleeding group(P<0.05).Furthermore,these ultrasound scores were positively correlated with the joint bleeding frequency,and had the highest correlation with the CEUS score(r=0.620,P<0.05).Conclusion CEUS can more accurately assess the degree of synovial hypertrophy and vascularization,and diagnose synovitis,when compared to conventional ultrasound.In addition,CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding,and providing more reliable evidence for individualized treatment.

Clinical, Therapeutic and Evolutive Aspects of Patients with Hemophilia in the Surgical Resuscitation Care Unit of Joseph Ravoahangy Andrianavalona JRA Hospital Antananarivo

Background: Hemophilia, a constitutional bleeding disease, has always been present in Madagascar considering children who died after bleeding circumcision, as reported in the family history of the diagnosed patients. Hemophilia is serious because of the potentially fatal risk of hemorrhage. The aim of this study was to evaluate the clinical, outcome and therapeutic aspects of inpatients with hemophilia in the Surgical Resuscitation Unit of JRA Hospital in Antananarivo. A descriptive and observational study was led about patients with hemophilia cared in the Surgical Resuscitation Unit from January 2011 to March 2018, studying age, type and severity of hemophilia, reason and duration of hospitalization, treatment instituted and outcome of patients. Results and comments: Thirty-six hemophiliacs (0.2%) were enrolled. The mean age was 9.52 years old;52.78% were with hemophilia B and 47.22% with hemophilia A, mainly severe. Clinical manifestations were muscle hematomas (25.71%), gum bleeding (14%), epistaxis (14.28%), gastrointestinal bleeding (11.42%), intracranial hemorrhage (11.42%), post circumcision bleeding (11.42%), hematuria, intraperitoneal hematomas and hemarthrosis. Treatment was based on factor concentrate substitution when available. The length of stay ranged from one to thirty days. The evolution was favorable except for two deaths related to delayed management of intracranial hemorrhage. Three patients with hemophilia A developed inhibitors. The results showed that throughout these years of study, a change in management was noted alongside. Conclusion: Hemophilia cases requiring hospitalization were managed in surgical resuscitation unit. The evolution was mainly related to the availability of clotting factor concentrates in coagulation factors, the delay in taking care of the patients and the presence of specialized staff.

Thromboelastography Use in the Perioperative Transfusion Management of a Patient with Hemophilia A Undergoing Liver Transplantation

The thrombelastogram is a method used to monitor clotting dynamics. Thrombelastography (TE) has been used to guide therapy of coagulation disorders mostly in cardiac surgery but also in liver surgery. TE is a useful tool for perioperative management of patients at risk for coagulopathy. There are several reports describing the use of the thrombelastogram in patients undergoing orthotopic liver transplantation (OLT), but only few cases include patients with both liver disease and inherited bleeding disorders. We describe the use of TE in a patient with hemophilia A and advanced cirrhosis undergoing OLT.

Successful esophagectomy in a patient with combined esophageal cancer and hemophilia B

Patients with esophageal cancer often require esophagectomy with esophagogastrostomy.However,the incidence of complications,such as hemorrhage,during operations for esophageal cancer is high,even with minimally invasive surgery.Without the appropriate interventions,the risk of major intraoperative and postoperative hemorrhage is very high in patients with esophageal cancer and hemophilia.We report the case of a 45-year-old man with esophageal cancer and hemophilia B who underwent a successful hybrid,minimally invasive Ivor-Lewis esophagectomy with appropriate perioperative management.

Hepatitis C treatment with triple therapy in a patient with hemophilia A

We report a case of successful treatment of chronic hepatitis C infection with telaprevir-based triple therapy in a patient with hemophilia A complicated by factor Ⅷ inhibitor. A twenty-two years old male with hereditary hemophilia A and high-titer factor Ⅷ inhibitor was taking maintenance doses of recombinant factor Ⅷ. He visited our clinic for treatment of his chronic hepatitis C with the newly instituted protease inhibitor based therapy. He was diagnosed with hepatitis C genotype 1a at one year of age. He was initiated on telaprevir, ribavirin and peg-interferon for treatment of hepatitis C and qualified for response-guided therapy. He completed treatment at 24 wk with minimal adverse effects. Notably, after 4 wk of hepatitis C treatment, his factor Ⅷ inhibitor screen was negative and the dose for recombinant factor Ⅷ decreased by half of the initial dosing before he was treated for hepatitis C. We suspect that suppressing hepatitis C may help decrease factor Ⅷ inhibitor level and the need for recombinant factor Ⅷ.

Reasons for failure to continue home therapy in patients with hemophilia: A qualitative study

Background: Home therapy for hemophilia reduces pain, deformity and incidence of complicationinduced hospitalizations. Therefore, it is an important component of comprehensive hemophilia care.Unfortunately, most hemophilic families in Shanxi province, China do not continue home therapy.Objective: To analyze the reasons that hemophilic families do not continue home therapy and to provide a foundation for formulating targeted interventions by the Hemophilia Treatment Center(HTC) in Shanxi Province.Methods: A qualitative phenomenological approach using purposeful sampling of 17 hemophilic families, two physicians, and one nurse from 11 branches across 11 cities in Shanxi Province. Interviews were recorded, transcribed verbatim and analyzed using qualitative content analysis.Results: Four themes were identified:(1) home therapy was generally positively evaluated;(2) concerns about the safety of home therapy;(3) an imperfect social medical security system; and(4) inadequate continuous nursing of hemophilia.Conclusions: Home therapy for hemophilia remains in a preliminary stage in Shanxi Province, and inadequate family and social support systems have obstructed the implementation of home therapy. It is necessary to develop a home therapy model suitable for hemophilic families in Shanxi Province as soon as possible. Such a model would improve the community and home care medical systems for hemophilia and guarantee home therapy throughout the entire medical care system, thus enabling more hemophilic families to carry out home therapy. Achieving these goals requires urgent research and attention from medical staff.

A Preliminary Study on the HCV Infection Status of Patients with Hemophilia and Their Family Members

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A Preliminary Study of Age and Sex of People with Hemophilia

Aim: This paper aims at providing more information of people with hemophilia for more targeted treatment. Methods: 1149 people with hemophilia are surveyed in 45 units, and then established by EpiData software. The number of people with hemophilia in 9 age intervals for the male and female is analyzed by Population Pyramid and Pareto Analysis. Results: It is found that the people with hemophilia are appearing in every age interval. Relative to the number of male patients, the number of female patients is extremely rare. Of 1134 male patients, relative frequencies for male ranked the first (23.0%), second (17.4%), third (17.2%) are 7 - 12, 2 - 3, 13 - 18 years old, respectively, while of 15 female patients, relative frequencies for female in these age intervals are only 13.3%, 13.3%, 6.7%, respectively. However, the most relative frequency of female patients is between 26 - 45 years old. Conclusion: There is a challenge of the aging hemophilia population. Most of male patients are between 7 - 12 and 2 - 3 years old. Most of female patients are between 26 - 45 years old.

Application of Gene Therapy in Hemophilia

Gene therapy refers to introducing normal exogenous genes into target cells to correct or compensate for the diseases caused by defective and abnormal genes for the purpose of therapy.It holds out hope of a cure for single-gene genetic diseases such as thalassemia,hemophilia,etc.At present,gene therapy is performed in two ways:introducing exogenous genes,and gene editing.A great number of clinical trials of gene therapy in hemophilia have been carried out using viral vectors to introduce foreign genes into target cells.However,the production of neutralizing antibodies following injection and the inability to prepare viral vectors in large quantities limit their application.Although gene-editing methods like CRISPR avoid the above problems,the potential risks of off-target effects are still unknown.More trials and evidence are needed to elucidate the safety and accuracy of gene therapy.This paper will review the bench and clinical work of gene therapy in hemophilia in recent years,and summarize the challenges and prospects of gene therapy,so as to provide directions for future scientific research in this field.

Replacement Therapy for Hemophilia Patients Undergoing Cardiac Surgery: Report of Three Cases

Hemophilia is an X-linked recessive inherited bleeding disorder.Despite the improved treatment in recent years with the advent of replacement therapies,the progression of atherosclerosis is not slowed down after the reduction of clotting factors in hemophilia.As life expectancy increases,more hemophilia patients will suffer from age-related cardiovascular diseases.Since cardiac surgery needs heparinization and cardiopulmonary bypass(CPB),it is extremely challenging to balance hemostasis and coagulation in patients with hemophilia.Here we report three cases of hemophilia patients who underwent cardiac surgery successfully.

Forearm compartment syndrome due to acquired hemophilia that required massive blood transfusions after fasciotomy:A case report

BACKGROUND Acquired hemophilia is rare.In some cases,the bleeding in muscle causes compartment syndrome.However,it is not clear whether fasciotomy should be performed for the compartment syndrome caused by acquired hemophilia because of the risk of bleeding and the unknown functional results.CASE SUMMARY A 75-year-old woman was admitted with severe pain of the right forearm with no preceding traumatic event.The right forearm was obviously swollen,and stretch pain was observed.Subcutaneous hematomas were suspected in various parts of the body.Compartment pressure was 110 mmHg on the volar side.Activated partial thromboplastin time(aPTT)was prolonged to 54.9 s.Fasciotomy was performed,and hematoma was observed in the volar compartment.Postoperative laboratory examinations revealed a low level of factor Ⅷ(FⅧ)activity(12.5%)and a high level of FⅧ inhibitor(15.2 bethesda units/mL).Acquired hemophilia A was diagnosed.Though recombinant clotting factors were administered,transfusion of red blood cells reached 46 units(140 mL/unit).Hemostasis was achieved 9 d after fasciotomy.The total cost of the clotting factor concentrates administered reached 28834600 yen.With prednisolone,FⅧ activity and aPTT recovered gradually.Final function of the hand was good in the index finger and excellent in the others.CONCLUSION Fasciotomy resulted in good function of the hand in a case of non-traumatic compartment syndrome caused by acquired hemophilia,but life-threatening bleeding occurred,and the cost of clotting factor treatment was high.Preparation of sufficient blood transfusion,preoperative administration of recombinant activated clotting factor Ⅶ,and prompt fasciotomy could be ideal for such cases.

Practical Guidance for Non-Specialist Physical Therapists Managing People with Hemophilia and Musculoskeletal Complications

People with hemophilia (PWH) have impaired blood coagulation and hemostasis. Bleeding into joints and muscles is the main manifestation of the disorder, causing severe joint damage and muscle complications. Lifelong, regular physical therapy is therefore important for PWH, in order to support recovery from bleeds and reduce recurrences. Ideally, these individuals should be in the care of a hemophilia treatment center (HTC), where a physical therapist (PT) should be a regular part of the comprehensive team. However, not all PWH have convenient access to an HTC, and they may be referred to local non-specialist PTs, who may have only limited experience with the condition, for day-to-day physical therapy treatment. This article, written by four experienced hemophilia PTs, introduces key aspects of the pathology of the hemophilic joint in adult PWH with musculoskeletal complications or established joint disease (or those with inhibitors) that are relevant to PTs. The characteristic differences between the joints of PWH and those of people with similar pathologies are clarified. Practical advice on how the physical therapy consultation can be adjusted for PWH is given, and the importance of communicating with the HTC emphasized. The aim of this narrative review is to raise awareness of hemophilia and joint disease for non-specialist PTs, and serve as helpful background information for PTs who encounter PWH with musculoskeletal complications or established joint disease in their clinics.

Study on Gene Mutations of Factor IX Gene of Chinese Hemophilia B Patients

DNA sequence of 2.2kb of factor IX gene from each of 27 cases of Hemophilia B patients living in Jiangsu, Hubei, Shandong, Guangdong, Fujian and Ningxia provinces was studied by using the PCR (Polymerase Chain Reaction) and GAWTS (Genomic Amplification with Transcript Sequencing) techniques. Twenty different mutations were found in 21 patients. Twelve of them were not reported before. Eight occured in CpG dinucleotide (38%) that was a hot spot of germ line mutations in Caucasian. No geographic specificity was found between 6 provinces. Six carriers were identified. Some advantages of the methodology were discussed.