Etiology, Clinical Profile, and Demographics of Hemophilia B in Eastern India

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Abstract Background: The most common severe inherited hemorrhagic disease is hemophilia, which means "love of blood." Deficiencies in Factors VIII and IX cause hemophilia, with inadequate levels or malfunctioning of these factors being the primary causes of hemophilia A and B, respectively. This study aims to assess the incidence and characteristics of inherited coagulation disorders, particularly hemophilia B. Objective: The present investigation aims to evaluate the incidence and clinical traits of congenital anticoagulation diseases, specifically hemophilia B. Method: The study included 98 Hemophilia B patients with a mean age of 25. Medical histories were recorded using a predesigned Performa, covering age, gender, bleeding site, and family history. Result: The study included 98 hemophilia B patients, with 39 having severe and 59 moderate forms. The majority (60.2%) had moderate hemophilia, while 39.7% had the severe type. Most patients (17.4 ± 10.5 years) were aged 21-30, with the mean age of onset being 17.4±10.5 years for severe hemophilia and 8.6±4.43 years for moderate cases. Knee joints were the most affected, found in 79.5% of cases and accounting for 98.9% of target joint infections, followed by elbow joints at 90.8%. Regular factor IX replacement was needed in 39.7% of severe cases. This highlights the importance of early diagnosis and treatment for managing joint-related complications in hemophilia B patients. Conclusion: The current study examines hemophilia B's sociodemographic and clinic-pathological characteristics. Early diagnosis may be beneficial only when the spectral manifestation of hemophilia B in the community is known.
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Deficiencies in Factors VIII and IX cause hemophilia, with inadequate levels or malfunctioning of these factors being the primary causes of hemophilia A and B, respectively. This study aims to assess the incidence and characteristics of inherited coagulation disorders, particularly hemophilia B. Objective: The present investigation aims to evaluate the incidence and clinical traits of congenital anticoagulation diseases, specifically hemophilia B. Method : The study included 98 Hemophilia B patients with a mean age of 25. Medical histories were recorded using a predesigned Performa, covering age, gender, bleeding site, and family history. Result: The study included 98 hemophilia B patients, with 39 having severe and 59 moderate forms. The majority (60.2%) had moderate hemophilia, while 39.7% had the severe type. Most patients (17.4 ± 10.5 years) were aged 21-30, with the mean age of onset being 17.4±10.5 years for severe hemophilia and 8.6±4.43 years for moderate cases. Knee joints were the most affected, found in 79.5% of cases and accounting for 98.9% of target joint infections, followed by elbow joints at 90.8%. Regular factor IX replacement was needed in 39.7% of severe cases. This highlights the importance of early diagnosis and treatment for managing joint-related complications in hemophilia B patients. Conclusion: The current study examines hemophilia B's sociodemographic and clinic-pathological characteristics. Early diagnosis may be beneficial only when the spectral manifestation of hemophilia B in the community is known. Hematology Epidemiology F9 gene hemophilia B Varanasi Utter Pradesh Figures Figure 1 Figure 2 Key Points For the best possible care and management in the future, hemophilia B must be accurately and promptly diagnosed, considering the patient's factor level, family history, disease severity, and clinical characteristics. The current study gives doctors and other healthcare professionals crucial information for accurate early disease diagnosis and management. Introduction The most common types of hemophilia are hemophilia A (classic hemophilia) and B (Christmas disease), which are prevalent hereditary disorders in India and worldwide. According to the World Federation of Hemophilia, approximately 400,000 people suffer from hemophilia globally, with India accounting for 80% of the cases [ 1 ]. Hemophilia A (HA) and hemophilia B (HB) are X-linked disorders caused by mutations in genes located on the long arms of the X chromosome (Xq28 for HA and Xq27 for HB). Hemophilia A accounts for about 80% of all cases, while hemophilia B constitutes 20%. Hemophilia A occurs in approximately one in 30,000 male births, while hemophilia B (HB) is found in about one in 10,000 male births. Factor deficiency, specifically Factor VIII and Factor IX, is one of the most prevalent coagulation irregularities. Hemophilia A and B are inherited in an X-linked recessive pattern [ 2 ]. Bleeding into muscles, joints, and soft tissues is a clinical hallmark of hemophilia. In impoverished and densely populated countries like India, where access to medical care is limited, individuals with hemophilia often rely on blood and blood products as a more affordable alternative to factor concentrates. This increases the risk of transfusion-transmitted infections [ 1 , 7 ]. However, the standard treatment for severe hemophilia is preventive therapy, which involves administering regular doses of clotting factors to prevent bleeding episodes. This approach reduces the long-term complications of the disease. Episodic treatment, which involves prompt administration of clotting factors during a bleeding episode, is also commonly used. In cases of mild hemophilia B, spontaneous bleeding is rare unless there is prior trauma to the affected area. The most common causes of bleeding in mild HB are injuries, surgical procedures, and dental operations. Pre-treatment is required to normalize FIX levels before undergoing surgery or dental procedures for all types of hemophilia. Treatment is now administered using recombinant FIX products, some of which have been modified to extend the half-life of FIX in circulation. Hemarthrosis is the most prevalent manifestation of hereditary coagulation disorders. Joint bleeding, along with the resulting damage to weight-bearing joints, is the most common and debilitating symptom of severe hemophilia. Bleeding into the joints can cause pain, swelling, inflammation, warmth, and restricted range of motion. Bleeding into joints can result in pain, swelling, inflammation, warmth, and a restricted range of motion. The most commonly affected joints include the knees, elbows, ankles, shoulders, wrists, and hips [ 4 ]. The incidence of spontaneous joint bleeding generally increases with age, reaching up to 60% by age 65. Recurrent joint bleeding often leads to hemophilic arthropathy, which is characterized by chronic proliferative synovitis and chronic osteochondral changes in major joints, primarily affecting the elbows, knees, and ankles (commonly referred to as "index joints"). Ecchymotic patches [Figure No.1] are also observed in some cases. The most critical treatment strategy for managing hemophilia is the continuous intravenous administration of prophylactic hematological therapy to prevent recurrent hemarthroses. In situations where intravenous treatment is only available on demand, regular monitoring is essential for the early diagnosis and management of intra-articular bleeding episodes [ 5 , 6 , 7 ]. Magnetic Resonance Imaging (MRI) scores are often used to assess radiological changes in the joints. This research aims to investigate the incidence and diagnostic characteristics of hereditary coagulation disorders, with a particular focus on hemophilia B, in eastern India [ 8 , 9 , 10 , 11 ]. Aims and Objective To evaluate the Clinical profile, demographics, and etiology of hemophilia B patients in Eastern India Materials and Methods Study Design The present cross-sectional study was conducted between 2021 and 2024. A total of 98 hemophilia B (HB) patients were included, with a mean age of 25 years. A predesigned proforma was used to record the complete medical history of the patients, including information on their age, gender, initial bleeding site, and family history. A semi-automated clot analyzer was used to perform a "one-stage test" for the factor assay. Factor concentrations were classified as follows: severe ( 5%-40% or 0.05–0.4 IU/mL) [ 8 ]. The data are presented as mean ± SD. Patients To document clinical details, a thorough clinical examination, pertinent laboratory testing, and the patient's history were used. Inclusion Criteria Patients with hemophilia B Exclusion Criteria Informed consent was obtained from each patient and their family members, with ages ranging from 30 years. The clinical profile and demographic characteristics of hemophilia B were evaluated through complete hematological investigations, including complete blood count (CBC), GBP, prothrombin time (PT), and activated partial thromboplastin time (APTT). Coagulation factor assay tests, X-rays of joints, ultrasonography of suspected muscles, and abdominal computed tomography (CT) scans were performed on selected severe patients based on their symptoms. Statistical Analysis The statistically significant differences in mean categorical variables were compared using the Student's t-test, one-way ANOVA, and the Chi-square test, and were analyzed. Statistical significance is defined as a P value < 0.05. Results This is a cross-sectional study. Out of the 98 patients, 39 (39.7%) had severe hemophilia, and 59 (60.2%) had moderate hemophilia [Table 1, Fig. 2]. Most respondents were aged between 21 and 30 years, with a mean age of 17.4 ± 10.5 years. Table no. 1 Shows the Patients are distributed based on severity. Patients are distributed based on severity. Severity of hemophilia Number of Patients Percentage (%) Severe hemophilia 39 39.7% Moderate hemophilia 59 60.2% Total 98 100% The majority of participants 72 (73.3%) were from rural areas, 32 (32.6%) had at least completed their primary education, 21 (21.4%) were enrolled in school, and 47.9% had a monthly family income of at least 15,000 BDT. Sociodemographic characteristics were consistent across the range of hemophilia severity. A family history of hemophilia was present in 75.5% of the participants. The median age at first bleeding and diagnosis was 5.0 and 6.0 years, respectively. According to the assessment, nearly 57.1% of the individuals were diagnosed with hemophilia at the time of their first bleeding. No significant differences were found between individuals with severe and moderate hemophilia [Table 2]. Table No. 2 Sociodemographic characteristics and disease profile of the patients Sociodemographic characteristics and Disease Profile of the patients Severity of Hemophilia Variable Total (n = 98) Severe n (%) Moderate n (%) Total, n (%) 98 39 (39.7%) 59(60.2%) Age (years), Mean ± SD (17.4 ± 10.5) (5.5 ± 2.7) (8.6 ± 4.4) Age group (years) 30 12 5 (12.8%) 7(11.8%) Residence Rural 72(73.3% 29(74.3%) 43(72.9%) Urban 26(26.5%) 10(25.6%) 16(27.1%) Education Llliterate 2(5.1%) 1(2.6%) 1(1.7%) Pre-schooler 19(19.4%) 8(20.5%) 11(18.6%) Primary 32(32.6%) 13(33.3%) 19(32.2%) SSC 21(21.4%) 9(23.1%) 12(20.3%) HSC 15(15.3%) 7(17.9%) 8 (13.5%) Graduate and Above 9(9.2%) 4(10.2%) 5(8.5%) Occupation Toddler 3(3.1%) 1(2.6%) 2(3.4%) Student 29(29.6%) 11(28.2%) 18(30.5%) Job 19(19.4%) 8(20.5%) 11(18.6%) Business 34(34.7%) 13(33.3%) 21(35.6%) Farmer 8(81.6%) 3(7.7%) 5(8.5%) Unemployed/dependent 5(5.1%) 2(5.1%) 3(5.1%) Monthly Family Income 30,000 13(13.3%) 6(15.4%) 7(11.8%) Family History Present 75(76.5%) 31(79.5%) 44(74.6%) Absent 23(23.5%) 8(20.5%) 15(25.4%) Median age at first bleeding (years) 5.0 2.0 3.0 Age at diagnosis (year) Median 6.0 6.4 6.0 The duration between the initial bleeding incident and the diagnosis None 56(57.1%) 25(64.1%) 31(52.5%) < 10 27(27.5%) 11(28.2%) 16(27.1%) ≥ 10 14(14.3%) 5(12.8%) 9(15.3%) Missing Value 1 Table no. 3 clinical presentation and Investigation of hemophilia B patients Clinical manifestation and Investigation Clinical Manifestation Total (n = 98) Severity of Hemophilia Severe (n = 39) Moderate (n = 59) Mode of Bleeding Spontaneous 98(100.0) 39(100.0) 59(100.0) After major trauma 98(100.0) 39(100.0) 59(100.0) After manor trauma 98(100.0) 39(100.0) 59(100.0) Joint Swelling Yes 97 (98.9%) 38(97.4%) 59(100) No 1(1.0%) 1(2.6%) 0 Target Joint Knee 78(79.6%) 24(61.5%) 45(76.3%) Knee + Elbow 56(57.1%) 33(84.6%) 23(38.9%) Ankle + Knee + Elbow 41(41.8%) 36(92.3%) 26(44.0%) Shoulder 23(23.5%) 13(33.3%) 18(30.5%) Hip 6(6.1%) 8(20.5%) 2(3.4%) No 1 2 0 Soft tissue/ Muscle swelling Yes 64(65.3%) 38(97.4%) 49(83.0%) No 34(34.69%) 1(2.56%) 10(16.9%) Muscle wasting Yes 97(98.9%) 36(92.3%) 59(100%) No 1(1.0%) 3(7.7%) 0 Bleeding/ecchymosis from skin/ other orifices Yes 75(76.5%) 35(89.7%) 47(79.7%) No 23(23.5%) 2(6.6%) 12(20.3%) According to [Table 3] , all types of bleeding were present in every patient. The knee was the most frequently targeted joint (79.6%), followed by the knee plus elbow (57.1%). Muscle wasting was observed in 98.9% of patients, while 70.7% experienced bleeding/ecchymosis from the skin or other orifices, and 65.3% had soft tissue or muscle swelling. The majority of respondents (48.9%) could attend school or work with some restrictions, while 42.8% had limited ability to work or attend school. Additionally, 2.0% could only manage minimal self-care, and 5.1% could carry out activities without limitations. However, none of these traits showed significant differences between individuals with moderate and severe hemophilia. 92.8% of cases displayed changes in the affected joint on X-ray, 66.3% had muscle hematomas visible on ultrasound, and 28.6% had a retroperitoneal hemorrhage in the abdomen on ultrasonography [Table 4]. Table no. 4 shows the Functional status of patients with hemophilia B Functional Status Unrestricted activity 5(5.1%) 3(7.7%) 0 Full school/work with some limitation 48(48.9%) 25(64.1%) 49(83.0%) Restricted school/work 42(42.8%) 9(23.0%) 10(16.9%) Restricted self-care 2(2.04%) 2(5.1%) 0 Investigation PT 65.6(13.5) 56.8(13.5) 65.3(13.5) APTT (sec) 90.20(45.1–122.0) 89.56(73.0–99.0) 89.3(49.5–121.0) X-ray of the affected joint Joint changes present 91(92.8%) 36(92.3%) 58(98.3%) No change 6(6.1%) 2(5.1%) 1(1.7%) Mixing Value 1(1.0%) 1(2.5%) 0 Ultra sonogram of the suspected muscle group Normal 31(31.6%) 6(15.4%) 21(35.6%) Muscle hematoma 65(66.3%) 31(79.5%) 37(62.7%) Missing value 1(1.0%) 0 Ultra sonogram of the whole abdomen Normal 69(70.4%) 21(53.8%) 43(72.9%) Retroperitoneal hemorrhage 28(28.6%) 17(43.6%) 15(25.4%) missing value 1(1.0%) 1(2.6%) Table No. 5 shows the location and incidence of spontaneous bleeding by severity of hemophilia. Location and Incidence of Spontaneous Bleeding by Severity of Hemophilia (n = 98) Clinical Manifestations Total (n = 98) Severe (n = 39) Moderate (n = 59) Spontaneous bleeding Bruises and ecchymosis 39(39.8%) 22(56.4%) 17(28.8%) Joint haemorrhage Knee 97(98.9%) 36(87.1%) 43(72.9%) Ankle 89(90.8%) 32(82.0%) 34(57.6%) Elbow 89(90.8%) 32(82.0%) 34(57.6%) Wrist Joint 40(40.8%) 11(11.2%) 6(6.1%) Hip joint 36(36.7%) 17(43.5%) 19(32.2%) Shoulders 34(34.7%) 12(28.2%) 22(37.3%) Mucosal Bleeding Gum Bleeding 49(50%) 25(64.1%) 24(40.6%) Epistaxis 23(23.4%) 12(30.7%) 11(18.6%) Gastrointestinal bleeding Hematemesis 7(7.1%) 4(10.3%) 3(5.1%) Retroperitoneal 19(19.4%) 8(20.5%) 11(18.6%) Oro-pharyngeal 13(13.2%) 5(12.8%) 7(11.8%) Melaena 14(14.3%) 7(7.1%) 7(11.8%) Haemoptysis 6(6.1%) 6(15.4%) - Muscle hemorrhage Thigh 50(51.0%) 26(66.6%) 24(40.7%) Calf Muscle 53(54.0%) 25(64.1%) 28(28.6%) Scalp 3(3.06%) - - Facial 7(7.1%) 4(10.2%) 3(5.08%) Iliopsoas 36(36.7%) 18(46.1%) 18(30.5%) Flexor Muscle of the forearm 26(26.5%) 12(30.7%) 14(23.7%) Buttock 28(28.6%) 9(23.0%) 19(32.2%) Ocular Bleeding Vitreous hemorrhage 6(6.1%) - 6(10.4%) Subconjunctival hemorrhage 11(11.2%) 9(23.0%) 3(3.38%) Genito-urinary bleeding Hematuria 47(47.9%) 28(71.8%) 19(32.2%) [Table No. 3] and [Figure No. 2] display the location and incidence of spontaneous bleeding among the study's hemophilia participants, categorized by severity. The average number of spontaneous bleeding incidents over the past two years for severe, moderate, and all hemophiliac participants was 5, 10, and 16, respectively. The knee joint was the most frequently affected (98.9%), followed by the ankle and elbow joints (90.8% each) [Table No. 5]. The knee joints had the highest median number of joint hemorrhage occurrences (12, range: 1–40). Elbow joints followed, with a median of 9 occurrences per episode and a range of 1 to 32. Joint hemorrhages in the knee, elbow, and ankle were more common in severe hemophiliacs, with the knee joint being the most frequently affected (88.6%), followed by the elbow and ankle joints (64% each). The knee joint had the highest median number of occurrences (12, range: 1–40), while the elbow joints had a median of 9 occurrences, with a range of 1 to 32. Severe hemophiliacs were more likely to experience knee joint bleeding, while moderate hemophiliacs had more frequent joint hemorrhages in the ankle, elbow, and shoulder. However, no statistically significant difference was observed. In terms of frequency, number of episodes, and range, the thigh muscle was the most commonly affected in moderate hemophiliacs compared to severe hemophiliacs. Again, no statistically significant difference was found. Nearly half of the patients in both groups experienced gum bleeding, with more severe patients experiencing a higher number of bleeding episodes. Melia was observed in both patient groups with almost equal frequency. Discussion Hemophilia is an X-linked genetic disorder caused by a mutation in the factor IX gene, leading to a bleeding disorder due to impaired coagulation [ 7 ]. Hemophilia patients can experience mild, moderate, or severe illness, depending on the plasma levels of clotting factors. The severity of hemophilia influences the variety of bleeding manifestations, which can occur at any age. This study examines bleeding occurrences in individuals with moderate and severe hemophilia in terms of their locations and frequency, as well as their socio-demographic profiles. A total of 98 patients were included in the study, with an average age of 17.4 ± 10.5 years. In our observation, the average age of symptom onset was 5.5 ± 2.7 years in severe patients and 8.6 ± 4.4 years in moderate patients. According to Karim MA et al. (2013), the average age of onset was 15.8 years [ 12 ]. This study included only male patients. Of the 98 patients, 59 (60.2%) had moderate hemophilia B (HB) with a factor IX concentration of 1–5%, while 39 (39.7%) had severe hemophilia B with a factor IX concentration of < 1%. According to Ahmad et al. (2008), 69.6% of hemophilia B patients had severe hemophilia, and 19.2% had moderate hemophilia [ 13 ]. Higher percentages of severe hemophilia cases (87% and 84%) were reported in studies by Sahoo et al. [ 14 ] and Pawan et al. [ 15 ] for the years 2020 and 2024, respectively. The location of initial bleeding can be influenced by various factors. Hemarthrosis in the joints is the most typical presentation, observed in 97% of cases. According to Ahmad et al. [ 16 ], 82% of hemophilia patients present with hemarthrosis as one of their primary symptoms. In the current study, joint bleeding (hemarthrosis) was the most prevalent clinical manifestation (57.3%), followed by skin bleeds (18%), muscle bleeds (10.7%), epistaxis (7.3%), and petechiae (6.7%). In contrast, Pawan et al. (2021) found that 88% of severe hemophilia B (HB) patients had hemarthrosis, and 96% had hematomas. Our study, however, found that 98.97% of all participants had hemarthrosis, with 87.17% of severe HB patients and 72.88% of moderate HB patients presenting with this symptom [ 2 ]. These differences may be due to variations in geographic areas and populations. This study included only male patients, as carriers are typically female, and patients with hemophilia A and B are more likely to have X-linked hereditary coagulation bleeding disorders. Persistent bleeding following a cut was the most common clinical characteristic in the current study (79.10%). Other bleeding manifestations included: hematemesis (33.44%), hematuria (31.73%), petechiae (22.45%), skin bleeds (16.40%), muscle bleeds (15.33%), post-traumatic bleeds (15.17%), epistaxis (10.68%), tooth extraction (3.25%), bleeding after tonsillectomy (3.26%), bleeding after circumcision (2.32%), and bleeding after cephalohematoma [ 17 ]. Treatment Modalities: The aPTT-based one-stage assay (OSA) is the most frequently used method for evaluating FIX activity, while the chromogenic test is used less often [58]. In contrast, both assays may be required for hemophilia A to accurately diagnose and classify the severity of the condition. The OSA is the recognized method for FIX concentrate potency labeling according to the European Pharmacopoeia. It is a quick, easy-to-automate, low-cost method. However, it is associated with a significant degree of variability depending on the aPTT reagent and apparatus used. While these assays are useful for diagnosing patients and measuring FIX or FVIII plasma levels, they do not contribute to our understanding of the clinical heterogeneity of hemophilia [ 18 ]. Hemophilia is a disorder characterized by impaired thrombin production, with most thrombin being generated during clot formation, a process not measured by the fibrin-clotting endpoints typically used to assess hemostasis. Recently, there has been a growing focus on global hemostatic assays. Global assays, which are based on the viscoelastic properties of blood or thrombin generation, provide a more comprehensive view of thrombin generation and clot formation. These assays have the potential to offer a more objective measurement of the hemophilic phenotype and predict clinical responses, as they quantitatively measure several variables using real-time monitoring of the entire clotting process. This is particularly useful after treatment with bypassing agents or novel non-factor replacement therapies [ 19 ]. Conclusion Hemophilia B, a genetic bleeding disorder, presents with diverse clinical signs that require ongoing management. Primary care physicians are often the first point of contact for diagnosis and treatment. The symptoms of hemophilia B usually necessitate comprehensive and continuous care. However, specialized tests, such as factor concentration and mutation analysis, which are essential for diagnosing inherited bleeding disorders, are available only in a limited number of clinics in our demographic region. Earlier studies on hemophilia B in India primarily focused on hospital-based data, which failed to provide an accurate assessment of disease severity across broader populations. This study aims to address that gap by offering insights into the relationship between factor concentration levels and disease severity. It also provides valuable demographic and clinicopathological data on hemophilia B within the studied population. Declarations Ethics approval and consent to participate- The institutional ethical approval was taken from the ethical committee (No: Dean/2022/EC/3611) Institute of Medical Science, Banaras Hindu University. Consent for publication- The written informed consent was obtained from the patient/participant for publication. Availability of data and material- The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Authors' contributions : Chanda Hemaliya 1 , Lalit Prashant Meena 1 , Arun Kumar Singh 1 , Ajeet Kumar 2 , Akhtar Ali 2 , , Avijit Howlader 1 , Anupam Aich 1 ,Sandip Kumar 3 , Vineeta Gupta 4 , Ishan Kumar 5 , Chanda Hemaliya- Experimental work, Data collection, reviewing the literature, Data analysis, and manuscript writing. Lalit Prashant Meena- Supervised the study, conceived and designed the experiments; Arun Kumar Singh- Data analysis, reviewing the literature, Ajeet Kumar, Contributions to the manuscript: data analysis, Akhtar Ali, Contributions to the manuscript: data analysis, reviewing the literature. Avijit Howlader- Data analysis, reviewing the literature, manuscript writing, Anupam Aich: Data analysis, reviewing the literature, Sandip Kumar- Sample collection, Data analysis, manuscript writing. Vineeta Gupta- Data analysis, reviewing the literature. Ishan Kumar- Data analysis, reviewing the literature, Acknowledgments statemen t: I would like to thank hemophilia patients for their cooperation. Chanda Hemaliya is also grateful to CSIR, New Delhi, India, for funding through the CSIR NET JRF. Mr. ved Prakash Singh Ph.D. Research Scholars are thanked for their contribution to this paper. References Payal V, Sharma P, Goyal V, Jora R, Parakh M, Payal D (2016) Clinical profile of hemophilia patients in Jodhpur Region. Asian J Transfuse Sci 10:101–104 Pawan PK, Mahima Y, Vijai T, Manjula L (2021) Clinicopathological features of hemophilia in a tertiary care center of India. J Family Med Prim Care 10:295–299 Kulkarni S, Hegde R, Hegde S, Kulkarni SS, Hanagvadi S, Das KK et al (2021) Mutation analysis and characterization of F9 gene in haemophilia B population of India. Blood Res 56:252–258 Bolton PH, Pasi KJ (2003) Haemophilias A and B. 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Bangladesh J Child Health 37:90–96 Ahmad F, Kannan M, Ranjan R, Bajaj J, Choudhary P, Saxena R (2008) Inherited platelet function disorders versus other inherited bleeding disorders: An Indian overview. Thromb Res 121:835–841 Sahoo T, Naseem S, Ahluwalia J, Marwaha RK, Trehan A, Bansal D (2020) Inherited bleeding disorders in North Indian children: 14 years experience from a tertiary care center. Indian J Hematol Blood Transfus 36:330–336 Pawan PK, Mahima Y, Vijai T, Manjula L (2021) Clinicopathological features of hemophilia in a tertiary care center of India. J Family Med Prim Care 10:295–299 Ahmad F, Kannan M, Ranjan R, Bajaj J, Choudhary P, Saxena R (2008) Inherited platelet function disorders versus other inherited bleeding disorders: An Indian overview. Thromb Res 121:835–841 Hemaliya C, Meena LP, Singh AK, Kumar A, Ali A, Kumar S, Kumar I, Clinical Demographic, And Haematological Profile of Haemophilia Patients at Sir Sunder Lal Hospital Varanasi With CoE Haemoglobinopathies And Day Care Centre Hazendonk HC, Lock J, Mathôt RA, Meijer K, Peters M, Laros-van Gorkom BA et al (2016) Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications. J Thromb Haemost 14(3):468–478 Tjärnlund-Wolf A, Lassila R (2019) Phenotypic characterization of haemophilia B–Understanding the underlying biology of coagulation factor IX. Haemophilia 25(4):567–574 Dolan G, Benson G, Duffy A, Hermans C, Jiménez-Yuste V, Lambert T, Ljung R, Morfini M, Šalek SZ (2018) Haemophilia B: Where are we now and what does the future hold? Blood Rev 32(1):52–60 Additional Declarations The authors declare no competing interests. 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hemaliya","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYDACCSDmYWBIAFKMB4CknIEERIKHGC0MIC3GJGoB4sQNEgTcxT+7+dmDNzUMefxihx8ceNhml75duseA4UcNg4w5LkvuHDM3nHOMoVhydprBgcS25Nydc84YMPYcY+CxbMCuxUAiwUyahw3ontsJIC3MuRtu5Bgw8DYw8BgcwKUl/Zs0zz+GxP230z8AtdSnGwC1MP7FqyXHTJq3DWiLdA7IlsMJIC3M+GyRuJFTJjm3TyJxxu2cggMJ544b7pyRVnBY5pgETi38M9K3Sbz5ZpPYPzt948MfZdXy5hLJGx++qbGxx6UFZhmEYmSD0AfgIoTBH2IVjoJRMApGwUgCALGgXSNJAJwKAAAAAElFTkSuQmCC","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":true,"prefix":"","firstName":"Chanda","middleName":"","lastName":"hemaliya","suffix":""},{"id":394091517,"identity":"1f2d8526-4a4b-4e3f-abf4-574492e4ad8a","order_by":1,"name":"Prof. Lalit Prashant Meena","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"Prof.","middleName":"Lalit Prashant","lastName":"Meena","suffix":""},{"id":394091518,"identity":"950ed85d-bca0-4677-b483-f5d7127ae476","order_by":2,"name":"Dr. Arun Kumar Singh","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"Dr.","firstName":"Arun","middleName":"Kumar","lastName":"Singh","suffix":""},{"id":394091519,"identity":"f5fd2b7b-779d-4c54-97ce-7a0c899d5511","order_by":3,"name":"Ajeet kumar","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"Ajeet","middleName":"","lastName":"kumar","suffix":""},{"id":394091520,"identity":"21a05461-4f1b-4ea7-8e5b-2fb1a97e278b","order_by":4,"name":"Dr.Akhtar Ali","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"Dr.","firstName":"Akhtar","middleName":"","lastName":"Ali","suffix":""},{"id":394091521,"identity":"75073578-23e2-4ad1-8f40-04ab1c035b4a","order_by":5,"name":"Avijit Howlader","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"Avijit","middleName":"","lastName":"Howlader","suffix":""},{"id":394091522,"identity":"6f320556-306f-4bfa-a0d7-84c8a5cb323b","order_by":6,"name":"anupam Aich","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"anupam","middleName":"","lastName":"Aich","suffix":""},{"id":394091523,"identity":"ba87e1b1-85a5-4831-b540-fca89b9c9811","order_by":7,"name":"Prof. Sandip Kumar","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"Prof.","middleName":"Sandip","lastName":"Kumar","suffix":""},{"id":394091524,"identity":"9a1822c8-f171-4f08-ac93-7563d4cb97bf","order_by":8,"name":"Prof. Vineeta Gupta","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"Prof.","middleName":"Vineeta","lastName":"Gupta","suffix":""},{"id":394091525,"identity":"21bb563a-b677-4cf0-87da-139b287a11a6","order_by":9,"name":"Dr. Ishan Kumar","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"Dr.","firstName":"Ishan","middleName":"","lastName":"Kumar","suffix":""}],"badges":[],"createdAt":"2024-12-24 11:27:44","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5705863/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5705863/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72333207,"identity":"1c1ff819-f087-4362-a63e-cf2e578e3a54","added_by":"auto","created_at":"2024-12-25 15:19:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":898150,"visible":true,"origin":"","legend":"\u003cp\u003eShown bleeding in the knee joint and Ecchymotic Patches\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5705863/v1/421a204a2ca46a8e35d033c0.png"},{"id":72332965,"identity":"350b8fa2-c114-442d-a139-aa9b3a9f3f49","added_by":"auto","created_at":"2024-12-25 15:11:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":90055,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eshows Patients are distributed based on severity.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5705863/v1/62573a85e8adbc00d02e7383.png"},{"id":72334345,"identity":"c5272dfd-3c6b-400f-ae3a-489325b06213","added_by":"auto","created_at":"2024-12-25 15:35:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2498714,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5705863/v1/0057d734-27c7-45c9-8687-0bf66767d373.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eEtiology, Clinical Profile, and Demographics of Hemophilia B in Eastern India\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Key Points","content":"\u003cp\u003eFor the best possible care and management in the future, hemophilia B must be accurately and promptly diagnosed, considering the patient's factor level, family history, disease severity, and clinical characteristics. The current study gives doctors and other healthcare professionals crucial information for accurate early disease diagnosis and management.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eThe most common types of hemophilia are hemophilia A (classic hemophilia) and B (Christmas disease), which are prevalent hereditary disorders in India and worldwide. According to the World Federation of Hemophilia, approximately 400,000 people suffer from hemophilia globally, with India accounting for 80% of the cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Hemophilia A (HA) and hemophilia B (HB) are X-linked disorders caused by mutations in genes located on the long arms of the X chromosome (Xq28 for HA and Xq27 for HB). Hemophilia A accounts for about 80% of all cases, while hemophilia B constitutes 20%. Hemophilia A occurs in approximately one in 30,000 male births, while hemophilia B (HB) is found in about one in 10,000 male births. Factor deficiency, specifically Factor VIII and Factor IX, is one of the most prevalent coagulation irregularities. Hemophilia A and B are inherited in an X-linked recessive pattern [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Bleeding into muscles, joints, and soft tissues is a clinical hallmark of hemophilia. In impoverished and densely populated countries like India, where access to medical care is limited, individuals with hemophilia often rely on blood and blood products as a more affordable alternative to factor concentrates. This increases the risk of transfusion-transmitted infections [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the standard treatment for severe hemophilia is preventive therapy, which involves administering regular doses of clotting factors to prevent bleeding episodes. This approach reduces the long-term complications of the disease. Episodic treatment, which involves prompt administration of clotting factors during a bleeding episode, is also commonly used. In cases of mild hemophilia B, spontaneous bleeding is rare unless there is prior trauma to the affected area. The most common causes of bleeding in mild HB are injuries, surgical procedures, and dental operations.\u003c/p\u003e \u003cp\u003ePre-treatment is required to normalize FIX levels before undergoing surgery or dental procedures for all types of hemophilia. Treatment is now administered using recombinant FIX products, some of which have been modified to extend the half-life of FIX in circulation. Hemarthrosis is the most prevalent manifestation of hereditary coagulation disorders. Joint bleeding, along with the resulting damage to weight-bearing joints, is the most common and debilitating symptom of severe hemophilia. Bleeding into the joints can cause pain, swelling, inflammation, warmth, and restricted range of motion.\u003c/p\u003e \u003cp\u003eBleeding into joints can result in pain, swelling, inflammation, warmth, and a restricted range of motion. The most commonly affected joints include the knees, elbows, ankles, shoulders, wrists, and hips [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The incidence of spontaneous joint bleeding generally increases with age, reaching up to 60% by age 65. Recurrent joint bleeding often leads to hemophilic arthropathy, which is characterized by chronic proliferative synovitis and chronic osteochondral changes in major joints, primarily affecting the elbows, knees, and ankles (commonly referred to as \"index joints\"). Ecchymotic patches \u003cb\u003e[Figure No.1]\u003c/b\u003e are also observed in some cases. The most critical treatment strategy for managing hemophilia is the continuous intravenous administration of prophylactic hematological therapy to prevent recurrent hemarthroses. In situations where intravenous treatment is only available on demand, regular monitoring is essential for the early diagnosis and management of intra-articular bleeding episodes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Magnetic Resonance Imaging (MRI) scores are often used to assess radiological changes in the joints. This research aims to investigate the incidence and diagnostic characteristics of hereditary coagulation disorders, with a particular focus on hemophilia B, in eastern India [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eAims and Objective\u003c/h3\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eTo evaluate the Clinical profile, demographics, and etiology of hemophilia B patients in Eastern India\u003c/b\u003e\u003c/h2\u003e \u003c/div\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThe present cross-sectional study was conducted between 2021 and 2024. A total of 98 hemophilia B (HB) patients were included, with a mean age of 25 years. A predesigned proforma was used to record the complete medical history of the patients, including information on their age, gender, initial bleeding site, and family history. A semi-automated clot analyzer was used to perform a \"one-stage test\" for the factor assay. Factor concentrations were classified as follows: severe (\u0026lt;\u0026thinsp;1% or 0.01 IU/mL), moderate (1\u0026ndash;5% or 0.05 IU/mL), and mild (\u0026gt;\u0026thinsp;5%-40% or 0.05\u0026ndash;0.4 IU/mL) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003ePatients\u003c/strong\u003e \u003cp\u003eTo document clinical details, a thorough clinical examination, pertinent laboratory testing, and the patient's history were used.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion Criteria\u003c/h3\u003e\n\u003cp\u003ePatients with hemophilia B\u003c/p\u003e\n\u003ch3\u003eExclusion Criteria\u003c/h3\u003e\n\u003cp\u003e \u003cstrong\u003eInformed consent\u003c/strong\u003e \u003cp\u003ewas obtained from each patient and their family members, with ages ranging from \u0026lt;\u0026thinsp;1 year to \u0026gt;\u0026thinsp;30 years. The clinical profile and demographic characteristics of hemophilia B were evaluated through complete hematological investigations, including complete blood count (CBC), GBP, prothrombin time (PT), and activated partial thromboplastin time (APTT). Coagulation factor assay tests, X-rays of joints, ultrasonography of suspected muscles, and abdominal computed tomography (CT) scans were performed on selected severe patients based on their symptoms.\u003c/p\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe statistically significant differences in mean categorical variables were compared using the Student's t-test, one-way ANOVA, and the Chi-square test, and were analyzed. Statistical significance is defined as a P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e "},{"header":"Results","content":"\u003cp\u003eThis is a cross-sectional study. Out of the 98 patients, 39 (39.7%) had severe hemophilia, and 59 (60.2%) had moderate hemophilia [Table 1, Fig. 2]. Most respondents were aged between 21 and 30 years, with a mean age of 17.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 years.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003cstrong\u003eTable no.\u003c/strong\u003e 1 \u003cstrong\u003eShows the Patients are distributed based on severity.\u003c/strong\u003e\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth colspan=\"3\" align=\"left\"\u003e\n \u003cp\u003ePatients are distributed based on severity.\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSeverity of hemophilia\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of Patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSevere hemophilia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eModerate hemophilia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe majority of participants 72 (73.3%) were from rural areas, 32 (32.6%) had at least completed their primary education, 21 (21.4%) were enrolled in school, and 47.9% had a monthly family income of at least 15,000 BDT. Sociodemographic characteristics were consistent across the range of hemophilia severity. A family history of hemophilia was present in 75.5% of the participants. The median age at first bleeding and diagnosis was 5.0 and 6.0 years, respectively. According to the assessment, nearly 57.1% of the individuals were diagnosed with hemophilia at the time of their first bleeding. No significant differences were found between individuals with severe and moderate hemophilia \u003cstrong\u003e[Table\u0026nbsp;2].\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table No. 2 Sociodemographic characteristics and disease profile of the patients\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eSociodemographic characteristics and Disease Profile of the patients\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSeverity of Hemophilia\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (39.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(60.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(17.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026ndash;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(16.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (12.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (20.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(16.94%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u0026ndash;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (25.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (12.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72(73.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(74.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43(72.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(25.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(27.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLlliterate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre-schooler\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(32.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(32.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(20.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(15.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (13.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGraduate and Above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(9.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOccupation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eToddler\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStudent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(29.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(30.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJob\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBusiness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(34.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFarmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(81.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnemployed/dependent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMonthly Family Income\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;15,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(47.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(41.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15,000\u0026ndash;30,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(38.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(43.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;30,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFamily History\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75(76.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(79.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44(74.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(25.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian age at first bleeding (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge at diagnosis (year) Median\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eThe duration between the initial bleeding incident and the diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(27.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(12.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(15.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMissing Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable no. 3 clinical presentation and Investigation of hemophilia B patients\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tabc\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClinical manifestation and Investigation\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClinical Manifestation\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eSeverity of Hemophilia\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSevere (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eModerate (n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMode of Bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpontaneous\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter major trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter manor trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eJoint Swelling\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97 (98.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(97.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTarget Joint\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKnee\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78(79.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45(76.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKnee\u0026thinsp;+\u0026thinsp;Elbow\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(84.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(38.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnkle\u0026thinsp;+\u0026thinsp;Knee\u0026thinsp;+\u0026thinsp;Elbow\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41(41.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(44.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eShoulder\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(30.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHip\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSoft tissue/ Muscle swelling\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64(65.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(97.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(83.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(34.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(16.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMuscle wasting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97(98.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBleeding/ecchymosis from skin/ other orifices\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75(76.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35(89.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(79.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(20.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAccording to \u003cstrong\u003e[Table\u0026nbsp;3]\u003c/strong\u003e, all types of bleeding were present in every patient. The knee was the most frequently targeted joint (79.6%), followed by the knee plus elbow (57.1%). Muscle wasting was observed in 98.9% of patients, while 70.7% experienced bleeding/ecchymosis from the skin or other orifices, and 65.3% had soft tissue or muscle swelling. The majority of respondents (48.9%) could attend school or work with some restrictions, while 42.8% had limited ability to work or attend school. Additionally, 2.0% could only manage minimal self-care, and 5.1% could carry out activities without limitations. However, none of these traits showed significant differences between individuals with moderate and severe hemophilia. 92.8% of cases displayed changes in the affected joint on X-ray, 66.3% had muscle hematomas visible on ultrasound, and 28.6% had a retroperitoneal hemorrhage in the abdomen on ultrasonography \u003cstrong\u003e[Table\u0026nbsp;4].\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable no. 4 shows the Functional status of patients with hemophilia B\u003c/strong\u003e\u003c/p\u003e\u0026nbsp;\n \u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tabd\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFunctional Status\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnrestricted activity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFull school/work with some limitation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48(48.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(83.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRestricted school/work\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42(42.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(16.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRestricted self-care\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(2.04%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eInvestigation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65.6(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.8(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.3(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPTT (sec)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.20(45.1\u0026ndash;122.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.56(73.0\u0026ndash;99.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.3(49.5\u0026ndash;121.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eX-ray of the affected joint\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eJoint changes present\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91(92.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58(98.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo change\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMixing Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eUltra sonogram of the suspected muscle group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31(31.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMuscle hematoma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65(66.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(79.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37(62.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMissing value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eUltra sonogram of the whole abdomen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e69(70.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(53.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43(72.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRetroperitoneal hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28(28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(43.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(25.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003emissing value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable No. 5 shows the location and incidence of spontaneous bleeding by severity of hemophilia.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tabe\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eLocation and Incidence of Spontaneous Bleeding by Severity of Hemophilia (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClinical Manifestations\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSevere (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eModerate (n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpontaneous bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBruises and ecchymosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(39.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(56.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(28.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eJoint haemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97(98.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(87.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43(72.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnkle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89(90.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(82.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(57.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eElbow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89(90.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(82.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(57.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWrist Joint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(40.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(11.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHip joint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(36.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(43.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(32.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShoulders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(34.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(37.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMucosal Bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGum Bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(40.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEpistaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(23.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(30.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGastrointestinal bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematemesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetroperitoneal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOro-pharyngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(13.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(12.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMelaena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHaemoptysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMuscle hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50(51.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(40.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCalf Muscle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53(54.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScalp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(3.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFacial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(5.08%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIliopsoas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(36.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(46.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(30.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFlexor Muscle of the forearm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(30.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(23.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eButtock\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(32.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOcular Bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVitreous hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(10.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSubconjunctival hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(11.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(3.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenito-urinary bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(47.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(71.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(32.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e[Table No. 3]\u003c/strong\u003e and \u003cstrong\u003e[Figure No. 2]\u003c/strong\u003e display the location and incidence of spontaneous bleeding among the study\u0026apos;s hemophilia participants, categorized by severity. The average number of spontaneous bleeding incidents over the past two years for severe, moderate, and all hemophiliac participants was 5, 10, and 16, respectively. The knee joint was the most frequently affected (98.9%), followed by the ankle and elbow joints (90.8% each) [Table No. 5]. The knee joints had the highest median number of joint hemorrhage occurrences (12, range: 1\u0026ndash;40). Elbow joints followed, with a median of 9 occurrences per episode and a range of 1 to 32. Joint hemorrhages in the knee, elbow, and ankle were more common in severe hemophiliacs, with the knee joint being the most frequently affected (88.6%), followed by the elbow and ankle joints (64% each). The knee joint had the highest median number of occurrences (12, range: 1\u0026ndash;40), while the elbow joints had a median of 9 occurrences, with a range of 1 to 32. Severe hemophiliacs were more likely to experience knee joint bleeding, while moderate hemophiliacs had more frequent joint hemorrhages in the ankle, elbow, and shoulder. However, no statistically significant difference was observed. In terms of frequency, number of episodes, and range, the thigh muscle was the most commonly affected in moderate hemophiliacs compared to severe hemophiliacs. Again, no statistically significant difference was found. Nearly half of the patients in both groups experienced gum bleeding, with more severe patients experiencing a higher number of bleeding episodes. Melia was observed in both patient groups with almost equal frequency.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHemophilia is an X-linked genetic disorder caused by a mutation in the factor IX gene, leading to a bleeding disorder due to impaired coagulation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Hemophilia patients can experience mild, moderate, or severe illness, depending on the plasma levels of clotting factors. The severity of hemophilia influences the variety of bleeding manifestations, which can occur at any age. This study examines bleeding occurrences in individuals with moderate and severe hemophilia in terms of their locations and frequency, as well as their socio-demographic profiles. A total of 98 patients were included in the study, with an average age of 17.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 years. In our observation, the average age of symptom onset was 5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7 years in severe patients and 8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 years in moderate patients. According to Karim MA et al. (2013), the average age of onset was 15.8 years [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This study included only male patients. Of the 98 patients, 59 (60.2%) had moderate hemophilia B (HB) with a factor IX concentration of 1\u0026ndash;5%, while 39 (39.7%) had severe hemophilia B with a factor IX concentration of \u0026lt;\u0026thinsp;1%. According to Ahmad et al. (2008), 69.6% of hemophilia B patients had severe hemophilia, and 19.2% had moderate hemophilia [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Higher percentages of severe hemophilia cases (87% and 84%) were reported in studies by Sahoo et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and Pawan et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] for the years 2020 and 2024, respectively.\u003c/p\u003e \u003cp\u003eThe location of initial bleeding can be influenced by various factors. Hemarthrosis in the joints is the most typical presentation, observed in 97% of cases. According to Ahmad et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], 82% of hemophilia patients present with hemarthrosis as one of their primary symptoms. In the current study, joint bleeding (hemarthrosis) was the most prevalent clinical manifestation (57.3%), followed by skin bleeds (18%), muscle bleeds (10.7%), epistaxis (7.3%), and petechiae (6.7%). In contrast, Pawan et al. (2021) found that 88% of severe hemophilia B (HB) patients had hemarthrosis, and 96% had hematomas. Our study, however, found that 98.97% of all participants had hemarthrosis, with 87.17% of severe HB patients and 72.88% of moderate HB patients presenting with this symptom [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These differences may be due to variations in geographic areas and populations. This study included only male patients, as carriers are typically female, and patients with hemophilia A and B are more likely to have X-linked hereditary coagulation bleeding disorders. Persistent bleeding following a cut was the most common clinical characteristic in the current study (79.10%). Other bleeding manifestations included: hematemesis (33.44%), hematuria (31.73%), petechiae (22.45%), skin bleeds (16.40%), muscle bleeds (15.33%), post-traumatic bleeds (15.17%), epistaxis (10.68%), tooth extraction (3.25%), bleeding after tonsillectomy (3.26%), bleeding after circumcision (2.32%), and bleeding after cephalohematoma [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eTreatment Modalities:\u003c/h3\u003e\n\u003cp\u003eThe aPTT-based one-stage assay (OSA) is the most frequently used method for evaluating FIX activity, while the chromogenic test is used less often [58]. In contrast, both assays may be required for hemophilia A to accurately diagnose and classify the severity of the condition. The OSA is the recognized method for FIX concentrate potency labeling according to the European Pharmacopoeia. It is a quick, easy-to-automate, low-cost method. However, it is associated with a significant degree of variability depending on the aPTT reagent and apparatus used. While these assays are useful for diagnosing patients and measuring FIX or FVIII plasma levels, they do not contribute to our understanding of the clinical heterogeneity of hemophilia [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Hemophilia is a disorder characterized by impaired thrombin production, with most thrombin being generated during clot formation, a process not measured by the fibrin-clotting endpoints typically used to assess hemostasis. Recently, there has been a growing focus on global hemostatic assays. Global assays, which are based on the viscoelastic properties of blood or thrombin generation, provide a more comprehensive view of thrombin generation and clot formation. These assays have the potential to offer a more objective measurement of the hemophilic phenotype and predict clinical responses, as they quantitatively measure several variables using real-time monitoring of the entire clotting process. This is particularly useful after treatment with bypassing agents or novel non-factor replacement therapies [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHemophilia B, a genetic bleeding disorder, presents with diverse clinical signs that require ongoing management. Primary care physicians are often the first point of contact for diagnosis and treatment. The symptoms of hemophilia B usually necessitate comprehensive and continuous care. However, specialized tests, such as factor concentration and mutation analysis, which are essential for diagnosing inherited bleeding disorders, are available only in a limited number of clinics in our demographic region. Earlier studies on hemophilia B in India primarily focused on hospital-based data, which failed to provide an accurate assessment of disease severity across broader populations. This study aims to address that gap by offering insights into the relationship between factor concentration levels and disease severity. It also provides valuable demographic and clinicopathological data on hemophilia B within the studied population.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate-\u003c/strong\u003e The institutional ethical approval was taken from the ethical committee (No: Dean/2022/EC/3611) Institute of Medical Science, Banaras Hindu University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication-\u003c/strong\u003e The written informed consent was obtained from the patient/participant for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material-\u003c/strong\u003e The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChanda Hemaliya\u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e, Lalit Prashant Meena\u003cstrong\u003e\u003csup\u003e1\u0026nbsp;\u003c/sup\u003e,\u0026nbsp;\u003c/strong\u003eArun Kumar Singh\u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e, Ajeet Kumar \u003cstrong\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e, Akhtar Ali\u003cstrong\u003e\u003csup\u003e2\u003c/sup\u003e,\u003c/strong\u003e , Avijit Howlader\u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e, \u0026nbsp;Anupam Aich\u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e,Sandip Kumar\u003cstrong\u003e\u003csup\u003e3\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e, Vineeta Gupta\u003cstrong\u003e\u003csup\u003e4\u003c/sup\u003e,\u0026nbsp;\u003c/strong\u003eIshan Kumar\u003cstrong\u003e\u003csup\u003e5\u003c/sup\u003e\u003c/strong\u003e,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChanda Hemaliya- Experimental work, Data collection, reviewing the literature, Data analysis, and manuscript writing. Lalit Prashant Meena- Supervised the study, conceived and designed the experiments; Arun Kumar Singh- Data analysis, reviewing the literature, Ajeet Kumar, Contributions to the manuscript: \u0026nbsp;data analysis, Akhtar Ali, Contributions to the manuscript: \u0026nbsp;data analysis, reviewing the literature.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Avijit Howlader- Data analysis, reviewing the literature, manuscript writing, Anupam Aich: Data analysis, reviewing the literature, Sandip Kumar- Sample collection, Data analysis, manuscript writing. Vineeta Gupta- Data analysis, reviewing the literature. Ishan Kumar- Data analysis, reviewing the literature,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments statemen\u003c/strong\u003et: \u0026nbsp; I would like to thank hemophilia patients for their cooperation. Chanda Hemaliya is also grateful to CSIR, New Delhi, India, for funding through the CSIR NET JRF. Mr. ved Prakash Singh Ph.D. Research Scholars are thanked for their contribution to this paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePayal V, Sharma P, Goyal V, Jora R, Parakh M, Payal D (2016) Clinical profile of hemophilia patients in Jodhpur Region. Asian J Transfuse Sci 10:101\u0026ndash;104\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePawan PK, Mahima Y, Vijai T, Manjula L (2021) Clinicopathological features of hemophilia in a tertiary care center of India. J Family Med Prim Care 10:295\u0026ndash;299\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKulkarni S, Hegde R, Hegde S, Kulkarni SS, Hanagvadi S, Das KK et al (2021) Mutation analysis and characterization of F9 gene in haemophilia B population of India. Blood Res 56:252\u0026ndash;258\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBolton PH, Pasi KJ (2003) Haemophilias A and B. Lancet 361:1801\u0026ndash;1809\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhattacharya DK (2006) Haemophilia in the Indian scenario. Int J Hum Genet ;633\u0026ndash;639\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeena L, Kumar S, Sinha S, Bharti A, Gupta V, Shukla J (2019) A study will be conducted to determine the prevalence, clinical profile, and incidence of the formation of inhibitors in patients with hemophilia in the northeastern part of India. J Family Med Prim Care 8:2463\u0026ndash;2467\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodriguez-Merchan EC (2010) Musculoskeletal complications of hemophilia. HSS J 6:37\u0026ndash;42\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValentino LA (2010) Blood-induced joint disease: the pathophysiology of hemophilic arthropathy. J Thromb Haemost 8:1895\u0026ndash;1902\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHilliard P, Funk S, Zourikian N et al (2006) Hemophilia joint health score reliability study. Haemophilia 12:518\u0026ndash;525\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePettersson H, Ahlberg A, Nilsson IM (1980) A radiological classification of hemophilic arthropathy. Clin Orthop Relat Res 149:153\u0026ndash;159\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarim MA, Siddique R, Jamal CY, Islam A (2013) Clinical profile of hemophilia in children in a tertiary care hospital. Bangladesh J Child Health 37:90\u0026ndash;96\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmad F, Kannan M, Ranjan R, Bajaj J, Choudhary P, Saxena R (2008) Inherited platelet function disorders versus other inherited bleeding disorders: An Indian overview. Thromb Res 121:835\u0026ndash;841\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahoo T, Naseem S, Ahluwalia J, Marwaha RK, Trehan A, Bansal D (2020) Inherited bleeding disorders in North Indian children: 14 years experience from a tertiary care center. Indian J Hematol Blood Transfus 36:330\u0026ndash;336\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePawan PK, Mahima Y, Vijai T, Manjula L (2021) Clinicopathological features of hemophilia in a tertiary care center of India. J Family Med Prim Care 10:295\u0026ndash;299\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmad F, Kannan M, Ranjan R, Bajaj J, Choudhary P, Saxena R (2008) Inherited platelet function disorders versus other inherited bleeding disorders: An Indian overview. Thromb Res 121:835\u0026ndash;841\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHemaliya C, Meena LP, Singh AK, Kumar A, Ali A, Kumar S, Kumar I, Clinical Demographic, And Haematological Profile of Haemophilia Patients at Sir Sunder Lal Hospital Varanasi With CoE Haemoglobinopathies And Day Care Centre\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHazendonk HC, Lock J, Math\u0026ocirc;t RA, Meijer K, Peters M, Laros-van Gorkom BA et al (2016) Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications. J Thromb Haemost 14(3):468\u0026ndash;478\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTj\u0026auml;rnlund-Wolf A, Lassila R (2019) Phenotypic characterization of haemophilia B\u0026ndash;Understanding the underlying biology of coagulation factor IX. Haemophilia 25(4):567\u0026ndash;574\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDolan G, Benson G, Duffy A, Hermans C, Jim\u0026eacute;nez-Yuste V, Lambert T, Ljung R, Morfini M, Šalek SZ (2018) Haemophilia B: Where are we now and what does the future hold? Blood Rev 32(1):52\u0026ndash;60\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Banaras Hindu University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Epidemiology, F9 gene, hemophilia B, Varanasi, Utter Pradesh","lastPublishedDoi":"10.21203/rs.3.rs-5705863/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5705863/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: The most common severe inherited hemorrhagic disease is hemophilia, which means \"love of blood.\" Deficiencies in Factors VIII and IX cause hemophilia, with inadequate levels or malfunctioning of these factors being the primary causes of hemophilia A and B, respectively. This study aims to assess the incidence and characteristics of inherited coagulation disorders, particularly hemophilia B.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe present investigation aims to evaluate the incidence and clinical traits of congenital anticoagulation diseases, specifically hemophilia B.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e: The study included 98 Hemophilia B patients with a mean age of 25. Medical histories were recorded using a predesigned Performa, covering age, gender, bleeding site, and family history.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e The study included 98 hemophilia B patients, with 39 having severe and 59 moderate forms. The majority (60.2%) had moderate hemophilia, while 39.7% had the severe type. Most patients (17.4 ± 10.5 years) were aged 21-30, with the mean age of onset being 17.4±10.5 years for severe hemophilia and 8.6±4.43 years for moderate cases. Knee joints were the most affected, found in 79.5% of cases and accounting for 98.9% of target joint infections, followed by elbow joints at 90.8%. Regular factor IX replacement was needed in 39.7% of severe cases. This highlights the importance of early diagnosis and treatment for managing joint-related complications in hemophilia B patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The current study examines hemophilia B's sociodemographic and clinic-pathological characteristics. Early diagnosis may be beneficial only when the spectral manifestation of hemophilia B in the community is known.\u003c/p\u003e","manuscriptTitle":"Etiology, Clinical Profile, and Demographics of Hemophilia B in Eastern India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-25 15:11:46","doi":"10.21203/rs.3.rs-5705863/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c819cdab-0ab3-48f3-b8e1-2309d3a1d844","owner":[],"postedDate":"December 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":42004579,"name":"Hematology"}],"tags":[],"updatedAt":"2024-12-25T15:11:46+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-25 15:11:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5705863","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5705863","identity":"rs-5705863","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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