scholarly journals Left paranasal hemophilic pseudotumor in a 5-year-old boy: A case report

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Saleh Yuguda ◽  
Ahmed Iya Girei ◽  
Rufai Abdu Dachi ◽  
Sani Adamu
Keyword(s):  
Case Report ◽  
Soft Tissue ◽  
Factor Viii ◽  
Hemophilia A ◽  
Severe Disease

Hemophilic pseudotumors are rare complications of hemophilia that are seen in 1-2% of patients commonly affecting patients with severe disease. Hemophilic pseudotumors occur as a result of recurrent poorly managed or untreated bleeding either in the soft tissue or bone. We report a 5-year-old boy with a previously undiagnosed hemophilia A who developed left paranasal swelling following a fall from a height. He was diagnosed with hemophilic pseudotumor and successfully managed conservatively with factor VIII replacement.

scholarly journals Early Prophylaxis Provides Continued Joint Protection in Severe Hemophilia A: Results of the Joint Outcome Continuation Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 382-382 ◽  
Author(s):  
Beth Boulden Warren ◽  
Dianne Thornhill ◽  
Jill Stein ◽  
Michael Fadell ◽  
Sharon Funk ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Board Of Directors ◽  
Research Funding ◽  
Hemophilia A ◽  
Joint Damage ◽  
Severe Hemophilia ◽  
Advisory Committees ◽  
Episodic Treatment ◽  
Bayer Healthcare

Abstract Background: The Joint Outcome Study (JOS) was a randomized controlled trial showing that, in severe hemophilia A, prophylactic factor VIII every other day starting prior to age 30 months leads to better joint outcomes at age 6 years than enhanced episodic treatment with factor VIII for bleeding1. After conclusion of the JOS, all participants were encouraged to continue on, or to transition to, prophylaxis. Here we describe the results of the Joint Outcome Continuation Study (JOS-C), which followed the participants of the JOS to age 18 years. Methods: All participants of the JOS were eligible for the JOS-C. MRIs of 6 index joints (right and left ankles, knees, and elbows), index joint physical exam scores using the Colorado Haemophilia Paediatric Joint Physical Examination Scale2 , estimates of joint bleeding episodes, and surgery information were collected. The primary endpoint, as in the initial JOS analysis, was evidence of hemophilia-related osteochondral joint damage on MRI, scored using the extended MRI scale3. Results: Of the 65 previous participants of the JOS, 37 gave informed consent for the JOS-C study, including 18 initially randomized to prophylaxis prior to age 30 months ("early prophylaxis"), and 19 initially randomized to enhanced episodic treatment who started prophylaxis at a mean age of 7.5 years (median 6.1, range 2.7-17.1, "delayed prophylaxis"). All initially on prophylaxis in the JOS continued on prophylaxis through the JOS-C. One participant (early prophylaxis arm) failed to complete an MRI, and four others (2 early and 2 delayed prophylaxis) had their MRIs excluded for technical reasons. Four participants (3 early prophylaxis and 1 delayed prophylaxis) developed high titer inhibitors during or shortly after the JOS and were analyzed separately. Osteochondral joint damage was defined as evidence of osteochondral damage on MRI or a need for joint surgery. The relative risk of osteochondral damage in those on delayed prophylaxis as compared to those on early prophylaxis was 6.5 (95% CI 1.3, 33.6; p=0.029). At age 18, 67% of those on early prophylaxis, and only 24% of those on delayed prophylaxis had zero index joints with osteochondral damage (Figure 1). Twenty-five percent of early prophylaxis and 47% of delayed prophylaxis participants had osteochondral damage to more than one joint. Most participants had some soft tissue changes on MRI, defined as effusion, synovial hypertrophy, or hemosiderin deposition. There was no difference in risk of soft tissue damage between initial treatment groups (p=0.48). Osteochondral damage scores were available for 3 patients with inhibitors: two with refractory inhibitors had osteochondral changes on at least one joint, and one with an inhibitor that tolerized within 3 months had no osteochondral damage. Total physical exam scores were also higher in the delayed prophylaxis arm (mean 22.6, standard deviation (SD) 15.5) than in the early prophylaxis arm (mean 16.2, SD 10.5), but this difference was not statistically significant (p=0.19). Conclusion: The JOS-C demonstrates that, in severe hemophilia A, initiation of prophylaxis prior to age 30 months provides continued protection against joint damage throughout childhood. Those who started on prophylaxis later in childhood had higher risk of joint damage at age 18. Initiation of factor VIII prophylaxis in the toddler years is critical to preventing osteochondral joint damage and should not be delayed. ReferencesManco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544.Hacker MR, Funk SM, Manco-Johnson MJ. The Colorado Haemophilia Paediatric Joint Physical Examination Scale: normal values and interrater reliability. Haemophilia. 2007;13(1):71-78.Hong W, Raunig D, Lundin B. SPINART study: validation of the extended magnetic resonance imaging scale for evaluation of joint status in adult patients with severe haemophilia A using baseline data. Haemophilia. 2016;22(6):e519-e526. Figure 1: Percentage of participants with zero joints with osteochondral damage at JOS exit (age 6 years) and JOS-C exit (age 18 years), excluding participants with inhibitors. Disclosures Warren: Bayer Healthcare: Research Funding; HTRS/Novo Nordisk: Research Funding; Bayer Hemophilia Awards Program Fellowship Project Award: Research Funding; CSL Behring Heimburger Award: Research Funding. Shapiro:Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Prometic Life Sciences: Consultancy, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Research Funding; Kedrion Biopharma: Consultancy, Research Funding; Bio Products Laboratory: Consultancy; Bioverativ, a Sanofi Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Healthcare: Other: International Network of Pediatric Hemophilia; Sangamo Biosciences: Consultancy; Octapharma: Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; OPKO: Research Funding; BioMarin: Research Funding. Recht:Shire: Research Funding; Biogen: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees. Manco-Johnson:Bayer AG: Honoraria, Research Funding; Novo Nordisk: Honoraria; Biogentek: Honoraria; CSL Behring: Honoraria; Baxalta, now part of Shire: Honoraria.

scholarly journals Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3015-3020
Author(s):  
VR Arruda ◽  
WC Pieneman ◽  
PH Reitsma ◽  
PP Deutz-Terlouw ◽  
JM Annichino-Bizzacchi ◽  
...  
Keyword(s):  
Factor Viii ◽  
Southern Blotting ◽  
Hemophilia A ◽  
Severe Disease ◽  
Point Mutations ◽  
Electrophoretic Pattern ◽  
Telomeric Region ◽  
Factor Viii Gene ◽  
Single Strand Conformational Polymorphism ◽  
Almost All

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.

scholarly journals Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3015-3020 ◽  
Author(s):  
VR Arruda ◽  
WC Pieneman ◽  
PH Reitsma ◽  
PP Deutz-Terlouw ◽  
JM Annichino-Bizzacchi ◽  
...  
Keyword(s):  
Factor Viii ◽  
Southern Blotting ◽  
Hemophilia A ◽  
Severe Disease ◽  
Point Mutations ◽  
Electrophoretic Pattern ◽  
Telomeric Region ◽  
Factor Viii Gene ◽  
Single Strand Conformational Polymorphism ◽  
Almost All

Abstract The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.

scholarly journals Large Cohort of Symptomatic Female Carriers of Hemophilia in an Extended Native American Family

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4700-4700
Author(s):  
Becki Berkowitz ◽  
Amber Federizo ◽  
Garrett E. Bergman ◽  
Paula J. Ulsh
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Board Of Directors ◽  
Gene Mutation ◽  
Hemophilia A ◽  
Clotting Factor ◽  
Factor Level ◽  
Advisory Committees ◽  
Low Levels ◽  
Female Carriers

Abstract Hemophilia A is an X-linked recessive genetic bleeding disorder resulting in a lack of clotting factor VIII. Although this disorder primarily affects males, a female who inherits one affected X chromosome from a parent becomes a carrier of hemophilia. While it is widely believed that carriers are asymptomatic, some of these women have mild hemophilia, defined by ISTH as a circulating factor VIII level > 0.5 to 0.40 IU/ml or 5 - 40 % of normal. (White et al Thromb Haemost 2001) Data demonstrates hemophilia A carriers have the same risk for bleeding as a male with mild hemophilia A at the corresponding factor level. Carriers report significantly more bleeding events than non-carriers from small wounds and after invasive procedures, and their bleeding tendency is inversely correlated to their factor level. (Plug et al Blood 2006) Carriers have been shown to demonstrate decreased joint range of motion, soft tissue and osteochondral changes on MRI, consistent with subclinical joint bleeds leading to structural abnormalities in their joints. (Gilbert et al Haemophilia 2014). Additionally, carriers have been shown to report higher scores on pictorial blood assessment charts, a semi-quantitative measure of menstrual blood loss. (Kadir et al Haemophilia 1999) We report here a unique patient population from our Owyhee Indian Health Hemophilia Treatment Center Outreach Clinic on the Duck Valley Indian Reservation in Owyhee, NV. On this reservation, a German Immigrant with hemophilia A married 2 women of the Shoshone Indian Tribe, and they had 14 children (8 females and 6 males). The family tree reveals after four generations there are currently 162 descendants with the same hemophilia A gene mutation, which has been identified. Factor VIII levels in the female family members range from 7% to 50%. The male hemophilia A patients are treated on demand with plasma-derived factor VIII products, currently Koate-DVI, for traumatic events, and prophylactically for medical or dental procedures, or surgery. Approximately 20-25% of the female carriers in this population have been treated with plasma-derived FVIII concentrates, currently Koate-DVI, for childbirth and surgeries. Additionally, all female carriers from teenage years to age 30 are treated with desmopressin acetate nasal spray (Stimate) for menorrhagia and are treated with oral aminocaproic acid (Amicar) for nose bleeds and soft tissue bleeds. Carriers of hemophilia A with factor VIII levels in the range observed in this family, particularly when symptomatic, should receive the diagnosis of "mild hemophilia". Their propensity for developing subclinical as well as clinical bleeding needs to be recognized to assure the receive treatment appropriate to their symptomatology. The low levels of FVIII observed in this family are likely due to extreme lyonization associated with their particular gene mutation. Familial low levels of FVIII can also be seen in some forms of type 2 von Willebrand Disease secondary to poor FVIII binding and a shortened half-life. However, since VWD is inherited in an autosomal recessive pattern, males would not selectively have the severity observed here. Optimal diagnostic and therapeutic strategies as well as many other aspects concerning mild hemophilia remain to be clarified. Additional studies to define these findings are underway. Disclosures Berkowitz: Pfizer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Speakers Bureau; Baxter: Speakers Bureau. Federizo:Emergent: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biogen Idec: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees. Bergman:Kedrion Biopharma: Employment. Ulsh:Kedrion Biopharma: Employment.

scholarly journals Collected Experience of the Pennsylvania Hemophilia Program

1977 ◽  
Author(s):  
S.S. Shapiro ◽  
M.E. Eyster ◽  
J. Lewis
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Severe Disease ◽  
Factor Ix ◽  
Hemophilia B ◽  
Home Therapy ◽  
Product Usage ◽  
Number Of Patients ◽  
Total State ◽  
Actual Prevalence

The Pennsylvania Hemophilia Program was initiated in March 1973, with the establishment of 9 Hemophilia Centers throughout the state. From an initial enrollment of 150, the number of patients has grown to 669 as of October 1976. Of these, 491 have Hemophilia A and 91 have Hemophilia B, a prevalence rate of 4.2 and 0.76 per 100,000, respectively in the total state population of some 11,800,000. A total of 210 patients (36%) with Hemophilia A or B are on home therapy programs. Two hundred fifty-five patients with Hemophilia A (52%) have severe disease, of whom 160 (63%) are on home therapy. Thirty-six patients with Hemophilia B (40%) have severe disease, of whom 22 (61%) are on home therapy. The remaining patients are treated in-center as necessary. Thirty-seven patients (7.5%) with Hemophilia A have inhibitors to Factor VIII, while only 1 of 91 patients with Hemophilia B has an inhibitor to Factor IX. Total Factor VIII and Factor IX usage for hemophiliacs in the past year was 15,040,000 and 1,282,000 biological units, respectively. At current prices, this represents $1.5 million for Factor VIII and approximately $150,000 for Factor IX. The average annual use of Factor VIII in severe Hemophilia A, excluding surgery, was 44,300 units/patient for patients on home therapy and 32,000 units/patient for patients on Center therapy. These figures are roughly comparable when corrected for patient age (14% of home therapy patients but 28% of Center therapy patients under the age of 10). These observations suggest that the actual prevalence rates of Hemophilia A and B are lower than previously quoted, that more patients with milder disease exist than expected and that home and Center therapy require equal product usage.

Effect on Joint Health of Routine Prophylaxis with Bayer’s Sucrose-Formulated Recombinant Factor VIII (rFVIII-FS) in Adolescents and Adults Previously Treated on Demand: MRI Analyses from the 3-Year Spinart Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2854-2854 ◽  
Author(s):  
Bjorn Lundin ◽  
Walter Hong ◽  
David Raunig ◽  
Sylvia Engelen ◽  
Charles Peterfy ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Structural Damage ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
On Demand ◽  
Routine Prophylaxis ◽  
Bayer Healthcare ◽  
Adolescents And Adults ◽  
Bleeding Episodes

Abstract Introduction: The benefits of primary prophylaxis with a factor VIII (FVIII) product in pediatric patients with severe hemophilia A are well established. Fewer data are available on the benefits of secondary prophylaxis (started after ≥2 joint bleeds but before the onset of documented joint disease). The 3-year SPINART study compared the efficacy and safety of routine prophylaxis vs on-demand treatment in adolescents and adults with severe hemophilia A, all of whom were treated with Bayer's sucrose-formulated recombinant FVIII (rFVIII-FS). Primary 3-year data on magnetic resonance imaging (MRI) joint assessments in SPINART have been recently reported. Here we present additional analyses of the SPINART 3-year MRI data. Methods: SPINART was a 3-year, randomized, controlled, parallel-group, open-label study conducted at 31 centers in the United States, Bulgaria, Romania, and Argentina. Male patients aged 12–50 years were eligible for SPINART if they had severe hemophilia A (FVIII:C <1%), ≥150 exposure days to any FVIII product, no current evidence or history of FVIII inhibitors, no prophylaxis for >12 consecutive months in the past 5 years, and 6–24 documented bleeding events or treatments in the previous 6 months. Eligible patients were randomly assigned 1:1 to on-demand treatment or prophylaxis. Patients assigned to prophylaxis received rFVIII-FS 25 IU/kg 3 times weekly; in patients with ≥12 bleeding episodes per year, dose increases of 5 IU/kg were permitted at years 1 and 2. All patients underwent MRI assessments at baseline and year 3 to evaluate the structure of 6 index joints (knees, ankles, elbows). Each MRI was read by 3 radiologists blinded to treatment assignment who independently completed the Extended MRI (eMRI) scale. The eMRI scale has 2 domains (soft tissue, osteochondral), and total eMRI scores range from 0 to 45 based on soft-tissue domain scores of 0 to 9 and osteochondral domain scores of 0 to 36; higher eMRI scores indicate greater joint structural damage. Change from baseline to year 3 in eMRI total score based on all 6 index joints was analyzed for the following baseline characteristics: region (US vs non-US), age (≤29 vs >29 years), and number of bleeding episodes in the previous 6 months (<8 vs ≥8). For patients with target joints, change from baseline to year 3 in eMRI scores in the worst target joint was analyzed using analysis of covariance adjusted for bleeding frequency during the prior 6 months. Results: Eighty-four patients (42 per treatment group) were enrolled in the SPINART study. Target joint analysis data for patients with target joints who completed the study were available for 28 on-demand and 20 prophylaxis patients. Least squares (LS) mean change from baseline to year 3 in eMRI total score in the analyzed target joint was 0.91 (95% CI, –0.06 to 1.88) and 1.09 (95% CI, 0.12–2.07) for the on-demand and prophylaxis groups, respectively; the difference was not statistically significant (LS mean difference, 0.18; 95% CI, –1.05 to 0.70; P=0.68). Results for the subgroup analyses are shown in the Table. Table.eMRI Total Score (Mean ± SD Change From Baseline to Year 3)Region Age, y Number of Bleeds in Past 6 MonthsUSNon-US≤29 >29 <8≥8On demand0.56±0.77 (n=14)1.24±1.35 (n=16)1.34±1.21 (n=18)0.29±0.70 (n=12)0.88±0.83 (n=4)0.93±1.20 (n=26)Prophylaxis1.05±1.36 (n=10)0.61±1.70 (n=22)0.46±1.88 (n=17)1.08±1.15 (n=15)0.91±0.69 (n=11)0.67±1.91 (n=21) Conclusions: Over 3 years of treatment, change in eMRI total score for target joints was similar for the on-demand and prophylaxis groups in SPINART. In the prophylaxis group, progression of joint structural damage after 3 years of treatment, as indicated by changes in eMRI total scores based on all 6 index joints, did not differ by number of bleeding episodes in the preceding 6 months but appeared to be less pronounced among younger patients compared with older patients and among those in the non-US group compared with the US group; results by age and region in the on-demand group were opposite of those seen in the prophylaxis group. These results must be interpreted with caution given the small patient numbers, the possibility that the study duration was not sufficient to show changes on MRI, and the fact that target joints were assessed. These results may underscore the importance of preventing target joint development and show that once a target joint has developed, MRI may not show reversal of pre-existing damage despite prophylaxis. Disclosures Lundin: Bayer: Received reimbursement from Bayer for symposium attendance, Received reimbursement from Bayer for symposium attendance Other; Bayer HealthCare : Employed by the Center for Medical Imaging and Physiology at Skåne University Hospital and is under contract to Bayer HealthCare for work performed for SPINART Other. Hong:Bayer HealthCare: Employment. Raunig:Employed by ICON Medical Imaging and is under contract to Bayer HealthCare for work performed for SPINART on the validation of the eMRI scale and Colorado Adult Joint Assessment Scale.: Consultancy. Engelen:Bayer HealthCare: Employment. Peterfy:Spire Sciences, Inc.: Owner of Spire Sciences, Inc., which provides central image analysis services to pharmaceutical and medical device companies. Other. Werk:Bayer HealthCare: Under contract to Bayer HealthCare for work performed for SPINART. Other. Manco-Johnson:Bayer: Membership on an entity's Board of Directors or advisory committees.

Acquired Hemophilia A: A Case Report

2019 ◽  
Vol 33 (4) ◽  
pp. 562-566 ◽  
Author(s):  
Mark Shen ◽  
Shan Wang ◽  
Julia Sessa ◽  
Adel Hanna ◽  
Alexander Axelrad ◽  
...  
Keyword(s):  
Case Report ◽  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viia ◽  
Spontaneous Mutation ◽  
Case Series ◽  
Rare Disorder ◽  
Bleeding Complications ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia

Hemophilia A, also known as factor VIII deficiency, is a rare disorder caused by an insufficient level of factor VIII, an essential clotting protein. Hemophilia A can be inherited or acquired. Inherited hemophilia A is caused by a mutation to the factor VIII gene on the X chromosome, which is commonly passed down from parents to children. However, in about one-third of cases, the cause is a spontaneous mutation in that gene. Acquired hemophilia A is due to an autoantibody to factor VIII, which is termed an inhibitor. This rare disorder can cause life-threatening bleeding complications. Management relies on a rapid and accurate diagnosis, control of bleeding episodes, and eradication of the inhibitor by immunosuppression therapy. Most treatment strategies are centered around anecdotal reports or small case series. This case report summarizes the successful treatment of a patient with acquired hemophilia A and major bleeding following a surgical procedure, with the use of desmopressin, recombinant factor VIIa, repeated doses of recombinant factor VIII, rituximab, and prednisone.

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