Case Report: Massive epistaxis from juvenile angiofibroma in an adolescent with severe haemophilia A

Epistaxis may be profuse in individuals with normal bleeding parameters, but in an individual with haemophilia, it may be life-threatening. It is even more dangerous when epistaxis is caused by an undetected concomitant juvenile angiofibroma, and only one such case has been reported in the English literature. We report another case, of an 18-year-old Filipino adolescent with severe haemophilia A who was referred for repeated massive epistaxis. The epistaxis had been attributed to his haemophilia and managed with nasal packing, multiple blood transfusions and Factor VIII administration. After two years of unsuccessful management, nasal endoscopy was performed for the first time, revealing an intranasal mass. Imaging showed a right intranasal vascular tumour supplied mainly by the right sphenopalatine artery. He subsequently underwent preoperative embolization and endoscopic excision of the tumour with Factor VIII transfused pre-, intra-, and post-operatively, and recombinant Factor VII added post-operatively. Final histopathology was consistent with juvenile angiofibroma. There has been no nasal obstruction or recurrence of epistaxis seven years since the surgery. Clinicians should be more meticulous in assessing epistaxis in any patient with a bleeding disorder and investigate more subtle symptoms such as nasal obstruction. Verification of the source by direct visualization and ancillary diagnostic techniques (such as imaging) when indicated should be the standard of care for all patients presenting with epistaxis, whether or not a concomitant bleeding disorder exists. A high index of suspicion for juvenile angiofibroma should be maintained in adolescent males with epistaxis and nasal obstruction.

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Successful immune tolerance in two children with severe haemophilia A

The Journal of Haemophilia Practice ◽

10.17225/jhp.00003 ◽

2013 ◽

Vol 1 (1) ◽

pp. 5-7

Author(s):

Bert Leenders

Keyword(s):

Factor Viii ◽

Case Studies ◽

Immune Tolerance ◽

Bleeding Disorder ◽

Haemophilia A ◽

Severe Haemophilia ◽

Igg Antibodies

Abstract Haemophilia A is an X-linked congenital bleeding disorder resulting from a deficiency of factor VIII (FVIII). Therapy to prevent or treat bleeding is by replacement of the missing FVIII. However, as a consequence of treatment, patients with HA may develop inhibitory IgG antibodies to FVIII, termed “inhibitors”. When this occurs, treatment becomes more complex and costly and morbidity increases. Inhibitor formation, occurring in up to 36% of patients with severe HA, is currently one of the most significant complications affecting patients with HA [1,2]. In these two case studies, the management of bleeds in patients with inhibitors, and the long-term inhibitor eradication will be discussed.

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Intranasal DDAVP induced increases in plasma von Willebrand factor alter the pharmacokinetics of high-purity factor VIII concentrates in severe haemophilia A patients

Haemophilia ◽

10.1046/j.1365-2516.1999.00282.x ◽

1999 ◽

Vol 5 (2) ◽

pp. 88 ◽

Cited By ~ 2

Author(s):

STEVEN R. DEITCHER

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

High Purity ◽

Haemophilia A ◽

Severe Haemophilia ◽

Factor Viii Concentrates ◽

Von Willebrand ◽

Willebrand Factor

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Management of Haemophilia in Sweden

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647991 ◽

1976 ◽

Vol 35 (03) ◽

pp. 510-521 ◽

Cited By ~ 13

Author(s):

Inga Marie Nilsson

Keyword(s):

Factor Viii ◽

Total Population ◽

Age Groups ◽

Factor Ix ◽

Haemophilia A ◽

Severe Haemophilia ◽

Haemophilia B ◽

Human Fraction ◽

Mild Haemophilia

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.

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Severe haemophilia A in a preterm girl with Turner syndrome: case report – a diagnostic and therapeutic challenge for a paediatrician (Part 2)

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01103-7 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Berendt Agnieszka ◽

Wójtowicz-Marzec Monika ◽

Wysokińska Barbara ◽

Kwaśniewska Anna

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Family History ◽

Factor Viii ◽

Turner Syndrome ◽

Factor Viii Inhibitor ◽

Haemophilia A ◽

Severe Haemophilia ◽

Prolonged Bleeding ◽

Increased Risk

Abstract Background Haemophilia A is an X-linked genetic condition which manifests itself mainly in male children in the first 2 years of life, during gross motor skill development. This disorder is rare in females. The clinical manifestation of severe haemophilia in preterm infants poses a great challenge to the therapeutic team. As extreme prematurity is linked to an increased risk of central nervous system or gastrointestinal bleeding, a well-informed and balanced treatment from the first days of life is crucial to prevent long-term damage. Haemophilia is most commonly caused by inheriting defective genes, and can also be linked to skewed X inactivation and Turner syndrome. The coincidental occurrence of haemophilia A and Turner syndrome is extremely rare, with only isolated cases described to date. Hence, a multidisciplinary approach is needed. Case presentation The authors report on a preterm girl (gestational age 28 weeks) diagnosed with haemophilia and Turner syndrome. The first manifestation of haemophilia was prolonged bleeding from injection sites on the second day of life. Indeterminate aPTT and factor VIII level < 1% confirmed the diagnosis of haemophilia A. Dysmorphic features which did not match the typical clinical picture of haemophilia, the female sex, and a negative paternal family history led to the diagnosis of Turner syndrome. While in hospital, the girl received multiple doses of recombinant factor VIII in response to prolonged bleedings from the injection sites and from a nodule on the girl’s head, and before and after retinal laser photocoagulation. No central nervous system or abdominal cavity bleeding was observed. The substitutive therapy was complicated by the development of factor VIII inhibitor (anti-factor VIII (FVIII) antibodies). Treatment was continued with recombinant factor VIIa. This article aims at demonstrating the complexity of the diagnostics and treatment of a preterm child with two genetic disorders. Conclusions Haemophilia should always be considered in the differential diagnosis of prolonged bleeding, even in patients with a negative family history. In the case of coinciding atypical phenotypic features, further diagnostics for another genetic disease are recommended. Infant care should follow current care standards, while considering certain individual features.

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Evaluation of EC50 of factor VIII as predictor of prophylaxis efficacy in patients with severe haemophilia A

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2018.12.003 ◽

2019 ◽

Vol 128 ◽

pp. 215-221

Author(s):

I. Fernández-Bello ◽

F. Rode ◽

M.T. Álvarez-Román ◽

N.V. Butta ◽

S. Rivas-Muñoz ◽

...

Keyword(s):

Factor Viii ◽

Haemophilia A ◽

Severe Haemophilia

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Orthotopic liver transplantation in a patient with severe haemophilia A and a high-titre factor VIII inhibitor from an antithrombin-deficient cadaveric donor

Haemophilia ◽

10.1111/hae.12086 ◽

2013 ◽

Vol 19 (2) ◽

pp. e96-e97 ◽

Cited By ~ 2

Author(s):

R. Gregg ◽

W. Lester ◽

S. Bramhall ◽

J. Wilde

Keyword(s):

Liver Transplantation ◽

Factor Viii ◽

Orthotopic Liver Transplantation ◽

High Titre ◽

Factor Viii Inhibitor ◽

Haemophilia A ◽

Severe Haemophilia ◽

Cadaveric Donor ◽

Viii Inhibitor

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Identification of a novel mutation in the factor VIII gene causing severe haemophilia A

BMC Hematology ◽

10.1186/s12878-018-0113-4 ◽

2018 ◽

Vol 18 (1) ◽

Author(s):

S. K. Nissen ◽

A. L. Laursen ◽

L. H. Poulsen ◽

T. H. Mogensen

Keyword(s):

Factor Viii ◽

Novel Mutation ◽

Haemophilia A ◽

Severe Haemophilia ◽

Factor Viii Gene

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Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study

BMJ Open ◽

10.1136/bmjopen-2018-022719 ◽

2019 ◽

Vol 9 (4) ◽

pp. e022719 ◽

Cited By ~ 2

Author(s):

Lisette M Schütte ◽

Marjon H Cnossen ◽

Reinier M van Hest ◽

Mariette H E Driessens ◽

Karin Fijnvandraat ◽

...

Keyword(s):

Factor Viii ◽

Combination Treatment ◽

Bleeding Risk ◽

Clotting Factor ◽

Haemophilia A ◽

Severe Haemophilia ◽

Registration Number ◽

Concentrate Treatment ◽

Factor Viii Concentrates ◽

Von Willebrand

IntroductionHaemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysisIn the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and disseminationThe DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences.Trial registration numberNTR5383; Pre-results.

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