Identifying hemophilia B carriers: Utility of aPTT, factor IX levels and ratios of factor IX to other Vitamin K dependent factors.
activated partial thromboplastin time
blood coagulation factors
factor IX
genetic carrier screening
hemophilia B
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
24 Jun 2024
24 Jun 2024
Historique:
revised:
24
05
2024
received:
11
10
2023
accepted:
27
05
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
aheadofprint
Résumé
Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status. To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status. In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated. Seventy-two female HB carriers (median age: 34 years; IQR 24-43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0-37.0] and 57 IU/dL [IQR 43-74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10-40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75. aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Canadian Pediatric Thrombosis and Hemostasis Network
Informations de copyright
© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.
Références
Carcao MD. The diagnosis and management of congenital hemophilia. Semin Thromb Hemost. 2012;38(7):727‐734.
Chaigneau M, Botros M, Grabell J, Hopman W, James P. Challenges and knowledge gaps facing hemophilia carriers today: perspectives from patients and health care providers. Res Pract Thromb Haemost. 2022;6(6):e12783.
James PD, Mahlangu J, Bidlingmaier C, et al. Evaluation of the utility of the ISTH‐BAT in haemophilia carriers: a multinational study. Haemophilia. 2016;22(6):912‐918.
Chaudhury A, Sidonio R Jr, Jain N, et al. Women and girls with haemophilia and bleeding tendencies: outcomes related to menstruation, pregnancy, surgery and other bleeding episodes from a retrospective chart review. Haemophilia. 2021;27(2):293‐304.
Staber J, Croteau SE, Davis J, Grabowski EF, Kouides P, Sidonio Jr RF. The spectrum of bleeding in women and girls with haemophilia B. Haemophilia. 2018;24(2):180‐185.
d'Oiron R, O'Brien S, James AH. Women and girls with haemophilia: lessons learned. Haemophilia. 2021;27(3):75‐81.
Becker J, Schwaab R, Moller‐Taube A, et al. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type‐dependent sex ratio of mutation frequencies. Am J Hum Genet. 1996;58(4):657‐670.
Kasper CK, Lin JC. Prevalence of sporadic and familial haemophilia. Haemophilia. 2007;13(1):90‐92.
Labarque V, Perinparajah V, Bouskill V, et al. Utility of factor VIII and factor VIII to von Willebrand factor ratio in identifying 277 unselected carriers of hemophilia A. Am J Hematol. 2017;92(6):E94‐E96.
Ljung RC, Sjorin E. Origin of mutation in sporadic cases of haemophilia A. Br J Haematol. 1999;106(4):870‐874.
Martensson A, Ivarsson S, Letelier A, Manderstedt E, Hallden C, Ljung R. Origin of mutation in sporadic cases of severe haemophilia A in Sweden. Clin Genet. 2016;90(1):63‐68.
Miller CH, Hilgartner MW, Aledort LM. Reproductive choices in hemophilic men and carriers. Am J Med Genet. 1987;26(3):591‐598.
Campbell S. Chapter 26 – Hemostasis. In: Clarke W, Marzinke MA, eds. Contemporary Practice in Clinical Chemistry (Fourth Edition). Academic Press; 2020:445‐467.
Paroskie A, Oso O, Almassi B, DeBaun MR. Both hemophilia health care providers and hemophilia a carriers report that carriers have excessive bleeding. J Pediatr Hematol Oncol. 2014;36(4):e224‐e230.
van Galen KPM, d'Oiron R, James P, et al. A new hemophilia carrier nomenclature to define hemophilia in women and girls: communication from the SSC of the ISTH. J Thromb Haemost. 2021;19(8):1883‐1887.
Plug I, Mauser‐Bunschoten EP, Brocker‐Vriends AH, et al. Bleeding in carriers of hemophilia. Blood. 2006;108(1):52‐56.
Olsson A, Hellgren M, Berntorp E, Ljung R, Baghaei F. Clotting factor level is not a good predictor of bleeding in carriers of haemophilia A and B. Blood Coagul Fibrinolysis. 2014;25(5):471‐475.
Shinozawa K, Amano K, Hagiwara T, et al. Genetic analysis of carrier status in female members of Japanese hemophilia families. J Thromb Haemost. 2021;19(6):1493‐1505.
Blanchette VS, Breakey VR, Revel‐Vilk S. SickKids Handbook of Pediatric Thrombosis and Hemostasis. S. Karger AG; 2013.
Akin M, Balkan C, Karapinar DY, Kavakli K. The influence of the ABO blood type on the distribution of von Willebrand factor in healthy children with no bleeding symptoms. Clin Appl Thromb Hemost. 2012;18(3):316‐319.
Albanez S, Ogiwara K, Michels A, et al. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms. J Thromb Haemost. 2016;14(5):953‐963.
Klarmann D, Eggert C, Geisen C, et al. Association of ABO(H) and I blood group system development with von Willebrand factor and Factor VIII plasma levels in children and adolescents. Transfusion. 2010;50(7):1571‐1580.
Vermeer C. Vitamin K: the effect on health beyond coagulation—an overview. Food Nutr Res. 2012;56.
Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(6):1‐158.
Peyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost. 2012;10(4):615‐621.