TY - JOUR
T1 - Bleeding symptoms in persons with rare bleeding disorders and a heterozygous genotype
T2 - data from the Rare Bleeding Disorders in the Netherlands study
AU - Willems, Sterre P E
AU - Cnossen, Marjon H
AU - van Es, Nick
AU - den Exter, Paul L
AU - Kruis, Ilmar C
AU - Maas, Dominique P M S M
AU - Meijer, Karina
AU - Nieuwenhuizen, Laurens
AU - Rijpma, Sanna
AU - Saes, Joline L
AU - Simons, Annet
AU - Schutgens, Roger E G
AU - Weiss, Marjan
AU - Blijlevens, Nicole M A
AU - van Heerde, Waander L
AU - Schols, Saskia E M
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/6
Y1 - 2025/6
N2 - BACKGROUND: Limited data exist on persons with rare bleeding disorders possessing a heterozygous genotype, as most studies focus on biallelic genotypes and more severe coagulation factor deficiencies. A growing body of evidence suggests that persons with a heterozygous genotype experience clinically relevant bleeding symptoms.OBJECTIVES: This study aimed to explore the incidence of bleeding symptoms and postoperative bleeding in persons with a heterozygous genotype.METHODS: This cross-sectional substudy of the Rare Bleeding Disorders in the Netherlands study (2017-2019) included persons with rare coagulation factor deficiencies and disorders of fibrinolysis with a heterozygous or biallelic genotype. Clinical data and laboratory samples were collected during a single study visit along with questionnaires.RESULTS: In total, 86 persons with a heterozygous genotype and 55 with a biallelic genotype were included. Median factor activity levels in persons with a heterozygous genotype approached 50% with considerable heterogeneity (range, 11%-93%). In 75%, persons with a heterozygous genotype reported bleeding severity of grade II or III. Female-specific bleeding was common. In total, 425 surgical procedures were performed. Persons with a heterozygous genotype were less likely to receive periprocedural treatment, and omission of periprocedural treatment was associated with postoperative bleeding in procedures with intermediate-high bleeding risk. Postoperative bleeding was comparable for persons with a heterozygous genotype (35%; 59/171) and a biallelic genotype (35%; 86/247; P = .926).CONCLUSION: In our population with rare bleeding disorders, the majority of persons possessing a heterozygous genotype exhibited spontaneous bleeding symptoms. Especially in intermediate-high risk procedures, a proactive approach to periprocedural hemostatic treatment in persons with a heterozygous genotype seems beneficial.
AB - BACKGROUND: Limited data exist on persons with rare bleeding disorders possessing a heterozygous genotype, as most studies focus on biallelic genotypes and more severe coagulation factor deficiencies. A growing body of evidence suggests that persons with a heterozygous genotype experience clinically relevant bleeding symptoms.OBJECTIVES: This study aimed to explore the incidence of bleeding symptoms and postoperative bleeding in persons with a heterozygous genotype.METHODS: This cross-sectional substudy of the Rare Bleeding Disorders in the Netherlands study (2017-2019) included persons with rare coagulation factor deficiencies and disorders of fibrinolysis with a heterozygous or biallelic genotype. Clinical data and laboratory samples were collected during a single study visit along with questionnaires.RESULTS: In total, 86 persons with a heterozygous genotype and 55 with a biallelic genotype were included. Median factor activity levels in persons with a heterozygous genotype approached 50% with considerable heterogeneity (range, 11%-93%). In 75%, persons with a heterozygous genotype reported bleeding severity of grade II or III. Female-specific bleeding was common. In total, 425 surgical procedures were performed. Persons with a heterozygous genotype were less likely to receive periprocedural treatment, and omission of periprocedural treatment was associated with postoperative bleeding in procedures with intermediate-high bleeding risk. Postoperative bleeding was comparable for persons with a heterozygous genotype (35%; 59/171) and a biallelic genotype (35%; 86/247; P = .926).CONCLUSION: In our population with rare bleeding disorders, the majority of persons possessing a heterozygous genotype exhibited spontaneous bleeding symptoms. Especially in intermediate-high risk procedures, a proactive approach to periprocedural hemostatic treatment in persons with a heterozygous genotype seems beneficial.
KW - blood coagulation disorders
KW - fibrinolysis
KW - genotype
KW - hemostasis
KW - heterozygote
KW - inherited
UR - http://www.scopus.com/inward/record.url?scp=105001846097&partnerID=8YFLogxK
U2 - 10.1016/j.jtha.2025.02.030
DO - 10.1016/j.jtha.2025.02.030
M3 - Article
C2 - 40056984
SN - 1538-7933
VL - 23
SP - 1787
EP - 1799
JO - Journal of thrombosis and haemostasis : JTH
JF - Journal of thrombosis and haemostasis : JTH
IS - 6
ER -