Abstract
Essentials How thrombocytopenia relates to bleeding in 22q11 deletion syndrome (22q11DS) is not clear. Bleeding severity, platelet count and volume, and GPIBB were examined in patients with 22q11DS. Macrothrombocytopenia and bleeding typified imperfectly overlapping subsets of 22q11DS patients. GPIBB hemizygosity does not cause macrothrombocytopenia or bleeding in patients with 22q11DS. Summary: Background and objectives Macrothrombocytopenia and bleeding are frequently associated with 22q11 deletion syndrome (22q11DS). GPIBB, which encodes the glycoprotein (GP) Ibβ subunit of GPIb–IX–V, is commonly deleted in patients with 22q11DS. Absence of functional GPIb–IX–V causes Bernard–Soulier syndrome, which is a severe bleeding disorder characterized by macrothrombocytopenia. Patients with 22q11DS are often obligate hemizygotes for GPIBB, and those with only a pathogenically disrupted copy of GPIBB present with Bernard–Soulier syndrome. The objective of this study was to determine how GPIBB hemizygosity and sequence variation relate to macrothrombocytopenia and bleeding in patients with 22q11DS who do not have Bernard-Soulier syndrome. Patients/methods We thoroughly characterized bleeding severity, mean platelet volume, platelet count and GPIBB copy number and sequence in patients with 22q11DS. Results and conclusions Macrothrombocytopenia and mild bleeding were observed in incompletely overlapping subsets of patients, and GPIBB copy number and sequence variation did not correlate with either macrothrombocytopenia or bleeding in patients with 22q11DS. These findings indicate that GPIBB hemizygosity does not result in either macrothrombocytopenia or bleeding in these patients. Alternative genetic causes of macrothrombocytopenia, potential causes of acquired thrombocytopenia and bleeding and ways in which platelet size, platelet count and GPIBB sequence information can be used to aid in the diagnosis and management of patients with 22q11DS are discussed.
Original language | English (US) |
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Pages (from-to) | 295-305 |
Number of pages | 11 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 17 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2019 |
Funding
This study was funded by awards from: the National Heart, Lung and Blood Institute from the National Institutes of Health (R35 HL-139937 to P. J. Newman and T32 HL-007209 to A. Moroi); the Hemostasis and Thrombosis Research Society/Novo Nordisk 2015 Mentored Research Award in Hemophilia or Rare Bleeding Disorders (to R. S. Bercovitz); Audrey's Fund, Children's Hospital of Wisconsin; the Medical College of Wisconsin; and the Comprehensive Center for Bleeding Disorders 340b Program and Blood Center Research Foundation of BloodCenter of Wisconsin, part of Versiti. The authors acknowledge all members of the Herma Heart Institute Pediatric Cardiac Thrombosis and Hemostasis Research Program. We specifically thank D. Woodrow Benson, H. Falet, G. Geddes and J. C. Gill for helpful discussions. This article is dedicated to the memory of Joan C. Gill.
Keywords
- 22q11 deletion syndrome
- Bernard–Soulier syndrome
- giant platelets
- glycoprotein Ib
- thrombocytopenia
ASJC Scopus subject areas
- Hematology