Main Article Content
Ankyrin repeat domain 26 protein, Blood platelets, Platelet disorder, familial, with associated myeloid malignancy, Pulmonary embolism, Thrombocytopenia.
Venous thrombosis affecting thrombocytopenic patients is challenging. We report the case of a thrombocytopenic woman affected by deep vein thrombosis and pulmonary embolism leading to the discovery of a heterozygous mutation in the gene encoding ankyrin repeat domain 26 (ANKRD26) associated with a heterozygous factor V (FV) Leiden mutation. This woman was diagnosed with left lower-limb deep vein thrombosis complicated by pulmonary embolism. Severe thrombocytopenia was observed. The genetic study evidenced a heterozygous FV Leiden mutation. Molecular study sequencing was performed after learning that her family had a history of thrombocytopenia. Previously described heterozygous mutation c-127C>A in the 5? untranslated region (5?UTR) of the ANKRD26 gene was detected in the patient, her aunt, and her grandmother. ANKRD26-related thrombocytopenia and thrombosis are rare. This is, to our knowledge, the first case reported in the medical literature. This mutation should be screened in patients with a family history of thrombocytopenia.
2. Sinzinger H, Kaliman J, O’Grady J. Platelet lipoxygenase defect (Wien-Penzing defect) in two patients with myocardial infaction. Am J Hematol 1991;36(3):202-205.
3. Kubisz P, Stanciakova L, Stasko J, Dobrotova M, Sterenova M, Ivankova J, Holly P. The sticky platelet syndrome: an important cause of life-threatening thrombotic complications. Expert Rev Hematol 2016 Jan;9(1):21-35. doi: 10.1586/17474086.2016.1121095. Epub 2015 Dec 9.
4. Althaus K, Greinacher A. MYH-9 related platelet disorders. Strategies for management and diagnosis. Transfus Med Hemother 2010;37(5):260-267. Epub 2010 Sep 15.
5. Zetterberg E, CarissonAlle MS, Najm J, Greinacher A. Thrombin generation in two families with MYH9 related platelet disorder. Platelets 2016;27(3):264-7. doi: 10.3109/09537104.2015.1064882. Epub 2015 Aug 6.
6. Nurden AT, Fiore M, Nurden P, Pilois X. Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability and animal models. Blood 2011 Dec 1;118(23):5996-6005. doi: 10.1182/blood-2011-07-365635. Epub 2011 Sep 13.
7. Ten Cate H, Brandjes DPM, Smits PHM, Van Mourik JA. The role of platelets in venous thrombosis: a patient with glanzmann’sthrombasthenia and a factor V Leiden mutation suffering from deep venous thrombosis. J Thromb Haem 2003; 1:394-395.
8. Rezende SM. Secondary prohylaxis with warfarin for recurrent thrombosis in a patient with Glanzmannthrombastenia and F5 G1691A. Br J Haematol2012;156:144-145.
9. Pippucci T, Savoia A, Perrotta S, Pujol-Noix N, Noris P, Castegnaro G, et al. Mutations in the 5? UTR of ANKRD26, the ankyrin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2. Am J Hum Genet 2011;88(1):115-120.
10. Noris P, Perrotta S, Seri M, Pecci A, Gnan C, Loffredo G et et al. Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia analysis of 78 patients from 21 families. Blood 2011;117(34):6673-6680.
11. Necchi V, Balduini A, Noris P, Barozzi S, Sommi P, Di Buduo C et al. Ubiquitin/proteasome rich particulate cytoplasmic structures (PaCs) in the platelets and megakaryocytes of ANKRD26-related thrombocytopenia. ThrombHaemost 2013;109 :263-71.
12. Balduini CL, SavoiaA,Seri M. Inherited thrombocytopenias frequently diagnosed in adults. JThrombHaemost 2013;11(6):1006-19.
13. Cerutti A, Custodi P, Duranti M, Cazzola M, Balduini CL.
Circulating thrombopoietin in reactive conditions behaves like an acute phase reactant. Clin Lab Haematol1999;21(4):271-275.
14. Marquez R, Hantel A, Lorentz R, Neistadt B, Wong J, Churpek JE et al. A new family with a germline ANKRD26 mutation and predisposition to myeloid malignancies. Leuk Lymphoma 2014;55:2945-6.
15. Al Daama SA, Housawi Y, Dridi W, Sager M, Otieno FG et al. A misssense mutation in ANKRD26 segregates with thrombocytopenia. Blood 2013;122:481-2.
16. Bluteau D, Balduini A, Balayn N, Currao M, Nurden P, Deswarte C et al. Thrombocytopenia associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation. J Clin Invest 2014;124(2):580-91.
17. Noris P, Favier R, Alessi MC, Geddis AE, Kunishima S, Heller PG, et al. ANKRD26-related thrombocytopenia and myeloid malignancies. Blood 2013;122(11):1987-9.
18. Babushok DV, Bessler M and Olson T. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. Leuk Lymphoma 2016; 57(3):520-36