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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2016

Open Access 01-12-2016 | Research

Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration

Authors: Albert Busch, Sabine Hoffjan, Frauke Bergmann, Birgit Hartung, Helena Jung, Daniela Hanel, Andeas Tzschach, Janos Kadar, Yskert von Kodolitsch, Christoph-Thomas Germer, Heiner Trobisch, Erwin Strasser, René Wildenauer

Published in: Orphanet Journal of Rare Diseases | Issue 1/2016

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Abstract

Background

The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations.

Results

22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity.

Conclusion

The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.
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Literature
1.
2.
De Paepe A, Malfait F. The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet. 2012;82(1):1–11.CrossRefPubMed
3.
Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. 1998;77(1):31–7.CrossRefPubMed
4.
Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, et al. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet. 1988;29(3):581–94.CrossRefPubMed
5.
6.
De Felice C, Bianciardi G, Dileo L, Latini G, Parrini S. Abnormal oral vascular network geometric complexity in Ehlers-Danlos syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98(4):429–34.CrossRefPubMed
7.
Lum YW, Brooke BS, Black 3rd JH. Contemporary management of vascular Ehlers-Danlos syndrome. Curr Opin Cardiol. 2011;26(6):494–501.CrossRefPubMed
8.
Oderich GS, Panneton JM, Bower TC, Lindor NM, Cherry KJ, Noel AA, Kalra M, Sullivan T, Gloviczki P. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005;42(1):98–106.CrossRefPubMed
9.
Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342(10):673–80.CrossRefPubMed
10.
Bergqvist D, Bjorck M, Wanhainen A. Treatment of vascular Ehlers-Danlos syndrome: a systematic review. Ann Surg. 2013;258(2):257–61.CrossRefPubMed
11.
Busch A, Suellner J, Anger F, Meir M, Kickuth R, Lorenz U, Wildenauer R. Critical care of kyphoscoliotic type Ehlers-Danlos syndrome with recurrent vascular emergencies. VASA Zeitschrift fur Gefasskrankheiten. 2014;43(3):216–21.CrossRefPubMed
12.
Horowitz MB, Purdy PD, Valentine RJ, Morrill K. Remote vascular catastrophes after neurovascular interventional therapy for type 4 Ehlers-Danlos Syndrome. AJNR Am J Neuroradiol. 2000;21(5):974–6.PubMed
13.
Malfait F, De Paepe A. Bleeding in the heritable connective tissue disorders: mechanisms, diagnosis and treatment. Blood Rev. 2009;23(5):191–7.CrossRefPubMed
14.
Asherson RA, Bosman C, Tikly M, Spiro F, Pope FM. Ehlers-Danlos syndrome type IV in a young man. J Rheumatol. 2006;33(10):2091–6.PubMed
15.
Stine KC, Becton DL. DDAVP therapy controls bleeding in Ehlers-Danlos syndrome. J Pediatr Hematol Oncol. 1997;19(2):156–8.CrossRefPubMed
16.
Anstey A, Mayne K, Winter M, Van de Pette J, Pope FM. Platelet and coagulation studies in Ehlers-Danlos syndrome. Br J Dermatol. 1991;125(2):155–63.CrossRefPubMed
17.
Calatzis A, Heesen M, Heesen M, Spannagl M. [Point-of-care testing of hemostatic alterations in anaesthesia and intensive care]. Anaesthesist. 2003;52(3):229–37.CrossRefPubMed
18.
Lindsay H, Lee-Kim YJ, Srivaths LV: Perioperative Hemostatic Management in Ehlers-Danlos Syndrome: A Report of 2 Cases and Literature Review. Journal of pediatric hematology/oncology 2015
19.
Ong KT, Perdu J, De Backer J, Bozec E, Collignon P, Emmerich J, Fauret AL, Fiessinger JN, Germain DP, Georgesco G, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet. 2010;376(9751):1476–84.CrossRefPubMed
20.
Hurst BS, Lange SS, Kullstam SM, Usadi RS, Matthews ML, Marshburn PB, Templin MA, Merriam KS. Obstetric and gynecologic challenges in women with Ehlers-Danlos syndrome. Obstet Gynecol. 2014;123(3):506–13.CrossRefPubMed
21.
Vo KT, Grooms L, Klima J, Holland-Hall C, O’Brien SH. Menstrual bleeding patterns and prevalence of bleeding disorders in a multidisciplinary adolescent haematology clinic. Haemophilia. 2013;19(1):71–5.CrossRefPubMed
22.
Yenicesu I, Uckan D, Soysal A, Buyukasik Y, Gumruk F. Platelet release defect in a child with Ehlers-Danlos syndrome. Pediatr Hematol Oncol. 2000;17(2):193–4.CrossRefPubMed
23.
Estes JW. Platelet size and function in the heritable disorders of connective tissue. Ann Intern Med. 1968;68(6):1237–49.CrossRefPubMed
24.
Arneson MA, Hammerschmidt DE, Furcht LT, King RA. A new form of Ehlers-Danlos syndrome. Fibronectin corrects defective platelet function. JAMA. 1980;244(2):144–7.CrossRefPubMed
25.
Deliyannis AA, Kontopoulou-Griva I, Tsevrenis HV. Normal platelet aggregating properties of Ehlers-Danlos syndrome “collagen”. Thromb Diath Haemorrh. 1974;32(1):203–6.PubMed
26.
Karaca M, Cronberg L, Nilsson IM. Abnormal platelet-collagen reaction in Ehlers-Danlos syndrome. Scand J Haematol. 1972;9(5):465–9.PubMed
27.
Kashiwagi H, Riddle JM, Abraham JP, Frame B. Functional and ultrastructural abnormalities of platelets in Ehlers-Danlos Syndrome. Ann Intern Med. 1965;63:249–54.CrossRefPubMed
28.
Mendoza-Londono R, Chitayat D, Kahr WH, Hinek A, Blaser S, Dupuis L, Goh E, Badilla-Porras R, Howard A, Mittaz L, et al. Extracellular matrix and platelet function in patients with musculocontractural Ehlers-Danlos syndrome caused by mutations in the CHST14 gene. Am J Med Genet A. 2012;158A(6):1344–54.CrossRefPubMed
29.
Espanol I, Hernandez A, Pujol RM, Urrutia T, Pujol-Moix N. Type IV Ehlers-Danlos syndrome with platelet delta-storage pool disease. Ann Hematol. 1998;77(1–2):47–50.PubMed
30.
Cross JA, Cole BJ, Spatny KP, Sundman E, Romeo AA, Nicholson GP, Wagner B, Fortier LA. Leukocyte-reduced platelet-rich plasma normalizes matrix metabolism in torn human rotator cuff tendons. Am J Sports Med. 2015;43(12):2898–906.CrossRefPubMed
31.
Morissette R, Schoenhoff F, Xu Z, Shilane DA, Griswold BF, Chen W, Yang J, Zhu J, Fert-Bober J, Sloper L, et al. Transforming growth factor-beta and inflammation in vascular (type IV) Ehlers-Danlos syndrome. Circ Cardiovasc Genet. 2014;7(1):80–8.CrossRefPubMed
32.
Bertin P, Treves R, Julia A, Gaillard S, Desproges-Gotteron R. Ehlers-Danlos syndrome, clotting disorders and muscular dystrophy. Ann Rheum Dis. 1989;48(11):953–6.CrossRefPubMedPubMedCentral
33.
Clough V, MacFarlane IA, O’Connor J, Wood JK. Acquired von Willebrand’s syndrome and Ehlers-Danlos syndrome presenting with gastro-intestinal bleeding. Scand J Haematol. 1979;22(4):305–10.CrossRefPubMed
34.
Estes JW. Platelet abnormalities in heritable disorders of connective tissue. Ann N Y Acad Sci. 1972;201:445–50.CrossRefPubMed
35.
Kaplinsky C, Kenet G, Seligsohn U, Rechavi G. Association between hyperflexibility of the thumb and an unexplained bleeding tendency: is it a rule of thumb? Br J Haematol. 1998;101(2):260–3.CrossRefPubMed
36.
Faber P, Craig WL, Duncan JL, Holliday K. The successful use of recombinant factor VIIa in a patient with vascular-type Ehlers-Danlos syndrome. Acta Anaesthesiol Scand. 2007;51(9):1277–9.PubMed
37.
Mast KJ, Nunes ME, Ruymann FB, Kerlin BA. Desmopressin responsiveness in children with Ehlers-Danlos syndrome associated bleeding symptoms. Br J Haematol. 2009;144(2):230–3.CrossRefPubMed
38.
Balduini CL, Noris P, Belletti S, Spedini P, Gamba G. In vitro and in vivo effects of desmopressin on platelet function. Haematologica. 1999;84(10):891–6.PubMed
39.
Yen JL, Lin SP, Chen MR, Niu DM. Clinical features of Ehlers-Danlos syndrome. J Formos Med Assoc. 2006;105(6):475–80.CrossRefPubMed
40.
Dolan AL, Arden NK, Grahame R, Spector TD. Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry. Ann Rheum Dis. 1998;57(10):630–3.CrossRefPubMedPubMedCentral
41.
42.
Gerrits KH, Voermans NC, de Haan A, van Engelen BG. Neuromuscular properties of the thigh muscles in patients with Ehlers-Danlos syndrome. Muscle Nerve. 2013;47(1):96–104.CrossRefPubMed
43.
Voermans NC, Bonnemann CG, Lammens M, van Engelen BG, Hamel BC. Myopathy and polyneuropathy in an adolescent with the kyphoscoliotic type of Ehlers-Danlos syndrome. Am J Med Genet A. 2009;149A(10):2311–6.CrossRefPubMed
44.
Targher G, Pichiri I, Lippi G. Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin Thromb Hemost. 2012;38(1):114–24.CrossRefPubMed
45.
Wong MS, Leisegang MS, Kruse C, Vogel J, Schurmann C, Dehne N, Weigert A, Herrmann E, Brune B, Shah AM, et al. Vitamin D promotes vascular regeneration. Circulation. 2014;130(12):976–86.CrossRefPubMed
Metadata
Title
Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration
Authors
Albert Busch
Sabine Hoffjan
Frauke Bergmann
Birgit Hartung
Helena Jung
Daniela Hanel
Andeas Tzschach
Janos Kadar
Yskert von Kodolitsch
Christoph-Thomas Germer
Heiner Trobisch
Erwin Strasser
René Wildenauer
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2016
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-016-0491-2

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