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Editorials
mice compared with control mice.11 Moreover, a significant- ly reduced platelet half-life was observed for VWD2B platelets that have captured mutant VWF.11 Similar to obser- vations in PT-VWD, this shorter platelet half-life was not due to differences in the apoptotic properties detected in VWD2B platelets.12 It was recently found that GPIba upon binding to active VWF (e.g. VWD2B plasma) under physio- logical shear stress unfolds its mechanosensory domain near the platelet surface. This then triggers intracellular sig- naling, with exposure of β-galactose on the platelet surface that could favor platelet clearance via its interaction with the Ashwell–Morell receptor.13 A follow-up study did quan- tify β-galactose, as a marker for sialic acid removal, on
its high-molecular-weight multimers. N Engl J Med. 1982;306(6):326-
333.
3. Murata M, Russell SR, Ruggeri ZM, Ware J. Expression of the pheno-
typic abnormality of platelet-type von Willebrand disease in a recom- binant glycoprotein Ib alpha fragment. J Clin Invest. 1993;91(5):2133- 2137.
4. BuryL,MalaraA,MomiS,PetitoE,BalduiniA,GreseleP.Mechanisms of thrombocytopenia in platelet-type Von Willebrand Disease. Haematologica. 2019;104(7):1473-1481.
5. Othman M. Platelet-type von Willebrand disease: a rare, often misdi- agnosed and underdiagnosed bleeding disorder. Semin Thromb Hemost. 2011;37(5):464-469.
6. Nurden P, Debili N, Vainchenker W, et al. Impaired megakaryocy- topoiesis in type 2B von Willebrand disease with severe thrombocy- topenia. Blood. 2006;108(8):2587-2595.
7. Nurden AT, Federici AB, Nurden P. Altered megakaryocytopoiesis in von Willebrand type 2B disease. J Thromb Haemost. 2009;7(S1):277-
platelets from VWD2B patients and mice and confirmed 281.
increased levels.14 However, treatment of VWD2B mice with sialidase inhibitors was not associated with the recov- ery of a normal platelet count.14 Further studies are definite- ly required to clarify the exact cause of enhance platelet clearance expected for VWD2B and PT-VWD.
A comparison of studies in PT-VWD versus VWD2B that have focused on the cause of thrombocytopenia in these platelet disorders clearly show similarities, but also point to unanswered questions. Platelet formation and clearance defects have been described for both, but it remains unclear if any process is dominant for these diseases. Genetic stud- ies are required to diagnose these disorders.15
References
1. Miller JL, Cunningham D, Lyle VA, Finch CN. Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease. Proc Natl Acad Sci U S A. 1991;88(11):4761-4765.
2. WeissHJ,MeyerD,RabinowitzR,etal.Pseudo-vonWillebrand'sdis- ease. An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of
8. Kauskot A, Poirault-Chassac S, Adam F, et al. LIM kinase/cofilin dys- regulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B. JCI Insight. 2016;1(16):e88643.
9. Slayton WB, Patel M, Sola-Visner M, et al. Type 2B von Willebrand dis- ease associated with the release of platelet agglutinates from megakaryocytes in the bone marrow. J Pediatr Hematol Oncol. 2008;30(9):708-711.
10. Saba HI, Saba SR, Dent J, Ruggeri ZM, Zimmerman TS. Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocy- topenia, circulating platelet aggregates, and spontaneous platelet aggre- gation. Blood 1985;66(2):282-286.
11. CasariC,DuV,WuYP,etal.AccelerateduptakeofVWF/plateletcom- plexes in macrophages contributes to VWD type 2B-associated throm- bocytopenia. Blood. 2013;122(16):2893-2902.
12. BerrouE,KauskotA,AdamF,etal.ApoptoticPlateletEventsAreNot Observed in Severe von Willebrand Disease-Type 2B Mutation p.V1316M. PLoS One. 2015;10(12):e0143896.
13. Deng W, Xu Y, Chen W, et al. Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor. Nat Commun. 2016;7:12863.
14. Dupont A, Soukaseum C, Cheptou M, et al. Relevance of platelet desialylation and thrombocytopenia in type 2B von Willebrand dis- ease: preclinical and clinical evidence. Haematologica. 2019 Feb 28. [Epub ahead of print]
15. HamiltonA,OzeloM,LeggoJ,etal.Frequencyofplatelettypeversus type 2B von Willebrand disease. An international registry-based study. Thromb Haemost. 2011;105(3):501-508.
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