specialist in Belgium is kathleen freson, at the KUL

Some genetic polymorphisms have been proposed. Among them the most important seam to be: PLA1A2 platelet glycoprotein polymorphism:

https://www.researchgate.net/publication/215640037_The_thrombin_generation_is_associated_with_the_PIA1A2_beta3_integrin_polymorphism_in_aspirin-treated_patients_with_coronary_artery_disease_a_role_of_statins?ev=prf_pub

and E-selectin gene polymorphism (S149R):

https://www.researchgate.net/publication/51558129_Effect_of_the_E-selectin_gene_polymorphism_(S149R)_on_platelet_activation_and_adverse_events_after_coronary_artery_surgery?ev=prf_pub

Please see also more predominant papers:

1. Feng D, Lindpaintner K, Larson MG, et al. Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol. 1999; 19: 1142–1147.

2. Ridker PM, Hennekens CH, Schmitz C. et al. PlA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet1997; 349: 385–388.

3. Bennett JS. Structure and function of the platelet integrin αIIbß3 J Clin Invest. 2005; 115: 3363-3369.

4. Vijayan KV, Goldschmidt-Clermont PJ, Christine Roos, Bray PF. The PlA2 polymorphism of integrin ß3 enhances outside-in signaling and adhesive functions J Clin Invest. 2000; 105: 793 - 802.

5. Wenzel K, Hanke R, Speer A. Polymorphism in the human E-selectin gene detected by PCR-SSCP. Hum Genet 1994;94:452–3.

6. Jilma B, Kovar FM, Hron G et al. Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selectin gene associated with recurrent venous thromboembolism. Arch Intern Med. 2006; 166: 1655-9.

Article The thrombin generation is associated with the PIA1/A2 beta3...

Article Effect of the E-selectin Gene Polymorphism (S149R) on Platel...

Some genetic polymorphisms have been proposed. Among them the most important seem to be: PLA1A2 platelet glycoprotein polymorphism. Two of my group referencies:

1. Μutations and polymorphisms in genes affecting hemostasis proteins and homocysteine metabolism in children with arterial ischemic stroke

Komitopoulou A, Platokouki H, Kapsimali Z, Pergantou H, Adamtziki E, Aronis S

Cerebrovasc Dis 2006;22:13-20

.2. Mutations and polymorphisms in genes affecting haemostasis components in children with thromboembolic events

Komitopoulou A, Platokouki H, Kapsikali Z, Moschovi M, Kattamis A, Pergantou H, Aronis S

Pathophysiol Haemost Thromb 2006;35(5):392-397

A publication from the Cambridge Platelet group:

Cedric Ghevaert; Alexandre Salsmann; Nicholas A Watkins; Elisabeth Schaffner-Reckinger; Angela Rankin; Stephen F Garner; Jonathan Stephens; Graham A Smith; Najet Debili; William Vainchenker; et al. A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the alphaIIbbeta3 integrin and cosegregates dominantly with abnormal proplatelet formation and macrothrombocytopenia. Blood 111, 3407 (2008).

Yes, PLA1A2 glycoprotein gene polymorphism is well known (as the others), but I specify my question. Is there any known association between the hereditary hyperaggregability to ADP and epinephrine with family occurence and genetic abnormalities?

Anne, thank you very much for an interesting contact. Can Kathleen Freson write us something about PEAR1 rs12566888 polymorphism in pregnancy loss in relation with platelet hyperaggregability to ADP and Epinephrine?

A comprehensive review of this subject matter was discussed in :

' Genetic risk factors of venous thrombosis' by RF Franco and PH Reitsma in Human Genetics, 109 (4), 369-384, 2001.

For questions to kathleen freson, you should ask her directly. Best regards!

In the GeneSTAR study of 2076 healthy persons, the G allele ( SNP located at a predicted leucine zipper factor binding site (AliBaba2.1) - possibly PEAR 1 gene regulation by the variant) was responsible for platelet hyperaggregability in response to all agonists before and after aspirin therapy.

I'm sure you've already have read the 2012 study looking at SPS patients for genetic variability of the GP6 gene (www.ncbi.nlm.nih.gov/pubmed/22821001).

Kleinfelter Syndrome (XXY) patients also have increased susceptibility to DVT speculated to be due to the associated hypogonadism and increased plasminogen activator inhibitor-1 (PAI-1) activity - I read a case study about this (also from 2012) but didn't keep the reference, probably easy to find though. All the best.

Dear David,

Thank you very much for the stimulating suggestion about Klineferters sy. Did you mean this articles: Gattringer C, Scheurecker C, Höpfl R, Müller H. Acta Derm Venereol. 2010 Nov;90(6):612-5. doi: 10.2340/00015555-0949.

Higgins EJ, Tidman MJ, Savidge GF, Beard J, MacDonald DM. Platelet hyperaggregability in two patients with Klinefelter’s syndrome complicated by leg ulcers. Br J Dermatol 1989; 120: 322.

Veraart JC, Hamulyak K, Neumann HA, Engelen J. Increased plasma activity of plasminogen activator inhibitor 1 (PAI-1) in two patients with Klinefelter’s syndrome complicated by leg ulcers. Br J Dermatol 1994; 130: 641–644.

Unfortunaletlly sticky platelet syndrome is more prevalent than Klineferters sy. and affects also person without this abnormality. However there could be some common genetic features.

May I have a question? Would you like to join us in studing this interesting issue?

Not to detract from all the foregoing discussion regarding genetic predispositions, there are additional recently identified risks that are more generally widespread.

Have you considered the role of extracellular DNA traps, as a response to bacteria or to inflammatory cytokines? Histones are very strongly thrombogenic.

The following paper may help: 2010.09.07.pnas.107(36).15880