Research Institute in Oncology and Hematology

Sara Israels

Platelet Function

Contact: Dr Sara Israels MD FRCPC

Department Head Pediatric Hematology/Oncology
675 McDermot Ave
Winnipeg, Mb
R3E 0V9




Platelets

Our platelet research laboratory studies basic mechanisms of platelet function and investigates patients with inherited platelet function abnormalities, in conjunction with the clinical Haemostasis Laboratory. Our projects include:

1) Investigating the role of CD63, a member of the tetraspanin superfamily present on platelet dense granule and lysosomal granule membranes, and expressed on the platelet surface following activation, where it associates with the platelet integrin alphaIIb/beta3, and with the contractile platelet cytoskeleton. It plays a role in platelet spreading on adhesive surfaces. We are presently investigating how it modulates outside-in integrin-mediated signaling pathways. Understanding the role of CD63 has implications beyond platelet function, as it, and similar molecules, may be involved in tumour cell migration and metastases.

2) Studies of patients with inherited platelet function disorders, with a particular interest in families with a congenital deficiency of platelet dense granules.

3) Investigation of in vivo platelet activation in adolescents with diabetes mellitus

4) Development of a national registry of patients with inherited platelet disorders, an opportunity to improve our understanding of these rare conditions, aid in their diagnosis, and evaluate treatment options.

5) Initiatives to standardize laboratory testing of platelet function at a national level and improve quality assurance for clinical testing.

Dr Israels' research was profiled in the Summer 2012 issue of CancerCare Manitoba Foundation's Community Check Up. To read about her patient's experience and Clinical Investigation's, please click here.

Team Members

  • Eileen McMillan-Ward (Technician)

Publications Since 2010

  1. Age at cancer diagnosis, non-O blood group and asparaginase therapy are independently associated with deep venous thrombosis in pediatric oncology patients: A risk model. Spavor M, Halton J, Dietrich K, Israels SJ, Shereck E, Yong J, Yasui Y, Mitchell LG. Thromb Res. 2016 Aug;144:27-31. doi: 10.1016/j.thromres.2016.05.015. Epub 2016 May 18.
  2. Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia. Chen Y, Henson ES, Xiao W, Huang D, McMillan-Ward EM, Israels SJ, Gibson SB. Autophagy. 2016 Jun 2;12(6):1029-46. doi: 10.1080/15548627.2016.1164357. Epub 2016 May 11.
  3. Geographical variation in the incidence of childhood leukaemia in Manitoba. Torabi M, Singh H, Galloway K, Israels SJ. J Paediatr Child Health. 2015 Nov;51(11):1121-6. doi: 10.1111/jpc.12930. Epub 2015 Jun 3.
  4. Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, Jaremko JL, Ho J, Shenouda N, Matzinger MA, Lentle B, Stephure D, Stein R, Sbrocchi AM, Rodd C, Lang B, Israels SJ, Grant RM, Couch R, Barr R, Hay J, Rauch F, Siminoski K, Ward LM; Canadian STOPP Consortium (National Pediatric Bone Health Working Group). Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis. J Clin Endocrinol Metab. 2015 Sep;100(9):3408-17. doi: 10.1210/JC.2015-2176. Epub 2015 Jul 14.
  5. Langley AR, Stain AM, Chan A, McLimont M, Chait S, Wu J, Poon MC, Card R, Israels SJ, Laferriere N, Klaassen RJ, Rivard GE, Cloutier S, Hawes S, Feldman B, Blanchette V. Experience with central venous access devices (CVADs) in the Canadian hemophilia primary prophylaxis study (CHPS). Haemophilia. 2015 Jul;21(4):469-76. doi: 10.1111/hae.12713.
  6. Torabi M, Singh H, Galloway K, Israels SJ. Geographical variation in the incidence of childhood leukaemia in Manitoba. J Paediatr Child Health. 2015 Jun 3. doi: 10.1111/jpc.12930. [Epub ahead of print]
  7. Israels SJ. Laboratory testing for platelet function disorders. Int J Lab Hematol. 2015 May;37 Suppl 1:18-24. doi: 10.1111/ijlh.12346.
  8. Stammers DM, Israels SJ, Lambert PJ, Cuvelier GD. Cancer incidence, morbidity, and survival in Canadian first nation children: a Manitoba population-based study from the cancer in young people in Canada (CYP-C) registry. Pediatr Blood Cancer. 2014 Dec;61(12):2164-9. doi: 10.1002/pbc.25005. Epub 2014 Feb 26.
  9. Israels SJ, McNicol A, Dean HJ, Cognasse F, Sellers EA. Markers of Platelet Activation Are Increased in Adolescents With Type 2 Diabetes.Diabetes Care. 2014 May 30. pii: DC_132718. [Epub ahead of print]
  10. Favaloro EJ, Bodó I, Israels SJ, Brown SA. von Willebrand disease and platelet disorders.Haemophilia. 2014 May;20 Suppl 4:59-64. doi: 10.1111/hae.12414.
  11. Stammers DM, Israels SJ, Lambert PJ, Cuvelier GD. Cancer incidence, morbidity, and survival in Canadian first nation children: A Manitoba population-based study from the cancer in young people in Canada (CYP-C) registry.Pediatr Blood Cancer. 2014 Feb 26. doi: 10.1002/pbc.25005. [Epub ahead of print]
  12. Bush JW, Hancock B, Israels SJ, Ellison DW, Stefanovici C, Krawitz S. Intracranial atypical teratoid/rhabdoid tumor presenting as an axillary mass: a case report and review of literature. Pediatr Dev Pathol. 2014 Mar-Apr;17(2):122-5. doi: 10.2350/14-01-1427-CR.1. Epub 2014 Feb 20.
  13. Hilliard P, Zourikian N, Blanchette V, Chan A, Elliott B, Israels SJ, Nilson J, Poon MC, Laferriere N, Van Neste C, Jarock C, Wu J, McLimont M, Feldman B. Musculoskeletal health of subjects with hemophilia A treated with tailored prophylaxis: Canadian Hemophilia Primary Prophylaxis (CHPS) Study. J Thromb Haemost. 2013 Mar;11(3):460-6. doi: 10.1111/jth.12113.
  14. Israels SJ, Rand ML. What we have learned from inherited platelet disorders. Pediatr Blood Cancer. 2013;60 Suppl 1:S2-7. doi: 10.1002/pbc.24345. Epub 2012 Oct 25. Review.
  15. de Vries Y, Lwiwski N, Levitus M, Kuyt B, Israels SJ, Arwert F, Zwaan M, Greenberg CR, Alter BP, Joenje H, Meijers-Heijboer H. A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites.Anemia. 2012;2012:865170. Epub 2012 Jun 4.
  16. Rimmer EK, Seftel MD, Israels SJ, Houston DS. Unintended benefit of anabolic steroid use in hemophilia B leiden. Am J Hematol. 2011 Sep 13.
  17. Houston BL, Zelinski T, Israels SJ, Coghlan G, Chodirker BN, Gallagher PG, Houston DS, Zarychanski R. Refinement of the hereditary xerocytosis locus on chromosome 16q in a large Canadian kindred. Blood Cells Mol Dis. 2011 Sep 22.
  18. Israels SJ, Kahr WH, Blanchette VS, Luban NL, Rivard GE, Rand ML. Platelet disorders in children: A diagnostic approach. Pediatr Blood Cancer. 2011 Jun;56(6):975-83.
  19. Israels SJ, El-Ekiaby M, Quiroga T, Mezzano D. Inherited disorders of platelet function and challenges to diagnosis of mucocutaneous bleeding. Haemophilia. 2010 Jul;16 Suppl 5:152-9. Review.
  20. McNicol A, Israels SJ. Mechanisms of oral bacteria-induced platelet activation. Can J Physiol Pharmacol. 2010 May;88(5):510-24. Review
  21. Israels SJ, McMillan-Ward EM. Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets. Thromb Res. 2010 Feb;125(2):152- 8.

Book Chapters/Review Articles/Monographs

  1. Rand M, Israels SJ, McNicol A. Platelet Structure and Function. In: Mechanisms in Hematology, 4th Ed. (ed. Israels SJ) (http://www.mechanismsinhematology.ca/contents.aspx), 2010
  2. Israels SJ, Schwetz N, Purves E. Home Infusion. In: All about Hemophilia: a guide for families. Second edition. Canadian Hemophilia Society pp. 7.1-7.11, 2010.
  3. Rand M, Israels SJ, McNicol A. Platelet Aggregation and Adhesion. Video from Mechanisms in Hematology. Available at: http://www.youtube.com/watch?v=0pnpoEy0eYE. Uploaded December 8, 2010.
  4. Israels SJ. Mini-Review: Inherited platelet function disorders. Microenvironment (Canadian Hematology Society) 2011.
  5. Israels SJ. Neonatal platelet function. In: Platelets, 3rd Ed. (Michelson AD, ed). Academic Press, pp. 503-15, 2013.
  6. Israels SJ, Rand ML. What we have learned from inherited platelet disorders. Pediatr Blood Cancer 2013; 60 (Suppl 1): S2-S7.
  7. Revel-Vilk S, Rand ML, Israels SJ. Understanding the basics of coagulation and fibrinolysis. In: SickKids Handbook of Pediatric Hemostasis and Thrombosis. (Blanchette VS, ed). Karger, pp. 5-13, 2013
  8. Revel-Vilk S, Rand ML, Israels SJ. An approach to the bleeding child. In: SickKids Handbook of Pediatric Hemostasis and Thrombosis. (Blanchette VS, ed). Karger, pp.14-22, 2013
  9. Favaloro EJ, Bodo I, Israels, SJ, Brown SA. Von Willebrand disease and platelet disorders. Haemophilia 2014; 20 (Suppl. 4): 59–64
  10. Rand M and Israels SJ. The molecular basis of platelet function. In: Hematology Basic Principles and Practice (Weitz J, ed) 2015 (in press)
  11. Revel-Vilk S, Rand ML, Israels SJ. Understanding the basics of coagulation and fibrinolysis. In: SickKids Handbook of Pediatric Hemostasis and Thrombosis, 2nd Ed. (Blanchette VS, ed) 2015 (in press)
  12. Revel-Vilk S, Rand ML, Israels SJ. An approach to the bleeding child. In: SickKids Handbook of Pediatric Hemostasis and Thrombosis, 2nd Ed. (Blanchette VS, ed) 2015 (in press).


Research Funding

Principal Investigator

1. Diagnostic Services Manitoba
Comparison of light transmission aggregometry and Multiple Electrode Aggregometry for the evaluation of platelet function in patients with mucocutaneous bleeding.
$60,000
2015-2017

2. CancerCare Manitoba Foundation
Platelet tetraspanin-enriched microdomains modulate integrin signaling and cytoskeletal assembly
$58,000 per annum
2011-2015

3. NovoNordisk Foundation investigator initiated research
Phenotypic heterogeneity in Hemophilia A: An Investigation of the Role of Platelet Function
$105,000
2013-2016

Co-Investigator
1. Children’s Hospital Research Institute of Manitoba
Geographical variation and related risk factors with childhood leukaemia in Manitoba
PI: Mahmoud Torabi
$40,000
2015-2016

2. The Canadian Hemophilia Prophylaxis Study II and extension study (CHPs)
Canadian Blood Services /Héma-Quebec Partnership Fund and Bayer Research Canada
PI: Brian Feldman
Escalating dose prophylaxis in young boys with severe Hemophilia A.
2006-2015

Invited Seminars and Presentations at Symposia/Meetings

• 2011 - Symposium on Congenital and Acquired Bleeding Disorders in Children.
Toronto ON, May 16. “Congenital platelet disorders”.

• 2011 - Department of Pediatrics & Child Health Grand Rounds, University of Manitoba.
November 17. “Investigation of platelet function disorders in children”.

• 2012 - Canadian Hemophilia Society-Manitoba Chapter. Women with Bleeding Disorders
Symposium. Winnipeg. February 19. “Von Willebrand Disease 101”.

• 2012 - Association des médecins hématologues et oncologues du Québec. Montreal PQ,
May 4. “Investigation of platelet function disorders in children”.

• 2012 - Canadian Pediatric Thrombosis and Hemostasis Network. Toronto ON, May 24.
“Gray platelet syndrome”.

• 2012 - Pediatric Hematology Update, University of Toronto, Toronto ON, October 19-20.
Workshop leader and presenter: “Evaluation of the bleeding child”.

• 2012 - Department of Pediatrics Grand Rounds, Memorial University. St. John’s, NFLD
Nov 1. “Investigation of platelet function disorders in children”.

• 2012 - Newfoundland & Labrador Thrombosis, Blood and Immune Disorders Education
and Research Project. St. John’s NFLD. Nov 1. “The Platelet, Friend or Foe?”

• 2013 - Canadian Pediatric Thrombosis and Hemostasis Network. Winnipeg, MB, May 23.
CPTHN strategic review.

• 2013 - Earl Davie Symposium. Center for Blood Research, Vancouver BC. Nov 13.
“Developmental hemostasis: Neonatal platelets acting their age”.

• 2014 - World Federation of Hemophilia World Congress. Melbourne Australia. May 14.
“Diagnostic approaches to platelet disorders”.

• 2015 - Department of Pediatrics & Child Health Grand Rounds, University of Manitoba.
April 30. “ITP, the known and the unknown”.

• 2015 - International Society of Laboratory Hematology Laboratory, Chicago IL, May 21.
“Laboratory testing for platelet function disorders”.

• 2015 - International Society of Thrombosis and Haemostasis, Toronto ON, June 23.
“Platelets function in neonates and children”. Master Class.



RIOH gratefully acknowledges the generous support of



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