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Effect of heparin administration on heparin-induced thrombocytopenia (HIT) in atherosclerotic New Zealand Rabbit (Oryctolagus cuniculus)

  • Victor Jesron Nababan ,
  • Agung Prasmono ,
  • Endang Retnowati ,
  • Djoko Legowo ,
  • Sofna Banjarnahor ,


Abstract

Background: Platelets have been associated with the pathogenesis of atherosclerosis by excreting various chemokines (i.e. PF4), which systematically interact with multiple molecules. The formation of circulating heparin-platelet factor-4 (PF4) complexes have been observed in heparin-induced thrombocytopenia (HIT) cases, raising questions about the role of PF4-derived atherosclerosis in the predisposition of HIT.  

Methods: An in vivo model of atherosclerosis was generated by feeding rabbits with a high-cholesterol diet for six weeks and a normal rabbit as a control group. HIT was induced by injecting heparin subcutaneously for ten days twice daily. Platelets count before and after heparinization was performed by hemocytometer, PF4 measurement was determined by ELISA assay. Histopathology examinations for artery thickness, foam cell, and endothelial denudation were conducted by Hematoxylin and Eosin (H&E) staining.

Results: There was no significant difference in the IgG PF4/heparin complex between the atherosclerotic and the normal groups (43.84±2.07 ng/mL vs. 41.87±3.44 ng/mL), platelet count was significantly reduced only in the atherosclerotic group (p=0.01; mean differences 7162.00±57311.02/mm3), endothelial denudation and foam cell formation were observed in the atherosclerotic group. Also, a significant difference observed in endothelial thickness between the atherosclerotic group compared to the normal group (470.32 ± 131.15 µm vs. 332.05±50.82 µm; p=0.032).

Conclusion: Our results suggest that atherosclerosis was significantly associated with the development of heparin-induced thrombocytopenia. However, atherosclerosis is not a risk factor for the formation of PF4-heparin complex in HIT.

Keywords: Heparin PF4 atherosclerosis.

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How to Cite

Nababan, V. J., Prasmono, A., Retnowati, E., Legowo, D., & Banjarnahor, S. (2020). Effect of heparin administration on heparin-induced thrombocytopenia (HIT) in atherosclerotic New Zealand Rabbit (Oryctolagus cuniculus). Bali Medical Journal, 9(3), 737–744. https://doi.org/10.15562/bmj.v9i3.2009
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Victor Jesron Nababan
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Agung Prasmono
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Endang Retnowati
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Djoko Legowo
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Sofna Banjarnahor
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