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Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II
Science Research
Volume 2, Issue 4, August 2014, Pages: 78-86
Received: Aug. 21, 2014; Accepted: Sep. 4, 2014; Published: Sep. 20, 2014
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Authors
Harunobu Iwase, Department of Biopharmaceutics, Nihon Pharmaceutical University, Saitama, Japan
Hiroko Kariyazono, Department of Pharmacy, Nagasaki International University, Nagasaki, Japan
Junko Arima, Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Hiroyuki Yamamoto, Department of Cardiovascular and Gastroenterological Surgery, Advanced Therapeutics Cardiovascular and Respiratory Disorder, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Kazuo Nakamura, Department of Biopharmaceutics, Nihon Pharmaceutical University, Saitama, Japan
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Abstract
Heparin-induced thrombocytopenia type II (HIT) is a significant adverse effect of heparin treatment in either therapeutic or prophylactic doses. HIT is an immune-mediated disorder caused by IgG antibodies that bind to platelet factor 4 (PF4), which becomes an antigenic target when bound to heparin. The possibility of HIT is suspected when patients show a reduction in the platelet count while receiving heparin. However, the diagnosis of HIT may be difficult on the basis of clinical symptoms alone, especially in patients with other diseases that may induce thrombocytopenia. Therefore, confirmation of HIT by using biologic or antigen assays is required. To analyze whether two patients in whom thrombocytopenia was induced after initiating administration of unfractionated heparin during percutaneous transluminal coronary angioplasty or coronary artery bypass grafting surgery had HIT, we measured levels of platelet aggregability, anti-heparin-PF4 complex antibody (anti-HIT antibody), tumor necrosis factor (TNF)-alpha, TNF-receptor 1 (TNF-R1), interleukin (IL)-6, and thrombin-antithrombin III complex (TAT). The two patients were judged to be HIT-positive from the results that platelet aggregation induced with induced by ADP 1 μM as well as collagen 0.2 μg/mL increased after addition of UFH. ELISA results of two patients showing optical density (OD) values greater than 0.40 were regarded as positive. Additionally, the levels of TNF-alpha and TAT in both patients were higher than in the control patients who underwent CABG without thrombocytopenia after heparin therapy initiation. The results suggest that blood coagulation is enhanced and an inflammatory reaction is induced in the endothelial cells of patients with HIT. In conclusion, the combined measurement of platelet aggregation and anti-HIT antibodies is crucial for defining HIT status, and measurement of TNF-alpha and TAT may play a significant role in the practice of anticoagulant therapy.
Keywords
HIT, Unfractionated Heparin, Platelet Aggregability, Anti-HIT Antibodies, TNF-alpha, TAT
To cite this article
Harunobu Iwase, Hiroko Kariyazono, Junko Arima, Hiroyuki Yamamoto, Kazuo Nakamura, Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II, Science Research. Vol. 2, No. 4, 2014, pp. 78-86. doi: 10.11648/j.sr.20140204.13
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