Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II

Harunobu Iwase; Hiroko Kariyazono; Junko Arima; Hiroyuki Yamamoto; Kazuo Nakamura

doi:doi:10.11648/j.sr.20140204.13

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Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II

Harunobu Iwase, Hiroko Kariyazono, Junko Arima, Hiroyuki Yamamoto, Kazuo Nakamura

Published in Science Research (Volume 2, Issue 4)

Received: 21 August 2014 Accepted: 4 September 2014 Published: 20 September 2014

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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.

Published in	Science Research (Volume 2, Issue 4)
DOI	10.11648/j.sr.20140204.13
Page(s)	78-86
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2014. Published by Science Publishing Group

Keywords

HIT, Unfractionated Heparin, Platelet Aggregability, Anti-HIT Antibodies, TNF-alpha, TAT

References

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Harunobu Iwase, Hiroko Kariyazono, Junko Arima, Hiroyuki Yamamoto, Kazuo Nakamura. (2014). Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II. Science Research, 2(4), 78-86. https://doi.org/10.11648/j.sr.20140204.13

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Harunobu Iwase; Hiroko Kariyazono; Junko Arima; Hiroyuki Yamamoto; Kazuo Nakamura. Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II. Sci. Res. 2014, 2(4), 78-86. doi: 10.11648/j.sr.20140204.13

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Harunobu Iwase, Hiroko Kariyazono, Junko Arima, Hiroyuki Yamamoto, Kazuo Nakamura. Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II. Sci Res. 2014;2(4):78-86. doi: 10.11648/j.sr.20140204.13

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@article{10.11648/j.sr.20140204.13,
  author = {Harunobu Iwase and Hiroko Kariyazono and Junko Arima and Hiroyuki Yamamoto and Kazuo Nakamura},
  title = {Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II},
  journal = {Science Research},
  volume = {2},
  number = {4},
  pages = {78-86},
  doi = {10.11648/j.sr.20140204.13},
  url = {https://doi.org/10.11648/j.sr.20140204.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sr.20140204.13},
  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.},
 year = {2014}
}

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TY  - JOUR
T1  - Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II
AU  - Harunobu Iwase
AU  - Hiroko Kariyazono
AU  - Junko Arima
AU  - Hiroyuki Yamamoto
AU  - Kazuo Nakamura
Y1  - 2014/09/20
PY  - 2014
N1  - https://doi.org/10.11648/j.sr.20140204.13
DO  - 10.11648/j.sr.20140204.13
T2  - Science Research
JF  - Science Research
JO  - Science Research
SP  - 78
EP  - 86
PB  - Science Publishing Group
SN  - 2329-0927
UR  - https://doi.org/10.11648/j.sr.20140204.13
AB  - 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.
VL  - 2
IS  - 4
ER  -

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Author Information

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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Harunobu Iwase, Hiroko Kariyazono, Junko Arima, Hiroyuki Yamamoto, Kazuo Nakamura. (2014). Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II. Science Research, 2(4), 78-86. https://doi.org/10.11648/j.sr.20140204.13

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Harunobu Iwase; Hiroko Kariyazono; Junko Arima; Hiroyuki Yamamoto; Kazuo Nakamura. Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II. Sci. Res. 2014, 2(4), 78-86. doi: 10.11648/j.sr.20140204.13

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Harunobu Iwase, Hiroko Kariyazono, Junko Arima, Hiroyuki Yamamoto, Kazuo Nakamura. Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II. Sci Res. 2014;2(4):78-86. doi: 10.11648/j.sr.20140204.13

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@article{10.11648/j.sr.20140204.13,
  author = {Harunobu Iwase and Hiroko Kariyazono and Junko Arima and Hiroyuki Yamamoto and Kazuo Nakamura},
  title = {Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II},
  journal = {Science Research},
  volume = {2},
  number = {4},
  pages = {78-86},
  doi = {10.11648/j.sr.20140204.13},
  url = {https://doi.org/10.11648/j.sr.20140204.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sr.20140204.13},
  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.},
 year = {2014}
}

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TY  - JOUR
T1  - Relationship between Platelet Aggregatory and Heparin-Induced Thrombocytopenia Type II
AU  - Harunobu Iwase
AU  - Hiroko Kariyazono
AU  - Junko Arima
AU  - Hiroyuki Yamamoto
AU  - Kazuo Nakamura
Y1  - 2014/09/20
PY  - 2014
N1  - https://doi.org/10.11648/j.sr.20140204.13
DO  - 10.11648/j.sr.20140204.13
T2  - Science Research
JF  - Science Research
JO  - Science Research
SP  - 78
EP  - 86
PB  - Science Publishing Group
SN  - 2329-0927
UR  - https://doi.org/10.11648/j.sr.20140204.13
AB  - 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.
VL  - 2
IS  - 4
ER  -

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