Original Article

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Korean J Hematol 2012; 47(1):

Published online March 31, 2012

https://doi.org/10.5045/kjh.2012.47.1.39

© The Korean Society of Hematology

Usefulness of anti-PF4/heparin antibody test for intensive care unit patients with thrombocytopenia

Sang Hyuk Park1, Seongsoo Jang1*, Hyoeun Shim1, Geum-Borae Park2, Chan-Jeoung Park1, Hyun-Sook Chi1, and Sang-Bum Hong3

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

2Department of Laboratory Medicine, Eulji University Daejeon Hospital, Daejeon, Korea.

3Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to : Correspondence to Seongsoo Jang, M.D., Ph.D. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 86, Asanbyungwon-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4512, Fax: +82-2-478-0884, ssjang@amc.seoul.kr

Received: January 30, 2012; Revised: March 6, 2012; Accepted: March 9, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

It is critical to differentiate heparin-induced thrombocytopenia (HIT) from disseminated intravascular coagulation (DIC) in heparinized intensive care unit (ICU) patients with thrombocytopenia because the therapeutic approach differs based on the cause. We investigated the usefulness of PF4/heparin antibody tests in these patients.

Methods

A total of 127 heparinized ICU patients whose platelet counts were <150×109/L or reduced by >50% after 5-10 days of heparin therapy were enrolled. PF4/heparin antibodies were measured using 2 immunoassays. We assessed the probability of HIT by using Warkentin's 4T's scoring system for antibody positive patients and compared routinely performed coagulation test results between patients with and without antibodies to evaluate the ability of these tests to discriminate between HIT and DIC.

Results

Positive results were obtained for 14 (11.0%) and 11 (8.7%) patients in the 2 assays. The analysis performed using the 4T's scoring system revealed that 11 of 20 (15.7%) patients with antibodies in at least 1 assay had intermediate or greater probability of HIT. Patients without antibodies had significantly higher levels of D-dimer than those with antibodies. However, there were no intergroup differences in platelet counts, PT, aPTT, fibrinogen, DIC score, and rate of overt DIC.

Conclusion

Seropositivity for PF4/heparin antibody was 8.7-11.0% in the patients with thrombocytopenia, and more than a half of them had an increased probability of HIT. Among the routine coagulation tests, only D-dimer was informative for differentiating HIT from DIC. PF4/heparin antibody test is useful to ensure appropriate treatment for thrombocytopenic heparinized ICU patients.

Keywords Intensive care units, Platelet factor 4, Heparin, Antibody, Heparin-induced thrombocytopenia

Article

Original Article

Korean J Hematol 2012; 47(1): 39-43

Published online March 31, 2012 https://doi.org/10.5045/kjh.2012.47.1.39

Copyright © The Korean Society of Hematology.

Usefulness of anti-PF4/heparin antibody test for intensive care unit patients with thrombocytopenia

Sang Hyuk Park1, Seongsoo Jang1*, Hyoeun Shim1, Geum-Borae Park2, Chan-Jeoung Park1, Hyun-Sook Chi1, and Sang-Bum Hong3

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

2Department of Laboratory Medicine, Eulji University Daejeon Hospital, Daejeon, Korea.

3Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to: Correspondence to Seongsoo Jang, M.D., Ph.D. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 86, Asanbyungwon-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4512, Fax: +82-2-478-0884, ssjang@amc.seoul.kr

Received: January 30, 2012; Revised: March 6, 2012; Accepted: March 9, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

It is critical to differentiate heparin-induced thrombocytopenia (HIT) from disseminated intravascular coagulation (DIC) in heparinized intensive care unit (ICU) patients with thrombocytopenia because the therapeutic approach differs based on the cause. We investigated the usefulness of PF4/heparin antibody tests in these patients.

Methods

A total of 127 heparinized ICU patients whose platelet counts were <150×109/L or reduced by >50% after 5-10 days of heparin therapy were enrolled. PF4/heparin antibodies were measured using 2 immunoassays. We assessed the probability of HIT by using Warkentin's 4T's scoring system for antibody positive patients and compared routinely performed coagulation test results between patients with and without antibodies to evaluate the ability of these tests to discriminate between HIT and DIC.

Results

Positive results were obtained for 14 (11.0%) and 11 (8.7%) patients in the 2 assays. The analysis performed using the 4T's scoring system revealed that 11 of 20 (15.7%) patients with antibodies in at least 1 assay had intermediate or greater probability of HIT. Patients without antibodies had significantly higher levels of D-dimer than those with antibodies. However, there were no intergroup differences in platelet counts, PT, aPTT, fibrinogen, DIC score, and rate of overt DIC.

Conclusion

Seropositivity for PF4/heparin antibody was 8.7-11.0% in the patients with thrombocytopenia, and more than a half of them had an increased probability of HIT. Among the routine coagulation tests, only D-dimer was informative for differentiating HIT from DIC. PF4/heparin antibody test is useful to ensure appropriate treatment for thrombocytopenic heparinized ICU patients.

Keywords: Intensive care units, Platelet factor 4, Heparin, Antibody, Heparin-induced thrombocytopenia

Table 1 . The Warkentin 4T's scoring system to estimate the probability of heparin-induced thrombocytopenia..

Pretest probability score: 6-8=high; 4-5=intermediate; 0-3=low..


Table 2 . The ISTH 2001 DIC scoring system for the diagnosis of overt DIC..

Abbreviations: PT, prothrombin time; DIC, disseminated intravascular coagulation; ISTH, International Society of Thrombosis and Hemostasis..

Overt DIC: ≥5 points..


Table 3 . The results of 2 ELISA tests for detecting anti-PF4/heparin antibodies in 127 heparin-treated ICU patients with thrombocytopenic events..

Twenty (15.7%) patients showed positivity in at least 1 of the 2 assays..

Abbreviation: ICU, intensive care unit..


Table 4 . Comparison of platelet count, PT, aPTT, fibrinogen, D-dimer, and DIC scores between patients with and without anti-PF4/heparin antibodies..

P-values obtained from Mann-Whitney U testa) and Chi-Square testb)..

c)Anti-PF4/heparin antibody was defined as negative when all the results of the 2 assays were within the Cutoff values (optical density of 0.304 for Asserachrom HPIA and 1U/mL for HemosIL HIT-Ab based on the manufacturer's recommendations) and was defined as positive when at least one of the 2 results was beyond the cutoff values..

Abbreviations: PT, prothrombin time; aPTT, activated partial prothrombin time; DIC, disseminated intravascular coagulation; PF4, platelet factor 4..


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