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Eduard Shantsila, MD; Gregory Y. H. Lip, MD
Author and Funding Information

Affiliations: Drs. Shantsila and Lip are affiliated with the Haemostasis Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, City Hospital.

Correspondence to: Eduard Shantsila, MD, Haemostasis Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK; e-mail: shantsila@yandex.ru


Financial/nonfinancial disclosures: The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(6):1704-1705. doi:10.1378/chest.09-1753
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To the Editor:

Pollack challenges the existence of heparin-induced thrombocytopenia (HIT) as an independent, clinically relevant entity. Admittedly, it may be difficult to establish precise pathophysiologic links in rare conditions such as HIT. However, a number of facts support the existence of a heparin-triggered, immune system-mediated platelet activation and thrombocytopenia phenomena, which are often accompanied by severe thrombotic complications.

The administration of heparin can increase platelet factor 4 levels 15-fold to 30-fold and often causes the formation of autoantibodies to heparin-platelet factor 4 complexes.1 Importantly, treatment with low-molecular-weight heparins rarely stimulates the formation of antibodies when compared with unfractioned heparin (ie, approximately 8% vs 20%, respectively), and, correspondingly, low-molecular-weight heparins have a much lower risk for the development of the syndrome defined as HIT.2,3

We agree that heparin is often associated with a reduction in platelet count, irrespective of the immune system response. However, in the majority of cases, thrombocytopenia occurs during the first few days of heparin administration, and is mild, is not progressive, and ultimately is not associated with an increased risk of thrombosis. The prognosis becomes very different in those patients in whom thrombocytopenia develops following prolonged heparin administration (usually between 4 and 15 days), as discussed in our recent review4 in CHEST (June 2009). This type of thrombocytopenia is consistently linked to the presence of circulating heparin-platelet factor 4 antibodies and, as Pollack admits in his letter, with a dramatically increased risk of thrombotic complications.5

Is it possible that the thrombotic risk associated with the syndrome described as HIT just reflects the natural risk of thrombosis that is attributable to the background disorders? Apparently not, as the risk of thrombosis in untreated HIT patients is estimated to be up to 50% and uniformly exceeds the probability of thrombosis related to background disorders.6 Of note, the risk of arterial thrombosis is also increased in patients with HIT, despite the presence of a very low platelet count.

These associations are further confirmed by the recognized ability of plasma from HIT patients to activate platelets from healthy donors. This phenomenon is not usually seen in patients with circulating heparin-platelet factor 4 antibodies and thus serves as a basis for diagnostic platelet activation tests (eg, the serotonin release assay). Additionally, HIT is more often seen with bovine heparin, when compared with porcine heparin, probably reflecting the different levels of immunogenicity of heparin derived from various species.7

Suh JS, Aster RH, Visentin GP. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis recognize different epitopes on heparin: platelet factor 4. Blood. 1998;91:916-922. [PubMed]
 
Jang IK, Hursting MJ. When heparins promote thrombosis: review of heparin-induced thrombocytopenia. Circulation. 2005;11:2671-2683. [CrossRef]
 
Amiral J, Peynaud-Debayle E, Wolf M, et al. Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular weight heparin. Am J Hematol. 1996;52:90-95. [PubMed]
 
Shantsila E, Lip GY, Chong BH. Heparin-induced thrombocytopenia: a contemporary clinical approach to diagnosis and management. Chest. 2009;135:1651-1664. [PubMed]
 
Warkentin TE. Management of heparin-induced thrombocytopenia: a critical comparison of lepirudin and argatroban. Thromb Res. 2003;110:73-83. [PubMed]
 
Warkentin TE, Kelton JG. A 14-year study of heparin induced thrombocytopenia. Am J Med. 1996;101:502-507. [PubMed]
 
Warkentin TE. Heparin induced thrombocytopenia: a ten-year retrospective. Annu Rev Med. 1990;50:129-147
 

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Tables

References

Suh JS, Aster RH, Visentin GP. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis recognize different epitopes on heparin: platelet factor 4. Blood. 1998;91:916-922. [PubMed]
 
Jang IK, Hursting MJ. When heparins promote thrombosis: review of heparin-induced thrombocytopenia. Circulation. 2005;11:2671-2683. [CrossRef]
 
Amiral J, Peynaud-Debayle E, Wolf M, et al. Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular weight heparin. Am J Hematol. 1996;52:90-95. [PubMed]
 
Shantsila E, Lip GY, Chong BH. Heparin-induced thrombocytopenia: a contemporary clinical approach to diagnosis and management. Chest. 2009;135:1651-1664. [PubMed]
 
Warkentin TE. Management of heparin-induced thrombocytopenia: a critical comparison of lepirudin and argatroban. Thromb Res. 2003;110:73-83. [PubMed]
 
Warkentin TE, Kelton JG. A 14-year study of heparin induced thrombocytopenia. Am J Med. 1996;101:502-507. [PubMed]
 
Warkentin TE. Heparin induced thrombocytopenia: a ten-year retrospective. Annu Rev Med. 1990;50:129-147
 
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