Chest

Chest

Volume 127, Issue 5, May 2005, Pages 1857-1861
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Selected Reports
Heparin-Induced Skin Lesions and Other Unusual Sequelae of the Heparin-Induced Thrombocytopenia Syndrome: A Nested Cohort Study

https://doi.org/10.1378/chest.127.5.1857Get rights and content

Background

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating, heparin-dependent IgG antibodies (HIT-IgG). Although HIT is known to predispose the patient to thrombosis, the relationship between the formation of HIT-IgG and various other unusual clinical sequelae putatively linked with the HIT syndrome, such as heparin-induced skin lesions and acute anaphylactoid reactions following treatment with an IV heparin bolus, is not clear.

Methods

We used data from a clinical trial of postoperative heparin prophylaxis to compare the frequency of one or more predefined unusual clinical sequelae developing in 20 patients who formed platelet-activating HIT-IgG with 80 control patients who did not form HIT-IgG (nested cohort study).

Results

Five of the 20 patients in whom HIT-IgG developed had one or more unusual clinical sequelae, compared with none of 80 control patients (25% vs 0%, respectively; odds ratio, ∞; 95% confidence interval, 4.3 to ∞; p < 0.001). The unusual complications included heparin-induced erythematous or necrotic skin lesions (n = 4), an anaphylactoid reaction following IV heparin bolus use (n = 1), and warfarin-associated venous limb ischemia (n = 1). Thrombocytopenia, as it is conventionally defined (ie, platelet count fall to < 150 × 109 cells/L) developed in only one of these five patients.

Conclusions

Certain unusual clinical sequelae, such as heparin-induced skin lesions, are strongly associated with the formation of HIT-IgG and should be considered as manifestations of the HIT syndrome, even in the absence of thrombocytopenia as conventionally defined.

Section snippets

Clinical Trial

Analysis was performed using data from a clinical trial of UFH and LMWH16, 17 that was approved by the institutional review board, and for which all participating patients provided written informed consent. In brief, the clinical trial compared the use of a UFH preparation (Calciparin; Anglo French Drug Company; Montreal, QC, Canada) [7,500 U subcutaneously twice daily] with the LMWH preparation enoxaparin (Lovenox; Rhoône-Poulenc Rorer; Montreal, QC, Canada) [30 mg subcutaneously twice daily],

Results

Inflammatory skin lesions (n = 3) or necrotic skin lesions (n = 1) at heparin injection sites were more likely to have developed in patients with test results that were positive for HIT-IgG, compared with patients in whom HIT-IgG did not develop (4 of 20 vs 0 of 80 patients, respectively; p < 0.001) [Table 1]. These lesions all began on postoperative day 7 or later. The patient in whom necrosis developed at the heparin injection sites had mesenteric artery thrombosis complicating an 81% fall in

Discussion

The association between thrombocytopenia and thrombosis in patients who form HIT-IgG has been recognized for > 25 years.26 Subsequently, a number of other unusual clinical events, including heparin-induced skin lesions,3, 4, 5, 6 acute systemic (anaphylactoid) reactions following IV bolus heparin use,6, 7, 15 and warfarin-associated peripheral limb or central skin necrosis syndromes,10, 11, 12, 13, 14 among others, have been reported in association with HIT.

In this study, we capitalized on our

Acknowledgement

We thank Luba Klama for assistance with data collection.

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

    The corresponding author had full access to all of the data and had final responsibility for the decision to submit for publication.

    This study was supported by Rhone-Poulenc Rorer (now Sanofi-Aventis). The serologic studies described were supported by the Heart and Stroke Foundation of Ontario (grants No. T-4502 [T.E.W], No. T-5207 [T.E.W.], and No. T-4404 [J.G.K]). Neither the clinical trial sponsor nor the funding agency had any role in the analysis or interpretation of the data, or in the decision to submit the manuscript for publication.

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    Copyright © 2005 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.