American Heart Journal
Volume 158, Issue 1 , Page e15, July 2009

Heparin/PF4 antibodies formation after heparin treatment: Temporal aspects and long-term follow-up—Letter to the Editor

Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Greifswald, Germany

Institut für Community Medicine, Ernst-Moritz-Arndt Universität, Greifswald, Germany

Klinik für Herz-, Thorax- und Gefäβchirurgie, Herz- und Diabeteszentrum Mecklenburg/Vorpommern, Karlsburg, Germany

Article Outline

 

We read with great interest the article by Mattioli et al.1 They found patients with anti-PF4/heparin antibodies on day 6 after cardiac surgery to be at an increased risk for thrombotic events and myocardial infarction/death (at 30-day follow-up). However, we have concerns about some methodological aspects of their study and the implications resulting from their interpretation of the data.

First, the authors present pretest probabilities of the patients using the 4Ts score, reporting that 80 of 500 (80/500, 16.0%) patients scored 6 points or higher (high pretest probability). This number appears to be too high. Most patients with post–cardiac surgery thrombocytopenia have a low 4Ts score because the platelet count fall occurs in association with surgery. To have a score of 6 points, the patient would need to have a platelet count decrease >50% and/or a new thrombosis, which begins between 5 and 10 days after surgery. Presumably, their high scores result primarily from including “late” thromboses (after day 10) in this patient population (ie, 70 thromboses reported in their study during the observation period of 30 days). In a very similar study,2 we found only 1 of 591 patients scoring 6 or higher. In this study, patients were adjudicated by two independent experts (A Greinacher and TE Warkentin).

Second, presentation of data on 30-day outcome is misleading. The corresponding table suggests, together with the presentation in the text, a comparison of 30-day outcome data using the Fisher exact test. Using this test, comparisons of death (7.6% vs 3.8%; P = .0948), myocardial infarction (6.9% vs 4.0%; P = .2331), pulmonary embolism (7.6 vs 3.8; P = .0948), stroke (3.0% vs 1.7%; P = .4896), and arterial thrombosis (3.0% vs 1.3%; P = .2503) provide no significant differences in short-term follow-up between antibody positive and antibody negative patients. This would be compatible with results of others.3, 4

Third, even if there is an association between anti-PF4/heparin antibody levels and adverse outcome after cardiac surgery, these antibodies need not necessarily be involved in adverse events but may represent a surrogate marker for patients at greater risk for postoperative complications. Therefore, one cannot recommend routine preoperative testing for anti-PF4/heparin antibodies, nor proscription against postoperative heparin administration, until future studies have investigated the overall risk/benefit ratio of alternative anticoagulation regimes in cardiac surgery patients who have only increased levels of anti-PF4/heparin antibodies without other signs of HIT.

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References 

  1. Mattioli AV, Bonetti L, Zennaro M, et al. Heparin/PF4 antibodies formation after heparin treatment: temporal aspects and long-term follow-up. Am Heart J. 2009;157:589–595
  2. Selleng S, Malowsky B, Bagemühl J, et al. Incidence and clinical significance of anti-platelet factor 4/heparin antibodies determined before cardiac surgery. Hämostaseologie. 2009;29:A64
  3. Bauer TL, Arepally G, Konkle BA, et al. Prevalence of heparin-associated antibodies without thrombosis in patients undergoing cardiopulmonary bypass surgery. Circulation. 1997;95:1242–1246
  4. Everett BM, Yeh R, Foo SY, et al. Prevalence of heparin/platelet factor 4 antibodies before and after cardiac surgery. Ann Thorac Surg. 2007;83:592–597

PII: S0002-8703(09)00361-5

doi:10.1016/j.ahj.2009.05.009

American Heart Journal
Volume 158, Issue 1 , Page e15, July 2009

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