Biotech Values

[DewDiligence]

Re: Heparin-PF4 antibodies (Lovenox immunogenicity)

With the caveat that the analysis is post hoc, here’s the abstract of a
paper from a peer-reviewed journal that investigates the association
between antibodies to heparin-PF4 complex and death or MI in ACS.

https://www.thieme-connect.de/DOI/DOI?10.1055/s-2004-831047

›Role of Anti-PF4/Heparin Antibodies in Recurrent Thrombotic Events After Acute Coronary Syndromes

Seminars in Thrombosis and Hemostasis (2004) 30:347-50.

Mary Ann Mascelli, Efthymios N. Deliargyris, Lakshmi V. Damaraju, Elliot S. Barnathan, David C. Sane

Centocor [a subsidiary of JNJ], Malvern, Pennsylvania; Wake Forest University School of Medicine, Winston-Salem, North Carolina

We postulated that patients with recent acute coronary syndromes and antibodies to the platelet factor 4/heparin complex would have an increased risk of myocardial infarction (MI), even in the absence of thrombocytopenia.

We analyzed sera from patients enrolled in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had a high likelihood of prior heparin exposure. We selected 109 patients without thrombocytopenia with the 30-day primary endpoint (death, MI, or revascularization) and 109 age-, gender-, and race-matched controls who did not achieve the primary endpoint. Twenty-three of 218 patients (10.6%) had anti-PF4/heparin antibodies.

Patients with anti-PF4/heparin were more likely to have death or MI (30.4% vs. 11.3%, p = 0.011) or MI (21.7% vs. 6.2%, p = 0.008) than patients who were negative for the antibody. Antibody-positive patients had higher levels of sVCAM-1 (892 ± 263 µg/L vs. 780 ± 228 µg/L; p = 0.04) and sICAM-1 (246 ± 50 µg/L vs. 222 ± 71 µg/L; p = 0.02) than antibody-negative patients.

In a multiple logistic regression model that included inflammatory markers and clinical risk factors, antibodies to PF4/heparin were a strong predictor of 30-day MI (odds ratio, 9.0; 95% confidence interval [2.1, 38.6]; p < 0.01), with IL-6 being the only other predictor (odds ratio, 1.1; 95% confidence intervals, 1.0 to 1.2; p = 0.03).

Conclusion: Antibodies to the platelet factor 4/heparin complex are a novel, independent predictor of MI at 30 days in patients presenting with acute coronary ischemic syndromes. Antibodies to PF4/heparin are a stronger predictor of MI than clinical characteristics or inflammation markers.‹