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Novel assay shows promise in heparin-induced thrombocytopenia
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A novel monoclonal antibody-inhibiting assay was associated with encouraging discriminatory capacities in heparin-induced thrombocytopenia, according to study findings.
Immunoassays such as the platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent assay (ELISA) often provide false-positive results in diagnosing thrombocytopenia, according to researchers. That’s because these assays may not have the capability to discriminate cellular activating-antibodies from non-pathogenic counterparts.
The C-serotonin release assay is a functional assay that may be more specific, but it is unfeasible for most clinical laboratories because it requires radioisotope and fresh platelets from reactive donors.
The current study investigates KKO, a monoclonal antibody that causes a heparin-induced–like thrombocytopenic disorder in a mouse model. Binding KKO to immobilized PF4/heparin is inhibited by human heparin-induced thrombocytopenia plasma, but not by plasma from patients with non-pathogenic anti-PF4/heparin antibodies.
The researchers used this property to develop an assay that inhibits KKO to detect platelet-activating antibodies. They compared this assay with two commercially available assays in 58 patients with suspected heparin-induced thrombocytopenia and circulating anti-PF4/heparin antibodies.
Twenty-one patients met prespecified criteria for heparin-induced thrombocytopenia, and 37 were negative for those criteria.
A polyspecific ELISA, an immunoglobulin G-specific ELISA, KKO-I, and DT40-luc assay were evaluated. Heparin-induced thrombocytopenia-positive plasma demonstrated a mean inhibition of KKO binding of 70.1% (95% CI, 64.8-75.4) vs. 40.4% (95% CI, 33.5-47.4) for heparin-induced thrombocytopenia-negative plasma (P<.0001). Plasma from positive participants also was linked to greater luciferase activity (3.14 vs. 0.96; P<.0001) in the DT40-luc assay, according to the results.
The KKO-I assay was associated with an area under the curve (AUC) of 0.92, which was significantly greater than that observed for the polyspecific (0.82) and IgG-specific (0.76) ELISAs (P<.05 for both comparisons).
The DT40-luc yielded an AUC of 0.89, which was significantly greater than that observed for the IgG-specific (P=.046), but not the polyspecific assay (P=.28).
“KKO-I and DT40-luc showed better discrimination than commercially available ELISAs in a small cohort of patients with suspected [heparin-induced thrombocytopenia] and anti-PF4/heparin [antibodies],” the researchers concluded. “These assays are simple to perform, do not require donor platelets or radioactivity, and hold promise for improving the specificity and feasibility of [heparin-induced thrombocytopenia] laboratory testing.”
For more information:
Cuker A. Abstract #267. Presented at: the 2012 ASH Annual Meeting and Exposition; Dec. 8-11, 2012; Atlanta.
Disclosure: Cuker reports researching funding from, as well as consulting, advisory and board membership roles with, Baxter, Bayer, Canyon, Daiichi Sankyo and Stago.
Perspective
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Keith McCrae, MD
This is an important study. Heparin-induced thrombocytopenia (HIT) is another major concern of hematologists. HIT can be diagnosed clinically, but there is some concern that the clinical diagnostic scores lack accuracy. There is a lot of subjectiveness to the scoring system. There are two kinds of tests that you can use for HIT. The first is called ELISA. The problem with this test is that there are a lot of false-positives. The second is called the serotonin release assay. There are only a couple of laboratories in the country that conduct that type of test and it requires radioactivity. The researchers in this study developed two new assays that can be conducted more rapidly. These have the potential to be more reproducible, more accurate and more consistent. This is still pre-application, but researchers have some interesting data showing the ability to potentially better discriminate than the previous existing tests.
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