IgG classification of anti‐PF4/heparin antibodies to identify patients with heparin‐induced thrombocytopenia during mechanical circulatory support

Abstract

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support. See also Warkentin TE. PF4-dependent immunoassays and inferential detection of HIT antibodies. This issue, pp 232-4.Summary. Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparininduced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and nonplatelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n ¼ 10), non-platelet-activating anti-PF4/heparin antibodies (n ¼ 53), and anti-PF4/ heparin antibody negative (n ¼ 50). Patients with plateletactivating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P ¼ 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients

“…Several groups have suggested that the magnitude of a positive ELISA is clinically relevant, 35,[38][39][40][41] and concerning the ID-H/PF4-PaGIA, we had already demonstrated the clinical utility of this approach. 3,22 In the present study, ROC analysis confirms a cut-off titer of 4 or over 3,22 as providing the best compromise between sensitivity and specificity, and shows that titers of 32 or over have a PPV of 100% for the presence of in vitro platelet-activating HIT antibodies.…”

The association of anti‐platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery

“…Most commercially available anti‐PF4/heparin antibody ELISA kits detect all three isotypes, whereas antibodies capable of activating platelets are typically of the IgG isotype . Lack of isotype specificity may reduce the overall specificity of a positive test result , although Selleng et al . noted no association between preoperative or postoperative IgG antibodies and thromboembolism, but rather an association between IgM antibodies and non‐thrombotic complications after cardiac surgery.…”

Management of anticoagulation in patients with subacute heparin-induced thrombocytopenia scheduled for heart transplantation

“…on April 30, 2019. by guest www.bloodjournal.org From unlikely to be present. 17,18 This strategy is feasible in countries where functional HIT tests are available from a network of trained laboratories, providing assays in a turnaround time and of sufficient quality that clinical decisions may be based on the test result. (Potential alternative approaches are given in Table 1.…”