Serological investigation of patients with a previous history of heparin-induced thrombocytopenia who are reexposed to heparin

Abstract

Key Points• Heparin rechallenge despite prior HIT often induces platelet-activating anti-PF4/ heparin antibodies but no faster than seen with typical HIT.• Risk of HIT recurring after heparin rechallenge is low but possible if IgG with heparinindependent plateletactivating properties are made.Heparin reexposure despite a history of previous heparin-induced thrombocytopenia (HIT) can be appropriate if platelet-activating antibodies are no longer detectable. We determined the frequency, timing, and magnitude of the antiplatelet factor 4 (anti-PF4)/ heparin immune response (by serotonin-release assay [SRA] and enzyme-immunoassay [EIA]), and the frequency of recurrent HIT in 20 patients with previous HIT reexposed to heparin 4.4 years (mean) post-HIT; 17 patients were given heparin intraoperatively (without postoperative heparin) for cardiac/vascular surgery. One patient developed recurrent HIT beginning 7 days after cardiac surgery, with newly regenerated HIT antibodies exhibiting strong heparin-independent platelet-activating properties. Intraoperative heparin induced EIA seroconversion in 11/17 (65%) patients (immunoglobulin G [IgG]>IgA>IgM) and SRA seroconversion in 8/17 (47%), whereas none of 3 medical patients reexposed to heparin developed seroconversion. Anti-PF4/heparin IgG became detectable at day 7 (median), ie, no sooner than observed in typical-onset HIT. The high proportion of SRA positivity among EIA-seroconverting patients (8/11 [73%]) suggests that patients with previous HIT may be especially predisposed to forming recurrent antibodies with platelet-activating properties. We conclude that among patients with a previous history of HIT who are reexposed to intraoperative (but not postoperative) heparin, the risk of recurrent HIT appears to be low, but is possible if antibodies with strong heparin-independent platelet-activating properties are formed. (Blood. 2014;123(16):2485-2493

Severe and persistent heparin‐induced thrombocytopenia despite fondaparinux treatment

“…No side effects are reported. Only one patient suffered of recurrent thrombocytopenia after cessation of IVIG [24]. He was treated with IVIG on two occasions and there was recurrence of thrombocytopenia after each treatment.…”

“…A total of 11 cases have been identified in the literature [16][17][18][19][20][21][22][23][24] showing the efficiency of treating HIT by IVIG (Table I). Interestingly, eight out of eleven patients were female.…”

How I treat patients with a history of heparin-induced thrombocytopenia

“…Fourth, a minimum of 5 days is required to generate, or to regenerate, pathogenic platelet-activating antibodies. 17,18 Thus, for certain patient populations, deliberate and planned reexposure to heparin has a rational basis. Indeed, this strategy was pioneered by Pötzsch et al, 19 who described unremarkable outcomes of heparin reexposure for CPB in 10 patients with previous HIT who were antibody negative at reexposure (and who remained antibody negative 10 days after reexposure).…”

Mechanical prophylaxis is a heparin-independent risk for anti–platelet factor 4/heparin antibody formation after orthopedic surgery

“…HIT has several features that are atypical for an immune-mediated disease: heparin-naïve patients can develop IgG antibodies as early as 25 ; and HIT antibodies are relatively short-lived (50-85 days), unlike those in a true secondary immune response. 26 To explain this atypical response, previous studies have proposed that the pattern of antibody formation might be more compatible with a non-T cell-dependent immune reaction, which is induced efficiently when an antigen is presented in a repetitive rigid form.…”