Use of intravenous immunoglobulin G to treat spontaneous heparin‐induced thrombocytopenia

Abstract

BACKGROUND Spontaneous heparin‐induced thrombocytopenia (HIT) is a rare but serious prothrombotic syndrome characterized by thrombosis, thrombocytopenia, and strong platelet‐activating HIT antibodies in the absence of heparin exposure, and is frequently characterized by a suboptimal response to standard therapies. Here, we present the first report of intravenous immunoglobulin G (IVIG) use in a patient with spontaneous HIT. STUDY DESIGN AND METHODS Patient information, including demographic, clinical, and laboratory results, were obtained from the electronic medical record. Laboratory testing was performed in the serotonin release assay, platelet factor 4 (PF4)‐dependent P‐selectin expression assay, and PF4/polyvinylsulfonate enzyme‐linked immunosorbent assay to study the impact of IVIG on HIT antibody‐mediated platelet activation. The patient was also genotyped for a polymorphism in the IgG receptor on platelets, FcγRIIa, at amino acid position 131. RESULTS A 30‐year‐old man had a thrombotic stroke and thrombocytopenia and strong HIT serologies in the absence of proximate heparin use. Direct thrombin inhibitor therapy was not associated with a prompt response. Due to severity and extent of thrombosis and persistent thrombocytopenia, he was treated with high‐dose IVIG. This treatment was associated with rapid and sustained normalization of platelet counts and a gradual improvement in thrombotic complications. Platelet activation induced by HIT antibodies in the PF4‐dependent P‐selectin expression assay (low PF4) was significantly lower after IVIG treatment, correlating well with platelet rise. Consistent with the severity of thrombosis, the patient was found to possess the 131HR polymorphism in FcγRIIa. CONCLUSION These results suggest that IVIG may be a useful adjunctive therapy in spontaneous HIT.

High‐dose intravenous immunoglobulin to treat spontaneous heparin‐induced thrombocytopenia syndrome

“…, the platelet count abruptly rose from 21 to 120 × 10 9 L −1 (this count was measured 42 h after starting the first dose of IVIg), and then continued to rise to 200 × 10 9 L −1 over the next 2 days, before reaching the peak platelet count of 303 × 10 9 L −1 3 days after that. Figure also shows that patient serum‐induced serotonin release in the absence of heparin fell abruptly (from 91% pre‐IVIg to 14% post‐IVIg), consistent with the known effects of high‐dose IVIg in inhibiting HIT antibody‐induced platelet activation . Although heparin‐independent serotonin release later rebounded to 49% (presumably reflecting waning of plasma IgG levels over time), the patient's platelet counts remained normal.…”

“…Autoimmune heparin‐induced thrombocytopenia (aHIT) indicates a subset of HIT in which patients have high levels of antiplatelet factor 4 (PF4)/heparin antibodies that are able to activate platelets via their FcγIIa receptors, even in the absence of heparin . Recognized aHIT disorders include delayed‐onset HIT , persisting HIT , heparin “flush”‐induced HIT , fondaparinux‐associated HIT , and spontaneous HIT syndrome . This last syndrome is defined as a disorder indistinguishable from HIT both clinically (thrombocytopenia, thrombosis) and serologically (high levels of HIT antibodies both by PF4‐dependent immunoassay and platelet activation assay) but without proximate heparin exposure to explain the presence of HIT antibodies.…”

Autoimmune heparin‐induced thrombocytopenia and venous limb gangrene after aortic dissection repair: in vitro and in vivo effects of intravenous immunoglobulin

“…In conclusion, high‐dose IVIG is an emerging therapy for severe HIT. Recent reports have emphasized its use in aHIT syndromes, such as delayed‐onset and persisting HIT and even a case of spontaneous HIT syndrome . We report a case of response to IVIG in a patient with delayed‐onset and persisting HIT, in which in vitro and in vivo response in a dose‐dependent fashion was demonstrated.…”

“…Other patients may also have had similar PLT count responses that were not reported (e.g., one patient was transferred to another institution, and subsequent PLT count values were not known; one patient was stated to have sustained PLT counts >80, without further details provided). This usual abrupt PLT count increase shortly after starting IVIG was especially noteworthy, given that the last 10 reported patients all had clear evidence for aHIT syndromes, with persistent thrombocytopenia associated with HIT; in all 10 patients, an abrupt upward change in PLT count trajectory occurred upon starting the course of high‐dose IVIG.…”

“…We identified 20 reports in the literature describing 27 cases of acute HIT that were treated with IVIG (Table ) . Two cases of putative HIT were excluded, one because the clinical picture was not sufficiently specific for HIT, and no testing for HIT antibodies was performed, and the other because IVIG was given for treatment of Group A puerperal toxic shock syndrome, with associated severe sepsis‐associated thrombocytopenia and with possible HIT only developing several days later, with prompt PLT count recovery after stopping heparin; thus, the impact of IVIG administration, if any, on PLT count changes in HIT could not be ascertained .…”