Treatment of refractory delayed onset heparin‐induced thrombocytopenia after thoracic endovascular aortic repair with intravenous immunoglobulin (IVIG)

Abstract

Essentials Delayed‐onset heparin‐induced thrombocytopenia can lead to severe thrombocytopenia in the setting of recent major vascular surgery.Intravenous immunoglobulin (IVIG) can be used as a supplementary treatment when platelet count fails to improve with conventional treatment.When platelet counts are severely low, benefits of using IVIG can outweigh the risks of thromboembolic events. Delayed onset heparin induced thrombocytopenia (HIT), is characterized by a late nadir due to persistent platelet‐activating IgG antibodies. It typically begins or worsens 5 or more days after heparin is discontinued with complications such as thrombosis up to 3 weeks after exposure to heparin.1–3 In 50% of cases, the platelet count can decrease to very low numbers (<20 000/μL), which is not usual for typical HIT. Here we report 2 cases of post‐operative delayed onset HIT manifesting as severe thrombocytopenia that persisted despite cessation of heparin and initiation of argatroban. Key Clinical Question: Is intravenous immunoglulin beneficial in severe refractory delayed‐onset HIT?

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

“…Only one patient had a dramatic recurrence of thrombocytopenia, despite having received two doses of IVIG (1 g/kg per dose), with an initial PLT count response (from 11 to 81) after 3 days, but then an abrupt decrease in PLT count from 81 to 5 over the next 4 days; after a third dose of IVIG (1 g/kg), the PLT count gradually increased. Interestingly, this last case was one of two patients reported by Doucette and coworkers, and both patients reported by these authors had less marked PLT count increases compared with the other patients reported. This raises the issue of whether a less effective preparation of IVIG was used in the two patients reported by Doucette and coworkers.…”

“…However, there were no clear thrombotic events identified after starting IVIG. There were two patients in whom imaging studies performed after starting IVIG showed evidence of thromboses; however, the authors did not claim that the thrombotic events occurred after IVIG administration. For example, Betrosian and colleagues noted that imaging studies performed after IVIG administration showed intraatrial thrombi and PE; however, there was no comment on interim symptoms to suggest thrombotic events occurring after IVIG administration, and given that their patient already had numerous documented events before initiation of IVIG (DVT, PE, thumb necrosis, DIC), these visualized thrombi may well have been present before starting 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 .…”

“…Interestingly, two patients received IVIG because of severe thrombocytopenia and active bleeding: one patient (PLT count nadir, 8 × 10 9 /L) had gastrointestinal bleeding related to colon adenocarcinoma (this patient also had recurrent pulmonary embolism (PE) with DVT progression associated with HIT), and the other patient also had gastrointestinal bleeding along with bleeding from an injured postpharyngeal area, without evidence for HIT‐associated thrombosis (PLT count nadir, 10 × 10 9 /L) . Two other patients had recent bleeding (PE‐associated hemoptysis, epistaxis/hemotypsis) that did not recur after IVIG.…”

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

“…2 There are less than 20 reported cases worldwide 2 and while the triggers for its development are not known, it is believed that HIT antibodies are directed to PF4 bound to the platelet surface likely via endogenous glycosaminoglycans. 13 Intravenous immunoglobulin G (IVIG) can be strikingly effective in patients with persistent HIT refractory to non-heparin anticoagulant treatment, rapidly and durably counteracting HIT antibody-mediated platelet activation [14][15][16][17][18] and this treatment may even prevent HIT from developing in the face of heparin exposure in subacute HIT. 19 Here, we describe a severely affected patient with spontaneous HIT who was treated successfully with IVIG.…”