Rapid and durable response to intravenous immunoglobulin in delayed heparin‐induced thrombocytopenia: a case report

Lei, Brandon Z.; Shatzel, Joseph J.; Sendowski, Merav

doi:10.1111/trf.13960

Cited by 17 publications

(36 citation statements)

References 25 publications

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“…In 35 cases, 17–46 the most common indication for IVIG and/or TPE was refractory HIT as manifested by persistent or worsening thrombocytopenia (n = 34; 97%) and/or new or progressive thrombosis (n = 4, 11%), bleeding, (n = 4, 11%), clinical deterioration (n = 3, 9%), or limb ischemia or gangrene (n = 2, 6%). Case‐level data for this category is detailed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin‐induced thrombocytopenia: A systematic review

et al. 2020

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Background: Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. Study Design and Methods: We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. Results: After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were

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Section: Resultsmentioning

confidence: 99%

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin‐induced thrombocytopenia: A systematic review

et al. 2020

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“…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 .…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder characterized by heparindependent antibodies that activate platelets (PLTs) via PLT FcγIIa receptors. "Autoimmune" HIT (aHIT) indicates a HIT subset where thrombocytopenia progresses or persists despite stopping heparin; aHIT sera activate PLTs strongly even in the absence of heparin (heparin-independent PLTactivating properties). Affected patients are at risk of severe complications, including dual macro-and microvascular thrombosis leading to venous limb gangrene. High-dose intravenous immunoglobulin (IVIG) offers an approach to interrupt heparin-independent PLT-activating effects of aHIT antibodies. CASE REPORT:A 78-year-old male who underwent cardiopulmonary bypass for aortic dissection developed aHIT, disseminated intravascular coagulation, and deep vein thrombosis; progression to venous limb gangrene occurred during partial thromboplastin time (PTT)-adjusted bivalirudin infusion (underdosing from "PTT confounding"). Thrombocytopenia recovered with high-dose IVIG, although the PLT count increase began only after the third dose of a 5-day IVIG regimen (0.4 g/kg/day × 5 days). We reviewed case reports and case series of IVIG for treating HIT, focusing on various IVIG dosing regimens used. RESULTS: Patient serum-induced PLT activation wasinhibited in vitro by IVIG in a dose-dependent fashion; inhibition of PLT activation by IVIG was much more marked in the absence of heparin versus the presence of heparin (0.2 U/mL). Our literature review indicated 1 g/kg × 2 IVIG dosing as most common for treating HIT, usually associated with rapid PLT count recovery. CONCLUSION:Our clinical and laboratory observations support dose-dependent efficacy of IVIG for decreasing PLT activation and thus correcting thrombocytopenia in aHIT. Our case experience and literature review suggests dosing of 1 g/kg IVIG × 2 for patients with severe aHIT. ABBREVIATIONS: aHIT = autoimmune heparin-induced thrombocytopenia; DIC = disseminated intravascular coagulation; DVT = deep vein thrombosis; HIT = heparin-induced thrombocytopenia; ITP = idiopathic thrombocytopenic purpura; PE = pulmonary embolism; PF4 = platelet factor 4; POD = postoperative day; PTT(s) = partial thromboplastin time(s); SRA = serotonin release assay; UFH = unfractionated heparin. From the

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“…Until recently, IVIg use had attracted little attention for the treatment of HIT, in part because of approval of alternative (non‐heparin) anticoagulants. However, the recognition of aHIT is changing this view: several recent reports have indicated a high probability of abrupt platelet count recovery following treatment with high‐dose IVIg.…”

Section: Treatment Of Ahitmentioning

confidence: 99%

Autoimmune heparin‐induced thrombocytopenia

Greinacher

Selleng

Warkentin

2017

Journal of Thrombosis and Haemostasis

354

444

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Summary Autoimmune heparin‐induced thrombocytopenia (aHIT) indicates the presence in patients of anti‐platelet factor 4 (PF4)–polyanion antibodies that are able to activate platelets strongly even in the absence of heparin (heparin‐independent platelet activation). Nevertheless, as seen with serum obtained from patients with otherwise typical heparin‐induced thrombocytopenia (HIT), serum‐induced platelet activation is inhibited at high heparin concentrations (10–100 IU mL−1 heparin). Furthermore, upon serial dilution, aHIT serum will usually show heparin‐dependent platelet activation. Clinical syndromes associated with aHIT include: delayed‐onset HIT, persisting HIT, spontaneous HIT syndrome, fondaparinux‐associated HIT, heparin ‘flush’‐induced HIT, and severe HIT (platelet count of < 20 × 109 L−1) with associated disseminated intravascular coagulation (DIC). Recent studies have implicated anti‐PF4 antibodies that are able to bridge two PF4 tetramers even in the absence of heparin, probably facilitated by non‐heparin platelet‐associated polyanions (chondroitin sulfate and polyphosphates); nascent PF4–aHIT‐IgG complexes recruit additional heparin‐dependent HIT antibodies, leading to the formation of large multimolecular immune complexes and marked platelet activation. aHIT can persist for several weeks, and serial fibrin, D‐dimer, and fibrinogen levels, rather than the platelet count, may be helpful for monitoring treatment response. Although standard anticoagulant therapy for HIT ought to be effective, published experience indicates frequent failure of activated partial thromboplastin time (APTT)‐adjusted anticoagulants (argatroban, bivalirudin), probably because of underdosing in the setting of HIT‐associated DIC, known as ‘APTT confounding’. Thus, non‐APTT‐adjusted therapies with drugs such as danaparoid and fondaparinux, or even direct oral anticoagulants, such as rivaroxaban or apixaban, are suggested therapies, especially for long‐term management of persisting HIT. In addition, emerging data indicate that high‐dose intravenous immunoglobulin can interrupt HIT antibody‐induced platelet activation, leading to rapid platelet count recovery.

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Rapid and durable response to intravenous immunoglobulin in delayed heparin‐induced thrombocytopenia: a case report

Abstract: This case, along with others accumulating in the literature, suggest that IVIg may be effective in treating delayed HIT with persistent thrombocytopenia.

Cited by 17 publications

References 25 publications

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin‐induced thrombocytopenia: A systematic review

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin‐induced thrombocytopenia: A systematic review

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

Autoimmune heparin‐induced thrombocytopenia

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