Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty

Elshoury, Amro; Khedr, Maha; Abousayed, Mostafa M.; Mehdi, Syed

doi:10.1016/j.artd.2015.07.003

Cited by 14 publications

(11 citation statements)

References 13 publications

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“…H eparin-induced thrombocytopenia (HIT) is a serious prothrombotic disorder caused by antibodies to platelet factor 4 (PF4): polyanion complexes that develop after heparin exposure. 1 Several reports indicate that a particularly severe form of HIT, spontaneous HIT, occurs in individuals with no prior heparin exposure and is characterized by thrombotic complications, strong HIT serologic test results [2][3][4][5][6][7][8][9][10][11][12] and suboptimal response to treatment with direct thrombin inhibitors (DTIs). 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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…Some aHIT patients with extremely low platelet counts may be at increased bleeding risk, as observed in four of 12 patients with a platelet nadir of < 20 × 10 9 L −1 . Bleeding sites include intracranial and adrenal . In some cases (e.g.…”

Section: Treatment Of Ahitmentioning

confidence: 96%

“…To date, ≈ 20 cases of spontaneous HIT syndrome have been reported [42][43][44][45][46][47][48][49][50][51][52][53][54]. Affected patients resemble those with HIT both clinically (thrombocytopenia and thrombosisoften including adrenal hemorrhagic infarction) and serologically (strong positive results in PF4-dependent EIA and SRA/HIPA), despite the absence of proximate (closely preceding) heparin exposure.…”

Section: Spontaneous Hit Syndromementioning

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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“…Over the past decade, it has become recognised that patients can develop a disorder identical to HIT—including presence of ‘HIT antibodies’—despite no proximate exposure to heparin 9 10. Known as ‘spontaneous HIT syndrome’, two clinical settings are described—postinfection9–11 and postorthopaedic surgery (almost always postknee arthroplasty) 12–20. We report a case of acute adrenal failure caused by bilateral adrenal infarction caused by spontaneous HIT syndrome postelective knee arthroplasty, with delayed recognition of evolving adrenal failure representing a ‘near-miss’ scenario.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous heparin-induced thrombocytopenia syndrome presenting as bilateral adrenal infarction after knee arthroplasty

et al. 2019

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Adrenal gland infarction resulting from adrenal vein thrombosis is an infrequently recognised entity with a limited differential diagnosis. When bilateral, it can result in acute life-threatening adrenal failure. Heparin-induced thrombocytopenia (HIT) is an antibody-mediated, prothrombotic state that represents an important cause of adrenal vein thrombosis leading to associated infarction. Sometimes, the clinical picture of HIT—including the presence of HIT antibodies—occurs despite absence of proximate heparin exposure (‘spontaneous HIT syndrome’). We report a case of nearly missed adrenal failure secondary to bilateral adrenal infarction that evolved during the second week following knee arthroplasty (a known trigger of spontaneous HIT syndrome). The combination of bilateral adrenal infarction, thrombocytopenia and presence of platelet-activating HIT antibodies not explainable by preceding heparin exposure led to a diagnosis of postknee arthroplasty spontaneous HIT syndrome. The case also highlights the clinical and laboratory findings associated with rapidly progressive acute adrenal failure.

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Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty

Cited by 14 publications

References 13 publications

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

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

Autoimmune heparin‐induced thrombocytopenia

Spontaneous heparin-induced thrombocytopenia syndrome presenting as bilateral adrenal infarction after knee arthroplasty

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