Heparin-Induced Thrombocytopenia: A Review of New Concepts in Pathogenesis, Diagnosis, and Management

Marchetti, Matteo; Zermatten, Maxime G.; Calderara, Debora Bertaggia; Aliotta, Alessandro; Alberio, Lorenzo

doi:10.3390/jcm10040683

Cited by 31 publications

(48 citation statements)

References 98 publications

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“…In turn, this triggers massive platelet activation, aggregation, and consumption, which reduces platelet count and results in thrombosis, similar to heparin-induced thrombocytopenia (HIT) [ 4 , 7 , 11 , 12 , 14 , 18 ]. HIT results from platelet activation and consumption against heparin-platelet complex, typically within 5–14 days of exposure to heparin [ 4 , 11 , 12 , 14 , 18 , 22 ]. This may occur in 0.5–5% of those treated with heparin, with thrombosis occurring in 20–64% of patients with HIT [ 11 , 12 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…HIT results from platelet activation and consumption against heparin-platelet complex, typically within 5–14 days of exposure to heparin [ 4 , 11 , 12 , 14 , 18 , 22 ]. This may occur in 0.5–5% of those treated with heparin, with thrombosis occurring in 20–64% of patients with HIT [ 11 , 12 , 22 ]. TTS differs from HIT in that platelet activation, aggregation, and consumption is not dependent on exposure to heparin and less sensitive to inhibition with high-dose heparin [ 4 , 11 , 12 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines

Long

Bridwell

Gottlieb

2021

The American Journal of Emergency Medicine

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Background Current vaccines for the Coronavirus Disease of 2019 (COVID-19) have demonstrated efficacy with low risk of adverse events. However, recent reports of thrombosis with thrombocytopenia syndrome (TTS) associated with adenovirus vector vaccines have raised concern. Objective This narrative review summarizes the current background, evaluation, and management of TTS for emergency clinicians. Discussion TTS, also known as vaccine-induced immune thrombotic thrombocytopenia, is a reaction associated with exposure to the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and AD26.COV2·S (Johnson & Johnson) vaccine, which may result in thrombocytopenia and thrombotic events. There are several case series of patients diagnosed with TTS, but the overall incidence is rare. TTS is characterized by exposure to one of the aforementioned vaccines 4–30 days prior to presentation, followed by thrombosis, mild-to-severe thrombocytopenia, and a positive platelet factor-4 (PF4)-heparin enzyme-linked immunosorbent assay (ELISA). Thrombosis typically involves atypical locations, including cerebral venous thrombosis and splanchnic vein thrombosis. Evaluation should include complete blood count, peripheral smear, D-dimer, fibrinogen, coagulation panel, renal and liver function, and electrolytes, as well as PF4-heparin ELISA if available. Consultation with hematology is recommended if suspected or confirmed. Treatment may include intravenous immunoglobulin and anticoagulation, while avoiding heparin-based agents and platelet transfusion. Conclusions With increasing vaccine distribution, it is essential for emergency clinicians to be aware of the evaluation and management of this condition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines

Long

Bridwell

Gottlieb

2021

The American Journal of Emergency Medicine

View full text Add to dashboard Cite

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“…While nonheparin anticoagulants and intravenous immunoglobulin (IVIg) have been proposed as firstline treatments for VITT patients, these approaches are not fail-safe and entail drawbacks that may curtail their effectiveness (e.g., risk of promiscuous FcR activation, acute anaphylaxis, or even thromboembolic events in the case of intravenous immunoglobulin) (4). Several secondline therapies for HIT have also been suggested including plasmapheresis, especially when non-heparin anticoagulation is contraindicated because of major bleeding events (5). Thus, more insight into the precise pathophysiology of VITT is needed to enable more personalized medicine approaches.…”

Section: Rare Thrombotic Reactions To Adenovirus-based Covid-19 Vaccinesmentioning

confidence: 99%

Is complement the culprit behind COVID-19 vaccine-related adverse reactions?

Mastellos¹,

Skendros²,

Lambris³

2021

Journal of Clinical Investigation

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“…HIT is an acquired prothrombotic disorder characterized by thrombocytopenia, coagulopathy, and a high risk of thrombosis 9 , 10 that is induced by antibodies targeting neoepitopes formed by the binding of PF4 to heparin. 11 , 12 Binding of these immune complexes to platelet FcγRIIa receptors leads to platelet activation, degranulation, NETosis, and endothelial activation, further aggravated by activation of the complement system.…”

Section: Discussionmentioning

confidence: 99%

A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2

Sørensen

Rolland²,

Hartmann

et al. 2021

Blood Advances

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Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged. We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine. Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases. Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs). Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumption coagulopathy are highly unusual. A maximum 4T heparin-induced thrombocytopenia (HIT) score and a positive immunoassay for anti-platelet factor 4/heparin antibodies identified autoimmune HIT as a potential pathogenic mechanism. Although causality has not been established, our case emphasizes the importance of clinical awareness. Further studies of this potentially new clinical entity have suggested that it should be regarded as a vaccine-induced immune thrombotic thrombocytopenia.

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Heparin-Induced Thrombocytopenia: A Review of New Concepts in Pathogenesis, Diagnosis, and Management

Cited by 31 publications

References 98 publications

Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines

Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines

Is complement the culprit behind COVID-19 vaccine-related adverse reactions?

A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2

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