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Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia.
Thromb Res. 2021 08; 204:40-51.TR

Abstract

Heparin-induced thrombocytopenia (HIT) is characterized clinically by thrombocytopenia, hypercoagulability, and increased thrombosis risk, and serologically by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Heparin-"induced" acknowledges that HIT is usually triggered by a proximate immunizing exposure to heparin. However, certain non-heparin medications (pentosan polysulfate, hypersulfated chondroitin sulfate, fondaparinux) can trigger "HIT". Further, naturally-occurring polyanions (bacterial lipopolysaccharide, DNA/RNA) can interact with PF4 to recapitulate HIT antigens. Indeed, immunologic presensitization to naturally-occurring polyanions could explain why HIT more closely resembles a secondary, rather than a primary, immune response. In 2008 it was first reported that a HIT-mimicking disorder can occur without any preceding exposure to heparin or polyanionic medications. Termed "spontaneous HIT syndrome", two subtypes are recognized: (a) surgical (post-orthopedic, especially post-total knee arthroplasty, and (b) medical (usually post-infectious). Recently, COVID-19 adenoviral vector vaccination has been associated with a thrombotic thrombocytopenic disorder associated with positive PF4-dependent enzyme-immunoassays and serum-induced platelet activation that is maximal when PF4 is added. Vaccine-induced immune thrombotic thrombocytopenia (VITT) features unusual thromboses (cerebral venous thrombosis, splanchnic vein thrombosis) similar to those seen in spontaneous HIT syndrome. The emerging concept is that classic HIT reflects platelet-activating anti-PF4/heparin antibodies whereas spontaneous HIT syndrome and other atypical "autoimmune HIT" presentations (delayed-onset HIT, persisting HIT, heparin "flush" HIT) reflect heparin-independent platelet-activating anti-PF4 antibodies-although the precise relationships between PF4 epitope targets and the clinical syndromes remain to be determined. Treatment of spontaneous HIT syndrome includes non-heparin anticoagulation (direct oral Xa inhibitors favored over direct thrombin inhibitors) and high-dose immunoglobulin.

Authors+Show Affiliations

Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Hamilton Regional Laboratory Medicine Program (Transfusion Medicine), Hamilton, Ontario, Canada; Service of Benign Hematology, Hamilton Health Sciences (Hamilton General Hospital), Canada. Electronic address: twarken@mcmaster.ca.From Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

34144250

Citation

Warkentin, Theodore E., and Andreas Greinacher. "Spontaneous HIT Syndrome: Knee Replacement, Infection, and Parallels With Vaccine-induced Immune Thrombotic Thrombocytopenia." Thrombosis Research, vol. 204, 2021, pp. 40-51.
Warkentin TE, Greinacher A. Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thromb Res. 2021;204:40-51.
Warkentin, T. E., & Greinacher, A. (2021). Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thrombosis Research, 204, 40-51. https://doi.org/10.1016/j.thromres.2021.05.018
Warkentin TE, Greinacher A. Spontaneous HIT Syndrome: Knee Replacement, Infection, and Parallels With Vaccine-induced Immune Thrombotic Thrombocytopenia. Thromb Res. 2021;204:40-51. PubMed PMID: 34144250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. AU - Warkentin,Theodore E, AU - Greinacher,Andreas, Y1 - 2021/06/09/ PY - 2021/05/03/received PY - 2021/05/26/revised PY - 2021/05/28/accepted PY - 2021/6/19/pubmed PY - 2021/7/16/medline PY - 2021/6/18/entrez KW - Autoimmune HIT (aHIT) KW - COVID-19 vaccination KW - Cerebral vein thrombosis (CVT) KW - Disseminated intravascular coagulation (DIC) KW - Heparin-induced thrombocytopenia (HIT) KW - Infection KW - Splanchnic vein thrombosis KW - Thrombocytopenia KW - Thrombosis KW - Total knee arthroplasty (TKA) SP - 40 EP - 51 JF - Thrombosis research JO - Thromb Res VL - 204 N2 - Heparin-induced thrombocytopenia (HIT) is characterized clinically by thrombocytopenia, hypercoagulability, and increased thrombosis risk, and serologically by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Heparin-"induced" acknowledges that HIT is usually triggered by a proximate immunizing exposure to heparin. However, certain non-heparin medications (pentosan polysulfate, hypersulfated chondroitin sulfate, fondaparinux) can trigger "HIT". Further, naturally-occurring polyanions (bacterial lipopolysaccharide, DNA/RNA) can interact with PF4 to recapitulate HIT antigens. Indeed, immunologic presensitization to naturally-occurring polyanions could explain why HIT more closely resembles a secondary, rather than a primary, immune response. In 2008 it was first reported that a HIT-mimicking disorder can occur without any preceding exposure to heparin or polyanionic medications. Termed "spontaneous HIT syndrome", two subtypes are recognized: (a) surgical (post-orthopedic, especially post-total knee arthroplasty, and (b) medical (usually post-infectious). Recently, COVID-19 adenoviral vector vaccination has been associated with a thrombotic thrombocytopenic disorder associated with positive PF4-dependent enzyme-immunoassays and serum-induced platelet activation that is maximal when PF4 is added. Vaccine-induced immune thrombotic thrombocytopenia (VITT) features unusual thromboses (cerebral venous thrombosis, splanchnic vein thrombosis) similar to those seen in spontaneous HIT syndrome. The emerging concept is that classic HIT reflects platelet-activating anti-PF4/heparin antibodies whereas spontaneous HIT syndrome and other atypical "autoimmune HIT" presentations (delayed-onset HIT, persisting HIT, heparin "flush" HIT) reflect heparin-independent platelet-activating anti-PF4 antibodies-although the precise relationships between PF4 epitope targets and the clinical syndromes remain to be determined. Treatment of spontaneous HIT syndrome includes non-heparin anticoagulation (direct oral Xa inhibitors favored over direct thrombin inhibitors) and high-dose immunoglobulin. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/34144250/Spontaneous_HIT_syndrome:_Knee_replacement_infection_and_parallels_with_vaccine_induced_immune_thrombotic_thrombocytopenia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(21)00357-1 DB - PRIME DP - Unbound Medicine ER -