Journal of thrombosis and haemostasis : JTH
October 12, 2026 · via Europe PMC
Heparin-PEAR-1 interaction contributes to platelet activation by HIT antibodies.
Buka RJ, Manickam J, Lagonotte H, +10 more, Montague SJ.
AI summary — for doctors, generated from the abstract only
Blocking the heparin-PEAR1 interaction reduced platelet activation by a HIT-like antibody and by HIT sera in vitro.
What was studied
Washed platelets from responsive donors were activated with the HIT-like mAb 5B9 and eight HIT sera plus heparin, with or without the inhibitory PEAR1 nanobody Nb138, using aggregometry and P-selectin flow cytometry.
Key findings
- Aggregation and activation to heparin (0.5 IU/mL) was blocked by Nb138 (100 nM)
- 5B9 and HIT sera with heparin induced full aggregation within 15 minutes, blocked or delayed by Nb138 in most donors
- P-selectin expression was reduced by Nb138 in all donors
Clinical relevance
Suggests PEAR1 contributes to HIT pathophysiology and might become a therapeutic target, though far from clinical use.
Who should care
Limitations
Ex vivo study with limited sera (eight) and donor variability; aggregometry was done for only three sera and the effect was not universal across donors.
PEAR1 appears to be a contributor to platelet activation in HIT in vitro.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
Heparin is a negatively charged, polysaccharide used as an anticoagulant. In 0.5-1% of patients receiving unfractionated heparin, heparin-induced thrombocytopenia (HIT) occurs 5-10 days after exposure. In HIT, heparin binds to platelet factor 4 (PF4), exposing PF4 neoepitopes, allowing binding of heparin-dependent anti-PF4 antibodies, forming immune complexes that activate platelets through FcγRIIA. Recently, we showed that heparin mediates weak/slow aggregation of platelets via platelet endothelial aggregation receptor-1 (PEAR1).
Objectives
To investigate the role of the heparin-PEAR1 interaction in platelet activation in HIT.
Methods
Activation of washed platelets from multiple responsive donors to 5B9 (HIT-like mAb) and eight HIT sera in the presence of heparin, and in the presence or absence of the inhibitory PEAR1 nanobody, Nb138, was assessed. Light transmission aggregometry over 30 minutes was used to measure the kinetics of platelet activation for three sera, whilst flow cytometry for P-selectin expression gave an end read-out after 60 minutes for all eight sera.
Results
Aggregation and activation to heparin (0.5 IU/mL) was blocked by Nb138 (100 nM). 5B9 and HIT patient sera in the presence of heparin induced full platelet aggregation within 15 minutes, which was blocked or delayed by Nb138 in most donors. P-selectin expression was increased with 5B9 and HIT sera in the presence of heparin and was reduced by Nb138 in all donors.
Conclusions
Our results demonstrate that PEAR1 blockade reduces/blocks platelet activation to a HIT-like monoclonal antibody and HIT sera in the presence of heparin suggesting the heparin-PEAR1 axis may contribute to the pathophysiology in HIT.
DOI
10.1016/j.jtha.2026.10.002
PMID
42863791
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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