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Antiplatelet factor 4/heparin antibodies in patients with gram negative bacteremia
Georgios Pongas1, Swapan Kumar Dasgupta, Perumal Thiagarajan
1Michael E. DeBakey Veterans Affairs Medical Center, Department of Medicine, Baylor College of Medicine, Houston, TX United States.
Abstract:
Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome of thrombocytopenia and prothrombotic state that follows exposure to heparin. However, spontaneous HIT has been described in the setting of infection, without evidence of previous heparin administration. Since PF4 binds to lipid A portion of lipopolysaccharide, we tested for the presence of antiPF4/heparin antibodies in patients with gram-negative bacteremia. Patients with bacteremia had higher titers of antiPF4/heparin antibodies compared to normal controls 26.3 ± SD 34 units, N=32 versus 6.3 ± SD 2.38 units, N=10, P=0.001. FITC-labeled PF4 interacted with lipopolysaccharide in a concentration-dependent manner as determined by quenching of the emission spectrum following excitation at λ 488. In addition, immunoaffinity purified antiPF4/Heparin antibodies from 3 patients with HIT cross-reacted with PF4/heparin complex. These results show that PF4/LPS complex is immunogenic and can elicit cross-reacting antibodies against PF4/Heparin, providing an explanation for the presence of these antibodies in individuals, who were never been exposed to heparin before. These antibodies may also be at least partly responsible for the thrombocytopenia associated with infection.
Insights
Infections can trigger heparin-induced thrombocytopenia (HIT) by causing antibodies to form against platelet factor 4 (PF4) and lipopolysaccharide (LPS). This immune response explains spontaneous HIT in patients without prior heparin exposure.
Area of Science:
- Immunology
- Hematology
- Infectious Diseases
Background:
- Heparin-induced thrombocytopenia (HIT) is an immune condition causing low platelets and blood clots after heparin exposure.
- Spontaneous HIT, occurring without heparin use, has been observed in infected patients, suggesting alternative triggers.
- Platelet factor 4 (PF4) binds to lipopolysaccharide (LPS), a component of gram-negative bacteria.
Purpose of the Study:
- To investigate the presence of anti-PF4/heparin antibodies in patients with gram-negative bacteremia.
- To explore the immunogenicity of PF4/LPS complexes and their role in spontaneous HIT.
Main Methods:
- Measured anti-PF4/heparin antibody titers in patients with bacteremia and healthy controls.
- Assessed the interaction between fluorescently labeled PF4 and LPS using spectral quenching.
- Tested cross-reactivity of HIT patient antibodies with PF4/heparin complexes.
Main Results:
- Patients with bacteremia exhibited significantly higher anti-PF4/heparin antibody titers than controls (26.3 ± 34 units vs. 6.3 ± 2.38 units, P=0.001).
- PF4 demonstrated concentration-dependent interaction with LPS.
- Antibodies from HIT patients cross-reacted with PF4/heparin complexes.
Conclusions:
- The PF4/LPS complex is immunogenic, inducing antibodies that cross-react with PF4/heparin.
- This cross-reactivity offers an explanation for spontaneous HIT in patients never exposed to heparin.
- These antibodies may contribute to the thrombocytopenia observed in infections.
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