Dataset Information

Optimization of a murine immunization model for study of PF4/heparin antibodies.

ABSTRACT:

Summary background

Heparin-induced thrombocytopenia (HIT) is a life-threatening thrombotic illness caused by drug-dependent antibodies recognizing complexes of platelet factor 4 (PF4) and heparin. Little is known about the immune pathogenesis of HIT, in particular factors influencing PF4/heparin antibody formation. To gain insight into the biologic basis of heparin sensitization, we have recently developed an animal model using wild-type (WT) mice in which murine PF4/heparin antibodies (anti-mPF4/H) arise de novo after antigen challenge.

Objectives and methods

This report describes technical refinements to the murine model and describes additional biologic features of the immune response to mPF4/heparin.

Results

Our studies indicate that antibody responses to mPF4/heparin are dependent on murine strain, injection routes and doses of mPF4 and heparin. C57BL/6 mice are more immunologically responsive to mPF4/heparin antigen than BALB/c mice and robust immunization can be achieved with intravenous, but not intraperitoneal, administration of antigen. We also observe a direct relationship between initial concentrations of mPF4 and antibody levels. Additionally, we demonstrate that mPF4/H immune response in mice decays with time, is not associated with thrombocytopenia and displays characteristics of immune recall on re-exposure to antigen.

Conclusions

These studies describe and characterize a murine model for studying the immunologic basis of PF4/heparin sensitization.

SUBMITTER: Suvarna S

PROVIDER: S-EPMC3711941 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

Optimization of a murine immunization model for study of PF4/heparin antibodies.

Suvarna S S Qi R R Arepally G M GM

Journal of thrombosis and haemostasis : JTH 20090224 5

<h4>Summary background</h4>Heparin-induced thrombocytopenia (HIT) is a life-threatening thrombotic illness caused by drug-dependent antibodies recognizing complexes of platelet factor 4 (PF4) and heparin. Little is known about the immune pathogenesis of HIT, in particular factors influencing PF4/heparin antibody formation. To gain insight into the biologic basis of heparin sensitization, we have recently developed an animal model using wild-type (WT) mice in which murine PF4/heparin antibodies ( ...[more]

PMID: 19245419

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Project description:AbstractPlatelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4/polyanion enzyme-immunoassays and negative/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile). We tested these patients by a standard chemiluminescence assay that detects anti-PF4/heparin antibodies found in HIT (HemosIL AcuStar HIT-IgG(PF4-H)) as well as a novel chemiluminescence assay for anti-PF4 antibodies found in VITT. Representative control sera included an exploratory anti-PF4 antibody-positive but HIPA-negative/weak cohort obtained before 2020 (n = 188). We identified 9 patients with a clinical-pathological profile of a VITT-like disorder in the absence of proximate heparin or vaccination, with a high frequency of stroke (arterial, n = 3; cerebral venous sinus thrombosis, n = 4), thrombocytopenia (median platelet count nadir, 49 × 109/L), and hypercoagulability (greatly elevated D-dimer levels). VITT-like serological features included strong reactivity by PIPA (aggregation <10 minutes in 9/9 sera) and positive testing in the novel anti-PF4 chemiluminescence assay (3/9 also tested positive in the anti-PF4/heparin chemiluminescence assay). Our exploratory cohort identified 13 additional patient sera obtained before 2020 with VITT-like anti-PF4 antibodies. Platelet-activating VITT-like anti-PF4 antibodies should be considered in patients with thrombocytopenia, thrombosis, and very high D-dimer levels, even without a proximate exposure to heparin or adenovirus vector vaccines.

Dataset Information

Optimization of a murine immunization model for study of PF4/heparin antibodies.

Summary background

Objectives and methods

Results

Conclusions

Publications

Optimization of a murine immunization model for study of PF4/heparin antibodies.

Similar Datasets

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