The use of angiogenic biomarkers to differentiate non-HELLP related thrombocytopenia from HELLP syndrome

Abstract

Objective. Preeclampsia (PE) is diagnosed using clinical criteria and in atypical cases the diagnosis may be inaccurate as there are no specific tests to confirm or exclude PE. This study sought to evaluate the utility of angiogenic biomarkers, sFlt1, sEng and PlGF to distinguish patients with gestational thrombocytopenia and immune thrombocytopenic purpura (ITP) from patients with thrombocytopenia resulting from the HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, a complication of severe PE.

Methods. Serum was collected and the angiogenic biomarkers of patients with ITP and gestational thrombocytopenia (N = 9) were compared to patients with HELLP (N = 11) and PE (N = 11). Circulating levels of these angiogenic biomarkers were also compared by gestational age to 1564 randomly selected normotensive women from the Calcium for Preeclampsia Prevention study.

Results. Patients with non-HELLP thrombocytopenia had lower sFlt1 (7.3 ± 3.8 ng/ml vs. 15.5 ± 5 ng/ml, P < 0.001), lower sEng (8.7 ± 3.6 vs. 34 ± 17, P < 0.001) and higher PlGF (484 ± 412 vs. 66.3 ± 44, P = 0.003) than patients with HELLP syndrome. Angiogenic factor abnormalities in patients with PE were similar to patients with HELLP syndrome, suggesting a common pathogenesis. Patients with non-HELLP thrombocytopenia had angiogenic profiles similar to normotensive controls, whereas patients with HELLP syndrome had levels higher than the 90th percentile for sFlt1 and sEng and lower than the 10th percentile for PlGF.

Conclusions. Angiogenic biomarkers may be useful in excluding conditions that mimic PE.

Keywords:

• Preeclampsia
• angiogenic factors
• thrombocytopenia

Acknowledgements

SR is supported by NIH grant WRHR 5k12HDOO1255. SAK is an investigator of the Howard Hughes Medical Institute. RJL receives salary support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Disclosures: Dr. Karumanchi is a co-investigator on patents filed by the Beth Israel Deaconess Medical Center for the use of angiogenic markers for the diagnosis and therapy of preeclampsia. Dr. Karumanchi is a consultant to Abbott Diagnostics, Beckman Coulter, Roche and Johnson & Johnson.