Alterations in the Von Willebrand Factor/ADAMTS13 axis in preeclampsia.

BACKGROUND: Preeclampsia is a gestational hypertensive disorder, characterised by maternal endothelial activation, and increased ratio of soluble fms-like tyrosine kinase inhibitor-1 (sFlt-1) to placental growth factor (PlGF). The von Willebrand Factor (VWF)/ADAMTS13 axis is of interest because of the underlying endothelial activation, and clinical overlap with pregnancy-associated thrombotic thrombocytopenic purpura.

OBJECTIVES: To assess VWF, ADAMTS13, and VWF/ADAMTS13 ratio in preeclampsia, and look for associations with sFlt-1/PlGF ratio, and clinical features.

PATIENTS/METHODS: 34 preeclampsia cases and 48 normal pregnancies were assessed in a case-control study. 12 normal pregnancies in women with a history of preeclampsia formed an additional comparator group. VWF antigen (VWF:Ag) and activity (VWF:Ac (VWF:GPIbM)) were measured via automated immunoturbidimetric assay; ADAMTS13 activity via FRETS-VWF73 assay; and sFlt-1 and PlGF via ELISA.

RESULTS: VWF:Ag was higher in preeclampsia than normal pregnancy (median 3.07 vs 1.87 iu/ml, P<0.0001). ADAMTS13 activity was slightly lower (89.6 vs 94.4 iu/dl, P=0.02), with no severe deficiencies. Significant elevations in VWF:Ac were not observed in preeclampsia, resulting in reduced VWF:Ac/VWF:Ag ratios (0.77 vs 0.97, P <0.0001). VWF:Ag/ADAMTS13 ratios were significantly higher in preeclampsia (3.42 vs 2.06, P <0.0001), with adjusted odds ratio of 19.2 for ratio>2.7 (>75th centile of normal pregnancy). Those with a history of preeclampsia had similar ratios to normal pregnant controls. VWF:Ag/ADAMTS13 and sFlt-1/PlGF were not correlated. However, % fall in platelets correlated positively with VWF:Ac (P=0.01); VWF:Ac/VWF:Ag ratio (P=0.004), and sFlt-1/PlGF ratio (P=0.01).

CONCLUSIONS: The VWF/ADAMTS13 axis is significantly altered in preeclampsia. Further investigation of potential clinical utility is warranted.