Intravenous Administration of Low Molecular Weight and Unfractionated Heparin Elicits a Rapid Increase in Serum Pregnancy-Associated Plasma Protein A

Background: Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a useful diagnostic and prognostic marker in acute coronary syndromes. Because low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are commonly used in these cases, we analyzed the effects of intravenous administration of these heparins on serum PAPP-A concentrations. Methods: Serum concentrations of total and free PAPP-A were analyzed in 14 patients on chronic hemodialysis and in 10 coronary angiography patients. Ten of the dialysis patients received standard LMWH anticoagulation at the start of dialysis, and 4 were treated with a heparin-free method. Two of the patients on heparin-free hemodialysis received a reduced LMWH bolus 2 h after the start of dialysis. All angiography patients received UFH at the start of the procedure, and 1 patient received 2 extra boluses of UFH. Serum PAPP-A concentrations were analyzed before and during the dialysis session and during the coronary angiography examination. Results: A rapid increase in total PAPP-A (median, 25-fold) was seen in all patients within 5 min of administration for both LMWH and UFH boluses. This response was due to an increase in free PAPP-A in the serum. PAPP-A did not increase significantly in the patients who underwent heparin-free hemodialysis. Repeated heparin boluses induced a new PAPP-A release. In vitro addition of heparins to samples of whole blood did not increase PAPP-A concentrations. Conclusions: Intravenous administration of heparin induces an intense and rapid increase in free PAPP-A in the serum. We recommend that this effect be considered when PAPP-A is assessed as a biomarker in acute coronary syndromes.