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

Abstract

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.

Pregnancy-associated plasma protein A: spotlight on kidney diseases

“…In our studies as well as in the study of Etter et al (43) Immunoanalyzer (Innotrac Diagnostics). Total PAPP-A concentration in hemodialysis patients was 9.0 (6.9 -11.9) mIU/L and concentration of free PAPP-A was 5.2 (4.2 -7.0) mIU/L (median and IQR) (40) .…”

“…This complex is also present at very low concentration in non-pregnant individuals. In hemodialysis patients, both total and free PAPP-A concentration is increased (40) . In patients with acute coronary syndromes, the PAPP-A increase is given by the increase of free (uncomplexed) PAPP-A and this increase might not always be detected by classical tests used in pregnancy (23,41,42) .…”

“…Another point that should be addressed is timing of PAPP-A collection since it can be infl uenced by previous application of heparin (see below) (40) . Of note, in vitro addition of heparin to blood does not infl uence PAPP-A concentration.…”

“…PAPP-A levels are signifi cantly increased by heparin administration (unfractionated heparin as well as low molecular weight heparin enoxaparin) but are not infl uenced by another anticoagulant, bivalirudin (40,58) . Total PAPP-A increased up to 25-fold within 5 min after heparin administration and the increase was given by free PAPP-A.…”

Identification of myocardial injury in the emergency setting

“…Other potential ACS biomarkers include growth differentiation factor-15 (GDF-15) [79], heart-type fatty acid-binding protein (FABP) [80] and pregnancy associated plasma protein-A (PAPP-A) [81], with the latter biomarker (PAPP-A) illustrating the need for prospective studies controlling for important variables to define its role in the ACS setting [82][83][84][85][86]. These assays may identify those at highest risk, and that information may allow for more aggressive treatment of those individuals.…”