Cor Vasa 2007, 49(9):303-311 | DOI: 10.33678/cor.2007.111

Potential uses of assessment of functional changes in primary hemostasis by the PFA-100 analyzer and modified assessment of platelet aggregation in rationalizing management of patients with familiar hypercholesterolemia treated by extracorporeal LDL-cholesterol elimination

Martin Blažek, Milan Bláha, Jaroslav Malý, Vladimír Bláha, Melanie Cermanová, Vladimír Mašín, Miroslav Pecka, Ladislav Slováček

II. interní klinika, Oddělení hematologie, Fakultní nemocnice Hradec Králové a Univerzita Karlova v Praze - Lékařská fakulta v Hradci Králové, Hradec Králové, Česká republika

Background:
LDL-apheresis is a method for extracorporeal LDL-cholesterol elimination, employed in patients with severe hyperlipidemia refractory to pharmacotherapy and dietary measures. As the method is medically demanding and costly, it is desirable to identify parameters defining optimal intensity and frequency of individual therapeutic sessions. While the tools for long-term evaluation have been identified (imaging methods), appropriate markers of the current status are not yet available. Some studies have suggested normalization of activated platelet function. However, it is not clear to what extent the changes in platelet function are expressed, how important the changes are, and how soon the function deteriorates again after a therapeutic session. Assessment of platelet function changes prior to and after LDL-apheresis is potentially fast and beneficial for indirect monitoring of atherogenesis and, hence, contributes to the medically and economically optimal guidance of therapy using LDL-apheresis. Appropriate tools for determining the efficacy of this therapeutic option in adequate reduction of atherosclerosis activity are yet to be identified.

Method:
The assessment was performed using a Dade Behring PFA-100 analyzer (Germany), allowing to measure platelet-mediated hemostasis in non-coagulable blood. The method mimics in vivo platelet activation by mechanical stress and collagen. Our group of patients included 9 individuals (4 women and 5 men) with familiar hypercholesterolemia, with a mean age of 55 years; of these 2 were homozygotes.
Platelet aggregation was examined by standard method on an APACKS-4 aggregometer (Helena Laboratories, Beaumont, USA). First, a standard spectrum-aggregation measurement was performed in a test probe with the only changes suggested following stimulation with ADP. Next, aggregation was determined using 3 different ADP dilutions, specifically 2.5 μmol/L; 1.25 μmol/L a 0.625 μmol/L.

Results:
While closure time (CT) increased in all cases upon separation, the degree of post-procedural CT increase did not reach statistical significance (p < 0.14). No differences between homozygotes and heterozygotes were seen. In modified tests of platelet aggregation, apheresis was followed by decreases in the aggregation curve slope and maximum amplitude (p < 0.05).

Conclusion:
In patients with familiar hypercholesterolemia, LDL-apheresis results in primary hemostasis normalization. Modified assessment of platelet aggregation might become another suitable tool for monitoring the activity of the process in these severely-ill patients. However, the assessment is a fairly technically demanding and costly procedure. While being relatively more available, judging by initial experience, separate examination using the PFA-100 analyzer seems unsuitable for current assessment of the optimal intensity of individual LDL-apheresis procedures.

Keywords: Hemostasis; PFA-100; LDL-apheresis; Atherosclerosis

Published: September 1, 2007  Show citation