Nucleotide deficit and functional platelet alterations in patients on regular dialysis treatment (RDT).
In RDT patients hemocoagulative changes are repeatedly found; of these the most important are platelets' functional defects. Biochemical and biophysical modifications responsible for this pathology have not been completely clarified. In 20 non-thrombocytopenic patients, dialyzed 3 times weekly for over 1 year, we evaluated, using standard methodology, platelet adhesivity and aggregation induced by collagen and ADP at varying dosages. All blood samples were collected after the longest interdialytic period and just before dialysis. At the same time we evaluated the basic metabolic pool and, after collagen stimulation, the intraplatelet functional storage pool of ATP and ADP. The dosages were obtained using simple, reproducible and modern bioluminescence technique, which utilises microorganism light emission (bioluminescence) due to the oxidation of the bacterial substrate by catalyzing enzyme (luciferase) (1251 Luminometer LKB). We compared this data with that obtained from 40 healthy subjects. In the patients examined, adhesivity and aggregation result altered. The intraplatelet content of all nucleotides in both pools is significantly reduced if compared to the control group. The ATP and ADP concentration of both metabolic and functional pools cannot be correlated to the following: serum creatinine, BUN, calcemia, PTH, Hb. On the contrary we found that basal metabolic ATP values are inversely related (p less than 0.01) to serum phosphate levels. An analysis of results of this preliminary study leads us to hypothesize that hyperphosphatemia could interfere with intraplatelet glycolysis inducing a reduction of intracellular ATP. As all platelet functions are ATP and ADP dependent, we could consider the nucleotide deficit a cause of "uraemic platelet" disfunction, not modifiable with RDT but perhaps only through an appropriate control of phosphate levels.
D000244:Adenosine Diphosphate / Q000097:blood; D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009711:Nucleotides / Q000097:blood / Q000172:deficiency*; D010974:Platelet Aggregation / Q000187:drug effects; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000097:blood / Q000628:therapy
D009711:Nucleotides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen