ristocetin and Neoplasms

Granulocyte colony-stimulating factor (G-CSF) stimulates the bone marrow to produce granulocytes and stem cells and is widely used to accelerate neutrophil recovery after chemotherapy. Interestingly, specific G-CSF receptors have been demonstrated not only on myeloid cells, but also on platelets. Data on the effects of G-CSF on platelet function are limited and partly conflicting. The objective of this study was to determine the effect of G-CSF on platelet aggregation and in vivo platelet activation. Seventy-eight, healthy volunteers were enrolled into this randomised, placebo-controlled trial. Subjects received 5 μg/kg methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) or placebo subcutaneously for four days. We determined platelet aggregation with a whole blood impedance aggregometer with various, clinically relevant platelet agonists (adenosine diphosphate [ADP], collagen, arachidonic acid [AA], ristocetin and thrombin receptor activating peptide 6 [TRAP]). Filgrastim injection significantly enhanced ADP (+40%), collagen (+60%) and AA (+75%)-induced platelet aggregation (all p<0.01 as compared to placebo and p<0.001 as compared to baseline). In addition, G-CSF enhanced ristocetin-induced platelet aggregation (+18%) whereas TRAP-induced platelet aggregation decreased slightly (-14%) in response to filgrastim. While baseline aggregation with all agonists was only slightly but insignificantly higher in women than in men, this sex difference was enhanced by G-CSF treatment, and became most pronounced for ADP after five days (p<0.001). Enhanced platelet aggregation translated into a 75% increase in platelet activation as measured by circulating soluble P-selectin. G-CSF enhances platelet aggregation and activation in humans. This may put patients suffering from cardiovascular disease and cancer at risk for thrombotic events.

Topics: Adenosine Diphosphate; Adolescent; Adult; Arachidonic Acid; Blood Platelets; Cardiovascular Diseases; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Neoplasms; P-Selectin; Peptide Fragments; Platelet Aggregation; Recombinant Proteins; Ristocetin; Sex Factors; Thrombosis

Functional defects of platelets are often studied by in-vitro aggregation tests with chemical compounds such as ADP, epinephrine and ristomycin (ristocetin). The aim of the present work was to investigate the effect of some diseases and that of nonsteroidal anti-inflammatory drug treatment on platelet aggregation in dogs. The examination had been carried out on 115 dogs by a Carat TX4 optical aggregometer (Entec GmbH, Ilmenau, Germany) first used in veterinary practice. The dogs were divided in three groups: healthy (control) dogs (n = 43), diseased dogs with normal haemostasis profile (n = 44), and dogs suffering from arthropathies with normal haemostasis profile treated with the nonsteroidal anti-inflammatory drugs ketoprofen or carprofen (n = 21). Following establishment of normal platelet aggregation curves in healthy dogs we found that some diseases such as diabetes mellitus, Cushing's disease, mastocytoma and lymphoma increased or decreased the aggregation maximum of platelets or caused changes in the feature of the aggregation curve. Carprofen treatment had no effect on platelet aggregation while ketoprofen decreased the aggregation maximum. These results showed that Carat TX4 aggregometer proved a useful instrument in studying platelet aggregation in platelet-rich plasma of dogs. For clinical pathologists it is important to know that the effects of some diseases and nonsteroidal anti-inflammatory drug treatments have to be taken into account when in-vitro platelet aggregation is evaluated. Based on our results and on those of other studies, we think standardization in aggregation methodology is highly recommended in veterinary laboratories.

Topics: Adenosine Diphosphate; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Case-Control Studies; Diabetes Mellitus; Dog Diseases; Dogs; Epinephrine; Ketoprofen; Neoplasms; Platelet Aggregation; Platelet Function Tests; Ristocetin

Topics: Antineoplastic Agents; Bleeding Time; Flavonoids; Humans; Neoplasms; Platelet Aggregation; Ristocetin