A study of platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin in hemodialyzed patients under erythropoietin therapy

• Published in: Thrombosis research 1995-01, Vol.77 (2), p.133-143
• Main Authors: Malyszko, J., Malyszko, J.S., Borawski, J., Rydzewski, A., Kalinowski, M., Azzadin, A., Mysliwiec, M., Buczko, W.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Anemia - etiology; Anemia - therapy; Arachidonic Acid - pharmacology; Biological and medical sciences; Biomarkers - blood; Bleeding Time; Blood Platelets - drug effects; Blood Platelets - physiology; Blood Proteins - analysis; erythropoietin; Erythropoietin - adverse effects; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Female; fibrinolysis; Fibrinolysis - drug effects; Fibrinolysis - physiology; Hematocrit; Hematology; Hemoglobins - analysis; hemostasis; Hemostasis - drug effects; Hemostasis - physiology; Humans; Investigative techniques, diagnostic techniques (general aspects); Kidney Failure, Chronic - blood; Kidney Failure, Chronic - complications; Male; Medical sciences; Middle Aged; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Platelet Aggregation - drug effects; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Renal Dialysis; Ristocetin - pharmacology; serotonin; Serotonin - blood; Serotonin - physiology; Thromboembolism - chemically induced; Time Factors; uremia
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(95)91619-V

Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. Therefore in the present study an attempt has been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week. Bleeding time was shortened significantly as early as after 1 week of the therapy, whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout the study. Only a transient rise in platelet count, collagen-induced platelet aggregation, β-thromboglobulin and VIII:C activity were observed during therapy relative to baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in platelet aggregation in response to ristocetin was found, starting from the 2nd week of the therapy. It lasted throughout the study and correlated inversely with the bleeding time and positively with a rise in both blood and platelet serotonin. rHuEPO did not alter plasminogen, fibrinogen, platelet factor 4, α 2macroglobulin levels, protein C activity and euglobulin clot lysis time. A decline in protein C and S concentrations and antithrombin III activity observed during the therapy were counterbalanced by a fall in the activity of α 2 antiplasmin, C1 esterase inhibitor and plasminogen activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy.