title: Effect of beta-blockers, Ca2+ antagonists, and benzodiazepines on bleeding incidence in patients with chemotherapy induced thrombocytopenia.
abstract: Beta-1-adrenoreceptor antagonists, Ca(2+) antagonists, and benzodiazepines negatively affect platelet aggregation in vitro. Few data exists on whether platelet function in vivo is relevantly influenced by exposure to any these substances. We analysed in three cohorts of 100 patients each treated with allogeneic hematopoietic stem cell transplantation (HSCT), autologous HSCT, and intensive chemotherapy, respectively, whether treatment with these drugs was associated with an increased risk of bleeding. Cumulative incidences of bleeding in the three cohorts were 47 +/- 5% after allogeneic transplants, 30 +/- 5% after autologous transplant, and 46 +/- 5% after chemotherapy (p = 0.008). Exposure to beta-blockers (hazard ratio [HR] 0.71, p = 0.32), Ca(2+) antagonists (HR 0.90, p = 0.73), and benzodiazepines (HR 1.18, p = 0.29) did not significantly increase the risk of bleeding in any cohort. Instead, bleeding risk was determined by platelet count, presence of inflammation, azotemia, presence of graft-versus-host disease and treatment with low-molecular weight heparin. After correcting for these factors, no differences in bleeding risk were seen between the three cohorts. In conclusion, therapy with Beta-1-adrenoreceptor antagonists, Ca(2+) antagonists, and benzodiazepines did not appear to significantly increase the risk for hemorrhagic complications in patients with iatrogenic severe thrombocytopenia.
authors.affiliation: Stem Cell Transplant Team, University Hospital, Basel, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Rysler
authors.forename: Nadina
authors.initials: N
authors.lastname: Stoffel
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Tsakiris
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006470:Hemorrhage / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced / Q000150:complications; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D001569:Benzodiazepines