title: Inhibitory effects of bortezomib on platelet aggregation in patients with multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) therapy affects prothrombotic and anticoagulant processes. Patients receiving thalidomide, especially in combination with steroids, are at increased risk of venous thromboembolism (VTE), while the incidence of VTE on bortezomib is low. In vitro studies indicate that bortezomib causes a reduction in ADP-induced platelet aggregation.
  
  
  OBJECTIVE
  To analyse the influence of bortezomib on platelet aggregation induced by various agonists in patients with MM.
  
  
  METHODS
  A total of 30 patients (median age 57.5years) with relapsed/refractory MM receiving bortezomib-based regimens were analysed. Optical platelet aggregometry was performed with the agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The results from two groups: those treated with bortezomib and thalidomide (BT group, n=11) and those without thalidomide (B group, n=19) were analysed.
  
  
  RESULTS
  During the second cycle, significantly decreased platelet aggregation was observed in the B group: 5μM ADP (p=0.0285, day 1 versus 8); 3.5μM ADP (p=0.0005, day 1 versus 8 and day 1 versus 11), collagen (p=0.0014, day 4 versus 8, day 4 versus 11), 1.25mg/ml ristocetin (p=0.0017, day 1 versus 8 and day 1 versus 11). Agonist-induced platelet aggregation tended to be reduced over time during the 1st cycle in group B. In the thalidomide group, significant platelet aggregation inhibition by collagen only was found. Transient reduction in platelet count was observed in all patients, but more prominently in group B.
  
  
  CONCLUSIONS
  The inhibitory effects of prolonged exposure of bortezomib on platelet aggregation were demonstrated in relapsed/refractory MM patients, but antithrombotic activity of bortezomib should be clarified in further prospective studies.
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: rupa.matysek@gmail.com.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rupa-Matysek
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Wojtasińska
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Nowicki
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Dytfeld
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kaźmierczak
authors.affiliation: Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001897:Boronic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests; D011446:Prospective Studies; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use; D054556:Venous Thromboembolism / Q000139:chemically induced*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib
keywords: Bortezomib; Mean platelet volume; Multiple myeloma; Platelet aggregation; Venous thromboembolism