title: OC-10 - Disseminated intravascular coagulation at diagnosis strongly predicts both arterial and venous thrombosis in acute myeloid leukemia patients.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) is associated with a slightly increased risk of VTE with an incidence of 1.7-8.9%, but only limited data are available. The mechanism of the occurrence of thrombosis in hematological disorders is still unresolved. Disseminated intravascular coagulation (DIC) is associated with VTE and bleeding in acute promyelocytic leukemia and acute lymphoblastic leukemia. Although DIC has also been reported in AML, no data exist on the relationship between DIC and VTE in AML patients.
  
  
  OBJECTIVE
  We hypothesized that the presence of DIC at diagnosis of AML may contribute to the risk of both venous and arterial thrombosis in AML. Therefore we studied a large cohort of adult patients with newly diagnosed AML aged <65 years by measuring DIC parameters at diagnosis prior to treatment and assessing the occurrence of both venous and arterial thrombosis during follow up. The findings of this study were validated in a second large cohort of patient with newly diagnosed AML aged >60 years.
  
  
  METHODS
  In a prospective study we analysed markers of DIC and their association with the occurrence of thrombosis during follow up in a cohort of 272 young AML patients (aged 18-65) and a validation cohort of 132 elderly AML patients (aged >60) patients that were all treated with intensive chemotherapy. DIC parameters (fibrinogen, D-dimer, alpha-2-antiplasmin, antitrombin, prothrombin time and platelets) were measured at presentation with AML before start of induction chemotherapy. The DIC score according to the International Society of Thrombosis and Haemostasis DIC scoring systemwas calculated of all patients.
  
  
  RESULTS
  The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in young patients over a median follow up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a Hazard Ratio (HR) for a high DIC score (=>5) of 4.79 (1.71-13.45) in the cohort of young AML patients. These results were confirmed in our validation cohort of elderly AML patients. (HR 11.08 (3.23-38.06)). Of all DIC parameters D-dimer levels are most predictive for thrombosis with a HR of 12.3 (3.39-42.64) in the cohort of young AML patients and a HR of 7.82 (1.95-31.38) in the elderly cohort for a D-dimer >4.0 mg/L.
  
  
  CONCLUSIONS
  It is concluded that both venous and arterial thrombosis occurs in around 10% of AML patients treated with intensive chemotherapy, which can be predicted by the presence of DIC, or individual DIC parameters at time of AML diagnosis.
authors.affiliation: Department of Hematology/Oncology, Sint Franciscus Gasthuis, Rotterdam.
authors.forename: E J
authors.initials: EJ
authors.lastname: Libourel
authors.affiliation: Clinical Trial Center - HOVON Data Center, Erasmus MC, Rotterdam; The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Klerk
authors.affiliation: Clinical Trial Center - HOVON Data Center, Erasmus MC, Rotterdam; The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: van Norden
authors.affiliation: Clinical Trial Center - HOVON Data Center, Erasmus MC, Rotterdam; The Netherlands.
authors.forename: M P M
authors.initials: MP
authors.lastname: de Maat
authors.affiliation: Department of Hematology/Oncology, Sint Franciscus Gasthuis, Rotterdam; Clinical Trial Center - HOVON Data Center, Erasmus MC, Rotterdam; The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kruip
authors.affiliation: Department of Hematology, VU Medical Center, Amsterdam; Clinical Trial Center - HOVON Data Center, Erasmus MC, Rotterdam; The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Hematology/Oncology, Sint Franciscus Gasthuis, Rotterdam.
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.affiliation: Department of Hematology/Oncology, Sint Franciscus Gasthuis, Rotterdam; Clinical Trial Center - HOVON Data Center, Erasmus MC, Rotterdam; The Netherlands.
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek