Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists

PLoS One. 2016 Dec 9;11(12):e0164485. doi: 10.1371/journal.pone.0164485. eCollection 2016.

Abstract

Background: Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.

Objectives: To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.

Methods: A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.

Results: Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.

Conclusion: BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

MeSH terms

  • Acenocoumarol / administration & dosage
  • Acenocoumarol / adverse effects*
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / physiopathology
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects*
  • Follow-Up Studies
  • Hemorrhage / blood
  • Hemorrhage / chemically induced
  • Hemorrhage / diagnosis*
  • Humans
  • International Normalized Ratio
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phenprocoumon / administration & dosage
  • Phenprocoumon / adverse effects*
  • Prognosis
  • Risk Factors
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / physiopathology
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • Vitamin K
  • Acenocoumarol
  • Phenprocoumon

Grants and funding

Hartstichting (2011 T12) https://www.hartstichting.nl/, Center for Translational Molecular Medicine (01 C-201) http://www.ctmm.nl/nl, and Hartstichting (99.165) https://www.hartstichting.nl/.