Definition of major bleeding in surgical studies

Taking into account historical criteria and additional consultations with European and North American surgeons with experience from clinical trials and event adjudication the Subcommittee on Control of Anticoagulation has approved the following recommendation for definition of major bleeding in surgical studies.

• 1
  Fatal bleeding, and/or
• 2
  Bleeding that is symptomatic and occurs in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, pericardial, in a non‐operated joint, or intramuscular with compartment syndrome, assessed in consultation with the surgeon, and/or
• 3
  Extrasurgical site bleeding causing a fall in hemoglobin level of 20 g L−1 (1.24 mmol L−1) or more, or leading to transfusion of two or more units of whole blood or red cells, with temporal association within 24–48 h to the bleeding, and/or
• 4
  Surgical site bleeding that requires a second intervention– open, arthroscopic, endovascular – or a hemarthrosis of sufficient size as to interfere with rehabilitation by delaying mobilization or delayed wound healing, resulting in prolonged hospitalization or a deep wound infection, and/or
• 5
  Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability, as assessed by the surgeon. There should be an associate fall in hemoglobin level of at least 20 g L−1 (1.24 mmol L−1), or transfusion, indicated by the bleeding, of at least two units of whole blood or red cells, with temporal association within 24 h to the bleeding.
• 6
  The period for collection of these data is from start of surgery until five half‐lives after the last dose of the drug with the longest half‐life and with the longest treatment period (in case of unequal active treatment durations).
• 7
  The population is those who have received at least one dose of the study drug.

It is important to note that these definitions only are valid if the study is double blind. Any other design is subject to unacceptable bias. There should be an independent, blinded adjudication committee to review all hemorrhagic complications