Table 3

Definition of adverse events
A fatal outcome
Definition of serious adverse reaction Any thrombotic event e.g. stroke, TIA
Major Bleeding- Defined as clinically overt bleeding that is associated with:
• A fall in haemoglobin of 2 g/dl or more, or
• A transfusion of 2 or more units of packed red blood cells or whole blood, or
• A critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or
• A fatal outcome
Definition of a non serious adverse reaction Defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact (visit or telephone call) with a clinician, (temporary) cessation of warfarin treatment, or associated with discomfort for the subject such as pain or impairment of activities of daily life.
Examples of non-major clinically relevant bleeding are:
• Epistaxis if it lasts for more than 5 minutes, if it is repetitive (i.e., 2 or more episodes of true bleeding, i.e., not spots on a handkerchief, within 24 hours), or leads to an intervention (packing, electrocautery, etc.) and no admission to hospital.
• Gingival bleeding if it occurs spontaneously (i.e., unrelated to tooth brushing or eating), or if it lasts for more than 5 minutes
• Haematuria if it is macroscopic, and either spontaneous or lasts for more than 24 hours after instrumentation (e.g., catheter placement or surgery) of the urogenital tract
• Macroscopic gastrointestinal haemorrhage: at least 1 episode of melena or hematemesis, if clinically apparent
• Rectal blood loss, if more than a few spots
• Haemoptysis, if more than a few speckles in the sputum, or
• Intramuscular hematoma
• Subcutaneous hematoma if the size is larger than 25 cm2 or larger than 100 cm2 if provoked
Definition of serious adverse event A serious adverse event is defined as an untoward medical occurrence in a participant of a study that does not necessarily have a causal relationship with the treatment that results in:
• Death,
• Is life threatening
• Requires hospitalisation or prolongation of existing hospitalisation
• Results in persistent or significant disability or incapacity
• Consists of a congenital abnormality or birth defect
Other known rare adverse reaction listed in the SmPC are:
Skin reactions: Purpura and ecchymosis
Pruritic lesions
Skin necrosis
Alopecia
Diarrhoea
An unexplained fall in haematocrit
Jaundice and hepatic dysfunction
Fever, nausea, vomiting and pancreatitis
Hypersensitivity reactions are extremely rare and if any of these reactions occur they will be reported and it will be recommended to the clinician responsible for the participants warfarin management that warfarin is replaced by an alternative anticoagulant drug
A thrombotic event can also be defined as a serious adverse event related to warfarin.

Tullett et al.

Tullett et al. BMC Cardiovascular Disorders 2013 13:16   doi:10.1186/1471-2261-13-16

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