Table 2.
Major bleeding data—observational studies
| Primary author | Publication year (midpoint of follow-up) | Patients, (N) | Major bleeding events (n) | Total patient-years | Rate per 100 patient-years | Definition of major bleeding |
|---|---|---|---|---|---|---|
| Abdelhafiz26 | 2004 (2001) | 402 | 11 | 634 | 1.74 | Major bleeding complications were defined as bleeding that led to hospital admission, emergency procedure, and/or blood transfusion |
| Blich27 | 2004 (1999) | 506 | 51 | 1228.5 | 4.15 | NR |
| Bosch28 | 2002 (1998) | 1283 | 119 | 4672 | 2.55 | Major haemorrhage in hospital setting |
| Boulanger29 | 2006 (2000) | 2568 | 103 | 3665 | 2.81 | Bleeding events included intracranial or GI haemorrhage and other bleeding episodes (e.g. haemopericardium, haematuria, haemarthrosis, epistaxis and haemoptysis) |
| Cheung30 | 2005 (2001) | 555 | 8 | 893 | 0.90 | GI bleeds |
| Copland31 | 2001 (1999) | 328 | 9 | 458 | 1.97 | Haemorrhages leading to fall in Hb level 2 g/L or transfusion (intracerebral and subdural not included) |
| Currie32 | 2005 (1999) | 1513 | 68 | 8500 | 0.80 | NR |
| Darkow33 | 2005 (2001) | 4895 | NR | NR | 2.68 | A haemorrhagic event was defined as acute inpatient hospitalization with a primary diagnosis of intracranial haemorrhage or other major bleeding |
| Fang34 | 2007 (1997) | 13 559 | 98 | 15 370 | 0.64 | Bleeding was defined as major extracranial haemorrhage, fatal, requiring transfusion of ≥2 units of packed red blood cells, or haemorrhage into a critical anatomical site, such as the retroperitoneum. To restrict analyses to the most serious haemorrhages, events not leading to hospitalization or death were excluded |
| Ghate35 | 2011 (2005) | 37 756 | 531 | 21 423 | 2.48 | Major GI bleeding events were defined as GI bleeding that required hospitalization, identified based on inpatient claims associated with an ICD-9 code for GI bleeding |
| Hansen36 | 2010 (2002) | 50 919 | 3642 | 93 492 | 3.90 | Bleeding was defined as admission to a Danish hospital, excluding emergency department visits, with a bleeding diagnosis (primary or secondary and classed as airway, intracranial, GI, urinary tract), a non-fatal bleeding episode, or a diagnosis of bleeding as the cause of death reported in the National Causes of Death Register (i.e. a fatal bleeding episode). |
| Ho37 | 2011 (2004) | 476 | 33 | 1 941 | 1.70 | Major bleeding was defined as intracranial bleeding, subarachnoid haemorrhage, subdural haematoma, haemorrhagic transformation of a primary ischaemic stroke (as documented by computed tomography scan, magnetic resonance imaging or autopsy) or any bleeding leading to transfusion of ≥2 units of whole blood or erythrocytes or bleeding requiring surgical or angiographic intervention, or bleeding resulting in permanent disability or involving a critical anatomical site |
| Hylek38 | 2007 (2002) | 472 | 26 | 360 | 7.22 | Major haemorrhage was defined as bleeding that was fatal, required hospitalization with transfusion of >2 units of packed RBCs, or involved a critical site (i.e. intracranial, retroperitoneal, intraspinal, intraocular, pericardial, or atraumatic intra-articular haemorrhage) |
| Jackson39 | 2001 (1998) | 505 | 9 | 267.7 | 3.40 | Bleeding complications were considered major if these involved intracranial or intracerebral haemorrhage, were life-threatening, or required blood transfusion |
| Mercaldi40 | 2011 (2005) | 70 057 | 12 039 | 158 408 | 7.60 | Major bleeding events included extracranial haemorrhages resulting in hospitalization or an emergency room visit |
| Naganuma41 | 2012 (2004) | 845 | 28 | 1900 | 1.47 | Major bleeding events were defined as intraocular haemorrhages leading to a substantial loss of vision, GI haemorrhage or other severe haemorrhage that was fatal or required endoscopic haemostasis, surgical intervention, hospital admission, or blood transfusion |
| Nichol42 | 2008 (2003) | 1107 | 84 | 2083 | 4.00 | The first diagnosis for a bleed resulting in hospitalization occurring 30 or more days after the index date was classified as an event (ICD-9 codes) |
| Njaastad43 | 2006 (1999) | 421 | 4 | 475.2 | 0.84 | Bleeding was defined as major if it was associated with at least one of the following: death; intracranial, retroperitoneal, intraocular, or intra-articular bleeding; a decrease in haemoglobin level ≥20 g/L; need for transfusion of ≥2 units of blood; or need for surgical or medical intervention |
| Olesen44 | 2011 (2003) | 37 425 | 5183 | 133 614 | 3.88 | Bleeding included GI bleeding, intracranial bleeding, bleeding from the urinary tract, and airway bleeding |
| Pengo45 | 2001 (1999) | 433 | 11 | 615 | 1.79 | The following were considered to be major bleeding events: fatal (death due to haemorrhage); intracranial (documented by CAT and/or NMR); ocular (with blindness); articular; retroperitoneal; bleeding requiring surgery or angiographic intervention to stop bleeding; bleeding leading to haemoglobin reduction of ≥2 g/dL and/or need for transfusion of ≥2 blood units |
| Poli46 | 2005 (2002) | 364 | 2 | 859 | 0.23 | GI bleeds |
| Poli47 | 2009 (2003) | 783 | 37 | 2567 | 1.44 | Bleeding was classified as major when fatal, intracranial (documented by imaging), ocular causing blindness, articular, or retroperitoneal; when surgery or transfusion of >2 blood units were required or when haemoglobin was reduced by ≥2 g/dL |
| Poli48 | 2011 (2009) | 3015 | 90 | 7630 | 1.18 | Major endpoints of the study were first major bleeding, defined fatal, ocular causing blindness, articular, or retroperitoneal bleeding; when surgery or an invasive manoeuvre was necessary to stop bleeding; when transfusion of >2 units of blood was required; or when Hb was reduced by >2 g/dL. |
| Poli49 | 2011 (2008) | 3302 | 97 | 10 019 | 0.97 | Bleeding was classified as ‘major’ when it was fatal, intracranial (documented by imaging), ocular causing blindness, articular, or retroperitoneal; when surgery or transfusion of >2 blood units was required; or when Hb was reduced by >2 g/dL. |
| Rose50 | 2008 (2001) | 3396 | 55 | 2892.1 | 1.90 | Major haemorrhage was defined according to the ISTH definition: a fatal event, an event requiring hospitalization with transfusion of at least 2 units of packed red blood cells, or bleeding involving a critical anatomical site such as the cranium or the retroperitoneum |
| Rosenman51 | 2009 (2003) | 1485 | 127 | 3364 | 3.80 | GI bleeds |
| Shireman52 | 2004 (1999) | 8131 | 98 | 2004 | 4.89 | Major bleeds included GI haemorrhages that resulted in an inpatient admission. Only the first episode of a major bleed per cohort member during the study period was included. Number of major bleeds and patient-years were imputed from the N and %, which in turn enabled rate per 100 patient-years to be imputed |
| Suzuki53 | 2007 (2005) | 667 | 9 | 503 | 1.79 | Major bleeding was defined as bleeding that required emergent hospitalization and included extracranial haemorrhages (GI haemorrhages, haematuria, haemoptysis) |
| Wess54 | 2008 (2000) | 501 | 52 | 876 | 5.94 | All GI bleeds and intracranial haemorrhages based on ICD-9-CM codes recorded on inpatient hospitalization claims |
| Wieloch55 | 2011 (2008) | 2491 | 53 | 2043 | 2.59 | ISTH guidelines include central nervous system, GI, and other bleeds |
| Yousef56 | 2004 (1999) | 739 | 28 | 1484 | 1.89 | Any bleeding event leading to hospitalization |
AF, atrial fibrillation; CAT, computed axial tomography; GI, gastrointestinal; Hb, haemoglobin; ICD-9-CM, International Classification of Diseases, 9th Revision, Clinical Modification; ISTH, International Society on Thrombosis and Haemostasis; NMR, nuclear magnetic resonance (imaging); NR, not reported; RBC, red blood cells.