Table 5.
Validation studies for risk assessment model.
| Reference | Bleeding Model | AF Model | Type of Sources | Follow Up (Months) | Anticoagulant Type | Number of Patients | Bleeding Outcome | Number of Major Bleeding | Number of Patient with Active Cancer (%) | Bleeding Outcome in Cancer Patients | OR/HR/RR/β-Coefficient Cancer | Limiting Exclusion Criteria | Conclusion of the Author on the Validation in Clinical Practice |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Scherz et al., 2013 [42] | ACCP, Kuijer, RIETE | OBRI | Prospective cohort, multicenter | 3 | Thrombolysis, UHF, LMWH, FONDAPARINUX | 663 | Major bleeding (ISTH) during anticoagulation | 28 | 98 (14.6%) | 9 | - | Patients <65 y.o. | - |
| VKA | |||||||||||||
| Nieto et al., 2013 [43] | Nieto | - | Prospective cohort, multicenter (RIETE) | - | Thrombolysis/LMWH/ UFH or VKA or Cava filter | 15,206 | Fatal bleeding | 52 | 3468 (22.8%) | 29 | - | Patients currently participating in a therapeutic clinical trial with a blinded therapy | better for predicting gastrointestinal than intracranial fatal bleeding |
| Poli et al., 2013 [44] | ACCP 2012, RIETE | ATRIA, HAS-BLED, HEMORR2HAGES, OBRI, | Prospective cohort (EPICA); 27 hospitals in Italy | 24 | VKA | 887 | Major bleeding (ISTH) during anticoagulation | 47 | 110 (10.1%) | 11 | 1.1 (0.6–2.3) | Judged too frail | No |
| Riva et al., 2014 [45] | ACCP 2012, Kuijer, RIETE | ATRIA, HAS-BLED, HEMORR2HAGES, Shireman | Retrospective cohort; anticoagulation clinics of 5 hospitals in Italy | 12 | VKA | 681 | Major bleeding (ISTH) and CRNMB (ISTH) during anticoagulation | 50 | 78 (11.4%) | / | - | - | No |
| Piovella et al., 2014 [46] | RIETE, KUIJER | mOBRI | Prospective cohort, multicenter (RIETE) | 3 | Thrombolysis, UHF, LMWH, | 8717 | Major bleeding = clinically overt with a need for transfusion of at least two units of red blood cells/retroperitoneal or intracranial/ permanent discontinuation of treatment/ fatal | 82 | 1807 (20.7%) | 22 | - | - | Slightly better performance of the RIETE |
| OBRI | RIVAROXABAN, VKA | ||||||||||||
| Kline et al., 2016 [47] | RIETE, KUIJER | mOBRI OBRI |
Pooled data of EINSTEIN PE and EINSTEIN DVT | 3 to 12 | RIVAROXABAN | 4130 | Major bleeding (ISTH) during anticoagulation | 40 | 232 (5.6%) | - | - | - | Good performance for RIETE |
| Klok et al., 2017 [48] | VTE-BLEED | - | RCT (HOKUSAI VTE) international study | 3 to 12 | VKA | 3903 | Major bleeding (ISTH) during chronic, stable anticoagulation (>30 days) | 40 | 181 (31%) | 6 | - | - | Yes |
| Palareti et al., 2018 [49] | ACCP 2016 | - | Prospective cohort (START2) in multiple hospitals in Italy | >12 | VKA DOAC (subtype not specified) | 2263 | Major bleeding (ISTH) and CRNMB (ISTH) during anticoagulation | 48 | 175 (23.4%) | 4 | HR = 1.0 (0.4–3.0) | - | No |
| Rief et al., 2018 [50] | VTE-BLEED | HAS-BLED | Prospective cohort study, 1 hospital in Austria | 12 | LMWH, VKA, APIXABAN, RIVAROXABAN, EDOXABAN, | 111 | Major bleeding (ISTH) during anticoagulation | 4 | 12 (11%) | - | - | - | Did not discuss validity of the VTE bleed |
| Zhang et al., 2018 [51] | ACCP, Kuijer, RIETE, NIEUWENHUIS | - | Prospective cohort | 3 | VKA, LMWH | 563 | Major bleeding (ISTH) and CRNMB (ISTH) during anticoagulation | 16 | 70 (12.4%) | - | - | - | Good performance of the ACCP |
| Klok et al., 2018 [52] | VTE-BLEED | - | RCT (Xalia); multiple hospitals in 12 countries | >12 | LMWH RIVAROXABAN | 4457 | Major bleeding (ISTH) during anticoagulation | 39 | 500 (11%) | - | HR = 1.0 (0.61–1.7) | - | Yes |
| Vedovati et al., 2019 [53] | Kuijer, RIETE, VTE-BLEED, | HAS-BLED, ATRIA | Prospective cohort | >12 | APIXABAN, RIVAROXABAN, EDOXABAN, DABIGATRAN | 1034 | Major bleeding (ISTH definition) during anticoagulation | 26 | 164 (15.9%) | 5 | HR = 1.930 (0.721–5.170) | - | No |
| Skowrońska et al., 2019 [30] | VTE-BLEED, RIETE | HEMORR2HAGES, HAS-BLED | PE-aWARE registry | 0.5 | Thrombolysis, UHF, LMWH, FONDAPARINUX, | 310 | Major bleeding (ISTH) and CRNMB (ISTH) during anticoagulation that occurred during the hospital stay | 17 | 56 (18.1%) | 11 | - | - | Good performance at identifying Acute PE patients at risk of in-hospital bleeding complication of the VTE bleed |
| RIVAROXABAN, VKA | |||||||||||||
| Combination therapy (VKA + LMWH) | |||||||||||||
| Keller et al., 2021 [54] | KUIJER | - | Nationwide German registry | - | DOAC, VKA | 1,204,895 | Hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or other major bleeding as defined by the International Classification of Diseases | - | 25885 (2.1%) | - | - | - | Good performance at predicting in hospital major bleeding |
| Mathonier et al., 2021 [55] | VTE-BLEED, RIETE | ORBIT, HEMORR2HAGES, ATRIA, HAS-BLED | BFC-FRANCE registry | 0.25 | UFH, LMWH, FONDAPARINUX, VKA and DOACs | 2754 | Major bleeding (ISTH) that occurred during the hospital stay | 82 | 507 (18.4%) | 17 | OR= 4.7 (3.2–6.8) | - | No |
| Frei et al., 2021 [56] | VTE-BLEED, Seiler, Kuijer, RIETE, ACCP, | OBRI, HEMORR2HAGES, HAS-BLED, ATRIA | Prospective, multicenter SWIss venous Thromboembolism COhort study 65+ (SWITCO 65+) | 36 | VKA | 743 | Major bleeding (ISTH) and CRNMB (ISTH) during anticoagulation | 45 | 10 (1.3%) | 16 | - | Terminal illness, catheter-related thrombosis, age under 65 | No |
| De Winter et al., 2021 [36] | VTE-BLEED, RIETE, Martinez, Kuijer, HOKUSAI, ACCP | HAS-BLED | HOKUSAI VTE cancer post hoc analysis | >12 | EDOXABAN, LMWH | 1046 | Major bleeding (ISTH) and CRNMB (ISTH) during anticoagulation that occurred during the hospital stay | 39 | 1024 (97.8%) | 39 | - | - | No good performance of the existing RAM in CAT population |