Evidence Table 6Patient Risk Factors - thrombophilias

Bibliographic referenceStudy TypeEvidence levelNo. of patientsPatients characteristicsExposureLength of follow up/exposureOutcome measuresEffect sizeComments
Edmonds et al., 2004169Systematic review

2 cohort studies
2+1125Patients undergoing elective hip or knee replacement

Other inclusion criteria:
1 study - 40 –80 yrs
1 study – no other specific patient group
Factor VS Leiden (FVL)8 to 14 days post-operatively in 1 study, 3 months in other studyRisk estimate for activated protein C resistance (95% cases had FVL) & postoperative DVT.Relative risk: 4.9
CI: 1.1 to 22.1 (1 study)
Diagnosis of DVT: 1 study bilateral ascending venography
1 study clinical diagnosis.
Risk estimate for FVL mutation & postoperative DVTOdds ratio: 3.18
CI: 0.99 to 10.2 (1 study)
Risk estimate for low sensitivity of FVL to APC & postoperative DVTOdds ratio: 2.97
CI: 1.27 to 6.92 (1 study)
den Heijer et al., 2005156Systematic review of 24 studies:
3 prospective
21 retrospective
2+3765 cases
5297 controls
Any population

Excluded studies in diseased populations (irritable bowel syndrome, systemic lupus erythematosis or Behcet's Syndrome)
Raised homocysteine levelsNot reportedRisk estimate for venous thrombosis for a 5μmol/L increase in measured plasma total homocysteineOdds ratio: 1.27 95% CI: 1.01 to 1.59 (3 prospective studies)

Odds ratio: 1.60 95% CI: 1.10 to 2.34 (21 retrospective studies)
Not reported how venous thrombosis was diagnosed.
den Heijer et al., 2005156Systematic review of 53 studies2+8364 cases
12,468 controls
Any population

Excluded studies in diseased populations (irritable bowel syndrome, systemic lupus erythematosis or Behcet's Syndrome)
MTHFR 677TT genotype compared to MTHFR 677CC genotypeNot reportedRisk estimate for venous thrombosis for TT vs CS genotype for MTHFROdds ratio: 1.20 CI: 1.08 to 1.32 (53 studies)Not reported how venous thrombosis was diagnosed.
Galli et al., 2003206Systematic review of 25 studies

11 case – control, 3 cross-sectional
2 ambispective
9 prospective
2+4184 patients
3151 controls
Medical patientsAntiphospholipid syndrome - lupus anticoagulants and/or anticardiolipin antibodiesNot reportedRisk estimate for DVT in studies of lupus anticoagulants and anticardiolipin antibodies*Odds ratios varied from 5.91 (any event) to 9.4 (first event) (5 studies) SignificantThrombosis verified by computerised ultrasonography, venography for DVT, angiography or radionuclide lung scanning for pulmonary embolism

Pooled odds ratios for studies were classified by type of event (first event, recurrent or any event, which means no distinction was possible between first and recurrent events)

* None of the studies found anticardioplatin to be a significant risk factor for thrombosis
Risk estimate for DVT in studies of lupus anticoagulants aloneOdds ratios varied from 4.09 (recurrent event) to 16.2 (any event) (4 studies) Significant
Risk estimate for DVT in studies of anticardiolipin antibodies (only G istope measured)Significant association No value given (6 studies) Significant
Risk estimate for DVT in studies of IgG and/or IgM anticardiolipin antibodies4 studies with 8 associations. Only 1 IgG anticardiolipin association significant
Rocha et al., 2007556Systematic review

6 cohort studies
3 case control studies
2+20665Unclear (data presented in paper as table only)Factor VS Leiden (FVL)UnclearRelative Risk estimate for medical patients with FVL mutation and VTE.Relative risk ranges in studies from 2.2–6.6
No confidence intervals (5 studies)
Definition and diagnosis of VTE is not provided.
Risk estimate for medical patients with FVL mutation and VTEOdds ratio ranges in studies from 3.2 to 5.8
No confidence intervals (4 studies)
Rocha et al., 2007556Systematic review

4 cohort studies

1 case control study
2+31871Unclear (data presented in paper as table only)Protein C deficiencyUnclear (1 study followed patients for 8.1 years)Relative Risk estimate for medical patients with protein C deficiency and VTE.Relative risk ranges in studies from 3.36 to 7.3
No confidence intervals (2 studies)
Definition and diagnosis of VTE is not provided.
Risk estimate for medical patients with protein C deficiency and VTEOdds ratio ranges in studies from 1.7 to 12.6
No confidence intervals (3 studies)
Rocha et al., 2007556Systematic review

2 cohort studies

2 case control studies
2+3048Unclear (data presented in paper as table only)Protein S deficiencyUnclearRelative Risk estimate for medical patients with protein S deficiency and VTE.Relative risk: 8.5
No confidence intervals (1 study)
Definition and diagnosis of VTE is not provided.
Risk estimate for medical patients with protein S deficiency and VTEOdds ratio ranges in studies from 0.7 to 19.9
No confidence intervals (3 studies)
Rocha et al., 2007556Systematic review

1 cohort study

7 case control studies
2+4475Unclear (data presented in paper as table only)Mutation of the pro-thrombin geneUnclearRisk estimate for medical patients with mutation of the pro-thrombin gene and VTEOdds ratio ranges in studies from 2.0 to 11.5
No confidence intervals (3 studies)
Definition and diagnosis of VTE is not provided.
Rocha et al., 2007556Systematic review

2 cohort studies

1 case control study
2+2404Unclear (data presented in paper as table only)Anti-thrombin III deficiencyUnclearRelative Risk estimate for medical patients with anti-thrombin III deficiency and VTE.Relative risk: 8.1
No confidence intervals (1 study)
Definition and diagnosis of VTE is not provided.
Risk estimate for medical patients with anti-thrombin III deficiency and VTEOdds ratio ranges in studies from 2.2 to 21.2
No confidence intervals (3 studies)

From: Appendix D, Evidence tables

Cover of Venous Thromboembolism
Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital.
NICE Clinical Guidelines, No. 92.
National Clinical Guideline Centre – Acute and Chronic Conditions (UK).
Copyright © 2010, National Clinical Guideline Centre - Acute and Chronic Conditions.

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