Retrospective Cohort of Unprovoked Venous Thromboembolism Patients: What Proportion Have Potent Thrombophilias Necessitating Indefinite Anticoagulants?
Bibliographic record
Abstract
Introduction Thrombophilia testing in unprovoked venous thromboembolism patients (VTE) is controversial. Common thrombophilias such as Factor V Leiden or prothrombin gene variant appear to not importantly increase the risk of VTE recurrence, and thus are not considered in anticoagulation management decisions. However, patients with potent thrombophilias such as antiphospholipid antibodies (APLA), antithrombin deficiency, protein C and S deficiency, and homozygous genetic thrombophilias or combined defects are at higher risk of recurrence and it is recommended that they receive long-term anticoagulation. If the proportion of patients with "potent" thrombophilia is high then thrombophilia testing should be conducted. We sought to determine the proportion of unprovoked VTE patients with "potent" thrombophilia. Methods All patients with managed in our oral anticoagulation management system in the period from 1998 to 2015 were potentially eligible for the study. Inclusion criteria were: 1) symptomatic, objectively confirmed VTE unprovoked proximal deep vein thrombosis or pulmonary embolism. Exclusion criteria were: 1) cancer or myeloproliferative disease at the time of VTE diagnosis; 2) no cast, surgery, trauma or immobilization (>3 days in bed 90% of waking hours) in the 90 days prior to diagnosis. We selected unprovoked VTE patients diagnosed between 2002 and 2010, as thrombophilia testing was relatively universal and available in our electronic system in that time frame (N=1344). We then selected a convenience sample of N=1165. The primary outcome measure was the proportion of patients with "potent" thrombophilia (potent= homozygous Factor V Leiden, homozygous Prothrombin gene variant, APLA, protein C, protein S or anti-thrombin deficiency or combined deficiencies). Results In 1165 patients with unprovoked VTE, complete screening was done in 470 patients (40.34%) and 976 (83.78%) had at least one thrombophilia test. Complete thrombophilia testing was defined as a screen including testing for factor V Leiden, prothrombin gene defect, APLA, anti-thrombin deficiency, protein C, and protein S. Potent thrombophilias were demonstrated in 103/1165 patients (8.84%; 95% CI, 7.34 to 10.61) (Table 2) in the total study population, and 103/976 (10.55%; 95% CI, 9.62-14.47) in patients with at least one thrombophilia test. Conclusion The proportion of unprovoked VTE patients with "potent" thrombophilia is high. Given a high proportion of "potent' thrombophilia patients who likely benefit from indefinite anticoagulation, complete thrombophilia testing appears warranted in patients with unprovoked VTE in whom anticoagulants maybe discontinued. Thrombophilia testing is warranted for a selected group of patients to detect high-risk thrombophilias that could impact anticoagulation management. Table 1. Thrombophilia screening Complete screening 470 (40.3%) No screening 189 (16.2%) At least one thrombophilia test 976 (83.8%) Table 2. Thrombophilia All patients (n=1165) Tested for individual thrombophilia % 95% CI % 95% CI FVL Heterozygous 162/1165 (13.9%) 12.0-16.0% 162/883 (18.4%) 15.9-21.0% FVL Homozygous 4/1165 (0.3%) 0.1-0.9% 4/883 (0.5%) 0.2-1.2% Prothrombin Heterozygous 63/1165 (5.4%) 4.3-6.9% 63/831 (7.6%) 6.0-9.6% Prothrombin Homozygous 1/1165 (0.0%) 0.0-0.5% 1/831 (0.1%) 0.0-0.7% Antithrombin deficiency 10/1165 (0.9%) 0.5-1.6% 10/815 (1.2%) 0.7-2.2% Protein C deficiency 18/1165 (1.6%) 1.0-2.4% 18/639 (2.8%) 1.8-4.4% Protein S deficiency 13/1165 (1.1%) 0.7-1.9% 13/635 (2.1%) 1.2-3.5% Lupus anticoagulant 24/1165 (2.1%) 1.4-3.1% 24/849 (2.8%) 1.9-4.2% Anticardiolipin IgM 16/1165 (1.4%) 0.9-2.2% 16/886 (1.8%) 1.1-2.9% Anticardiolipin IgG 20/1165 (1.7%) 1.1-2.6% 20/885 (2.2%) 1.5-3.5% β-2 microglobulin IgM 10/1165 (0.9%) 0.5-1.6% 10/333 (3.0%) 1.6-5.4% β-2 microglobulin IgG 8/1165 (0.7%) 0.4-1.4% 8/333 (2.4%) 1.2-4.7% Homocysteine 50/1165 (5.7%) 4.3-7.4% 50/668 (7.5%) 5.7-9.7% Factor VIII elevated 11/1165 (0.9%) 0.5-1.7% 11/646 (1.7%) 1.0-3.0% At least one or more of the above 331/1165 (28.4%) 25.9-31.1% 331/976 (33.9%) 31.0-36.9% Potent thrombophilia 103/1165 (8.8%) 7.34-10.6% 103/976 (10.6%) 9.6-14.5% Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".