THROMBELASTOGRAPHY-DEFINED HYPERCOAGULABILITY IS PLATELET-MEDIATED IN PATIENTS WITH SURGICALLY TREATED METASTATIC BONE DISEASE
Notice bibliographique
Résumé
The incidence of venous thromboembolism (VTE) is high in patients with pathologic fractures due to metastatic bone disease (MBD), with a 4.7% VTE rate reported following orthopaedic surgery. The optimal thromboprophylaxis for effective VTE prevention is unknown, as mechanisms driving hypercoagulability in patients with MBD are poorly understood. The platelet contribution to hypercoagulability can be evaluated using thrombelastography-based platelet mapping (PLM) analysis, which activates the adenosine diphosphate (ADP) and thromboxane A2 (AA) platelet receptors, and subsequently measures clot strength (maximal amplitude, MA) to enable quantification of platelet activity in these receptor pathways. The aim of this study was to use serial PLM analysis to evaluate platelet receptor activity in patients with MBD who required orthopaedic surgery. We hypothesized that post-operative hypercoagulability would be platelet-mediated, as demonstrated by elevated ADP-MA and AA-MA values, and that platelet hyperactivity would be highest in patients with VTE complications. Consecutive adults with MBD or haematological malignancy involving bone (i.e., multiple myeloma) who required surgical treatment for pathologic fractures were enrolled into this single-centre, prospective cohort study. Patients anticoagulated for acute VTE or who had primary bone tumours were excluded. Whole blood samples for serial PLM analysis were collected pre-operatively, on post-operative days (POD) one, three, and five, and at 2-, 6-, and 12-weeks post-operatively. Screening lower extremity Doppler ultrasounds were performed on POD3. All patients received thromboprophylaxis, with low-molecular-weight heparin commonly prescribed for 28 days post-operatively. A VTE event was defined as image-confirmed pulmonary embolism (PE) or clinically significant proximal deep vein thrombosis (DVT). Platelet hyperactivity was defined using MA ≥55 mm as a threshold. Descriptive statistics were performed, and MA values were compared with the platelet hyperactivity threshold using one-sample t-tests (p<0.05 indicated statistical significance). Thirty-seven patients (20 female, 54.1%) were enrolled, with a mean age of 66 ± 11 years. Breast (n=10, 27.0%) and lung (n=7, 18.9%) cancers were most common. The VTE rate was 13.9% (PE=1; DVT=4), and all events occurred by POD5. Platelet hyperactivity was elevated in patients who had VTE complications (Figure 1), with significant (p<0.01) hyperactivity observed at the time of VTE diagnosis (mean ADP-MA: 69.5 ± 5.4 mm; mean AA-MA: 69.6 ± 5.6 mm). Patients who did not develop VTE still demonstrated platelet hyperactivity in both receptor pathways; however, this was ADP pathway predominant throughout the study with platelet hyperactivity in this pathway identified in proportionately more patients from POD1 (71.0% ADP, 36.7% AA) until 12-weeks post-operatively (72.2% ADP, 61.1% AA). Mean platelet hyperactivity persisted in both receptor pathways at 6-weeks post-operatively, after thromboprophylaxis discontinuation (Figure 1). In patients with MBD who underwent orthopaedic surgery, serial PLM analysis identified prolonged ADP and AA platelet receptor hyperactivity, indicating that hypercoagulability is, in part, platelet-mediated. Patients who developed VTE complications had significantly elevated platelet hyperactivity, supporting further investigation into the use of pathway-specific antiplatelet agents for thromboprophylaxis, such as ADP pathway inhibitors (i.e., P2Y12 receptor antagonists (clopidogrel)) and thromboxane A2 synthesis inhibitors (i.e., acetylsalicylic acid)). Future research into safety and efficacy of extended thromboprophylaxis should be considered. For any figures or tables, please contact the authors directly.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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