THROMBELASTOGRAPHY-DEFINED HYPERCOAGULABILITY IS PLATELET-MEDIATED IN PATIENTS WITH SURGICALLY TREATED METASTATIC BONE DISEASE
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".