Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and clinically distinct syndrome
Bibliographic record
Abstract
Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis remain uncertain. We identified 10 patients with metastatic cancer (7 pathologically proven) who developed severe venous limb ischemia (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8 patients, cancer was not known or suspected at presentation. The patients exhibited a novel, clinically distinct syndrome: warfarin-associated supratherapeutic international normalized ratio (INR; median, 6.5) at onset of limb ischemia, rising platelet count during heparin anticoagulation, and platelet fall after stopping heparin. Despite supratherapeutic INRs, patient plasma contained markedly elevated thrombin-antithrombin (TAT) complex levels (indicating uncontrolled thrombin generation) and protein C (PC) depletion; this profile resembles the greatly elevated TAT/PC activity ratios reported in patients with warfarin-associated VLG complicating heparin-induced thrombocytopenia. Analyses of vitamin K-dependent factors in 6 cancer patients with available serial plasma samples showed that variations in the INR corresponded most closely with changes in factor VII, with a highly collinear relationship between VII and PC. We conclude that venous limb ischemia/gangrene is explained in some cancer patients by profoundly disturbed procoagulant-anticoagulant balance, whereby warfarin fails to block cancer-associated hypercoagulability while nonetheless contributing to severe PC depletion, manifest as a characteristic supratherapeutic INR caused by parallel severe factor VII depletion.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.001 | 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".