Unexpected Harmful Side Effects Triggered by Immune Modulation.
Bibliographic record
Abstract
Abstract A 66 year old man was referred urgently to Hematology for severe, spontaneous bruising, bleeding and acute onset anemia. His Past History revealed long standing, poorly controlled rheumatoid arthritis, ischemic cardiac disease with a prior MI, hypertension and elevated Homocystein. Medications included: Leflunomide, Hydroxychloroquine, Ramipril, Bisoprolol, vitamins B12 and B6 and the recently initiated Adalimumab (Humira), an anti-Tumor Necrosis Factor (TNF) immune modulator. On examination he was covered by extensive ecchymoses, large hematomas and had a knee effusion, feeling tired and light headed. He denied any injury. Hemostatic screening showed a normal PT and a markedly prolonged PTT, first 71, later over 100 seconds. A mix of patient and control plasma did not correct the PTT. An inhibitor was detected. Factors XI and IX were normal, Factor VIII was less than 1%. Factor VIII inhibitor was 60 Units Bethesda. White cell and Platelet counts were normal. Hemoglobin was 91 g/l from a previous 120. He was treated with Prednisone and Cyclophosphamide as well as Hexacapron. Activated Factor VIIa was on standby and was used on one occasion for a huge lower lip hematoma oozing intractably, that required also topical Aprotinin. Investigations for an underlying lympho-proliferative disorder or solid tumor neoplasia were negative. His complete response to chemotherapy took several months. Factor VIII inhibitors in non-hemophiliacs are the commonest autoantibodies against clotting factors. Their incidence is 0.2 to 1.0 case per million per year and mostly associated with hematological neoplasias, solid tumors and post-partum. This appears to be first occurrence of Anti-Factor VIII triggered by this type of immune modulation. Since Monocyte-Macrophages are a major source of TNF, it is possible, that by the interaction of Adalimumab, as Anti-TNF and the TNF receptor, the antigen presenting cell becomes altered, permitting in a patient with underlying autoimmune disease, a monoclonal B-Lymphocyte expansion with anti-Factor VIII properties.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".