Sickle hemoglobin: How critical are laboratory quality measures for accurate identification?
Bibliographic record
Abstract
Madam, Adult haemoglobin (Hb) comprises of 2 alpha and 2 beta-globin chains, each having a haem molecule attached. In healthy individuals, around 95-98% HbA (?2?2) and 2–3.5% of Hb A2 (?2?2) are present. The genetic defect of globin chain in which valine is replaced for glutamic acid at position 6 of ? globin chain results in sickle haemoglobin (HbS). Homozygous genetic defect (?S?S) results in a symptomatic disease called 'sickle cell anaemia' whereas, heterozygous (??S) state is asymptomatic and commonly called as "sickle cell trait' [1]. On deoxygenation and dehydration, HbS undergoes irreversible polymerization causing deleterious effects in vivo [2]. Around 3.2 million people have sickle-cell disease worldwide, with about 80% cases in Africa. About 0.5 to 1 per cent of the Pakistani population carries HbS3. Currently, high-performance liquid chromatography (HPLC) is the preferred method in which HbS elutes at retention time ranging in between 4.1 to 4.7 minutes. Several other variant haemoglobins cause interference by co-eluting at same retention time include HbA2, Hb Q-Thailand, Hb Manitoba, Hb Russ, Hb Stanlivelly-II, HbE- Saskatoon, Hb Montgomery and many more[4]. Therefore, it is difficult to identify and differentiate HbS precisely from interfering variant haemoglobins for proper diagnosis and future genetic counselling of patients. The definitive test for this purpose is molecular detection of underlying mutation either by polymerase chain reaction (PCR) or sequencing of the beta-globin gene. Molecular tests, however, are expensive and require expertise. Therefore, these tests are not widely available in Pakistan and other resource constraint countries. World's leading quality assurance organizations such as College of American Pathologists (CAP) recommend that all cases found HbS positive in the primary screening should be confirmed by secondary testing [5], this can easily be achieved by sickling test. In the sickling test, the sample is combined with reducing agent (Sodium Met bisulfate) resulting in red cell hypoxia. Cells with HbS change to sickle shape from their normal biconcave shape, diagnosed by microscopic examination along with controls. This cost-effective and readily available technique helps to differentiate HbS from other variants. Therefore, every laboratory should confirm the presence of HbS by sickling test, and the government should ensure the availability of molecular tests at the mass level at a reduced cost supported by the efficient health insurance system. The impact of these strategies will provide accurate and timely diagnosis, Continuous...
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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 | 0.029 | 0.066 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.008 | 0.007 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.008 | 0.007 |
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".