Insights into Disturbed Hemostasis in the Quebec Platelet Disorder Using Thromboelastography, Blood Clots Formed at Low Shear, and Perfusion Studies of Fibrinolysis.
Bibliographic record
Abstract
Abstract The Quebec Platelet Disorder (QPD) is an inherited disorder associated with delayed bleeding, increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets, normal to increased u-PA in plasma, consumption of platelet plasminogen activator inhibitor-1 (PAI-1), and increased plasmin generation in platelets with proteolysis of stored α-granule proteins, including factor V. Although accelerated fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood on the lysis of forming and preformed fibrin have not been evaluated. In this study, we modeled fibrinolysis in vitro using thromboelastography, biochemical evaluations of whole blood clots formed at low shear, and perfusion of blood over preformed fibrin. Thromboelastography (TEG) indicated that the clot formation and lysis phases were normal in QPD whole blood clots generated with tissue factor and observed for 180 min, which is the maximum time allowed by the TEG® software. However, when the TEG® were done with limiting amounts of tissue-type plasminogen activator (t-PA), QPD clots showed a shortened lysis phase. The addition of QPD platelets to normal blood hastened t-PA mediated lysis. In QPD whole blood clots, generated at low shear with exogenous thrombin (without t-PA), there was abnormal plasmin generation, with increased fibrinolysis unless fibrinolytic inhibitors were used to inhibit plasmin. These data excluded the defect in platelet factor V as the cause of abnormal lysis. Perfusion studies indicated that QPD platelets adhered to fibrin, although the amount of adhesion was reduced compared to control samples, likely because of the reduced platelet count in QPD blood. When QPD blood was perfused over labeled, preformed fibrin, without a stimulus for thrombin generation, there was accelerated loss of fibrin, and a corresponding increased generation of labeled fibrin degradation products. These results indicate that the QPD is associated with a “gain of function” abnormality that increases the lysis of forming or preformed clots, independent of thrombin generation. Our findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding and support the clinical observation that transfusion of normal platelets does not correct the defect in this bleeding disorder.
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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) | 0.000 | 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 | 0.000 | 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".