Primary Hemostatic Plug Failure Module

This is a mechanism module, not a specific disease. It is NOT an Xogenesis module - nothing pathological is formed; a normal, programmed process fails, so the OGMS pathological-structure anchor convention does not apply. SCOPE - the qualitative arm only. This module models the FUNCTIONAL failure of a platelet that reaches the site of injury. It deliberately does NOT model the quantitative arm - impaired thrombopoiesis, defective proplatelet formation, or accelerated clearance producing thrombocytopenia and macrothrombocytopenia. That is a mechanistically distinct route (megakaryocyte maturation and platelet biogenesis, GO:0030220 platelet formation) that happens to share many genes: GP1BA/GP1BB/GP9, MYH9, ACTN1, TUBB1, FLI1, GFI1B and NBEAL2 all break both arms at once. A disorder with a combined qualitative-plus-quantitative defect conforms here for the functional arm and curates its platelet-count arm on its own entry. Conforming to this module is not an assertion that the platelet count is normal. ARM SELECTION IS THE CURATOR'S FIRST DECISION, and the four amplifier arms are not interchangeable. Attach at the arm the disorder's evidence actually supports: - `#Impaired Platelet Adhesion to the Injured Vessel Wall` - GPIb-IX-V loss (Bernard-Soulier syndrome), GPVI deficiency, integrin alpha2beta1 deficiency, and, from the opposite direction, the gain-of-function GPIbalpha of platelet-type von Willebrand disease, where excessive constitutive VWF capture depletes the high-molecular-weight multimers that adhesion depends on. - `#Impaired Platelet Activation, Granule Secretion, and Integrin Inside-Out Signalling` - P2Y12 (BDPLT8), thromboxane A2 receptor (BDPLT13), cyclooxygenase-1 (BDPLT12) and thromboxane synthase (BDPLT14) defects, CalDAG-GEFI/RASGRP2 (BDPLT18), the storage pool diseases (gray platelet syndrome, Hermansky-Pudlak, Chediak-Higashi), Quebec platelet disorder, and the megakaryocyte transcription-factor disorders (FLI1, GFI1B, RUNX1) that reduce the platelet's secretable and receptor content wholesale. - `#Failure of Integrin alphaIIbbeta3-Mediated Platelet Aggregation` - Glanzmann thrombasthenia and the leukocyte adhesion deficiency III (kindlin-3/FERMT3) thrombasthenia-like phenotype. Reserve this arm for a demonstrated failure of the final common aggregation step itself, not for any disorder in which aggregometry is abnormal - almost every disorder here has abnormal aggregometry, because every upstream arm reads out through it. - `#Impaired Platelet Procoagulant Membrane Response` - Scott syndrome (ANO6/TMEM16F). This arm is narrowly evidenced and should not be inferred from a prolonged clotting time; it needs phosphatidylserine-exposure or platelet-procoagulant-activity data. A disorder may conform at more than one arm when its evidence supports more than one, and a conformer need not name any arm to conform at the central effector. Conversely, mucocutaneous bleeding alone is NOT sufficient to infer conformance: coagulation-factor deficiencies (hemophilia, plasma von Willebrand disease), vascular and connective-tissue bleeding (hereditary haemorrhagic telangiectasia, Ehlers-Danlos), hyperfibrinolytic bleeding, and immune thrombocytopenia all produce the same clinical output without a platelet primary-hemostatic component being lost. Quebec platelet disorder is the instructive edge case - it is a platelet-type bleeding disorder whose proximate defect is intraplatelet alpha-granule proteolysis by overexpressed urokinase, so it conforms through the secretion arm and additionally carries a hyperfibrinolytic mechanism that this module does not model. Key conformance target (the rate-limiting node): `#Failure of Primary Hemostatic Plug Formation`. The treatments block is a mechanistic target pattern, not an inherited treatment recommendation. Recombinant activated factor VIIa is the worked example because it is the one agent whose mechanism is defined against this module's central node: it does not repair any arm, it BYPASSES the failed plug by driving thrombin generation on whatever activated platelet surface remains. Conforming disorders do not inherit it - its evidence base is Glanzmann thrombasthenia, and its use elsewhere in the series is extrapolation. Pathophysiology nodes bind GO biological processes, GO cellular components and CL cell types only; chemistry and disease identity are described in prose. GO has no `platelet adhesion` class, so the adhesion node binds the parent GO:0007155 cell adhesion with a specific `preferred_term`; this is a noted ontology gap. Modifier convention on the arm nodes. The arms carry the quantitative, PATO-bound modifier (`DECREASED`) rather than the unbound qualitative one, deliberately: an arm must accommodate the full range of lesions that enter it, including partial and hypomorphic ones, and `DECREASED` is the documented default. A conformer whose own lesion is qualitative should use `LOSS_OF_FUNCTION` on its own node - `Scott_Syndrome` does exactly that on GO:0017121, because biallelic ANO6 loss abolishes scrambling rather than reducing it. The resulting difference between that conformer and this module's procoagulant arm is intended, not an oversight: the module states the general case, the conformer states its own.