{"id":"d8fa32bb-cd68-52a4-84a1-4677aa0a72e0","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-no-selectivity-at-higher-dose","predicate":"reduces","statement":"Two hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b380cac1-e068-518e-ae7a-b369dbcb45a2","mechanism_event_label":"At ordinary tablet doses the vessel wall is hit about as hard as the platelet.","subject":{"id":"8ac405bf-3ea0-539a-8e5e-abf503dc7081","slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"},"object":{"id":"429b3d06-eaed-54e6-9444-48a98a537ed0","slug":"vessel-wall-prostacyclin","display_name":"Prostacyclin synthesis by the vessel wall","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b380cac1-e068-518e-ae7a-b369dbcb45a2","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-no-selectivity-at-higher-dose-event","event_type":"observed_intervention","label":"At ordinary tablet doses the vessel wall is hit about as hard as the platelet.","description":"Two hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c5e111fb-13e9-53ab-8931-9b553fa5a263","slug":"serum-thromboxane-b2","display_name":"Serum thromboxane B2 after whole blood clotting","entity_type_key":"cellular_process"},"role":"co_measured","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9a90612b-517d-5811-9454-2ff927206423","slug":"template-bleeding-time","display_name":"Template bleeding time","entity_type_key":"cellular_process"},"role":"unexplained_endpoint","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"25063538-7b79-5cd4-9839-511490482e03","slug":"prostacyclin","display_name":"Prostacyclin / prostaglandin I2","entity_type_key":"small_molecule"},"role":"suppressed_product","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8ac405bf-3ea0-539a-8e5e-abf503dc7081","slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"429b3d06-eaed-54e6-9444-48a98a537ed0","slug":"vessel-wall-prostacyclin","display_name":"Prostacyclin synthesis by the vessel wall","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/aspirin-research/7003384.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38\", \"start_char\": 0, \"end_char\": 1148, \"text_sha256\": \"b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"150 or 300 milligrams of oral aspirin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.","comparator":null,"unit":null,"notes":"","entity":{"slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"At ordinary tablet doses the vessel wall is hit about as hard as the platelet.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Vein wall and platelets","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"98243b50-4869-545d-9aba-a8039b4ce80e","evidence_kind":"source_excerpt","locator":"Lines 377-388","start_line":377,"end_line":388,"excerpt":"### asa-no-selectivity-at-higher-dose\nTwo hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: At ordinary tablet doses the vessel wall is hit about as hard as the platelet.\norganism: Human\ntissue_or_cell_type: Vein wall and platelets\nexperimental_model: Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites\nlimitations: Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold.\nexposure: 150 or 300 milligrams of oral aspirin\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/7003384.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38\", \"start_char\": 0, \"end_char\": 1148, \"text_sha256\": \"b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38\"}\n[asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203","model_system":"Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"712cf519-cd27-5a8b-9e2f-961a98d7a27e","stable_key":"import-f8641d02-8413-5bd8-92e9-62ad49286e81","title":"Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"93dd4343051c131e40d4fc3c95a978cd65478c13dcdb3f2d42507c49b09cb647","revision_id":"694e8ee7-49ca-5e6c-b58b-8ba8f82c2ad8","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"64f8af68-7114-5f3a-8fad-07faaea2e473","title":"Does aspirin spare the vessel wall and kidney while suppressing the platelet?","kind":"context_difference","status":"open","why":"A study in 46 healthy subjects found that 0.45 milligrams per kilogram daily, roughly thirty milligrams, suppressed platelet thromboxane production virtually completely and cumulatively while leaving urinary prostaglandin excretion unchanged and renal prostacyclin still inducible by furosemide. A study in five subjects given 150 or 300 milligrams found 81 to 100% inhibition of vein-wall prostacyclin synthesis alongside complete platelet inhibition, and concluded there is little difference between the two tissues. The doses differ by about tenfold and the tissues sampled differ, vein wall against kidney, so the records are better read as a dose-response than as a flat contradiction: selectivity is a property of the dose rather than of the drug, and it is lost as the dose rises. A third record in this collection, in rabbits and humans, places the transition around a quarter of a 300 milligram tablet. What dose achieves selectivity in a given person is not settled here, and the second study also shows that the prolonged bleeding time is not explained by platelet thromboxane suppression alone.","resolution":"Unresolved; needs review.","created_at":"2026-09-22 06:15:08","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/64f8af68-7114-5f3a-8fad-07faaea2e473","sides":[{"conflict_id":"64f8af68-7114-5f3a-8fad-07faaea2e473","ordinal":0,"label":"A very small daily dose wipes out platelet thromboxane and leaves the kidney untouched.","revision_id":"694e8ee7-49ca-5e6c-b58b-8ba8f82c2ad8","start_line":364,"end_line":375,"quote":"### asa-cumulative-and-selective\nSingle doses of 6 to 100 milligrams of aspirin produced a linear inhibition of platelet thromboxane B2 production ranging from 12 to 95% after 24 hours, and a daily dose of 0.45 milligrams per kilogram for 7 days produced cumulative and virtually complete inhibition without significantly reducing urinary excretion of prostaglandin E2, prostaglandin F2-alpha or 6-keto-prostaglandin F1-alpha in both men and women, an effect maintained unaltered through one month of therapy with no cumulative inhibition of renal prostaglandin synthesis, while furosemide-induced renal prostacyclin synthesis and renin release were unaffected.\nCondition category: biomarker_context\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: A very small daily dose wipes out platelet thromboxane and leaves the kidney untouched.\norganism: Human\ntissue_or_cell_type: Platelets and kidney\nexperimental_model: Radioimmunoassay of serum thromboxane B2 and urinary prostaglandin excretion in 46 healthy subjects given single or repeated oral aspirin\nlimitations: The dose-ranging design across 46 subjects is what makes the selectivity claim testable. Urinary prostaglandin excretion is an indirect measure of renal synthesis.\nexposure: Single doses of 6 to 100 milligrams, and 0.45 milligrams per kilogram daily for 7 days and up to one month\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/7045161.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"58bb82650f675f1ba3dd21b6dcf3d83b71a56c437a687f72d2af9dcdc07abadb\", \"start_char\": 0, \"end_char\": 1963, \"text_sha256\": \"58bb82650f675f1ba3dd21b6dcf3d83b71a56c437a687f72d2af9dcdc07abadb\"}\n[asa-p7045161] Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. (1982). https://pubmed.ncbi.nlm.nih.gov/7045161/ DOI: 10.1172/jci110576","source_key":"import-f8641d02-8413-5bd8-92e9-62ad49286e81","source_title":"Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22)","claim_ids":["644500b4-9851-5c29-ac2c-081eae1c2a17"]},{"conflict_id":"64f8af68-7114-5f3a-8fad-07faaea2e473","ordinal":1,"label":"At ordinary tablet doses the vessel wall is hit about as hard as the platelet.","revision_id":"694e8ee7-49ca-5e6c-b58b-8ba8f82c2ad8","start_line":377,"end_line":388,"quote":"### asa-no-selectivity-at-higher-dose\nTwo hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: At ordinary tablet doses the vessel wall is hit about as hard as the platelet.\norganism: Human\ntissue_or_cell_type: Vein wall and platelets\nexperimental_model: Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites\nlimitations: Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold.\nexposure: 150 or 300 milligrams of oral aspirin\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/7003384.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38\", \"start_char\": 0, \"end_char\": 1148, \"text_sha256\": \"b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38\"}\n[asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203","source_key":"import-f8641d02-8413-5bd8-92e9-62ad49286e81","source_title":"Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22)","claim_ids":["d8fa32bb-cd68-52a4-84a1-4677aa0a72e0"]}]}],"corrections":[],"research":null}