Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial.

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

Orthostatic hypotension following acute intracerebral haemorrhage.

BACKGROUND: Blood pressure regulation may be impaired following acute stroke. Typically, there is overactivity of the sympathetic nervous system and underactivity of the parasympathetic system resulting in transient hypertension. Orthostatic hypotensive responses in acute stroke are less well documented. CASE REPORT: We present a case of severe persistent orthostatic hypotension (OH) following acute intracerebral haemorrhage in a previously fit and well man. Symptomatic OH persisted for 60 days post-stroke. No known causes of OH could be identified. CONCLUSIONS: Such profound and persistent orthostatic hypotension following an acute intracerebral haemorrhage has not previously been documented. The precise cause of this finding in the case described is unknown, but may have been due to impaired higher-level regulation of the autonomic nervous system. A conservative approach with prolonged physical methods proved successful in rehabilitating this patient without the need for pharmacological intervention.