Thromb Haemostasis
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Inflammatory cytokines promote the activation of coagulation through the induction of tissue factor, downregulation of thrombomodulin and upregulation of plasminogen activator inhibitor. In addition to these mechanisms, infections can trigger the release of extracellular traps from leukocytes consisting of DNA and histones. Tissue injury results in release of nucleosomes. ⋯ In addition to the direct prothrombotic activity of histone-DNA complexes, the complexes trigger activation of the toll-like receptors 2, 4 and 9 thereby increasing inflammatory cytokine formation and fostering thrombotic responses through the mechanisms mentioned previously. Furthermore, these cytokines are likely to increase cell necrosis and apoptosis releasing nucleosomes and further augmenting the activation of leukocytes with the subsequent release of extracellular traps. Blocking this histone-mediated cascade has the potential to impact a variety of clinical conditions including sepsis, trauma, chemical toxicity, transplant injury and reperfusion injury.
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Randomized Controlled Trial Multicenter Study
Decrease in high on-treatment platelet reactivity (HPR) prevalence on switching from clopidogrel to prasugrel: insights from the switching anti-platelet (SWAP) study.
The prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥ 50%. ⋯ A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p<0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥ 50 % (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.
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Multicenter Study
Prevalence of thrombocytosis in critically ill patients and its association with symptomatic acute pulmonary embolism. A multicentre registry study.
It is uncertain whether thrombocytosis without underlying myeloproliferative diseases is associated with an increased risk of acute pulmonary embolism (PE). We investigated the relationship between thrombocytosis and risk of symptomatic acute PE, and whether Pulmonary Embolism Severity Index (PESI) was reliable in predicting mortality of acute PE. This multicentre registry study involved a total of 609,367 critically ill patients admitted to 160 intensive care units (ICUs) in Australia or New Zealand between 2006 and 2011. ⋯ The PESI had a reasonable discriminative ability (area under receiver-operating-characteristic curve = 0.78) and calibration to predict mortality across a wide range of severity of acute PE. In summary, thrombocytosis was associated with an increased risk of symptomatic acute PE. PESI was useful in predicting mortality across a wide range of severity of acute PE.
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Vitamin K antagonists (e.g. warfarin) are commonly underutilised, due to limitations such as the need for monitoring, in high-risk atrial fibrillation (AF) patients. We therefore aimed to model the potential impact on clinical outcomes in patients with AF with the use of the novel oral anticoagulant (OAC) drugs, apixaban and dabigatran. We identified all high-risk (CHA₂DS₂-VASc score ≥2 ) patients with non-valvular AF and known one-year follow-up from the EuroHeart Survey on AF (EHS-AF). ⋯ With use of dabigatran 150 mg BID, 34 strokes could have been prevented and for dabigatran 110 mg BID, 16 strokes and six major bleeds would be avoided. Extrapolation of the data from the EHS-AF to the whole of Europe would translate into the prevention of an additional 64,573 major cardiovascular events and deaths each year among patients with a CHA₂DS₂-VASc ≥2 , by the use of apixaban, 43,235 with the use of dabigatran 150 mg bid and 27,272 with the use of dabigatran 110 mg bid. In conclusion, based on this modelling exercise, the utilisation of apixaban and dabigatran for thromboprophylaxis could provide a profound annual mathematical net clinical benefit on stroke and major bleeds, in European AF patients.