Spontaneous regression of ALK fusion protein-positive non-small cell lung carcinoma: a case report and review of the literature.

BACKGROUND: ALK-rearrangement is observed in < 5% non-small cell lung cancer (NSCLC) cases and prior to the advent of oral tyrosine kinase inhibitors, the natural history of oncogenic NSCLC was typically poor. Literature relating to regression of treatment-naïve NSCLC is limited, and regression without treatment has not been noted in the ALK-rearranged sub-population. CASE PRESENTATION: A 76 year old 'never smoker' female with an ALK-rearranged left upper lobe T2 N0 NSCLC experienced a stroke following elective DC cardioversion for new atrial fibrillation. Following a good recovery, updated imaging demonstrated complete regression of the left upper lobe lesion and a reduction of the previously documented mediastinal lymph node. Remaining atelectasis was non-avid on repeat PET-CT imaging, 8 months from the baseline PET-CT. When the patient developed new symptoms 6 months later a further PET-CT demonstrated FDG-avid local recurrence. She completed 55 Gy in 20 fractions but at 18 months post-radiotherapy there was radiological progression in the lungs with new pulmonary metastases and effusion and new bone metastases. Owing to poor performance status, she was not considered fit for targeted therapy and died 5 months later. CONCLUSION: All reported cases of spontaneous regression in lung cancer have been collated within. Documented precipitants of spontaneous regression across tumour types include biopsy and immune reconstitution; stroke has not been reported previously. The favourable response achieved with radical radiotherapy alone in this unusual case of indolent oncogenic NSCLC reinforces the applicability of radiotherapy in locally advanced ALK-rearranged tumours, in cases not behaving aggressively. As a common embolic event affecting the neurological and pulmonary vasculature is less likely, an immune-mediated mechanism may underpin the phenomenon described in this patient, implying that hitherto unharnessed principles of immuno-oncology may have relevance in oncogenic NSCLC. Alternatively, high electrical voltage applied percutaneously adjacent to the tumour during cardioversion in this patient may have induced local tumour cell lethality.

Coronary microcirculation and peri-procedural myocardial injury during elective percutaneous coronary intervention.

BACKGROUND: Coronary microvascular dysfunction before percutaneous coronary intervention (PCI) predicts PCI-related myocardial injury in patients with stable coronary artery disease (CAD). Whether the dynamic changes of the microcirculation during PCI might be associated with the occurrence of procedure-related myocardial injury and infarction is still unclear. We aimed to investigate the impact of pre- and post-PCI microvascular function, evaluated with the index of microvascular resistance (IMR) on the occurrence of PCI-related myocardial injury and infarction. METHODS: In consecutive patients with stable CAD referred for elective PCI, coronary physiological indexes, including IMR, were measured before and after revascularization. High sensitivity Troponin T (hs-TnT) was assessed up to 24 h after PCI, and PCI-related myocardial injury and type 4a myocardial infarction (MI) were defined according to the fourth universal definition of myocardial infarction. RESULTS: In the 50 patients enrolled, a significant correlation was found between maximum post-PCI hs-Tn and IMR, both at baseline (rho = 0.309, p=0.029) and post-PCI (rho = 0.378, p=0.007). Patients who developed type 4a MI, compared with patients who did not, presented significantly higher IMR levels, both at baseline (28.3 ± 12.2 vs. 19.6 ± 8.8, p=0.020) and post-PCI (45.4 ± 21.3 vs. 21.6 ± 11.2, p<0.0001). Patients with post-PCI IMR > 38 showed significantly higher maximum post-PCI hs-Tn levels (105.4 [49.4-126.9] vs. 22.4 [11.7-38.6] ng/ml, p<0.0001), and developed type 4a MI more frequently (66.8% vs. 4.9%, p<0.0001). CONCLUSIONS: Dynamic changes of microvascular resistance post-PCI are strongly correlated with PCI-related myocardial injury and post-PCI IMR is a strong predictor of type 4a MI in patients with stable CAD undergoing elective PCI.

Platelet reactivity and coronary microvascular impairment after percutaneous revascularization in stable patients receiving clopidogrel or prasugrel.

BACKGROUND AND AIMS: Increased platelet reactivity (PR) associated with variable degree of coronary microvascular impairment has been reported in patients on clopidogrel after elective percutaneous coronary intervention (PCI). Prasugrel provides more potent platelet inhibition than clopidogrel, though it is unknown whether it might also prevent PCI-related platelet activation. In stable patients undergoing elective PCI, we compared: (1) the effects of prasugrel vs. clopidogrel on peri-procedural variations of PR and (2) the correlation of platelet inhibition potency with PCI-induced coronary microvascular impairment. METHODS: Forty thienopyridine-naive patients were randomly assigned to a loading dose of either prasugrel 60 mg (n = 20) or clopidogrel 600 mg (n = 20) at least 12 h before PCI. At the time of PCI, we assessed adenosine diphosphate (ADP)-induced PR with the Multiplate Analyzer, and the pressure-derived index of microvascular resistance (IMR) in the treated coronary, both at baseline and post-procedure. RESULTS: ADP-induced PR was significantly lower in the prasugrel compared with clopidogrel group both at baseline (16.0 ±â€¯8.7 vs. 33.9 ±â€¯18.0 aggregation units [AU], p < 0.001) and post-procedure (16.2 ±â€¯9.0 vs. 39.0 ±â€¯18.6 AU, p < 0.001). A significant peri-procedural increase in PR was observed in the clopidogrel group (p = 0.008), but not in the prasugrel group (p = 0.822). A significant correlation was found between IMR and PR both at baseline (r = 0.458, p = 0.003) and post-PCI (r = 0.487, p = 0.001). CONCLUSIONS: A loading dose of prasugrel compared with clopidogrel is able to attenuate PCI-related increase in PR in patients with stable CAD undergoing PCI, which might contribute to the beneficial effect of this drug on peri-procedural coronary microvascular function.

A decision support system and rule-based algorithm to augment the human interpretation of the 12-lead electrocardiogram.

BACKGROUND: The 12-lead Electrocardiogram (ECG) has been used to detect cardiac abnormalities in the same format for more than 70years. However, due to the complex nature of 12-lead ECG interpretation, there is a significant cognitive workload required from the interpreter. This complexity in ECG interpretation often leads to errors in diagnosis and subsequent treatment. We have previously reported on the development of an ECG interpretation support system designed to augment the human interpretation process. This computerised decision support system has been named 'Interactive Progressive based Interpretation' (IPI). In this study, a decision support algorithm was built into the IPI system to suggest potential diagnoses based on the interpreter's annotations of the 12-lead ECG. We hypothesise semi-automatic interpretation using a digital assistant can be an optimal man-machine model for ECG interpretation. OBJECTIVES: To improve interpretation accuracy and reduce missed co-abnormalities. METHODS: The Differential Diagnoses Algorithm (DDA) was developed using web technologies where diagnostic ECG criteria are defined in an open storage format, Javascript Object Notation (JSON), which is queried using a rule-based reasoning algorithm to suggest diagnoses. To test our hypothesis, a counterbalanced trial was designed where subjects interpreted ECGs using the conventional approach and using the IPI+DDA approach. RESULTS: A total of 375 interpretations were collected. The IPI+DDA approach was shown to improve diagnostic accuracy by 8.7% (although not statistically significant, p-value=0.1852), the IPI+DDA suggested the correct interpretation more often than the human interpreter in 7/10 cases (varying statistical significance). Human interpretation accuracy increased to 70% when seven suggestions were generated. CONCLUSION: Although results were not found to be statistically significant, we found; 1) our decision support tool increased the number of correct interpretations, 2) the DDA algorithm suggested the correct interpretation more often than humans, and 3) as many as 7 computerised diagnostic suggestions augmented human decision making in ECG interpretation. Statistical significance may be achieved by expanding sample size.

A computer-human interaction model to improve the diagnostic accuracy and clinical decision-making during 12-lead electrocardiogram interpretation.

INTRODUCTION: The 12-lead Electrocardiogram (ECG) presents a plethora of information and demands extensive knowledge and a high cognitive workload to interpret. Whilst the ECG is an important clinical tool, it is frequently incorrectly interpreted. Even expert clinicians are known to impulsively provide a diagnosis based on their first impression and often miss co-abnormalities. Given it is widely reported that there is a lack of competency in ECG interpretation, it is imperative to optimise the interpretation process. Predominantly the ECG interpretation process remains a paper based approach and whilst computer algorithms are used to assist interpreters by providing printed computerised diagnoses, there are a lack of interactive human-computer interfaces to guide and assist the interpreter. METHODS: An interactive computing system was developed to guide the decision making process of a clinician when interpreting the ECG. The system decomposes the interpretation process into a series of interactive sub-tasks and encourages the clinician to systematically interpret the ECG. We have named this model 'Interactive Progressive based Interpretation' (IPI) as the user cannot 'progress' unless they complete each sub-task. Using this model, the ECG is segmented into five parts and presented over five user interfaces (1: Rhythm interpretation, 2: Interpretation of the P-wave morphology, 3: Limb lead interpretation, 4: QRS morphology interpretation with chest lead and rhythm strip presentation and 5: Final review of 12-lead ECG). The IPI model was implemented using emerging web technologies (i.e. HTML5, CSS3, AJAX, PHP and MySQL). It was hypothesised that this system would reduce the number of interpretation errors and increase diagnostic accuracy in ECG interpreters. To test this, we compared the diagnostic accuracy of clinicians when they used the standard approach (control cohort) with clinicians who interpreted the same ECGs using the IPI approach (IPI cohort). RESULTS: For the control cohort, the (mean; standard deviation; confidence interval) of the ECG interpretation accuracy was (45.45%; SD=18.1%; CI=42.07, 48.83). The mean ECG interpretation accuracy rate for the IPI cohort was 58.85% (SD=42.4%; CI=49.12, 68.58), which indicates a positive mean difference of 13.4%. (CI=4.45, 22.35) An N-1 Chi-square test of independence indicated a 92% chance that the IPI cohort will have a higher accuracy rate. Interpreter self-rated confidence also increased between cohorts from a mean of 4.9/10 in the control cohort to 6.8/10 in the IPI cohort (p=0.06). Whilst the IPI cohort had greater diagnostic accuracy, the duration of ECG interpretation was six times longer when compared to the control cohort. CONCLUSIONS: We have developed a system that segments and presents the ECG across five graphical user interfaces. Results indicate that this approach improves diagnostic accuracy but with the expense of time, which is a valuable resource in medical practice.

Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA.

α2A-Adrenergic receptor polymorphism potentiates platelet reactivity in patients with stable coronary artery disease carrying the cytochrome P450 2C19*2 genetic variant.

OBJECTIVE: Platelet α2A-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α2A-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α2A-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy). APPROACH AND RESULTS: Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 µmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (P<0.05) apart from 10 µmol/L (P=0.077). Percentage inhibition was lower (P=0.048) in 6.3-kb α2A-AR carriers. Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037) and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3-kb α2A-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own. CONCLUSIONS: The 6.3-kb α2A-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy.

Intracoronary EnalaPrilat to Reduce MICROvascular Damage During Percutaneous Coronary Intervention (ProMicro) study.

OBJECTIVES: This study investigated the influence of intracoronary enalaprilat on coronary microvascular function and peri-procedural outcome measures in patients with stable angina undergoing percutaneous coronary intervention (PCI). BACKGROUND: Intracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation. METHODS: We randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 µg) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury. RESULTS: Infusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 ± 11 at baseline vs. 19 ± 9 after drug vs. 15 ± 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 ± 15 at baseline vs. 24 ± 15 after drug vs. 33 ± 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p < 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p = 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p = 0.025). CONCLUSIONS: Intracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedure-related injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit.

A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome Validation Effort) study.

OBJECTIVES: This study sought to validate the ability of the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in predicting both ischemic and bleeding events after elective percutaneous coronary intervention (PCI). BACKGROUND: High and low levels of platelet reactivity are associated with ischemic and bleeding events, respectively, after PCI. METHODS: A total of 732 patients on dual antiplatelet therapy undergoing elective PCI were recruited. Platelet reactivity was measured before PCI. The primary endpoint was the 30-day incidence of net adverse clinical events (NACE), defined as the occurrence of ischemic or bleeding events, in relation to P2Y(12) reaction unit (PRU) distribution. RESULTS: At receiver-operating characteristic curve analysis, PRU values could significantly discriminate between patients with and without bleeding events (area under the curve [AUC]: 0.72; 95% confidence interval [CI]: 0.65 to 0.80; p < 0.0001) and those with and without ischemic events (AUC: 0.68; 95% CI: 0.61 to 0.76; p < 0.0001). The optimal cutoffs for bleeding (PRU ≤ 178) and ischemic events (PRU ≥ 239) were used to define 3 groups: low platelet reactivity (LPR) (LPR = PRU ≤ 178), normal platelet reactivity (NPR) (NPR = PRU 179 to 238), and high platelet reactivity (HPR) (HPR = PRU ≥ 239). The incidence of NACE was 14.1% in the LPR group, 7.8% in the NPR group (p = 0.025 vs. LPR group), and 15.4% in the HPR group (p = 0.005 vs. NPR group). At multivariate analysis, PRU values in the NPR group were an independent predictor of reduced risk of 30-day NACE (odds ratio: 0.47, 95% CI: 0.27 to 0.81). CONCLUSIONS: A therapeutic window for platelet reactivity measured with the VerifyNow P2Y12 assay can be identified using specific thresholds that define a group of patients at lower risk for both ischemic and bleeding events. Adjunctive measures may be beneficial in patients with higher or lower platelet reactivity in order to improve clinical outcomes after PCI.

High cholesterol levels are associated with coronary microvascular dysfunction.

OBJECTIVES: We investigated the potential association between serum cholesterol levels and coronary microvascular function, using the index of microvascular resistance (IMR), in patients with coronary artery disease. METHODS: At the time of coronary angiography, IMR was measured in one or more epicardial vessel with an intermediate stenosis (>30%). Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol and triglyceride concentrations were measured before cardiac catheterization. RESULTS: A total of 110 coronary arteries were investigated in 95 patients. The mean IMR was 26 ± 12 with evidence of microvascular dysfunction in 32 arteries (29%). A significant correlation was seen between IMR, total cholesterol (r=0.28, P=0.003) and LDL cholesterol (r=0.30, P=0.001). At multivariate analysis, LDL cholesterol was the only independent predictor of IMR, even after adjustment for the extent of epicardial coronary atherosclerosis and fractional flow reserve values. CONCLUSION: Our data obtained with invasive measurement of microvascular resistance suggest a significant correlation between cholesterol levels and coronary microvascular dysfunction.

Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy.

BACKGROUND: Current or recent use of abacavir for treating human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased rates of myocardial infarction (MI). Given the role of platelet aggregation in thrombus formation in MI and the reversible nature of the abacavir association, we hypothesized that patients treated with abacavir would have increased platelet reactivity. METHODS: In a prospective study in adult HIV-infected patients, we determined associations between antiretrovirals (ARVs), and in particular the nucleoside reverse transcriptase inhibitor abacavir, and platelet reactivity by measuring time-dependent platelet aggregation in response to agonists: adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), collagen, and epinephrine. RESULTS: Of 120 subjects, 40 were ARV-naive and 80 ARV-treated, 40 of whom were receiving abacavir. No consistent differences in platelet reactivity were observed between the ARV-naive and ARV-treated groups. In contrast, within the ARV-treated group, abacavir-treated subjects had consistently higher percentages of platelet aggregation upon exposure to ADP, collagen, and epinephrine (P = .037, P = .022, and P = .032, respectively) and had platelets that were more sensitive to aggregation upon exposure to TRAP (P = .025). CONCLUSIONS: The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients.

Lack of correlation between platelet reactivity and glycaemic control in type 2 diabetes mellitus patients treated with aspirin and clopidogrel.

The relationship between glycaemic control and platelet reactivity in patients with type 2 diabetes mellitus (DM) on dual antiplatelet therapy is still unclear. A total of 155 consecutive stable angina patients with type 2 DM scheduled for elective percutaneous coronary intervention (PCI) were recruited. All patients were taking aspirin and received a 600-mg loading dose of clopidogrel at least 12 h before intervention. Platelet reactivity was assessed prior to PCI using the VerifyNow(®) device (Accumetrics Inc., San Diego, California). High platelet reactivity on clopidogrel (HPR(Clopidogrel)) was defined as a PRU value ≥240. HPR on aspirin (HPR(Aspirin)) defined as an ARU value ≥550. Poor glycaemic control was defined as a HbA1C value >7 mg/dL. There was no significant difference in either PRU or ARU values in patients with poor glycaemic control compared to those with good glycaemic control (PRU: 230 ± 92 vs. 228 ± 110, P = 0.90; ARU: 440 ± 63 vs. 435 ± 60, P = 0.61). Patients with and without poor glycaemic control did not show significantly different prevalence of HPR(Aspirin) (8 vs. 6%; P = 0.23) or HPR(Clopidogrel) (46 and 44%; P = 0.80). There was no significant correlation found between HbA1C and either ARU values (r = 0.040, P = 0.71) or PRU values (r = 0.018, P = 0.87). Overall these data suggest that glycaemic control does not appear to influence platelet reactivity in patients with type 2 DM following a loading dose of 600 mg of clopidogrel and aspirin treatment.

Platelet function and HIV: a case-control study.

OBJECTIVE: Cardiovascular disease and myocardial infarction are of increasing concern in HIV-infected populations. Although platelets mediate arterial thrombosis, central to myocardial infarction, data on platelet function in HIV infection are lacking. We hypothesized that HIV-infected patients would have altered platelet reactivity. DESIGN: A case-control study of platelet reactivity in 20 HIV-infected (HIVpos) and 20 age and sex-matched HIV-negative (HIVneg) individuals. METHODS: Time-dependent platelet aggregation was measured in response to increasing concentrations of platelet agonists: epinephrine, collagen, thrombin receptor-activating peptide and ADP using light absorbance. RESULTS: In both groups, mean age was 34 years, and 65% were men. Sixteen out of 20 (80%) of the HIVpos patients were on antiretroviral therapy with 12 out of 20 (60%) patients having HIV RNA less than 50 copies/ml. There were significant between-group differences in platelet reactivity across all four agonists. Platelets from HIVpos patients were more reactive to epinephrine [mean (SD) log concentration required to induce 50% maximal aggregation, 1.9 (1.2) versus 3.0 (1.7) mumol/l in HIVneg individuals, P = 0.028], whereas less platelet aggregation was observed in response to submaximal concentrations of the other agonists [thrombin receptor-activating peptide 72.5 (14.5)% versus 82.2 (7.6)% at 10 mumol/l, P = 0.011; ADP 67.3 (12.1)% versus 75.2 (8.8)% at 10 mumol/l, P = 0.035; collagen 16.6 (25.1)% versus 35.4 (31.5)% at 71.25 microg/ml, P = 0.007]. CONCLUSION: Between-group differences in platelet responses to all agonists suggest multiple underlying defects in platelet function in HIV infection. Further research is required to determine the contribution of antiretroviral therapy and relationships between platelet function and the increased cardiovascular disease observed in HIV-infected populations.

Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target.

OBJECTIVE: To assess the influence of disease activity on platelet function in patients with inflammatory arthritis (IA). METHODS: Ninety-six patients with an established diagnosis of IA (RA, PsA, seronegative SpA) were recruited. Patients with a history of cardiovascular disease (CVD), diabetes mellitus or receiving anti-platelet therapy were excluded. Demographic data, traditional CVD risk factors and medication use were recorded. Patients were characterized as active disease (n = 38) or control disease (n = 58) groups, respectively, based on internationally validated measures of disease activity [comprising serological markers (ESR, CRP, fibrinogen), patient measures (visual analogue scale of disease activity), evaluator global assessment and the 28-joint disease activity score]. Platelet function was assessed using a novel assay of platelet reactivity. Platelet aggregation to multiple concentrations of arachidonic acid, collagen, epinephrine, thrombin receptor activating peptide and adenosine diphosphate (ADP) were measured simultaneously using a modification of light transmission aggregometry. RESULTS: The two groups (active vs control) were similar in terms of demographics and CVD risk factors. Anti-TNF-alpha therapy use was higher in the control group (P = 0.004), whereas NSAID use was higher in the active group (P = 0.001). There was a significant difference between the two groups in platelet response to ADP (P < 0.001). Platelet aggregation, in response to submaximal concentrations of ADP, was increased in the active disease group compared with the control group. There was no difference in platelet reactivity between the groups in response to any of the other agonists. CONCLUSION: Patients with active IA demonstrate enhanced platelet reactivity, unique to the ADP pathway. This potential pro-thrombotic bias may contribute to their increased cardiovascular risk.