Evaluation of the role of the new INNOVANCE PFA P2Y test cartridge in detection of clopidogrel resistance.

Light transmittance aggregometry (LTA) has been extensively used in monitoring clopidogrel therapy. However, the availability of simple and rapid point-of-care platelet function assays is of great clinical importance. Thus, the manufacturer of the Platelet Function Analyzer (PFA)-100 System has recently produced the INNOVANCE PFA P2Y test cartridge. We assessed the ability of this new test to reliably detect clopidogrel resistance. We enrolled 90 consecutive patients with coronary artery disease receiving chronic clopidogrel maintenance therapy in combination with aspirin. Twenty healthy volunteers served as controls. Clopidogrel resistance was simultaneously analysed by the INNOVANCE PFA P2Y test cartridge, ADP-induced LTA, the flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and the multiple electrode aggregometry (Multiplate). Agreement among the four platelet function methods by two was assessed using Cohen's kappa coefficient. According to the cut-off points for clopidogrel resistance proposed by the literature, agreement was fair between INNOVANCE PFA-100 P2Y and LTA (74.4%) and Multiplate (75.6%), while poor agreement was noticed in VASP assay (63.3%). Based on cut-off points indicating a higher thrombotic risk, agreement between the PFA-100 System and the other three methods did not significantly differ compared to the previous cut-offs (72.2%, 71.1% and 55.1%, respectively). The INNOVANCE PFA-100 P2Y test seems to be comparable to other established platelet function assays in detecting clopidogrel resistance. However, the modest agreement among platelet function methods makes the performance of platelet function testing crucial with more than one technique in order to reliably identify poor responders to clopidogrel treatment.

The role of the Platelet Function Analyzer (PFA)-100 and platelet aggregometry in the differentiation of essential thrombocythemia from reactive thrombocytosis.

INTRODUCTION: The most crucial component of all diagnostic criteria for essential thrombocythemia (ET) has been the exclusion of reactive thrombocytosis (RT). Our aim was to evaluate the diagnostic performance of the PFA-100 collagen-epinephrine (CEPI) cartridge test and epinephrine-induced aggregometry individually, but mainly combined, in the differentiation of ET from RT. MATERIALS AND METHODS: 26 patients with ET and 25 with RT were studied. Platelet function was analyzed by the PFA-100 and by light transmission aggregometry with epinephrine and ADP. The JAK2 mutational status was identified and hematological parameters, plasma von Willebrand factor antigen and activity levels were also assessed. RESULTS: The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and the negative predictive value (NPV) of PFA-100 CEPI vs epinephrine-induced aggregometry in the differentiation of ET from RT were estimated as follows: Se (%): 78.9 vs 84.6, Sp (%): 92.0 vs 96.0, PPV (%): 88.2 vs 95.7, NPV (%): 85.2 vs 85.7, respectively. When both of these methods were combined, a lower sensitivity of 68.4%, but a specificity of 100% was attained. The PPV observed with this double abnormal combination was 100% and the NPV 80.6%. Lastly, when we assessed the abnormality for either CEPI CT or epinephrine-induced aggregometry, the sensitivity was 100%, the specificity 88.0%, PPV 86.4% and NPV 100%. Thus, an abnormal combination was strongly suggestive of ET, while normal results with both methods excluded ET. CONCLUSIONS: If our results are replicated by further studies, these two methods could be used very effectively as adjunct markers in the differentiation between ET and RT.

The effect of plasma homocysteine levels on clinical outcomes of patients with acute lung injury/acute respiratory distress syndrome.

BACKGROUND: Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS. METHODS: Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment. RESULTS: In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days (P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs (P = 0.38), the probability of being free from mechanical ventilation at day 28 (P = 0.63), and days without ventilation assistance (P = 0.73). CONCLUSION: Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.