Common use of Interferences Clause in Contracts

Interferences. <Pseudothrombocytopenia, though infrequent, can result from EDTA-dependent platelet agglutination. Pseudothrombocytopenia may be suspected with the Plateletworks assay if the platelet count determined using the agonist tube is higher than the platelet count determined using the baseline tube (containing EDTA anticoagulant). If pseudothrombocytopenia is suspected, common laboratory practice is to re-draw the blood sample into a sodium citrate collection tube and perform the blood count; the results should be corrected by a factor of 1.1 to account for the sample dilution that occurs with the use of sodium citrate as an anticoagulant. This procedure should be followed using the sodium citrate tube in lieu of the Plateletworks baseline tube, followed by the Plateletworks agonist tube, to determine percent platelet aggregation. <Cell counters utilizing electronic impedance cell counting principles may be subject to known interfering substances which can impact platelet count results. These include: < Microcytes, schizocytes, and WBC fragments, which may interfere with the proper counting of platelets and cause elevated platelet counts < Agglutinated erythrocytes, which may trap platelets and cause an erroneously low platelet count < Giant platelets, which may cause an erroneously low platelet count since they may exceed the upper limit threshold for the platelet parameter < Chemotherapy, which may increase the fragility of platelets and cause low platelet counts < Hemolysis, which contains red cell stroma and may elevate platelet counts < Acid-citrate-dextrose (ACD) blood, which may contain platelet aggregates that could depress the platelet count < RBC inclusions, which may produce a spuriously increased platelet count < Platelet agglutination, due to poor collection techniques or EDTA activation, which may cause a decreased platelet count REFERENCE VALUES The reference value for each Plateletworks agonist tube was determined on samples collected from healthy volunteers. Each laboratory should establish their own reference range with their normal patient population.13 The data are as follows: Agonist Reference Range Collagen 70-100% ADP 86-100% PERFORMANCE CHARACTERISTICS Correlation Study Correlation of the Plateletworks assay to platelet aggregometry on platelet rich plasma (PRP) is supported by data generated by testing male and female adults, between the ages of 18 and 85, at three clinical sites. This includes normal, healthy volunteers, patients undergoing cardiopulmonary bypass surgery, and patients undergoing cardiac catherization. All blood samples were acquired from in-dwelling lines or venipuncture using established methods. For the Plateletworks assays and PRP aggregometry, the manufacturers’ recommendations were adhered to as per instructions provided in the package insert. Regression analysis (correlation coefficients) was performed to assess the agreement between the two methods. A positive correlation was demonstrated for each agonist. See Figures 1 and 2. Figure 1: ADP Figure 2: Collagen However, it is recognized that correlation coefficients measure the strength of the relationship between the methods and not the agreement between them.2 Further, since the aggregation system is bounded by 100% as the upper limit of aggregation regression analysis is not expected to describe a predictive relationship. Therefore, the data from the clinical sites where substantial equivalence testing was performed were also subjected to the non-parametric analysis of Xxxxxxxx Rho which “tests for a positive correlation without specifying linearity”. The results from these analyses are shown (with the regression analysis).

Interferences. <Pseudothrombocytopenia, though infrequent, can result from EDTA-dependent platelet agglutination. Pseudothrombocytopenia may be suspected with the Plateletworks assay if the platelet count determined using the agonist tube is higher than the platelet count determined using the baseline tube (containing EDTA anticoagulant). If pseudothrombocytopenia is suspected, common laboratory practice is to re-draw the blood sample into a sodium citrate collection tube and perform the blood count; the results should be corrected by a factor of 1.1 to account for the sample dilution that occurs with the use of sodium citrate as an anticoagulant. This procedure should be followed using the sodium citrate tube in lieu of the Plateletworks baseline tube, followed by the Plateletworks agonist tube, to determine percent platelet aggregation. <• Cell counters utilizing electronic impedance cell counting principles may be subject to known interfering substances which can impact platelet count results. These include: < • Microcytes, schizocytes, and WBC fragments, which may interfere with the proper counting of platelets and cause elevated platelet counts < counts. • Agglutinated erythrocytes, which may trap platelets and cause an erroneously low platelet count < count. • Giant platelets, which may cause an erroneously low platelet count since they may exceed the upper limit threshold for the platelet parameter < parameter. • Chemotherapy, which may increase the fragility of platelets and cause low platelet counts < • Hemolysis, which contains red cell stroma and may elevate platelet counts < counts. • Acid-citrate-dextrose (ACD) blood, which may contain platelet aggregates that could depress the platelet count < count. • RBC inclusions, which may produce a spuriously increased platelet count < count. • Platelet agglutination, due to poor collection techniques or EDTA activation, which may cause a decreased platelet count REFERENCE VALUES The reference value for each Plateletworks agonist tube was determined on samples collected from healthy volunteerscount. Each laboratory should establish their own reference range with their normal patient population.13 The data are as follows: Agonist Reference Range Collagen 70-100% ADP 86-100% PERFORMANCE CHARACTERISTICS Correlation Study Correlation of the Plateletworks assay to platelet aggregometry on platelet rich plasma (PRP) is supported by data generated by testing male and female adults, between the ages greater than 18 years of 18 and 85age, at three clinical sites. This includes normal, healthy volunteers, patients undergoing cardiopulmonary bypass surgery, and patients undergoing cardiac catherizationand volunteers who were taking aspirin. All blood samples were acquired from in-dwelling lines or venipuncture using established methods. For the Plateletworks assays and PRP aggregometry, the manufacturers’ recommendations were adhered to as per instructions provided in the package insert. Regression analysis (correlation coefficients) A positive result was performed equal to assess the agreement between the two methodsor greater than 60% aggregation and a negative result was less than 60% aggregation. A comparison study of 337 specimens gave an overall agreement of 87.5%; positive correlation was demonstrated for each agonistagreement of 93.2%; and negative agreement of 85.0%. See Figures 1 and 2Note: Thrombocytopenic samples may be tested using the Plateletworks assay. Figure 1: ADP Figure 2: Collagen HoweverAs this system utilizes electrical impedance cell counting principles (i.e., it is recognized that correlation coefficients measure Ichor Hematology Analyzer), instrument platelet counts >10 x 103/µL can be accurately obtained. Agonist platelet counts can be measured in samples meeting the strength of the relationship between the methods and not the agreement between them.2 Further, since the aggregation system is bounded by 100% as the upper limit limits of aggregation regression analysis is not expected to describe a predictive relationshipdetection (>27 x 103/µL). ThereforeAlthough EDTA-induced thrombocytopenic samples may be tested using the Plateletworks assay, the data from the clinical sites where substantial equivalence no actual testing was performed were also subjected to on this sample type. Precision Precision of the non-parametric analysis of Xxxxxxxx Rho which “tests for Plateletworks assay was determined using duplicate samples from a positive correlation without specifying linearity”healthy volunteer. The results from these analyses are shown (duplicate samples were tested on each of twenty(20) days with the regression analysis).AA agonist. The mean was 67%, coefficients of variation were 7.1% within-run and 13.9% for the total test period. BIBLIOGRAPHY Literatur/Bibliografia/Bibliografie/Bibliografia

Interferences. <Pseudothrombocytopenia, though infrequent, can result from EDTA-dependent platelet agglutination. Pseudothrombocytopenia may be suspected with the Plateletworks assay if the platelet count determined using the agonist tube is higher than the platelet count determined using the baseline tube (containing EDTA anticoagulant). If pseudothrombocytopenia is suspected, common laboratory practice is to re-draw the blood sample into a sodium citrate collection tube and perform the blood count; the results should be corrected by a factor of 1.1 to account for the sample dilution that occurs with the use of sodium citrate as an anticoagulant. This procedure should be followed using the sodium citrate tube in lieu of the Plateletworks baseline tube, followed by the Plateletworks agonist tube, to determine percent platelet aggregation. <• Cell counters utilizing electronic impedance cell counting principles may be subject to known interfering substances which can impact platelet count results. These include: < • Microcytes, schizocytes, and WBC fragments, which may interfere with the proper counting of platelets and cause elevated platelet counts < counts. • Agglutinated erythrocytes, which may trap platelets and cause an erroneously low platelet count < count. • Giant platelets, which may cause an erroneously low platelet count since they may exceed the upper limit threshold for the platelet parameter < parameter. • Chemotherapy, which may increase the fragility of platelets and cause low platelet counts < • Hemolysis, which contains red cell stroma and may elevate platelet counts < counts. • Acid-citrate-dextrose (ACD) blood, which may contain platelet aggregates that could depress the platelet count < count. • RBC inclusions, which may produce a spuriously increased platelet count < count. • Platelet agglutination, due to poor collection techniques or EDTA activation, which may cause a decreased platelet count REFERENCE VALUES The reference value for each Plateletworks agonist tube was determined on samples collected from healthy volunteerscount. Each laboratory should establish their own reference range with their normal patient population.13 The data are as follows: Agonist Reference Range Collagen 70-100% ADP 86-100% PERFORMANCE CHARACTERISTICS Correlation Study Correlation of the Plateletworks assay to platelet aggregometry on platelet rich plasma (PRP) is supported by data generated by testing male and female adults, between the ages greater than 18 years of 18 and 85age, at three clinical sites. This includes normal, healthy volunteers, patients undergoing cardiopulmonary bypass surgery, and patients undergoing cardiac catherizationand volunteers who were taking aspirin. All blood samples were acquired from in-dwelling lines or venipuncture using established methods. For the Plateletworks assays and PRP aggregometry, the manufacturers’ recommendations were adhered to as per instructions provided in the package insert. Regression analysis (correlation coefficients) A positive result was performed equal to assess the agreement between the two methodsor greater than 60% aggregation and a negative result was less than 60% aggregation. A comparison study of 337 specimens gave an overall agreement of 87.5%; positive correlation was demonstrated for each agonistagreement of 93.2%; and negative agreement of 85.0%. See Figures 1 and 2Note: Thrombocytopenic samples may be tested using the Plateletworks assay. Figure 1: ADP Figure 2: Collagen HoweverAs this system utilizes electrical impedance cell counting principles (i.e., it is recognized that correlation coefficients measure Ichor Hematology Analyzer), instrument platelet counts >10 x 103/µL can be accurately obtained. Agonist platelet counts can be measured in samples meeting the strength of the relationship between the methods and not the agreement between them.2 Further, since the aggregation system is bounded by 100% as the upper limit limits of aggregation regression analysis is not expected to describe a predictive relationshipdetection (>27 x 103/µL). ThereforeAlthough EDTA-induced thrombocytopenic samples may be tested using the Plateletworks assay, the data from the clinical sites where substantial equivalence no actual testing was performed were also subjected to the non-parametric analysis of Xxxxxxxx Rho which “tests for a positive correlation without specifying linearity”. The results from these analyses are shown (with the regression analysis)on this sample type.

Interferences. <Pseudothrombocytopenia, though infrequent, can result from EDTA-dependent platelet agglutination. Pseudothrombocytopenia may be suspected with the Plateletworks assay if the platelet count determined using the agonist tube is higher than the platelet count determined using the baseline tube (containing EDTA anticoagulant). If pseudothrombocytopenia is suspected, common laboratory practice is to re-draw the blood sample into a sodium citrate collection tube and perform the blood count; the results should be corrected by a factor of 1.1 to account for the sample dilution that occurs with the use of sodium citrate as an anticoagulant. This procedure should be followed using the sodium citrate tube in lieu of the Plateletworks baseline tube, followed by the Plateletworks agonist tube, to determine percent platelet aggregation. <• Cell counters utilizing electronic impedance cell counting principles may be subject to known interfering substances which can impact platelet count results. These include: < • Microcytes, schizocytes, and WBC fragments, which may interfere with the proper counting of platelets and cause elevated platelet counts < counts. • Agglutinated erythrocytes, which may trap platelets and cause an erroneously low platelet count < count. • Giant platelets, which may cause an erroneously low platelet count since they may exceed the upper limit threshold for the platelet parameter < parameter. • Chemotherapy, which may increase the fragility of platelets and cause low platelet counts < • Hemolysis, which contains red cell stroma and may elevate platelet counts < counts. • Acid-citrate-dextrose (ACD) blood, which may contain platelet aggregates that could depress the platelet count < count. • RBC inclusions, which may produce a spuriously increased platelet count < count. • Platelet agglutination, due to poor collection techniques or EDTA activation, which may cause a decreased platelet count REFERENCE VALUES The reference value for each Plateletworks agonist tube was determined on samples collected from healthy volunteerscount. Each laboratory should establish their own reference range with their normal patient population.13 The data are as follows: Agonist Reference Range Collagen 70-100% ADP 86-100% PERFORMANCE CHARACTERISTICS Correlation Study Correlation of the Plateletworks assay to platelet aggregometry on platelet rich plasma (PRP) is supported by data generated by testing male and female adults, between the ages greater than 18 years of 18 and 85age, at three clinical sites. This includes normal, healthy volunteers, patients undergoing cardiopulmonary bypass surgery, and patients undergoing cardiac catherizationand volunteers who were taking aspirin. All blood samples were acquired from in-dwelling lines or venipuncture using established methods. For the Plateletworks assays and PRP aggregometry, the manufacturers’ recommendations were adhered to as per instructions provided in the package insert. Regression analysis (correlation coefficients) A positive result was performed equal to assess the agreement between the two methodsor greater than 60% aggregation and a negative result was less than 60% aggregation. A comparison study of 337 specimens gave an overall agreement of 87.5%; positive correlation was demonstrated for each agonistagreement of 93.2%; and negative agreement of 85.0%. See Figures 1 and 2Note: Thrombocytopenic samples may be tested using the Plateletworks assay. Figure 1: ADP Figure 2: Collagen HoweverAs this system utilizes electrical impedance cell counting principles (i.e., it is recognized that correlation coefficients measure Ichor Hematology Analyzer), instrument platelet counts >10 x 103/µL can be accurately obtained. Agonist platelet counts can be measured in samples meeting the strength of the relationship between the methods and not the agreement between them.2 Further, since the aggregation system is bounded by 100% as the upper limit limits of aggregation regression analysis is not expected to describe a predictive relationshipdetection (>27 x 103/µL). ThereforeAlthough EDTA-induced thrombocytopenic samples may be tested using the Plateletworks assay, the data from the clinical sites where substantial equivalence no actual testing was performed were also subjected to on this sample type. Precision Precision of the non-parametric analysis of Xxxxxxxx Rho which “tests for Plateletworks assay was determined using duplicate samples from a positive correlation without specifying linearity”healthy volunteer. The results from these analyses are shown (duplicate samples were tested on each of twenty(20) days with the regression analysis)AA agonist. The mean was 67%, coefficients of variation were 7.1% within-run and 13.9% for the total test period. BIBLIOGRAPHY Literatur/Bibliografia/Bibliografie/Bibliografia 1. Xxxxxx, M.B., The Functioning of Blood Platelets, Sci Amer 242(6):86-103, 1980.