Huyen My Tran - Academia.edu (original) (raw)

Papers by Huyen My Tran

Applied and Environmental Microbiology, 1999

Teichoic acid-associated N-acetylglucosamine and rhamnose have been shown to serve as phage recep... more Teichoic acid-associated N-acetylglucosamine and rhamnose have been shown to serve as phage receptors in Listeria monocytogenes serotype 1/2a. We generated and characterized two single-copy Tn916ΔE mutants which were resistant to phage A118 and several other serotype 1/2a-specific phages. In one mutant the insertion was immediately upstream of the recently identifiedptsHI locus, which encodes two proteins of the phosphoenolpyruvate-dependent carbohydrate uptake system, whereas in the other the insertion was immediately upstream of an operon whose most distal gene was clpC, involved in stress responses and virulence. Transduction experiments confirmed the association of the phage-resistant phenotype of these mutants with the transposon insertion. Phage A118 resistance of the mutants could be attributed to inability of the phage to adsorb onto the mutant cells, and biochemical analysis of cell wall composition showed that the teichoic acids of both mutants were deficient in N-acetylgl...

British Journal of Haematology, 2016

British journal of haematology, 2014

The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refra... more The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 10(9) /l and ≤50 × 10(9) /l) idiopathic thrombocytopenic purpura (ITP). Patients received two doses of rituximab (1000 mg) on days 1 and 15 and were followed-up on weeks 1-8, 12, 26, 39 and 52. A total of 122 patients were included in the safety population; efficacy was analysed in 108 patients. Overall response rate (ORR) at week 8, defined as the proportion of patients achieving complete response (CR; platelet count >150 × 10(9) /l) or partial response (PR; platelet count >50 × 10(9) /l) was 44%. Therapeutic response, defined as achieving a response at week 8, with at least a minor response (MR; platelet count >30 × 10(9) /l), sustained up to weeks 26 and 52 and accompanied by a reduction in ITP medications, was achieved in 44% (week 26) and 35% (week 52) of patients, respectively. Treatment was well tolerated with no safety ...

Journal of cardiac surgery, 2015

This study presents the experience of a large Australian hospital in performing cardiac surgery o... more This study presents the experience of a large Australian hospital in performing cardiac surgery on patients with hereditary bleeding disorders (HBDs) and provides a suggested approach for their perioperative management. Medical records of patients with HBDs who underwent cardiac surgery from January 1997 to December 2013 were reviewed. Seventeen patients were included in this study, 13 with Hemophilia A, one symptomatic Hemophilia A carrier, one with Hemophilia B, and two with von Willebrand Disease. Cardiac surgical procedures performed included 10 coronary artery bypass graft (CABG) operations, two aortic valve replacements, two mitral valve repairs, two aortic root replacements, and one combined aortic valve replacement and CABG. Perioperative management centered on factor substitution to maintain normal factor levels. Perioperative outcomes including length of hospital stay, mortality, and return to the operating room for bleeding were recorded. Two patients returned to the oper...

Cardiology Clinics, 2008

Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonar... more Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable riskbenefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.

Seminars in Thrombosis and Hemostasis, 2012

The term resistance has been applied to interindividual variability in platelet reactivity during... more The term resistance has been applied to interindividual variability in platelet reactivity during antiplatelet therapy or to thrombosis despite appropriate therapy. In particular "aspirin resistance" and "clopidogrel resistance" have been the subject of intense investigation for their association with poor cardiovascular outcomes. Several mechanisms have been investigated including resistance arising from poor bioavailability, especially in clopidogrel therapy as resulting from a loss of function variant in hepatic metabolism required for prodrug activation. A limitation of studies linking on-treatment reactivity and clinical outcome is that they have been performed in high-risk patients with recent atherothrombotic disease. On-treatment platelet reactivity correlates with acuity of recent atherothrombosis, and variability in pretreatment platelet function predicts on-treatment platelet function for both aspirin and clopidogrel. It is therefore likely that high on-treatment platelet function at the time of testing may often result from underlying platelet hyperreactivity related to acute atherothrombosis, rather than true pharmacological resistance. The association of high on-treatment platelet reactivity with poor clinical outcomes may therefore be attributed to variability in underlying burden of disease instead of, or in addition to, pharmacological resistance to antiplatelet therapy.

Monatshefte fuer Chemie/Chemical Monthly, 1998

Monatshefte fuer Chemie/Chemical Monthly, 1998

Monatshefte fuer Chemie/Chemical Monthly, 1999

Monatshefte f?r Chemie / Chemical Monthly, 2002

It was found that the hypericinate salts of (R)-1-phenylethylamine and (S)-1-(1-naphthyl)ethylami... more It was found that the hypericinate salts of (R)-1-phenylethylamine and (S)-1-(1-naphthyl)ethylamine display a small chiroptical signal of the same sign only at high concentrations in an apolar solvent. No further indications of a chiral discrimination between the helical conformers of hypericinate could be found in these cases. However, upon esteri®cation of the 3-hydroxyl group of hypericin with (1S)-camphanic chloride, the two diastereomers were found in an 1:1 ratio equilibrating rather fast at temperatures above 30 C with one diastereomer in excess. From the temperature dependence of the equilibrium positions (measured by means of CD and 1 H NMR), a ÁG 0 value of 5.8 AE 0.5 kJ Á mol À 1 was derived. Accordingly, the chiral discrimination of the (M)-con®gured enantiomer of the helix by the (S)-con®gured auxiliary occurred at an intermediate level. From the temperature dependence of the equilibration kinetics an activation energy of E a 70 AE 0.5 kJ Á mol À 1 was derived, which thus de®nes the upper limit of the helix inversion of hypericin and hypericinate. This value is by about 10 kJ Á mol À 1 lower than the recently estimated limit.

Monatshefte fuer Chemie/Chemical Monthly, 1998

The dissociation of hypericin (1) was investigated using atmospheric pressure ionization mass spe... more The dissociation of hypericin (1) was investigated using atmospheric pressure ionization mass spectrometry of 80% ethanolic solutions under variation of their pH values. Thus, it could be unequivocally established that the species predominant within the pH region of 3±10 and 11±13 are the mono-and dideprotonated compounds 1 À and 1 2À. These results nicely corroborate the hitherto accumulated mostly spectrophotometric evidence for the ®rst deprotonation step occurring at a pK a value in the order of 2 and the second one at about 12. Moreover, this example demonstrates the potential of atmospheric pressure ionization mass spectrometry as a valuable tool to investigate dissociation equilibria.

Monatshefte fuer Chemie/Chemical Monthly, 1999

Summary. Based on the interpretation of UV/Vis, IR, and NMR spectra of hypericin as well as of it... more Summary. Based on the interpretation of UV/Vis, IR, and NMR spectra of hypericin as well as of its salts and the products of total O-methylation, it was concluded that hypericin transfers from solid state to low or moderate polar organic media as its 1,6-dioxo-tautomer, thereby ...

Monatshefte für Chemie / Chemical Monthly, 1998

Summary. Sulfonation of hypericin leads to its di-, tri-, and tetrasulfonic acid derivatives. The... more Summary. Sulfonation of hypericin leads to its di-, tri-, and tetrasulfonic acid derivatives. The latter is soluble in water up to millimolar solutions. Homoaggregate formation (J-aggregates) was observed only above 5Á10À4 mol/l. In water solutions, the tetrasulfonic acid ...

Journal of Vascular Surgery, 2007

Conclusion: Men have a 50% higher risk of recurrent venous thromboembolism (VTE) after cessation ... more Conclusion: Men have a 50% higher risk of recurrent venous thromboembolism (VTE) after cessation of anticoagulant therapy. Summary: The authors performed a meta-analysis to examine the question of risk of recurrent VTE in men versus women after cessation of anticoagulation treatment. Eligible articles were identified using the Coch

Internal Medicine Journal, 2011

Prothrombinex-VF (a three-factor prothrombin complex concentrate) contains little factor VII. The... more Prothrombinex-VF (a three-factor prothrombin complex concentrate) contains little factor VII. Therefore, the Warfarin Reversal Consensus Guidelines from 2004 published by The Australasian Society of Haemostasis and Thrombosis recommend that it be administered with fresh frozen plasma to reverse warfarin anticoagulation. To evaluate the efficacy and safety of Prothrombinex-VF used alone in warfarin reversal. Adult patients requiring urgent reversal of warfarin anticoagulation were defined as having achieved complete (target international normalized ratio (INR) <1.4) or partial reversal (target INR 1.4-2.0) of their anticoagulation. Prothrombinex-VF was given at doses of between 25 and 50 IU/kg based on the intent of reversal and an INR was obtained 30min post infusion. A total of 50 patients (mean age 72years, range 32-85years) was included. The median initial INR in the complete reversal arm (n= 35) was 3.5 (range 1.7-20) with 91% achieving the target INR (mean 1.1, range 0.9-1.4). In the partial reversal arm (n= 15) the mean initial INR was 5.6 (range 2.5-12) with 93% achieving the target INR (mean 1.6, range 1.4-2.2). There were no adverse effects attributed to Prothrombinex-VF. Prothrombinex-VF is very effective and safe when used alone to reverse warfarin anticoagulation. The supplementary use of fresh frozen plasma in these patients is not required. A review of the current Warfarin Reversal Consensus Guidelines is needed.

Thrombosis and haemostasis, 2011

Dear Sirs, Antiphospholipid syndrome (APS) is diagnosed when arterial or venous thrombosis, or re... more Dear Sirs, Antiphospholipid syndrome (APS) is diagnosed when arterial or venous thrombosis, or recurrent miscarriage, is associated with the presence of antiphospholipid antibodies. The antiphospholipid antibody must be persistent (present in two separate blood samples taken more than 12 weeks apart) (1). The laboratory tests should use screening, mixing and confirmation stages, and more than one test system should be used due to the heterogeneity of lupus anticoagulants.

Critical Reviews in Clinical Laboratory Sciences, 2012

People with diabetes have an increased risk of life-threatening cardiovascular disease compared t... more People with diabetes have an increased risk of life-threatening cardiovascular disease compared to the general population. Furthermore, people with diabetes are at greatly increased risk of not responding to standard anti-platelet therapy, such as aspirin, for the prevention of atherothrombotic events. This phenomenon is often referred to as treatment failure. Those who are at increased risk of such events despite aspirin therapy can be prospectively identified by a variety of laboratory measures of residual on-treatment platelet function, known as aspirin resistance. However, there is little agreement among laboratories on the approaches to these measurements, and insufficient data to guide the clinical management of people with diabetes-associated aspirin resistance if it is prospectively identified. This review provides a critical appraisal of the different approaches to the detection and evidence of mechanisms which contribute to this phenomenon, as well evidence for the potential effectiveness of different clinical approaches to overcoming aspirin treatment failure in diabetes. Potential mechanisms of aspirin resistance in diabetes include elevated platelet turnover that results in an immature platelet fraction able to synthesise the uninhibited therapeutic target of aspirin, cyclooxygenase-1 (COX-1); residual thromboxane production by both COX-1-dependent and COX-1-independent pathways; up-regulation of aspirin-insensitive pathways of platelet function, such as adenosine diphosphate signalling; and increased underlying atherosclerotic disease burden that results in elevated underlying platelet hyper-reactivity. High on-aspirin platelet reactivity in diabetes may be related to glycemic control. Potential approaches to treatment include controlling modifiable risk factors to achieve effective glycemic control, guided increases in aspirin dose or frequency of administration, or the use of additional antiplatelet therapies. While evidence suggests that altering antiplatelet therapy, particularly by increasing frequency of aspirin administration, can overcome incomplete inhibition of thromboxane synthesis, no clinical studies to date have assessed the effectiveness of these in preventing breakthrough atherothrombosis. While some clinicians currently alter therapy on the basis of theoretical potential benefit of these strategies following identification of aspirin resistance in the laboratory, this is not yet supported by clinical evidence of a benefit, and clear clinical guidelines for the management of aspirin resistance are lacking.

Clinical Nuclear Medicine, 1991

Blood Coagulation & Fibrinolysis, 2014

Applied and Environmental Microbiology, 1999

Teichoic acid-associated N-acetylglucosamine and rhamnose have been shown to serve as phage recep... more Teichoic acid-associated N-acetylglucosamine and rhamnose have been shown to serve as phage receptors in Listeria monocytogenes serotype 1/2a. We generated and characterized two single-copy Tn916ΔE mutants which were resistant to phage A118 and several other serotype 1/2a-specific phages. In one mutant the insertion was immediately upstream of the recently identifiedptsHI locus, which encodes two proteins of the phosphoenolpyruvate-dependent carbohydrate uptake system, whereas in the other the insertion was immediately upstream of an operon whose most distal gene was clpC, involved in stress responses and virulence. Transduction experiments confirmed the association of the phage-resistant phenotype of these mutants with the transposon insertion. Phage A118 resistance of the mutants could be attributed to inability of the phage to adsorb onto the mutant cells, and biochemical analysis of cell wall composition showed that the teichoic acids of both mutants were deficient in N-acetylgl...

British Journal of Haematology, 2016

British journal of haematology, 2014

The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refra... more The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 10(9) /l and ≤50 × 10(9) /l) idiopathic thrombocytopenic purpura (ITP). Patients received two doses of rituximab (1000 mg) on days 1 and 15 and were followed-up on weeks 1-8, 12, 26, 39 and 52. A total of 122 patients were included in the safety population; efficacy was analysed in 108 patients. Overall response rate (ORR) at week 8, defined as the proportion of patients achieving complete response (CR; platelet count >150 × 10(9) /l) or partial response (PR; platelet count >50 × 10(9) /l) was 44%. Therapeutic response, defined as achieving a response at week 8, with at least a minor response (MR; platelet count >30 × 10(9) /l), sustained up to weeks 26 and 52 and accompanied by a reduction in ITP medications, was achieved in 44% (week 26) and 35% (week 52) of patients, respectively. Treatment was well tolerated with no safety ...

Journal of cardiac surgery, 2015

This study presents the experience of a large Australian hospital in performing cardiac surgery o... more This study presents the experience of a large Australian hospital in performing cardiac surgery on patients with hereditary bleeding disorders (HBDs) and provides a suggested approach for their perioperative management. Medical records of patients with HBDs who underwent cardiac surgery from January 1997 to December 2013 were reviewed. Seventeen patients were included in this study, 13 with Hemophilia A, one symptomatic Hemophilia A carrier, one with Hemophilia B, and two with von Willebrand Disease. Cardiac surgical procedures performed included 10 coronary artery bypass graft (CABG) operations, two aortic valve replacements, two mitral valve repairs, two aortic root replacements, and one combined aortic valve replacement and CABG. Perioperative management centered on factor substitution to maintain normal factor levels. Perioperative outcomes including length of hospital stay, mortality, and return to the operating room for bleeding were recorded. Two patients returned to the oper...

Cardiology Clinics, 2008

Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonar... more Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable riskbenefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.

Seminars in Thrombosis and Hemostasis, 2012

The term resistance has been applied to interindividual variability in platelet reactivity during... more The term resistance has been applied to interindividual variability in platelet reactivity during antiplatelet therapy or to thrombosis despite appropriate therapy. In particular "aspirin resistance" and "clopidogrel resistance" have been the subject of intense investigation for their association with poor cardiovascular outcomes. Several mechanisms have been investigated including resistance arising from poor bioavailability, especially in clopidogrel therapy as resulting from a loss of function variant in hepatic metabolism required for prodrug activation. A limitation of studies linking on-treatment reactivity and clinical outcome is that they have been performed in high-risk patients with recent atherothrombotic disease. On-treatment platelet reactivity correlates with acuity of recent atherothrombosis, and variability in pretreatment platelet function predicts on-treatment platelet function for both aspirin and clopidogrel. It is therefore likely that high on-treatment platelet function at the time of testing may often result from underlying platelet hyperreactivity related to acute atherothrombosis, rather than true pharmacological resistance. The association of high on-treatment platelet reactivity with poor clinical outcomes may therefore be attributed to variability in underlying burden of disease instead of, or in addition to, pharmacological resistance to antiplatelet therapy.

Monatshefte fuer Chemie/Chemical Monthly, 1998

Monatshefte fuer Chemie/Chemical Monthly, 1998

Monatshefte fuer Chemie/Chemical Monthly, 1999

Monatshefte f?r Chemie / Chemical Monthly, 2002

It was found that the hypericinate salts of (R)-1-phenylethylamine and (S)-1-(1-naphthyl)ethylami... more It was found that the hypericinate salts of (R)-1-phenylethylamine and (S)-1-(1-naphthyl)ethylamine display a small chiroptical signal of the same sign only at high concentrations in an apolar solvent. No further indications of a chiral discrimination between the helical conformers of hypericinate could be found in these cases. However, upon esteri®cation of the 3-hydroxyl group of hypericin with (1S)-camphanic chloride, the two diastereomers were found in an 1:1 ratio equilibrating rather fast at temperatures above 30 C with one diastereomer in excess. From the temperature dependence of the equilibrium positions (measured by means of CD and 1 H NMR), a ÁG 0 value of 5.8 AE 0.5 kJ Á mol À 1 was derived. Accordingly, the chiral discrimination of the (M)-con®gured enantiomer of the helix by the (S)-con®gured auxiliary occurred at an intermediate level. From the temperature dependence of the equilibration kinetics an activation energy of E a 70 AE 0.5 kJ Á mol À 1 was derived, which thus de®nes the upper limit of the helix inversion of hypericin and hypericinate. This value is by about 10 kJ Á mol À 1 lower than the recently estimated limit.

Monatshefte fuer Chemie/Chemical Monthly, 1998

The dissociation of hypericin (1) was investigated using atmospheric pressure ionization mass spe... more The dissociation of hypericin (1) was investigated using atmospheric pressure ionization mass spectrometry of 80% ethanolic solutions under variation of their pH values. Thus, it could be unequivocally established that the species predominant within the pH region of 3±10 and 11±13 are the mono-and dideprotonated compounds 1 À and 1 2À. These results nicely corroborate the hitherto accumulated mostly spectrophotometric evidence for the ®rst deprotonation step occurring at a pK a value in the order of 2 and the second one at about 12. Moreover, this example demonstrates the potential of atmospheric pressure ionization mass spectrometry as a valuable tool to investigate dissociation equilibria.

Monatshefte fuer Chemie/Chemical Monthly, 1999

Summary. Based on the interpretation of UV/Vis, IR, and NMR spectra of hypericin as well as of it... more Summary. Based on the interpretation of UV/Vis, IR, and NMR spectra of hypericin as well as of its salts and the products of total O-methylation, it was concluded that hypericin transfers from solid state to low or moderate polar organic media as its 1,6-dioxo-tautomer, thereby ...

Monatshefte für Chemie / Chemical Monthly, 1998

Summary. Sulfonation of hypericin leads to its di-, tri-, and tetrasulfonic acid derivatives. The... more Summary. Sulfonation of hypericin leads to its di-, tri-, and tetrasulfonic acid derivatives. The latter is soluble in water up to millimolar solutions. Homoaggregate formation (J-aggregates) was observed only above 5Á10À4 mol/l. In water solutions, the tetrasulfonic acid ...

Journal of Vascular Surgery, 2007

Conclusion: Men have a 50% higher risk of recurrent venous thromboembolism (VTE) after cessation ... more Conclusion: Men have a 50% higher risk of recurrent venous thromboembolism (VTE) after cessation of anticoagulant therapy. Summary: The authors performed a meta-analysis to examine the question of risk of recurrent VTE in men versus women after cessation of anticoagulation treatment. Eligible articles were identified using the Coch

Internal Medicine Journal, 2011

Prothrombinex-VF (a three-factor prothrombin complex concentrate) contains little factor VII. The... more Prothrombinex-VF (a three-factor prothrombin complex concentrate) contains little factor VII. Therefore, the Warfarin Reversal Consensus Guidelines from 2004 published by The Australasian Society of Haemostasis and Thrombosis recommend that it be administered with fresh frozen plasma to reverse warfarin anticoagulation. To evaluate the efficacy and safety of Prothrombinex-VF used alone in warfarin reversal. Adult patients requiring urgent reversal of warfarin anticoagulation were defined as having achieved complete (target international normalized ratio (INR) <1.4) or partial reversal (target INR 1.4-2.0) of their anticoagulation. Prothrombinex-VF was given at doses of between 25 and 50 IU/kg based on the intent of reversal and an INR was obtained 30min post infusion. A total of 50 patients (mean age 72years, range 32-85years) was included. The median initial INR in the complete reversal arm (n= 35) was 3.5 (range 1.7-20) with 91% achieving the target INR (mean 1.1, range 0.9-1.4). In the partial reversal arm (n= 15) the mean initial INR was 5.6 (range 2.5-12) with 93% achieving the target INR (mean 1.6, range 1.4-2.2). There were no adverse effects attributed to Prothrombinex-VF. Prothrombinex-VF is very effective and safe when used alone to reverse warfarin anticoagulation. The supplementary use of fresh frozen plasma in these patients is not required. A review of the current Warfarin Reversal Consensus Guidelines is needed.

Thrombosis and haemostasis, 2011

Dear Sirs, Antiphospholipid syndrome (APS) is diagnosed when arterial or venous thrombosis, or re... more Dear Sirs, Antiphospholipid syndrome (APS) is diagnosed when arterial or venous thrombosis, or recurrent miscarriage, is associated with the presence of antiphospholipid antibodies. The antiphospholipid antibody must be persistent (present in two separate blood samples taken more than 12 weeks apart) (1). The laboratory tests should use screening, mixing and confirmation stages, and more than one test system should be used due to the heterogeneity of lupus anticoagulants.

Critical Reviews in Clinical Laboratory Sciences, 2012

People with diabetes have an increased risk of life-threatening cardiovascular disease compared t... more People with diabetes have an increased risk of life-threatening cardiovascular disease compared to the general population. Furthermore, people with diabetes are at greatly increased risk of not responding to standard anti-platelet therapy, such as aspirin, for the prevention of atherothrombotic events. This phenomenon is often referred to as treatment failure. Those who are at increased risk of such events despite aspirin therapy can be prospectively identified by a variety of laboratory measures of residual on-treatment platelet function, known as aspirin resistance. However, there is little agreement among laboratories on the approaches to these measurements, and insufficient data to guide the clinical management of people with diabetes-associated aspirin resistance if it is prospectively identified. This review provides a critical appraisal of the different approaches to the detection and evidence of mechanisms which contribute to this phenomenon, as well evidence for the potential effectiveness of different clinical approaches to overcoming aspirin treatment failure in diabetes. Potential mechanisms of aspirin resistance in diabetes include elevated platelet turnover that results in an immature platelet fraction able to synthesise the uninhibited therapeutic target of aspirin, cyclooxygenase-1 (COX-1); residual thromboxane production by both COX-1-dependent and COX-1-independent pathways; up-regulation of aspirin-insensitive pathways of platelet function, such as adenosine diphosphate signalling; and increased underlying atherosclerotic disease burden that results in elevated underlying platelet hyper-reactivity. High on-aspirin platelet reactivity in diabetes may be related to glycemic control. Potential approaches to treatment include controlling modifiable risk factors to achieve effective glycemic control, guided increases in aspirin dose or frequency of administration, or the use of additional antiplatelet therapies. While evidence suggests that altering antiplatelet therapy, particularly by increasing frequency of aspirin administration, can overcome incomplete inhibition of thromboxane synthesis, no clinical studies to date have assessed the effectiveness of these in preventing breakthrough atherothrombosis. While some clinicians currently alter therapy on the basis of theoretical potential benefit of these strategies following identification of aspirin resistance in the laboratory, this is not yet supported by clinical evidence of a benefit, and clear clinical guidelines for the management of aspirin resistance are lacking.

Clinical Nuclear Medicine, 1991

Blood Coagulation & Fibrinolysis, 2014