Liver function tests in COVID 19: A retrospective record-based study from a tertiary care centre in urban Maharashtra, India.

Background: COVID-19 is a multi system disorder and causes various abnormalities in liver function tests. The aim of this study was to estimate the prevalence of abnormal liver function tests in patients of COVID-19 and to describe the association of liver function tests with clinical features and disease severity in these patients. Methods: We retrospectively evaluated and analyzed the liver function tests of all real-time polymerase chain reaction (RT-PCR) positive COVID-19 patients admitted to a tertiary care hospital in Western Maharashtra. The Institutional Ethics Committee of our hospital approved the study. Results: Of the 533 patients included in our study, 50% had abnormal albumin levels while 40.1%, 43.5%, 9.3%, and 6.3% patients had deranged alanine transaminase (ALT) aspartate transaminase (AST), total protein and bilirubin levels, respectively. Hepatocellular injury was observed in 21 (3.9%) patients, and cholestatic liver injury was observed in seven (1.3%) patients. Abnormal liver function test (LFT) was significantly associated with disease severity but not with mortality. Conclusion: Abnormal LFT in patients of COVID-19 is associated with severe disease but not mortality. Liver injury is common in patients of COVID-19.

Genetic polymorphisms of the platelet receptors P2Y(12), P2Y(1) and GP IIIa and response to aspirin and clopidogrel.

INTRODUCTION: There is wide variability in the responses of individual patients to aspirin and clopidogrel. Polymorphisms of several platelet receptors have been related to increased platelet aggregation. We therefore aimed to evaluate whether these polymorphisms are related to altered response to aspirin or clopidogrel. MATERIALS AND METHODS: Patients (n=120) undergoing percutaneous coronary intervention who received aspirin for > or =1 week but not clopidogrel were included. Blood samples were drawn at baseline and 20-24h after a 300-mg clopidogrel dose. Aspirin insensitivity was defined as 5 microM ADP-induced aggregation > or =70% and 0.5 mg/mL arachidonic acid-induced aggregation > or =20%. Clopidogrel insensitivity was defined as baseline minus post-treatment aggregation < or =10% in response to 5 and 20 microM ADP. PlA polymorphism of glycoprotein IIIa, T744C polymorphism of the P2Y(12) gene and the 1622A>G polymorphism of the P2Y(1) gene were genotyped by polymerase chain reaction. RESULTS: There were no differences in polymorphism frequencies between drug-insensitive vs. drug-sensitive patients. There were also no significant differences in response to aspirin (assessed by arachidonic acid-induced aggregation) or to clopidogrel (assessed by ADP-induced aggregation or activation markers) when patients were grouped according to genotype. The only trend observed was lower reduction in PAC-1 binding following clopidogrel in PlA(2) carriers (P=0.065). CONCLUSIONS: We did not find an association between polymorphisms in the platelet receptors GP IIIa, P2Y(12) or P2Y(1) and response to aspirin or clopidogrel in cardiac patients. These findings suggest that the variability in response to anti-platelet drugs is multi-factorial and is not caused only by single gene mutations.

Platelet reactivity among Asian Indians and Caucasians.

Asian Indians are reported to have higher mortality and morbidity from coronary artery disease (CAD) than other ethnic groups. This variation in events cannot be explained only by differences in conventional risk factors. Platelet activation is an important factor in the pathogenesis of CAD, however, there are limited data concerning platelet reactivity in Asian Indians. Therefore, we aimed to examine platelet reactivity in healthy Asian Indians vs. Caucasians. Thirty-five healthy, nonsmoking Asian Indians (mean age 30.1 +/- 3.6 years, 31.4% women) were matched for age and sex with 35 healthy, nonsmoking Caucasians (mean age 30.8 +/- 5 years, 31.4% women). Platelet reactivity was evaluated by measuring platelet aggregation, platelet leukocyte aggregates (PLA) formation in response to a 6-mer thrombin receptor agonist peptide (TRAP) at a final concentration of 40 microM and flow cytometry determined P-selectin expression induced by ADP, TRAP and arachidonic acid (AA). In addition, P-Selectin glycoprotein ligand-1 (PSGL-1) density on leukocytes was measured. There were no differences in platelet aggregation, basal PLA or PSGL-1 density on leukocytes between the two groups. AA-stimulated P-selectin expression was significantly higher in Asian Indians than in Caucasians (6.1 +/- 0.51 vs. 4.2 +/- 0.41 MFI, P < 0.02). After stimulation with TRAP, platelets from Asian Indians had increased PLA formation compared with Caucasians (41.6 +/- 2.9% vs. 31.4 +/- 2.7%, P < 0.02). AA induced P-selectin expression and TRAP stimulated PLA formation is increased in Asian Indians compared with Caucasians. These differences indicate an increase in measures of platelet reactivity among Asian Indians and may help elucidate the reported disparity in cardiovascular disease rates between the two ethnic groups.

Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance.

UNLABELLED: We evaluated the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing elective coronary stenting. Patients (n = 150) treated with aspirin but not clopidogrel had blood samples drawn at baseline and 24 h after clopidogrel loading. Depending on the definition used, 9% to 15% were resistant to aspirin and 24% to clopidogrel. About half of the aspirin-resistant patients were also resistant to clopidogrel. As a group, aspirin-resistant patients had lower response to clopidogrel (assessed by platelet aggregation and activation markers) than aspirin-sensitive patients. Both aspirin- and clopidogrel-resistant patients had higher incidence of creatine kinase-MB elevation than the respective sensitive patients. OBJECTIVES: We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs. METHODS: Elective PCI patients (n = 150) who received aspirin for > or = 1 week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by > or = 2 of 3 criteria: rapid platelet function analyzer-ASA score > or = 550, 5 micromol/l adenosine diphosphate (ADP)-induced aggregation > or = 70%, and 0.5 mg/ml arachidonic acid-induced aggregation > or = 20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation < or = 10% in response to 5 and 20 micromol/l ADP. RESULTS: Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 17.3%; p = 0.06). CONCLUSIONS: Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.