Spontaneous heparin-induced thrombocytopaenia with adrenal haemorrhage following orthopaedic surgery: a case report and literature review

A 68-year-old woman was admitted to the hospital for elective total knee arthroplasty in both knees without preceding heparin exposure. She developed adrenal haemorrhage and thrombocytopaenia on postoperative day 12, followed by right leg arterial occlusion and multiple venous intra-abdominal sites thrombosis. After given unfractionated heparin to treat arterial occlusion, platelet count was gradually declined. Spontaneous heparin-induced thrombocytopaenia was diagnosed by heparin-induced platelet activation test with light transmission aggregometry. The patient was successfully treated with fondaparinux and intravenous immunoglobulin. Apixaban was given after recovery of platelet count. Resolution of both thrombus along aorta and adrenal haemorrhage were shown by CT of whole abdomen after 2 months of treatment. Our case demonstrates that this serious complication is important but seldom recognised early.

The effect of loss-of-function allele (CYP2C19*3) with Clopidogrel efficacy in coronary heart disease patients

Introduction: Clopidogrel is the most widely prescribed antiplatelet for patients with coronary heart disease (CHD) who cannot take aspirin. Despite its effectiveness, Clopidogrel has several side effects caused by its metabolite. Clopidogrel resistance has been identified in some patients, and patient factors such as genetic polymorphisms in CYP2C19 may play a role in this resistance. The researchers wanted to look at CYP2C19*3 polymorphisms and platelet aggregation in CHD patients who were taking clopidogrel. Methods: This research used a cross-sectional design. The research enrolled CHD patients at a local hospital's cardiology unit with certain inclusion and exclusion requirements. In the clinical laboratory, CYP2C19*3 polymorphisms was investigated using polymerase chain reaction (PCR), and platelet aggregation will be measured using light transmission aggregometry (LTA). Results: This research enlisted the participation of 53 patients. The majority of the patients (68%) were men, with the highest age group being 60-69 years old. The most common comorbid disorder was hypertension. The result of CYP2C19*3 polymorphisms as follows: GA (75%), AA (21%), and GG (4%). Hypo-aggregation (89%) and normal-aggregation (89%) are seen in the majority of patients (11%). The authors were unable to locate the patient who had hyper-aggregation. Conclusion: According to descriptive research, CYP2C19*3 polymorphisms caused hypo-aggregation in more patients than normal aggregation in this study.

Determination of reference ranges for automated platelet aggregometry on Sysmex CS‑5100 analyzer

Measurement of platelet function by light transmission aggregometry (LTA) using a special device – an aggregometer requires significant time and is time-consuming. In this study, an automated LTA procedure was evaluated to establish the reference ranges. On the Sysmex CS-5100 analyzer, aggregation measurements were performed using several agonists at a certain concentration: ADP (2 µmol/L); arachidonic acid (1 mmol/L); collagen (2 µg/ml); ristocetin (1.2 mg/ml); epinephrine (5 µmol/L). For each agonist, the maximum and final aggregation, the Lag phase and the Area under the aggregation curve were measured. Reference ranges for a standard panel of activators were determined on 40 samples of healthy subjects in the concentrations recommended by the International Society on Thrombosis and Haemostasis. A standard panel of agonists can be used on Sysmex CS series analyzers: ADP, arachidonic acid; collagen; ristocetin, epinephrine, so these devices can replace specialized aggregometers or perform platelet aggregation where this investigation is not currently performed.

Comparison of Light Transmission Aggregometry and VerifyNow in Detecting Clopidogrel Resistance and Factors Affecting Clopidogrel Resistance in AMI-EST Patients Undergoing Percutaneous Coronary Intervention: A Cross-Sectional Study

BACKGROUND: Light transmission aggregometry (LTA) and VerifyNow is commonly used to measure platelet responsiveness to clopidogrel. This study aimed to compare the results of LTA and VerifyNow P2Y12 assay for assessing the clopidogrel resistance in patients undergoing percutaneous coronary intervention and determine factors affecting clopidogrel resistance.METHODS: The subjects were 119 patients who underwent percutaneous coronary intervention (PCI) and had given loading dose of 600 mg clopidogrel. Blood samples were taken at 6 hour after clopidogrel loading dose. Platelet aggregation was measured by LTA and VerifyNow.RESULTS: LTA and VerifyNow assay showed fair agreement with Kappa=0.270, p=0.001. The proportion of resistance to clopidogrel using VerifyNow was 21.8% and LTA was 47.1%. Patients with diabetes melitus were more likely to develop clopidogrel resistance than patients without diabetes (OR of 7.67; 95% CI: 1.87-31.50; p=0.005).CONCLUSION: The ability of LTA and VerifyNow in detecting clopidogrel resistance were not comparable. Multivariate analysis results for VerifyNow shows diabetes mellitus as the greatest predictors of clopidogrel resistance.KEYWORDS: agreement, clopidogrel resistance, LTA, predictor, VerifyNow

Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets

Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (COG) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of COG on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, COG did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by COG or CORM-A1, was dependent on sGC. We conclude that the source (COG vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.

Association between renal function and platelet reactivity during aspirin therapy in elderly patients with atherosclerotic cardiovascular disease

Background Aspirin is the key treatment in the secondary prevention of atherosclerotic cardiovascular disease. High on-treatment platelet reactivity (HTPR) to aspirin has been reported to partially account for the enhanced risk of thrombotic events. In particular, HTPR has been described more frequently among elderly patients. The aim of this study was to identify the clinical and biological factors associated with HTPR in a real-life elderly population. Methods In this retrospective study, elderly patients with atherosclerotic cardiovascular disease on regular aspirin treatment were enrolled. Cardiovascular risk factors, routine biological parameters, comorbidities, and concomitant medications were recorded. The upper quartile of the platelet aggregation rate, determined by light transmission aggregometry with arachidonic acid, was defined as the HTPR group. Results A total of 304 patients were included (mean age 77 ± 8 years, 76% men). Patients in the HTPR group were older than the patients in the non-HTPR group (mean age: 79 ± 7 vs. 76 ± 8 years, p = 0.008). Patients with moderately decreased estimated glomerular filtration rate (eGFR) had a higher frequency of HTPR than patients with slightly decreased eGFR or normal eGFR (35.8, 22.5, 12.2%, respectively, p < 0.05). In multivariate analysis, an independent risk factor for HTPR was the eGFR (OR: 0.984, 95% CI: 0.980–0.988, p < 0.001). Conclusions Advanced age and decreased eGFR are correlated with poor pharmacodynamic response to aspirin.