Patients with cardiovascular disease (CVD) are at increased risk of suffering myocardial infarction. Platelets are key players in thrombus formation and, therefore, antiplatelet therapy is crucial in the treatment and prevention of CVD. MicroRNAs (miRs) may hold the potential as biomarkers for platelet function and maturity. This systematic review was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To identify studies investigating the association between miRs and platelet function and maturity in patients with CVD, PubMed and Embase were searched on October 13 and December 13, 2020 without time boundaries. Risk of bias was evaluated using a standardized quality assessment tool. Of the 16 included studies, 6 studies were rated “good” and 10 studies were rated “fair.” In total, 45 miRs correlated significantly with platelet function or maturity (rho ranging from –0.68 to 0.38, all p < 0.05) or differed significantly between patients with high platelet reactivity and patients with low platelet reactivity (p-values ranging from 0.0001 to 0.05). Only four miRs were investigated in more than two studies, namely miR-223, miR-126, miR-21 and miR-150. Only one study reported on the association between miRs and platelet maturity. In conclusion, a total of 45 miRs were associated with platelet function or maturity in patients with CVD, with miR-223 and miR-126 being the most frequently investigated. However, the majority of the miRs were only investigated in one study. More data are needed on the potential use of miRs as biomarkers for platelet function and maturity in CVD patients.
Patient: Male, 19-year-old Final Diagnosis: Peripheral neuropathy • pulmonary embolism • vitamin B 12 deficiency Symptoms: Balance problems • muscle weakness • sensorial deficit • thoracic pain Medication:— Clinical Procedure: — Specialty: Cardiology • Laboratory Diagnostics • Neurology Objective: Unusual clinical course Background: Recreational use of nitrous oxide (laughing gas) is a growing phenomenon among young people due to easy accessibility and a presumed innocent effect. However, complications have been reported, especially following high and long-term use, including nerve damage, spontaneous pneumo-mediastinum, myocardial infarction, and macrocytic anemia. Case Report: We report a case of a 19-year-old previously healthy man with occasional recreational use of nitrous oxide of up to 10 times within recent months, who presented with severe peripheral neuropathy. Laboratory examination revealed severely elevated homocysteine values of 92 µmol/L (reference range, <10 µmol/L), strongly elevated methylmalonic acid level of >10 µmol/L (range, 0.1–0.4 µmol/L), vitamin B 12 level of 234 pmol/L (range, 200–600 pmol/L), hemoglobin level of 9.3 mmol/L (range, 8.3–10.5 mmol/L), platelets of 384×10 9 /L (range, 145–350×10 9 /L), and leucocytes of 6.2×10 9 /L (range, 3.5–10.0×10 9 /L). Nitrous oxide can result in vitamin B 12 inactivation and nerve damage due to lack of myelination. During hospitalization, the patient had a bilateral central pulmonary embolism, probably caused by a combination of nitrous oxide abuse and some extent of immobilization. After 6 months of nitrous oxide cessation and treatment with B vitamins, the patient experienced almost no residual symptoms, and homocysteine and methylmalonic acid levels normalized. Conclusions: Our case shows that even moderate recreational use of nitrous oxide can lead to severe peripheral neuropathy as well as increase the risk of thromboembolic complications. Especially young and previously healthy individuals presenting with unexplained neuropathy or thromboembolic events should therefore be asked about possible use of nitrous oxide.
Background Patients with essential thrombocythemia (ET) and coronary artery disease (CAD) have increased risk of thromboembolic complications. In addition, a reduced antiplatelet effect of aspirin has been demonstrated in both patient groups. As ET is a platelet disorder, platelets may be more important for the thromboembolic risk in ET than in CAD. We aimed to investigate the antiplatelet effect of aspirin and platelet turnover in ET versus CAD patients. Methods We included 48 ET patients and an age-matched group of 48 CAD patients. The effect of aspirin was evaluated by thromboxane B2 (TXB2) levels and platelet aggregation. Platelet turnover was assessed by immature platelet count (IPC) and immature platelet fraction (IPF). Results ET patients had reduced effect of aspirin compared with CAD patients, demonstrated by significantly higher TXB2 levels (median of differences = 22.3 ng/mL, p < 0.0001) and platelet aggregation (median of differences = 131.0 AU*min, p = 0.0003). Furthermore, ET patients had significantly higher IPC (p < 0.0001) and IPF (p = 0.0004) than CAD patients. Conclusion ET patients have lower 24-hour antiplatelet effect of aspirin than CAD patients. This may be explained by an increased platelet production and turnover counteracting the antiplatelet effect of aspirin. These findings strengthen the rationale for exploring novel antiplatelet regimens in ET patients to reduce the risk of cardiovascular events.
Newly produced immature platelets are larger, contain higher amounts of residual RNA, and are more reactive than mature platelets. Flow cytometry using the SYTO-13 dye is a method for the subdivision of immature platelets from mature platelets based on the labelling of intracellular platelet RNA, enabling the simultaneous investigation of the reactivity of each platelet population. This method provides detailed information on several aspects of platelet physiology using a combination of platelet surface markers and agonists. Currently, no standardized protocol exists across laboratories. Here, we describe a flow cytometry protocol in detail to investigate platelet reactivity and its relation to platelet maturity. We analyzed 20 healthy individuals with the protocol and compared the platelet subpopulation with the highest SYTO-13 labelling (in the first quintile, “SYTO-high”) corresponding to the most immature platelets (highest RNA content) with the platelet subpopulation with the lowest SYTO-13 labelling (in the fifth quintile, “SYTO-low”) corresponding to the mature platelets with the lowest RNA content. SYTO-high platelets had overall significantly increased platelet reactivity compared with that of SYTO-low platelets. The presented method may be a valuable research tool for the analysis of platelet reactivity and its relation to platelet maturity.
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