Ilona Fatorova

Prothrombotic changes due to an increase in thyroid hormone levels.

OBJECTIVE With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxons test for paired data. RESULTS During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 μg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

Mean platelet volume and platelet count: overlooked markers of high on-treatment platelet reactivity and worse outcome in patients with acute coronary syndrome.

Address for Correspondence: Dr. Martin Jakl, 1st Department of Medicine, University Hospital Hradec Kralove 581, 500 02 Sokolska-Czech Republic Phone: +420 607 514 662 Fax: +420 495 513 018 E-mail: jaklm@seznam.cz Accepted Date: 24.06.2013 Available Online Date: 09.12.2013 ©Copyright 2014 by AVES Available online at www.anakarder.com doi:10.5152/akd.2013.4803 Martin Jakl1,2, Robert Sevcik2, Jiri Ceral2, Ilona Fatorova3, Jan M. Horacek1,3, Jan Vojacek2

The importance of rheological parameters in the therapy of the dry form of age-related macular degeneration with rheohaemapheresis

To date, rheological treatment is the only chance to control the advanced dry form of age-related macular degeneration and arrest its progression to legal blindness. Rheohaemapheresis can change the main rheological parameters, blood and plasma viscosity, as well as change erythrocyte aggregability, improve erythrocyte flexibility and lead to substantial improvement when other methods of therapy fail. In this study, we describe changes in the levels of rheological efficacy indicators after rheohaemapheresis and their clinical significance in the dry form of age-related macular degeneration (AMD). Seventy-two patients with AMD were randomised; 34 controls, and 38 patients were treated with rheohaemapheresis (separator Cobe Spectra + Evaflux filter). After the procedures, α2-macroglobulin levels decreased by approximately 58%, fibrinogen by approximately 65%, IgM by approximately 67%, LDL cholesterol by approximately 71%, apolipoprotein B by approximately 65%, and lipoprotein (a) by approximately 42%. These decreases correspond with a decrease in blood and plasma viscosity (14/12%), clinical improvement (arrest of disease progression, even visual improvement in some cases), and heretofore-unreported improvement (even reattachment) of drusen retinal pigment epithelium detachment. Our modification of rheohaemapheresis is safe (5.4% of patients experienced clinically insignificant side effects).

High on-treatment platelet reactivity: risk factors and 5-year outcomes in patients with acute myocardial infarction.

Objective: The aim of the present study was to assess long-term prognostic value of high on-treatment platelet reactivity (HTPR) in patients after acute myocardial infarction (MI) and its association with possible risk factors. Methods: This prospective, case-control study was an observation of 198 patients who had acute MI. Response to aspirin and clopidogrel was assessed using impedance aggregometry. Patients were divided into groups of adequate response, dual poor responsiveness (DPR), poor responsiveness to aspirin (PRA), and poor responsiveness to clopidogrel (PRC). Simultaneously, potential risk factors of HTPR development were recorded. After 5 years, MI recurrence and overall mortality were assessed. Results: HTPR was more frequent in New York Heart Association Class III and IV patients, and in patients with left ventricle systolic dysfunction. Five-year mortality rate was higher in all groups of patients with HTPR compared to patients with sufficient response to antiplatelet treatment: in PRA patients, 38.1% vs. 19.2%, p<0.01; in PRC patients, 45.2% vs. 17.3%, p<0.001; and in DPR patients, 50.0% vs. 19.9%, p<0.05. Risk of repeat MI also increased (hazard ratio [HR] 4.0, p<0.05 for DPR group; HR 4.37, p<0.01 for PRA group; and HR 3.25, p<0.05 for PRC group). Conclusion: PRA, PRC, and DPR are independent predictors of increased 5-year mortality and risk of repeat non-fatal MI. The study has demonstrated that HTPR is frequently observed in patients with severe heart failure and left ventricle systolic dysfunction.

Good Short-Term but not Long-Term Reproducibility of the Antiplatelet Efficacy Laboratory Assessment

Background: The antiplatelet effect of acetylsalicylic acid (ASA) varies among individual patients. We assessed the short-term reproducibility (STR) and long-term reproducibility (LTR) of light transmission aggregometry (LTA). Methods: Residual platelet reactivity was measured twice using LTA in a group of 207 consecutive patients (56 females, mean age 67 ± 9 years) on ASA therapy in 10 ± 6 months interval. The STR was assessed in 15 patients (6 females, mean age 61 ± 7 years) with 10 measurements on 2 consecutive days. Results: There was no correlation between both measurements in the long-term part of the study, and also Bland-Altman plot showed a diverging pattern. However, LTA STR was good with a correlation coefficient of .800 (P < .05) confirmed by Bland-Altman plot. Conclusions: Although short-term intraindividual reproducibility of LTA assessment of platelet reactivity is very good, in the long-term perspective the antiplatelet ASA effectivity may be influenced by additional variables and repeated measurements are warranted.

ASPIRIN RESISTANCE IN NEUROVASCULAR DISEASES

INTRODUCTION The issue of resistance to antiplatelet therapy has raised many questions in the area of neurovascular diseases. The first objective of this work was to determine the prevalence of aspirin resistance in neurovascular patients with clinical non-responsiveness to aspirin treatment and a high-risk of atherothrombotic complications using two interpretable and independent methods (aggregation and PFA 100). The second objective was to find the correlation between both assays and to evaluate the results in groups at risk for various cerebrovascular diseases. MATERIAL AND METHODS Laboratory tests of aspirin resistance were performed in 79 patients with clinical non-responsiveness to aspirin treatment suffering from neurovascular diseases. Patients were divided into the two groups: expected low risk for aspirin resistance due to the first manifestation of a neurovascular disease (n = 34) and expected high risk due to the second clinical manifestation of a neurovascular disease (n = 45). RESULTS The prevalence of aspirin resistance in both groups combined as determined by the PFA-100 and CPG techniques were 50.6% and 17.7%, respectively. No correlation was found between the two techniques. CONCLUSIONS No significant prevalence of aspirin resistance was demonstrated by either method despite the heterogeneous pathophysiological mechanisms. However, we are presently unable to provide an accurate opinion on the value of laboratory test result or routine monitoring in clinical neurology.