Predicting the risk of recurrent venous thromboembolism: Impact and therapeutic consequences of inherited thrombophilia.

BACKGROUND: Over the past decades, thrombophilia testing in patients with venous thrombo-embolism has increased tremendously. However, the role of inherited thrombophilie in prediction the risk of recurrence remains controversial. Consequently, it is still unclear whether thrombophilia testing influences decisions regarding duration of anticoagulation in clinical practices. The aim of this study was to evaluate the impact if inherited thrombophilia on venous thrombosis treatment decisions and on predicting the risk of recurrence. METHODS: A retrospective longitudinal study (January 2011-Decembre 2016) including 131 patients with confirmed venous thrombo-embolism referred to the hematology laboratory from the internal medicine department for inherited thrombophilia screening was carried out. RESULTS: The mean age patients was 39.4 years and the sex ratio (M/F) was 0.61. Inherited thrombophilia was confirmed in 27.5% of patients. A long term anticoagulation was decided in 46.9% of patients with thrombophilia. There was no significant difference in the duration of anticoagulation between patients with or without thrombophilia. Thrombosis recurrence was recorded in 16 (17%) patients. The 24 years cumulative incidence of recurrence was 19% in patients with thrombophilia and 17% in those without (plog Rank= 0.6). Inherited thrombophilia was not associated with increased risk of recurrence after treatment withdrawal (Hazard ratio=1.31 IC (0.47-3.63); P=0.6). CONCLUSION: In clinical practice, inherited thrombophilia did not influence anticoagulation duration and was not associated with a higher venous thrombosis risk of recurrence. It seems to be less relevant for decision making than presumed.

Metabolic effects of Ramadan fasting in patients at high risk of cardiovascular diseases.

BACKGROUND AND AIM: The effects of Ramadan fasting on health are a little controversial. The present study is aimed at evaluating the metabolic effects on a group of 517 patients with ≥2 cardiovascular risk factors over a period running from 2012 to 2014. METHODS: Each patient was assessed at three visits: before, during, and after Ramadan. Demographical, clinical and biological tests were performed at each visit. RESULTS: Metabolically, we noted a significant and discrete rise in blood glucose level (+1.2 mmol/L), triglycerides (+0.3 mmol/L), cholesterol (+0.12 mmol/L) and creatinine (+3 µmol/L) during Ramadan. These disturbances decreased significantly after Ramadan. The same variations were observed among diabetics (n=323). However, there was a significant decrease in HbA1c after Ramadan (9.0% vs 7.6%, p<0.001). Our findings also revealed there was no significant correlation between variations of metabolic parameters and dietary intake. No acute metabolic incidents were reported during the study period. CONCLUSION: The current study showed that Ramadan is responsible for a transient but well tolerated disturbance of metabolic parameters followed by a significant post-Ramadan improvement. These changes did not seem to be directly related to dietary intake.

The international normalized ratio (INR): What reagent, what instrument? The assessment of the agreement between INR values according to different reagent/instrument combinations.

WHAT IS KNOWN AND OBJECTIVE: The international normalized ratio (INR) is widely used to monitor patients on vitamin K antagonists. This study aimed to assess the agreement of INR values obtained with different thromboplastin/instrument combinations. MATERIAL AND METHODS: International normalized ratio was determined on plasmas from 330 patients undergoing antivitamin K treatment (with acenocoumarol), using two calibration methods and four reagent/instrument combinations: Both Neoplastine CI and Neoplastine CI Plus on STA-R instrument from Diagnostica STAGO, Asnières, France; and both Thromborel S and Innovin on SYSMEX 2100i instrument from Siemens Health Care Diagnostics, Marbung, Germany. The agreement analysis was done using the Bland-Altman plot and the Cohen Kappa coefficient. RESULTS: The mean of the differences between the INR values and the limits of agreement were -0.07 [-0.51 to 0.38] for the Neoplastine CI plus and Neoplastine CI reagents, -0.08 [-1.18 to 1.03] for the Thromborel S and Innovin reagents when the INR was calculated, -0.1 [-1.15 to 0.95] for the Thromborel S and Innovin reagents when the INR was directly calibrated and -0.1 [-0.7 to 0.5] for the Neoplastine CI plus and Thromborel S. Cohen's kappa coefficients were 0.94, 0.76, 0.85 and 0.82, respectively. NEW FINDINGS AND CONCLUSION: The agreement between the four reagent/instrument combinations was high enough to classify patients as inefficaciously or efficaciously anticoagulated. The data interpretation should always be related to the clinical purpose.

Effects of Ramadan fasting on platelet reactivity in diabetic patients treated with clopidogrel.

BACKGROUND: The effects of Ramadan fasting (RF) on clopidogrel antiplatelet inhibition were not previously investigated. The present study evaluated the influence of RF on platelet reactivity in patients with high cardiovascular risk (CVR) in particular those with type 2 diabetes mellitus (DM). METHODS: A total of 98 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking clopidogrel at a maintenance dose of 75 mg. Clinical findings and serum lipids data were recorded before Ramadan (Pre-R), at the last week of Ramadan (R) and 4 weeks after the end of Ramadan (Post-R). During each patient visit, nutrients intakes were calculated and platelet reactivity assessment using Verify Now P2Y12 assay was performed. RESULTS: In DM patients, the absolute PRU changes from baseline were +27 (p = 0.01) and +16 (p = 0.02) respectively at R and Post-R. In addition, there was a significant increase of glycemia and triglycerides levels with a significant decrease of high-density lipoprotein. In non DM patients there was no significant change in absolute PRU values and metabolic parameters. Clopidogrel resistance rate using 2 cut-off PRU values (235 and 208) did not change significantly in DM and non DM patients. CONCLUSIONS: RF significantly decreased platelet sensitivity to clopidogrel in DM patients during and after Ramadan. This effect is possibly related to an increase of glycemia and serum lipids levels induced by fasting. TRIAL REGISTRATION: Clinical Trials.gov NCT02720133. Registered 24 July 2014.Retrospectively registered.

The evaluation of the relevance of thrombin generation and procoagulant activity in thrombotic risk assessment in BCR-ABL-negative myeloproliferative neoplasm patients.

INTRODUCTION: It has been recently suggested that microparticles (MP) play a role in the pathogenesis of thrombotic complications. This study aimed to assess the contribution of procoagulant activity expressed by circulating MP in thrombotic events in MPN patients. METHODS: Seventy-four MPN patients were enrolled in a trans-sectional study. The MP procoagulant activity was measured using two assays: (i) the thrombin generation (TG) assay used in different conditions with the addition of both tissue factor (TF) and phospholipids (PL) and with the addition of TF or PL alone and (ii) the PROCOAG-PPL assay. RESULTS: The mean age was 62 (26 men and 48 women). The prevalence of thrombotic events was 28%. When comparing patients with thrombosis to those without, age, sex, MPN type, cardiovascular risk factors, and history of thrombosis were not significantly associated with thrombosis. The JAK2 V617F mutation was significantly associated with thrombotic events (90% vs 67%; P=.04). Results from the TG assay and the PROCOAG-PPL assays did not demonstrate a significant association between the MP procoagulant activity and thrombotic events. CONCLUSION: The MP procoagulant activity did not predict thrombosis in MPN patients. The contribution of TG assay in the assessment of the thrombotic risk is still in debate.

[Hemovigilance: State 2007-2013 Tunis]. / Hémovigilance à Tunis (hôpital La Rabta) : bilan 2007­2013.

INTRODUCTION: Despite its lifesaving role, blood transfusion still has risks associated with it. Hemovigilance is a set of surveillance procedures of the transfusion chain intended to promote safe and effective use of blood components. This work aims to present a descriptive analysis of adverse reactions, which were notified over a period of 5 years (incidence and etiology); to identify malfunctions and to propose corrections. MATERIALS AND METHODS: All transfusion adverse reactions accidents reported to the blood bank of the hospital La Rabta (n=120) are explored (clinical and laboratory tests). RESULTS: The average age of patients with transfusion reaction was 51.2 years (25 days to 89 years). The transfusion accident rates ranged from 0.59 to 2.19 accidents/1000 labile blood products (LBP) distributed. The investigations were used to classify 71 % of accidents in different categories. The most prevalent reaction is the hemolytic reaction, n=24 (19.8 %), followed by allergic reactions, n=21 (17.5 %) and non-hemolytic feverish reaction, n=19 (15.8 %). Transfusion reactions of grade 1 severity were the most frequent (n=94); followed by those of grade 3 severity (n=16), accidents grade 4 (n=4) including two cases of acute pulmonary edema, one case of hyperkalemia, and the last case classified undetermined. CONCLUSION: These data are particularly rich in learning lessons. This study identified several levels failures: under-reporting of certain transfusion accidents, malfunctions at certain stages of the transfusion chain. In order to achieve an accurate statement of each transfusion reaction, it is important to plan in-service training.

Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis.

OBJECTIVE: To evaluate the incidence of coronary vasospasm as a possible pathophysiological mechanism causing chest pain symptoms in patients with clinically suspected myocarditis. DESIGN AND SETTING: Prospective study in a teaching hospital. PATIENTS: 85 patients who presented at hospital with atypical chest pain and demonstrated clinical signs suggestive of myocarditis. MAIN OUTCOME MEASURES: Incidence of coronary vasospasm demonstrated by intracoronary acetylcholine (ACh) testing. METHODS: The combined procedure of intracoronary ACh testing and endomyocardial biopsy (EMB) was performed after ruling out significant coronary artery disease (CAD). EMBs were analysed for myocardial inflammation by immunohistological methods and for virus genome persistence. RESULTS: Pathological biopsy results, including myocardial inflammation or detection of viral genomes, or both, were found in 55 (64.7%) patients while 30 (35.3%) patients showed neither cardiac inflammation nor viral genomes and were defined as the control group. Coronary vasospasm was demonstrated in 39/55 (70.9%) patients with pathological results compared with only 12/30 (40.0%) with normal biopsy results (p = 0.01). Patients with isolated PVB19 infection (n = 22) demonstrated a significantly higher incidence of coronary vasospasm than both those with isolated HHV6 infection (86.4% vs 46.7%; p = 0.025) and those with normal biopsy results (86.4% vs 40.0%; p<0.001). Univariate and multivariate logistic regression analysis showed that only PVB19 infection was independently correlated with coronary vasospasm (OR = 4.9, 95% CI 1.56 to 15.28, p = 0.006). CONCLUSIONS: Coronary vasospasm is one of the main reasons for atypical chest pain in patients with clinical signs of myocarditis and biopsy-proven PVB19 myocarditis in the absence of significant CAD.