Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery

Introduction

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.

Materials and Methods

Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.

Results

TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.

Conclusions

TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.     

Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

BackgroundElevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease.AimsThe rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine.MethodsA total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach.ResultsTraditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia.ConclusionsHyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics’ intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.     

Comparison of baseline predictors of prognosis in pulmonary arterial hypertension in patients surviving ≤2 years and those surviving ≥5 years after baseline right-sided cardiac catheterization

Idiopathic pulmonary arterial hypertension (PAH) is usually associated with a poor outcome but the prognosis with other forms of PAH is not well-described. Advances in therapy have furthered clouded the disease course. We sought to determine the baseline indicators of prognosis in patients with PAH. We reviewed the records of patients with PAH followed up at our institution to identify those who died within 2 years (reduced survival group; n = 21) and those who survived >5 years (long survival group; n = 60). The groups were compared for prognostic significance of the baseline clinical parameters. The reduced survival group were older (p = 0.001) and more likely to have scleroderma-associated PAH (p = 0.01), have pericardial effusion (p = 0.01), have a shorter 6-minute walk test (6MWT) distance (p = 0.001), to require oxygen during 6MWT (p = 0.02), have a worse World Health Organization functional class (p <0.001), and have greater serum brain natriuretic peptide levels (p = 0.01). Regression analysis showed age, World Health Organization functional class, 6MWT distance, the need for oxygen during the 6MWT, and renal disease to be independently associated with a poor prognosis. In conclusion, age, PAH etiology, World Health Organization functional class, pericardial effusion, 6MWT distance, the need for oxygen during the 6MWT, and brain natriuretic peptide are predictors of prognosis in patients PAH receiving specific therapy and might help identify a group that could benefit from aggressive upfront therapy.     

Efficacy of Vitamin D in patients with active rheumatoid arthritis receiving methotrexate therapy

To determine the efficacy of oral vitamin D [25(OH)D] in patients with active rheumatoid arthritis (RA) who are in methotrexate (MTX) therapy, patients receiving stable doses of MTX were randomized to one of two dose groups and received 12?weeks of double-blind vitamin D[25(OH)D] (50,000?IU per week) or matching placebo. The moderate and major efficacy measure was the proportion of patients with >0.6 and >1.2 improvement in RA based on the Disease Activity Score 28(DAS 28) at 12?weeks. Safety measures included adverse events and laboratory assessments. On a background of MTX, the percentage of patients with a moderate/major DAS 28 response at week 12 in the vitamin D groups (76/44%) was not significantly different from placebo (64.6/33.4%). Adverse events were typically mild and included small hepatic enzyme elevation; we did not have any undesirable events resulting in discontinuation of study drug. In patients with active RA receiving stable doses of MTX, vitamin D showed non-significant improvement in efficacy outcomes compared to placebo.     

Therapeutic Liposomal Dry Powder Inhalation Aerosols for Targeted Lung Delivery

Therapeutic liposomal powders (i.e., lipospheres and proliposomes) for dry powder inhalation aerosol delivery, formulated with phospholipids similar to endogenous lung surfactant, offer unique opportunities in pulmonary nanomedicine while offering controlled release and enhanced stability. Many pulmonary diseases such as lung cancer, tuberculosis (TB), cystic fibrosis (CF), bacterial and fungal lung infections, asthma, and chronic obstructive pulmonary disease (COPD) could greatly benefit from this type of pulmonary nanomedicine approach that can be delivered in a targeted manner by dry powder inhalers (DPIs). These delivery systems may require smaller doses for efficacy, exhibit reduced toxicity, fewer side effects, controlled drug release over a prolonged time period, and increased formulation stability as inhaled powders. This state-of-the-art review presents these novel aspects in depth.     

Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson’s disease

ObjectiveThe function of synchronous oscillatory activity at beta band (15–30 Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement.MethodsWe recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson’s disease during a synchronized tapping task at three different externally cued rates.ResultsBeta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate.ConclusionOur results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping,SignificanceThese findings implicate consistent beta suppression in the facilitation of continuous movement sequences.