Systemic and local factors associated with coronary plaque disruption

Introduction

Yellow plaques are regarded vulnerable; and disrupted yellow plaques are the major cause of acute coronary syndrome. We examined the factors associated with the disruption of yellow plaques among patients and lesion characteristics.

Materials and Methods

Consecutive 161 patients with ischemic heart diseases who received coronary angioscopic examination were analyzed. Yellow plaques in the segments to which intervention had never been performed were included, and their yellow color grade and presence/ absence of disruption were examined. Associated factors for plaque disruption were examined among patients and lesion characteristics.

Results

In 161 patients, 392 yellow plaques were included for analysis and 70 of them were disrupted. Frequency of plaque disruption (= disrupted / all yellow plaques) was significantly higher at the segments of severer stenosis (stenosis≥75% vs. 75-25% vs. < 25%: 34% vs. 21% vs. 14%, p = 0.006). Multivariate analysis revealed angiographic stenosis (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.005-1.023; p = 0.003), yellow color grade (OR, 3.297; 95% CI, 2.062-5.273, p < 0.001), LDL-cholesterol (OR, 1.012; 95% CI, 1.004-1.020, p = 0.003), male gender (OR, 3.608; 95% CI, 1.538-8.465; p = 0.003), and hypertension (OR, 2.552; 95% CI, 1.094-5.953; p = 0.030) as significant associated factors for plaque disruption.

Conclusion

Angiographic stenosis, yellow color grade, LDL-cholesterol, male gender, and hypertension were significantly associated with the disruption of yellow plaques.     

Shared impairment in associative learning in schizophrenia and bipolar disorder

Background

Schizophrenia (SCZ) and bipolar disorder (BD) share some cognitive commonalities. However, the role of associative learning, which is a cornerstone of human cognition mainly relying on hippocampus, has been under-investigated. We assessed behavioral performance during associative learning in a group of SCZ, BD and healthy controls (HC).

Methods

Nineteen patients with SCZ (36 ± 8.1 years; 13 males, 6 females; all Caucasians), 14 patients with BD (41 ± 9.6 years; 5 males, 9 females; all Caucasians) and 45 HC (27.7 ± 6.9 years; 18 males, 27 females; all Caucasians) were studied. Learning was assessed using an established object-location paired-associative learning paradigm. Subjects learned associations between nine equi-familiar common objects and locations in a nine-location grid. Performance data were analyzed in a repeated measures analysis of variance with time (repeated) and group as factors.

Results

Learning curves (performance = 1−e^−k?time) fitted to average performance data in the three groups revealed lower learning rates in SCZ and BD (k = 0.17 and k = 0.34) than HC (k = 0.78). Significant effects of group (F = 11.05, p < 0.001) and time (F = 122.06, p < 0.001) on learning performance were observed.

Conclusions

Our study showed that associative learning is impaired in both SCZ and BD, being potentially not affected by medication. Future studies should investigate the neural substrates of learning deficits in SCZ and BD, particularly focusing on hippocampus function and glutamatergic transmission.     

Plasma homocysteine level and left ventricular thrombus formation in acute anterior myocardial infarction patients following thrombolytic therapy with t-PA

Aims

The aim of this study was to evaluate the relationship between homocysteine levels and the development of left ventricular thrombus in acute anterior myocardial infarction patients directed to thrombolytic therapy.

Methods and Results

Seventy-nine patients presenting with ST elevated acute anterior myocardial infarction and treated with thrombolytic agent, t-PA, were included in the study. Two-dimensional echocardiography was used to divide patients into 2 groups according to the presence (n = 14) or absence (n = 65) of thrombus in the left ventricle following myocardial infarction. The levels of fasting plasma total homocysteine, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, vitamin B12 and folic acid were assessed. There were no significant differences between two groups in terms of age, gender, hyperlipidemia and smoking. History of diabetes mellitus (28.57% versus 6.15%, p = 0.04), peak creatine phosphokinase levels (4153.54 ± 1228.41 U/L versus 2456.92 ± 1421.36 U/L, p < 0.001), mean left ventricular wall motion score index (2.21 ± 0.18 versus 1.83 ± 0.23, p < 0.001) and total fasting homocysteine levels (18.24 ± 5.67 mmol/L versus 12.31 ± 3.52 mmol/L, p < 0.001) were significantly higher in patients with left ventricular thrombus. In multivariate analysis; only diabetes mellitus (p = 0.03), higher wall motion score index (p = 0.001) and higher homocysteine levels (p = 0.04) were independent predictors of left ventricular thrombus formation.

Conclusion

Our results suggest that; diabetes mellitus, higher wall motion score index and hyperhomocysteinemia independently increases the risk for the development of left ventricular thrombus formation in patients with acute anterior myocardial infarction following thrombolytic therapy.     

Stent implantation in the superficial femoral artery: Short thrombelastometry-derived coagulation times identify patients with late in-stent restenosis

Introduction

The mechanisms of restenosis, the recurrence of luminal narrowing, are complex and incompletely understood to date. Thrombin, the pivotal enzyme in haemostasis, presumably contributes to the formation of in-stent restenosis (ISR). It was therefore the aim of our study to investigate whether blood coagulation/thrombin generation plays a critical role in the formation of ISR in peripheral artery disease patients with stent angioplasty in the superficial femoral artery.

Materials and Methods

We aimed to examine in this retrospective study whether patients with high-degree restenosis (50-75% lumen diameter reduction, n = 20) are in a hypercoaguable state implying enhanced readiness to generate thrombin compared to patients with low-degree restenosis (< 50% lumen diameter reduction, n = 14).

Results

The coagulation tests calibrated automated thrombography, activated partial thromboplastin time, platelet aggregation, platelet adhesion, fibrinogen, and microparticles’ procoagulant activity did not indicate a different coagulation status in the two patient groups. However, the thrombelastometry-derived value Coagulation Time (CT) was significantly shorter in the high-degree restenosis group (p = 0.012), indicating a hypercoagulable state of patients with high-degree restenosis. Under our experimental conditions, CTs shorter than 444.5 s identify patients at high risk (sensitivity = 95%) for luminal narrowing.

Conclusions

Our study supports the assumption that blood coagulation/thrombin generation plays a critical role in the development of ISR in peripheral arteries after stent insertion and that the thrombelastometry-derived CT might be a suitable value to identify peripheral artery disease patients at risk for development of high-degree in-stent restenosis in the superficial femoral artery.     

Activated inflammatory cells participate in thrombus size through tissue factor and plasminogen activator inhibitor-1 in acute coronary syndrome: Immunohistochemical analysis

Introduction

Recent studies have suggested that circulating inflammatory cells augment the growth of thrombus in acute coronary syndrome (ACS). We therefore immunohistochemically analyzed thrombi in aspirates obtained from patients immediately after the onset of ACS.

Materials and Methods

Two hundred twenty samples were studied. Total thrombus area, white thrombus area, and red thrombus area were measured. As antibodies in immunohistochemical staining, myeloperoxidase (MPO), CD66b, CD68, p-selectin, tissue factor (TF) and PAI-1were employed respectively.

Results

The ratios of areas of red and white thrombi correlated with whole sample areas of enlarged thrombi (r = 0.48, p < 0.001). The immunohistochemical findings revealed granulocytes and macrophages aggregated around p-selectin-positive platelets that shared the boundary between white and red thrombi, a region where MPO and CD66b expression was abundant in neutrophils. The ratios (%) of MPO- and CD66b-positive cells significantly correlated with whole sample areas (r = 0.50; p < 0.001 and r = 0.49; p < 0.001, respectively). Neutrophils and macrophages within thrombi were positive for TF and PAI-1. Along the boundary between red and white thrombi, TF and PAI-1 positivity coincided with MPO-, CD66b- and CD68-positive cells. The ratios of cells positive for both TF and PAI-1 in this area significantly correlated with the whole sample area (r = 0.43, p < 0.001 and r = 0.60, p < 0.001, respectively).

Conclusions

These results suggested that enhanced activation of peripheral neutrophils together with increased TF and PAI-1 expression might comprise a considerable portion of thrombus enlargement.     

The relationship between aortic aneurysm sac thrombus volume on coagulation, fibrinolysis and platelet activity

Aim

Abdominal aortic aneurysm (AAA) is associated with chronic mural inflammation and a pro-thrombotic diathesis. It has been suggested that both may be related to biologically active intra-sac thrombus. The aim of this study was to examine the relationship between thrombin generation, fibrinolysis, platelet activity and AAA sac thrombus volume.

Methods

30 patients (29 men) of median (IQR) age 75 (71-82) years with an infra-renal AAA > 5.5 cm in antero-posterior diameter were prospectively studied. AAA, lumen and thrombus volumes were calculated using a CT workstation (Vitrea). Plasma thrombin-antithrombin (TAT), plasminogen activator inhibitor (PAI)-1, and soluble (s) P-selectin were measured as biomarkers of coagulation, fibrinolysis and platelet activity, respectively

Results

Median (IQR) AAA total, lumen and thrombus volumes were 188 (147-247) cm³, 80 (54.3-107) cm³ and 97.6 (63-127) cm³ respectively.TAT levels were significantly higher (median, QR, 7.15 [4.7-31.3] μg/L, p = < 0.001) and sP-selectin levels significantly lower (median, IQR, 80.5 [68-128] ng/ml, p = < 0.0001) than the normal range. PAI-1 levels (median, IQR, 20.9 [8.4-50.7] ng/ml) were normal. There was no correlation between AAA thrombus volume and PAI-1 (r = − 0.25, p = 0.47), sP-Selectin (r = 0.26, p = 0.43) or TAT plasma levels (r = − 0.21, p = 0.54).

Conclusion

The present study confirms that patients with AAA demonstrate haemostatic derangement, but the extent of the haemostatic derangement does not correlate with AAA sac thrombus volume.     

The ‘carry-over’ effects of patient self-testing: Positive effects on usual care management by an anticoagulation management service

Introduction

Patient self-testing (PST) of the international normalised ratio (INR) has a positive effect on anticoagulation control. This study investigated whether the benefits of PST (other than increased frequency of testing, e.g. patient education, empowerment, compliance etc.) could be ‘carried-over’ into usual care management after a period of home-testing has ceased.

Material and methods

Patients that completed a six month period of PST (as part of a randomised controlled trial) but returned to clinic management when the trial ended were included in the study. The primary outcome variable was the difference in anticoagulation control (measured using the time in therapeutic range) between the two periods. A group of patients who were managed solely by the anticoagulation clinic served as the control.

Results

There was no significant difference in median time in therapeutic range (TTR) between the 52 patients during clinic management post-PST and the six month period of PST (75% vs 75.3%; p = 0.061). Patients tested more frequently while home-testing compared with the subsequent six month period of clinic management (once every 5.6 ± 0.7 days compared with once every 23.2 ± 7.4 days; p = 0.000). Patients with previous experience of PST performed significantly better than the control group of patients (n = 107) that were managed solely by the anticoagulation clinic (75% vs 59.7%; p = 0.009) despite less frequent monitoring of the INR (every 23.2 ± 7.4 days vs. 17.4 ± 6.7 days; p = 0.000).

Conclusions

The improvements in anticoagulation control observed during a period of PST can be sustained when patients cease home-testing and revert back to usual care management.     

Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials

Background

There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Objectives

To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.

Methods

The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists. Two reviewers independently extracted data on study characteristics, quality and the frequency of total, symptomatic and proximal DVT.

Results

Fourteen studies (4,423 patients) were included. Total and proximal DVT after TKA declined over time (r = − 0.75, p = 0.031; r = − 0.86, p = 0.007 respectively). Total and proximal DVT after THA did not change. The risk of developing DVT after TKA was significantly higher than after THA (OR 1.85, 95% CI 1.6 - 2.14; p < 0.0001). The risk of developing symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95% CI 1.11 - 4.27; p = 0.012).

Conclusions

The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis.     

Incidence and predictive factors of symptomatic thrombosis related to peripherally inserted central catheters in chemotherapy patients

Introduction

The incidence of symptomatic catheter-related deep vein thrombosis (DVT) in cancer patients remains unclear and there is a lack of reliable data on the risk factors of PICC-related DVT.

Materials and Methods

We performed a retrospective cohort study of consecutive cancer patients who received an ultrasound guided PICC line for the administration of chemotherapy. Univariable and multivariable logistic regression analyses were performed to identify risk factors for symptomatic PICC-related DVT.

Results

In total, 340 cancer patients obtained PICC lines for the administration of chemotherapy. Of these patients, 19 (5.6%; 95% CI: 3.6-8.6) developed symptomatic PICC-related DVT. Factors previously associated with catheter-related DVT, including side of catheter placement, lumen size, tip location, need for repositioning, and number of insertion attempts, were not significant determinants in our analysis. Patients with diabetes were three times more likely to develop PICC-related DVT (OR 3.0, p = 0.039), while the presence of COPD and metastatic cancer also increased the odds (OR 3.3, p = 0.078 and OR 2.3, p = 0.083 respectively). Diabetes remained a significant risk factor after adjustment for effect of metastases and COPD (OR 3.175, p = 0.039). Further, the presence of metastases was a significant predictor (OR 3.34, p = 0.024) in our multivariable model.

Conclusions

Symptomatic PICC-related DVT are frequent in cancer patients receiving chemotherapy. Previously described factors associated with catheter-related thrombosis were not predictive of PICC-related DVT in our study. Diabetes, advanced disease and COPD appear to increase the risk of developing PICC-related DVT in chemotherapy patients.     

Impact of clopidogrel resistance on thrombotic events after percutaneous coronary intervention with drug-eluting stent

Objectives

This study examines whether patient resistance to clopidogrel is associated with long-term thrombotic events after elective coronary drug-eluting stent (DES) implantation.

Methods

We prospectively enrolled 386 patients with stable angina who received elective percutaneous coronary intervention (PCI) with DES. Before the procedure, platelet reactivity was measured by light transmittance aggregometry (LTA) at baseline and approximately 24 h after the 300 mg loading dose of clopidogrel. Clopidogrel resistance was conservatively defined as ≤ 10% absolute difference between baseline and post-treatment platelet aggregation. All patients received chronic dual antiplatelet treatment (aspirin 300 mg and clopidogrel 75 mg daily) for 12 months. Patients were followed for 1 year after coronary stenting for the occurrence of composite thrombotic events, including cardiovascular death, non-fatal myocardial infarction (MI), stent thrombosis or cerebrovascular ischemic accident (CVA).

Results

Clopidogrel resistance was present in 65 patients (16.8%). During follow-up, composite thrombotic events occurred in 16.9% of clopidogrel resistant patients, yet in only 6.2% of non-resistant patients (p = 0.010). The incidence of definite or probable stent thrombosis was 9.2% in clopidogrel resistant patients and 2.5% in non-resistant patients (p = 0.018). After adjustment for other factors that affect cardiovascular outcome, clopidogrel resistance, diabetes, and left ventricular (LV) dysfunction were independently associated with 1-year composite thrombotic events. The hazard ratio (HR) for clopidogrel resistance was 2.44 (95% CI = 1.09 to 5.45; p = 0.031).

Conclusion

This study demonstrates the natural history of clopidogrel resistance among patients with stable cardiovascular disease, and shows that this resistance is an independent predictor of thrombotic events in patients undergoing PCI with DES.     

High levels of platelet-monocyte aggregates after valve replacement for aortic stenosis: relation to soluble P-selectin and P-selectin glycoprotein ligand-1 genes

Background

Calcific aortic valve stenosis is linked to atherosclerosis. The latter is associated with increased levels of platelets adhering to monocytes (PMA).

Objective

The hemodynamic impairment in symptomatic aortic valve stenosis can be abated by valve replacement. We investigated the effect of valve replacement on PMA and receptor-ligand axis P-selectin - P-selectin glycoprotein ligand-1 (PSGL-1) in severe aortic valve stenosis.

Patients and Methods

PMA, plasma P-selectin (sP-selectin) and polymorphisms within the coding region for PSGL-1 (SELPLG) were determined in 42 patients with severe aortic valve stenosis before and 4 to 8 months after valve replacement. Ten patients suffered from significant coronary artery disease and received also a coronary artery bypass graft. Thirty-four patients received a bioprosthetic valve and 8 patients who were < 65 years old received a mechanical valve.

Results

Before the intervention, PMA levels were significantly higher in patients with aortic valve stenosis than in two control cohorts, namely healthy indviduals and 88 age- and sex-matched patients with severe atherosclerosis, but without aortic valve stenosis (p < 0.001). PMA decreased after surgery, but normalized in only 3 patients, while further increases were noted in 11 patients. sP-selectin was elevated in 3 and 4 patients before and after valve replacement, respectively. sP-selectin increased significantly after surgery, but remained within the normal range. There was no correlation between changes of PMA and sP-selectin or any of the polymorphisms within SELPLG.

Conclusions

Exceedingly high PMA in aortic stenosis are independent of SELPLG polymorphisms, and largely of the hemodynamic compromise caused by the stenotic valve.     

Decline in platelet microparticles contributes to reduced hemostatic potential of stored plasma

Introduction

In an effort to administer life-saving transfusions quickly, some trauma centers maintain thawed plasma (TP). According to AABB, TP is approved for transfusion for up to five days when stored at 1 - 6 °C. However, the alterations in microparticles (MP) contained in the plasma, which are an integral component of plasma's hemostatic capacity, are not well characterized. We report on MP changes in TP between its initial thaw (FFP-0) and five days (FFP-5) of storage.

Materials and Methods

FFP units (n = 30) were thawed at 37 °C and kept refrigerated for five days. Phenotypes of residual cells, which include platelets, erythrocytes, leukocytes, monocytes, endothelial cells, and MP counterparts of each cell type, were analyzed by flow cytometry. Functional assays were used for MP procoagulant activity, plasma thrombin generation, and clotting properties (thromboelastography).

Results

In FFP-0 the majority (94%) of residual cells were platelets, along with significant levels of platelet MPs (4408 × 10³/L). FFP-5 showed a decline in MP count by 50% (p < 0.0001), and procoagulant activity by 29% (p < 0.0001). FFP-5 exhibited only 54% (p < 0.0001) of the potential for thrombin generation as FFP-0, while thromboelastography indicated a slower clotting response (p < 0.0001) and a longer delay in reaching maximum clot (p < 0.01). Removal of MP by filtration resulted in reduced thrombin generation, while the MP replacement restored it.

Conclusions

Decline in MP with storage contributes to FFP-5's reduced ability to provide the hemostatic potential exhibited by FFP-0, suggesting the presence of platelet MPs in freshly TP may be beneficial and protective in the initial treatment of hemorrhage.     

Reduced platelet response to aspirin in patients with coronary artery disease and type 2 diabetes mellitus

Introduction

Diabetes mellitus is complicated by accelerated atherosclerosis, resulting in an increased risk of coronary artery disease (CAD) and thrombosis. Despite the proven benefits of aspirin, previous studies indicate a reduced cardiovascular protection from aspirin in diabetic patients. We aimed to investigate whether diabetes mellitus influenced the platelet response to aspirin in patients with CAD.

Materials and Methods

Platelet aggregation and activation were evaluated during aspirin treatment in 85 diabetic and 92 non-diabetic patients with CAD. Adherence to aspirin was carefully controlled. All patients had CAD verified by coronary angiography and were taking 75 mg non-enteric coated aspirin daily.

Results

Diabetic patients showed significantly higher levels of platelet aggregation compared to non-diabetic patients evaluated by VerifyNow^® Aspirin (p = 0.03) and Multiplate^® aggregometry using arachidonic acid (AA) 0.5 mM (p = 0.005) and 1.0 mM (p = 0.009). In addition, platelet activation determined by soluble P-selectin was significantly higher in diabetics compared to non-diabetics (p = 0.005). The higher AA-induced aggregation was associated with higher levels of HbA_1c. Compliance was confirmed by low levels of serum thromboxane B₂ (below 7.2 ng/mL). Diabetics had significantly higher levels of serum thromboxane B₂ (p < 0.0001).

Conclusions

Diabetic patients with CAD had significantly higher levels of both platelet aggregation and activation compared to non-diabetic patients with CAD despite treatment with the same dosage of aspirin. These findings may partly explain the reduced cardiovascular protection from aspirin in diabetic patients.     

P-selectin/ PSGL-1 Inhibitors versus enoxaparin in the resolution of venous thrombosis: A meta-analysis

Background

P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT).

Objective

To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis.

Methods

Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects.

Results

Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95% CI; 44.37 [17.77^_70.96], p = 0.001, I² = 97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88^_18.95], p = 0.48, I² = 41%). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95% CI; -17.84 [-14.98 ^_ -8.30], p < 0.00001, I² = 80%). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95% CI; -3.59 [-10.67^_3.48], p = 0.32, I² = 66%). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95% CI; -1.12[-2.36^_0.11], p = 0.07, I² = 92%), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p < 0.0001).

Conclusion

P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.     

Serum BDNF levels before treatment predict SSRI response in depression

Objectives

The “neurotrophin hypothesis” of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response.

Methods

Thirty un-medicated depressed subjects were treated with escitalopram (N = 16) or sertraline (N = 14) for 8 weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects.

Results

Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p = 0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p < 0.001), and BDNF levels increased with treatment (p = 0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p < 0.01), and “Responders” to treatment (≥ 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did “Non-responders” (p < 0.05).

Conclusions

These results confirm low serum BDNF levels in un-medicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants.     

Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy

Introduction

Currently, there is an intense debate about whether comedication with proton pump inhibitors (PPIs) weakens the antiplatelet effect of clopidogrel in patients undergoing coronary stent implantation. Competing mechanisms on the hepatic cytochrome 2C19 level are proposed. The aim of this study was to assess the impact of PPI treatment on clopidogrel response by measuring the ex vivo platelet aggregation in patients with coronary intervention.

Methods

1425 consecutive patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention were enrolled in this single centre study. PPI comedication was defined as PPI intake ≥ 1 week prior to a 600 mg clopidogrel loading dose. PPI treatment was based on physician preference. Residual platelet aggregation (RPA) was measured by optical aggregometry. To correct for potential selection bias, propensity score matching was applied.

Results

RPA was significantly higher in PPI-treated patients compared with non-PPI-users (final aggregation 34.0% vs. 29.8%, p < 0.001). Low responder defined as RPA in the upper tertile were more often found in PPI-users. After adjustment for relevant confounders, PPI treatment was independently associated with higher RPA-levels.

Discussion

We demonstrated that peri-procedural co-administration of PPIs significantly decreases the effect of clopidogrel on RPA. To assess if clopidogrel-PPI interaction results in a higher susceptibility for cardiovascular events remains subject to further investigations.     

Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an Internal Medicine setting

Introduction

Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department.

Materials and methods

Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12 weeks.

Results

One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p = 0.014, p = 0.009 and p = 0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p = 0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients.

Conclusions

We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.     

Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

Introduction

Puumala virus (PUUV) infection is a viral hemorrhagic fever with renal syndrome (HFRS) characterized by thrombocytopenia and acute impairment of renal function. We aimed to assess whether genetic polymorphisms of platelet antigens together with those of von Willebrand factor (VWF) and plasminogen activator inhibitor (PAI-1) correlate with disease severity.Patients and methods172 consecutive hospital-treated patients with serologically confirmed acute PUUV infection were included. Platelet glycoprotein (GP) IIIa T > C (rs5918), GP Ia T > C (rs1126643), GP Ib C > T (rs6065), GP VI T > C (rs1613662), VWF A > G (rs1063856) and PAI-1 A > G (rs2227631) were genotyped. The associations of the rarer alleles with variables reflecting the severity of the disease were analyzed.

Results

PAI-1 G-carriers had higher maximum creatinine level compared with the non-carriers (median 213 μmol/l, range 60-1499 μmol/l vs. median 122 μmol/l, range 51-1156 μmol/l, p = 0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 μmol/l, 204 μmol/l and 122 μmol/l, respectively, p = 0.03). Polymorphisms of GP VI and VWF associated with lower creatinine levels during PUUV infection. The minor C-allele of GP Ia associated with lower platelet counts (median 44 × 10⁹/l, range 20-90 × 10⁹/l vs median 64 × 10⁹/l, range 3-238 × 10⁹/l; p = 0.02).

Conclusions

Polymorphism of PAI-1, a major regulator of fibrinolysis, has an adverse impact on the outcome of kidney function in PUUV-HFRS. Platelet collagen receptor GP Ia polymorphism associates with lower platelet count.     

Safety of coronary artery bypass surgery during therapeutic oral anticoagulation

Introduction

Therapeutic (international normalized ratio, INR 2.0-3.5) oral anticoagulation (TOAC) is assumed to increase perioperative bleeding complications and a standard recommendation is to discontinue warfarin before coronary bypass grafting (CABG).

Materials and Methods

To assess the safety of TOAC we retrospectively analyzed consecutive patients (n = 270) with long-term warfarin therapy referred for CABG in two centers where TOAC strategy is employed. The main in-hospital outcomes of interest were death, stroke, acute myocardial infarction, new onset renal failure, resternotomy, and their composite. In the TOAC group of 103 patients CABG was performed during therapeutic oral anticoagulation and in the control group (81 patients) preoperative INR was lowered to a subtherapeutic (≤ 1.5) level.

Results

The patients in TOAC group were more often operated on an emergency basis (p = 0.02) and their EuroSCORE was higher (p = 0.02). There were no significant differences in the major outcome events or their composite (17.5 vs. 11.1%, p = 0.30) between the groups. Patients in the TOAC group had more postoperative blood loss (941 ± 615 vs. 754 ± 610 ml, p < 0.01) and received more fresh frozen plasma (2.8 ± 3.0 vs. 1.3 ± 2.4 units, p < 0.001), but transfused red blood cells (2.1 ± 2.8 vs. 2.1 ± 3.4 units) were comparable in the groups. Preoperative clopidogrel (OR 4.8, 95% CI 1.4-16.2, p = 0.01) and enoxaparin therapy (OR 2.6, 95% CI 1.1-6.5, p = 0.04) were the only significant independent predictors for any major adverse event.

Conclusions

Our study suggests that CABG is a safe procedure during TOAC with no excess bleeding or major complications. Prospective trials are needed to confirm this observation.     

Venlafaxine or a second SSRI: Switching after treatment failure with an SSRI among depressed inpatients: a retrospective analysis

Background

Approximately 50% of patients with major depressive disorder (MDD) do not respond after adequate first-line treatment with a selective serotonin reuptake inhibitor (SSRI). Special interest is paid to whether specialist level inpatient psychiatric care results differ from community studies.

Aim

To compare switching alternatives after treatment failure with an SSRI; switching to venlafaxine (Dexcel Pharma Israel) versus switching to another SSRI in depressed inpatients.

Method

A retrospective register study of inpatients was undertaken in a psychiatric tertiary care university center serving an urban catchment area in Israel with a population of more than 900,000.

Results

A total of 401 MDD inpatients were assigned to antidepressant treatment. Of these, 232 records (47 venlafaxine, 185 SSRI) were included in the analysis. Patients assigned to venlafaxine treatment were older (mean age 64.3 ± 15 years versus 53.6 ± 17; p < 0.01) and had more comorbid physical disorders (80% versus 57%; p < 0.001).In the primary analysis, there was no statistical difference between groups in reduction in CGI-S total scores. The secondary end point of achieving a CGI-S score of 2 or less (1 = normal, not at all ill or 2 = borderline mentally ill) was statistically significantly better for the venlafaxine treated inpatients (P = 0.02). AEs were reported less than 10% of patients in both groups.

Conclusion

Patients who remain severely depressed following treatment with an SSRI may gain benefit from the dual-action drug venlafaxine, rather than switching to another SSRI. These findings need to be further supported by prospective studies.