Facial sensibility of patients with trigeminal neuralgias

Objectives

Idiopathic trigeminal neuralgia (ITN) is an excruciating shock-like paroxysmal pain restricted to the trigeminal area of innervation, with discrete loss of sensibility (thermal, tactile and painful). Trigeminal postherpetic neuralgia (PHN) is a neuropathic pain at the trigeminal territory that persists after Herpes zoster infection, which also is associated to sensorial compromise. The objective of this study was to evaluate the somesthetic facial sensibility (pain, thermal and tactile) and to compare the findings between PHN and ITN.

Methods

18 patients with PHN and 26 patients with ITN were diagnosed by the IASP criteria. They were evaluated with a systematic approach, which included mechanical, thermal (cold and warm) and painful stimuli.

Results

We found statistical significance at the ophthalmic branch of PHN in pain (p = 0.001), tactile (p = 0.002), cold (p = 0.016) and warm (p = 0.013); in ITN, the maxillary branch had higher threshold with pinpricks (p = 0.016) and the mandibular branch had higher tactile threshold.

Conclusions

The trigeminal area affected by the disease had the higher sensorial losses (ophthalmic branch in PHN and maxillary/mandibular branches in ITN). PHN patients had losses in large and small fibers; therefore, ITN patients had the losses mostly in large fibers, which support different peripheral neural mechanisms for these neuropathic diseases.     

Plasma fibrin clot properties in arterial hypertension and their modification by antihypertensive medication

Background

We sought to determine plasma fibrin clot properties in hypertensive subjects and to evaluate potential effects of antihypertensive therapy on these parameters.

Patients and Methods

Sixty-one patients (30 men, 31 women) with essential arterial hypertension stage 1 or 2 (aged 46.6 ± 14.4 years), free of clinically evident vascular disease, were randomly allocated for monotherapy with one of the 5 antihypertensive agents, i.e. quinapril, losartan, amlodipine, hydrochlorothiazide, or bisoprolol. Plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated at baseline and after 6 months of therapy.

Results

Baseline systolic blood pressure in a 24-hour ambulatory monitoring was correlated with clot permeability (r = − 0.37, p < 0.05), lysis time (r = 0.42, p < 0.05) and maximal D-dimer concentration released from clots (r = 0.45, p < 0.05). Antihypertensive treatment resulted in reduction of systolic/diastolic blood pressure in office measurements and 24-hour monitoring (all p < 0.001), accompanied by an increase in clot permeability, reduction in clot lysis time and lower maximal D-dimer concentration released from fibrin clots (all p < 0.05). No changes were observed in turbidimetric variables. Posttreatment changes in plasma fibrin clot properties were related to reductions in systolic blood pressure, complement component C3 and total cholesterol.

Conclusions

Reduction in systolic blood pressure during antihypertensive treatment leads to increased plasma fibrin clot permeation and susceptibility to lysis, which might be a novel antithrombotic mechanism of blood pressure lowering therapy.     

Effect of increased aspirin dose after stenting in association with ClOpidogrel: the FIASCO randomized study

Background

Increased doses of antiplatelet therapy have been proposed to overcome the variability of response. However, the chronic dose of aspirin after DES remains controversial.

Methods and results

We assessed in a prospective and randomized study the benefit of higher dose of aspirin, in association with clopidogrel, on aspirin response and non COX-specific platelet testing in patients receiving Drug Eluting Stent (DES) for stable angina pectoris. 50 consecutive patients receiving DES for stable angina pectoris were prospectively included. They received loading dose of 250 mg aspirin and 600 mg clopidogrel and antiplatelet response was assessed with Arachidonic Acid-induced aggregation (AA-Ag) and ADP-induced aggregation (ADP-Ag) for aspirin and clopidogrel response respectively. Patients were randomized to either 75 or 160 mg of aspirin with 150 mg clopidogrel and platelet testing were repeated one month after hospital discharge. The two groups (aspirin “75 mg” or “160 mg”) had no difference for aspirin response: AA-Ag (5.2 ± 1.7% vs 6 ± 2%, p = 0.75) and non COX-specific pathway testing: ADP-Ag (47 ± 3% vs 49 ± 4%, p = 0.61).

Conclusion

The present study did not show any benefit of higher dose of aspirin neither on aspirin responsiveness, nor on inhibition of non COX-specific pathway. These data does not support use of higher dose than 75 mg of aspirin in association with clopidogrel in patients receiving DES, especially while higher doses have been associated with increased bleeding risk.     

Central thromboembolism is a possible predictor of right heart dysfunction in normotensive patients with acute pulmonary embolism

Background

Right heart dysfunction is a crucial factor in risk stratification of normotensive patients with pulmonary embolism. Apart from biomarkers, determinants of right heart dysfunction in this group of patients are not yet well established.

Aim and method

In order to identify such determinants, we analysed data of 252 patients with acute pulmonary embolism admitted to our hospital in 2008.

Results

69 out of 140 patients showed right heart dysfunction by echocardiography within 24 hours after diagnosis, 71 did not. Right ventricular dysfunction was significantly more frequent in patients with central clots on computed tomography (p = 0.004), a history of syncope (p < 0.001) and among women on oral contraceptives (p = 0.003). In multiple regression analysis, only central thromboembolism (p < 0.001) was identified as individual predictor of right ventricular dysfunction. Age, gender, body mass index, idiopathic or recurrent thromboembolism, duration of symptoms, preceding surgery, room air oxygen saturation, carcinoma, hypertension, diabetes, renal disease, congestive left heart failure and concomitant lung disease were equally distributed. In comparison with NT-pro brain natriuretic peptide (PPV 67%, NPV 75%, p = 0.782) and troponin I (PPV 76%, NPV 62%, p = 0.336), central thromboembolism has shown to have a greater statistical power in predicting right heart dysfunction in normotensive patients with pulmonary embolism (PPV 78%, NPV 88%, p < 0.001).

Conclusion

Among normotensive patients with acute pulmonary embolism, those with central clots seem to be at greater risk for echocardiographically evaluated right ventricular dysfunction.     

Platelet glycoprotein VI (GPVI) for early identification of acute coronary syndrome in patients with chest pain

Background

Platelet glycoprotein VI (GPVI) is elevated in patients with acute coronary syndrome (ACS), stroke and associated with acute coronary events. GPVI may be helpful to distinguish an imminent ACS from non-coronary (NC) causes in patients with chest pain who were transferred to chest pain unit, before the myocardial necrosis is evident with classical biomarkers.

Methods

Based on the findings of our previous studies, we consecutively examined 1004 patients with chest pain in a prospective study design. ACS was found in 416 (41.4%), stable angina pectoris (SAP) in 233 (23.2%), and NC causes of chest pain (hypertension, musculoskeletal disease, pulmonary embolism, myocarditis, cardiophobia) in 355 patients (35.4%). Platelet surface expression of GPVI was measured by flow cytometry.

Results

Patients with ACS showed significantly enhanced GPVI expression levels compared to patients with SAP or NC causes of chest pain (ACSvs.SAP(mean fluorescence intensity (MFI) ± SD):18.9 ± 7.4vs.17.9 ± 9.5;P = 0.028;ACSvs.NC:15.4 ± 6.9;P = 0.002). Elevated GPVI expression was associated with ACS independent of markers of myocardial necrosis like troponin and creatine kinase-MB. Patients with an elevated GPVI expression (MFI ≥ 18.6) had a poorer clinical outcome than patients with baseline GPVI expression in regard to composite cumulative survival that included myocardial infarction, stroke, and cardiovascular death at three months (Log rank;P = 0.025).

Discussion

Platelet GPVI surface expression is enhanced in patients at risk for an ACS and is an early marker for imminent acute coronary events in patients with chest pain.     

Evidence of increased platelet reactivity in the first six months after acute ST segment elevation myocardial infarction

Introduction

Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI).

Materials and methods

Fifty-nine patients (58 ± 11 years, 45 men), treated with primary angioplasty, were studied 1 month after STEMI. Thirty-five patients were retested at 6 months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate.

Results

Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1 month (p = 0.001 and p = 0.002, respectively) and at 6 months (p = 0.03 and p = 0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P < 0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6 months (P < 0.001).

Conclusion

Platelet reactivity is increased in the first 6 months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI.     

Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD

Background

Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD).

Aim of the study

To evaluate the diagnostic efficiency of a rapid quantitative test for the measurement of VWF antigen (VWF:Ag) in type 1 VWD.

Patients and methods

VWF:Ag was measured with an ELISA in a robotic instrument, as a reference method, and with a fully automated latex-immunoassay (LIA) on an ACL 9000 analyser in 1,716 subjects enrolled within the Molecular and Clinical Markers for Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Study. Among these subjects, 1,049 were healthy controls, 281 healthy family members and 386 affected members from 127 European families with type 1 VWD.

Results

The assay linearity range was 10-125 IU/dL for LIA (R² = 0.99) and 5-133 IU/dL for ELISA (R² = 0.99). The inter-assay CV for low VWF levels (∼ 30 IU/dL) was 2% for the LIA test and 8.7 % for ELISA. The sensitivity for detection of type 1 VWD affected members was 86% and the specificity 91% for LIA, 87% and 90% for ELISA. A receiver-operator (ROC) analysis disclosed only a marginal difference between the two tests, LIA having a slightly greater area under the curve (0.94 vs. 0.93, p = 0.03).

Conclusion

VWF:Ag LIA compared well to standard ELISA in this large population of patients and controls, showing better CV. However the lower detection limit for the VWF:Ag LIA compared to the VWF:Ag ELISA means that the LIA assay is less good at discriminating between type 3 VWD and moderate type 1 VWD.     

High kurtosis of intracranial electroencephalogram as a marker of ictogenicity in pediatric epilepsy surgery

Objective

We determined whether kurtosis analysis of intracranial electroencephalogram (EEG) can estimate the localization of the epileptogenic zone.

Methods

We analyzed 29 pediatric epilepsy patients who underwent intracranial EEG before focal resective surgery. We localized the brain regions with high kurtosis, the seizure onset zone (SOZ) and the regions with high-rate, high-amplitude and long-duration interictal paroxysms ?20 Hz. We tested correlations between the surgical resection of those regions and post-surgical seizure outcome, and correlations between kurtosis and the rate/amplitude/duration of interictal paroxysms.

Results

The resection of the regions with high kurtosis correlated with 1-year post-surgical seizure outcome (p = 0.028) but not with 2-year outcome. Kurtosis showed more significant correlation with 1-year seizure outcome than the SOZ and the rate/amplitude/duration of interictal paroxysms. Kurtosis showed positive, independent correlations with the amplitude and duration of interictal paroxysms (p < 0.0001) but not with the rate (p = 0.4).

Conclusions

The regions with high kurtosis provide more reliable information to predict seizure outcome than the SOZ and the regions with high-rate/amplitude and long-duration interictal paroxysms. Kurtosis reflects combined effects of the amplitude and duration of the interictal paroxysms.

Significance

High kurtosis suggests the regions with acquired ictogenicity within the irritative zone.     

Is the surgical repair of unruptured atherosclerotic aneurysms at a higher risk of intraoperative ischemia?

Background

The incidence of ischemia might be increased in the surgical repair of atherosclerotic unruptured aneurysms compared to non-atherosclerotic aneurysms. The atherosclerotic wall might increase the occurrence of thrombembolic events or its rigidity might endanger the occlusion of perforators within the aneurysm vicinity.

Methods

87 patients (53 patients without and 34 patients with atherosclerotic unruptured aneurysms, 50.5 ± 9.7 years) were analyzed for severity of atherosclerosis within the aneurysm and the aneurysm bearing vessel, surgical maneuvers, intraoperative alterations in evoked potentials and clinical and neuroradiological results.

Results

Temporary vessel occlusion (25% vs. 50%, p = 0.021), repositioning of a permanent clip (21% vs. 56%, p = 0.001) and aneurysm remnants (2% vs. 18%, p = 0.012) occurred more often in patients with atherosclerotic aneurysms. At 6 months, 3/34 patients with atherosclerosis (8.8%) had an unfavorable outcome, all patients without atherosclerosis had a favorable outcome (p = 0.056).

Conclusion

The surgical repair of unruptured aneurysms is safe but patients with atherosclerotic altered vessels and aneurysms accounted to a minor increase in unfavorable outcome and an increased risk of morbidity at 6 months postoperatively. This factor should be taken into consideration when performing surgery of atherosclerotic, unruptured aneurysms.     

Impact of thromboprophylaxis guidelines on clinical outcomes following total hip and total knee replacement

Background

The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’).

Methods

This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression.

Results

Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004).

Conclusions

This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.     

The relationship between plasma and placental tissue factor, and tissue factor pathway inhibitors in severe pre-eclampsia patients

Objective

To investigate the mechanism underlying the hypercoagulable state in severe pre-eclampsia.

Methods

Plasma tissue factor (TF) and tissue factor pathway inhibitor (TFPI) expression from pre-eclampsia patients and healthy pregnant controls were determined by ELISA. Placental TF and TFPI gene and protein expression were detected by quantitative RT-PCR, immunohistochemistry, and Western analysis.

Results

The plasma TF level in the pre-eclampsia group was significantly higher than the control group (p < 0.01), and surprisingly, the plasma TFPI-1 and TFPI-2 in the pre-eclampsia group were significantly lower (p < 0.01). Placental TF gene and protein expression levels in the pre-eclampsia group was significantly higher than the control group, while TFPI-1 and TFPI-2 levels were significantly lower (p < 0.05). Lastly, a significant correlation was found between plasma and placental TF protein levels in the pre-eclampsia group (p < 0.01).

Conclusion

Higher expression and/or release of TF from the placenta may contribute towards a pathological hypercoagulable state in pre-eclampsia patients.     

Visual naming performance after ATL resection: Impact of atypical language dominance

Purpose

To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL).

Methods

Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus.

Results

Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size = 0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n = 14; p < 0.05), but did not reach statistical significance in patients with left language dominance (n = 36; p = 0.09). Chi-square test revealed a trend of higher proportions of patients experiencing significant postsurgical deterioration in naming performance in atypical (57.1%) as compared to left language dominance (30.6%; p = 0.082). Surgical failure was also associated with greater decline of BNT scores and was more common in atypical than in left language dominant patients (χ² (1, n = 98) = 4.62, p = 0.032). Age of onset, duration of epilepsy, and seizure frequency had no impact on changes in BNT performance.

Conclusion

Atypical language dominance is a predictor of change in visual naming performance after left ATL and may also impact postsurgical seizure control. This should be considered when counseling surgical candidates.     

Clinical relevance of pulmonary infarction in patients with pulmonary embolism

Introduction

Data regarding the clinical relevance of pulmonary infarction (PI) in patients with pulmonary embolism (PE) are lacking. The aim of this study was to investigate the clinical features of PE patients with PI and the prognostic role of PI for PE patients.

Materials and Methods

Based on computed tomography scan, 509 patients with PE were divided into two groups, the infarction group (n = 45) and the non-infarction group (n = 464). A variety of clinical parameters were compared between the two groups.

Results

In the infarction group, the largest pulmonary arteries involved by emboli were central rather than peripheral and more proximal as compared to the non-infarction group (p = 0.01 and p < 0.03, respectively). Thrombolytic agents tended to be more frequently administered in the infarction group (13.3% [n = 6] versus 6.3% [n = 29], p = 0.07). In-hospital mortality, PE-related deaths, and the recurrence rate of PE did not differ between the two groups.

Conclusions

The present study did not demonstrate that PI is a prognostic indicator of recurrence and mortality in PE patients. We suggest the possibility that blood clot burden is greater in PE patients with PI, although PI by itself occurs in small pulmonary arteries.     

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.     

A new method measuring the interaction between von Willebrand factor and coagulation factor VIII

Introduction

There is a need for more reliable methods measuring the binding of coagulation factor VIII (FVIII) to von Willebrand factor (VWF) in plasma samples, for use in the clinical routine. We have developed such a method measuring FVIII binding in plasma, utilizing an ELISA system.

Materials and Methods

Microtiter plates were coated with a monoclonal antibody (ESH-8), reacting with the C2 domain in FVIII. Thereafter the wells were treated with recombinant FVIII (Kogenate Bayer®). After washing, diluted plasma samples were added and incubated for 1 h. Then HRP-conjugated antibodies against VWF were added and used for quantification of bound VWF.

Results

A strong signal to VWF concentration response was obtained. Plasma from patients with different types of von Willebrand disease gave frequently diminished responses. However, after correction for the VWF antigen levels, by calculation of FVIII binding/VWF antigen ratio, only the patients with known von Willebrand disease type 2 N (n = 4) had clearly abnormal results. The FVIII binding in 40 healthy individuals was determined as 1.08 ± 0.48 U/mL (SD). After correction for the VWF antigen levels the result was 0.94 ± 0.15. Thus, the SD declined substantially by this correction. The within-series CV and between-series CV were determined as 6.8 and 11.3%, respectively.

Conclusions

We have established a simple and reliable method to detect decreased binding of FVIII to von Willebrand factor in plasma samples. The method can conveniently be used to study large populations, as well as finding minor binding defects in patients.     

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.     

Thrombocyte serotonin and serum cholesterol concentration in suicidal and non-suicidal depressed patients

Introduction

Numerous studies have confirmed the connection of reduced serum cholesterol and thrombocyte serotonin concentration with suicidal behavior in psychiatric patients. The purpose of such studies was to determine the link among cholesterol and serotonin concentration, comparing depressed patients with and without attempted suicide with phenotypically healthy control group.

Materials and methods

The examinees' groups consisted of 55 depressed patients with suicide attempt and 77 depressed patients with no suicide attempt. In accordance to ICD-10, the above patients were separated in two subgroups; F32.2 and F33.2. Phenotypically healthy control group was presented by the group of healthy blood donors. The fasting serum cholesterol concentration was established using standard enzymatic method, while the thrombocyte serotonin concentration was determined by the enzymatic immune-chemical method (ELISA).

Results

The ANOVA test (N = 228, F_ratio = 8.26, p < 0.001) found significant difference of cholesterol concentration between groups, with lowest concentration in depressed patients with attempted suicide (SNK post hoc test, p < 0.05). Upon gender stratification, the significance remained for the female patients (ANOVA, N = 125, F_ratio = 6.06, p = 0.003). The serum cholesterol was shown to be statistically lower in the group of depressed patients with attempted suicide, diagnoses F32.2 (p = 0.031) and F33.2 (p = 0.011), compared to the group of depressed patients without attempted suicides. The thrombocyte serotonin was found to be significantly different in all examined groups, with the lowest thrombocyte serotonin in the group of depressed patients with no suicide attempt (SNK post hoc test, p < 0.05, N = 187, F_ratio = 37.69, p < 0.001). The same significance was found for the group of female (ANOVA, N = 103, F_ratio = 11.81, p < 0.001) and the group of male patients (ANOVA, N = 84, F_ratio = 30.40, p < 0.001). The thrombocyte serotonin was significantly lower in the group of depressed patients with no suicide attempt (F32.2), compared to the same diagnosis in the group of depressed patients with suicide attempt (MW-test, p = 0.018).

Conclusion

In the group of depressed patients with attempted suicide, statistically significant lower serum cholesterol values have been confirmed. In the group of depressed patients with no suicide attempt, statistically significant lower values of thrombocyte serotonin have been confirmed, presumably as the response to the psychopharmacological therapy.     

P2Y12 platelet reactivity after thrombolytic therapy for ST-segment elevation myocardial infarction

Introduction

Thrombolysis, as reperfusion therapy for ST segment elevation myocardial infarction (STEMI), induces a pro-thrombotic status with enhanced platelet activity; this study aims to evaluate P2Y12 platelet reactivity and response to clopidogrel in the post-thrombolysis scenario.

Materials and Methods

Observational, prospective study, including consecutive patients with elective angiography after thrombolytic therapy for STEMI. Every patient received antiplatelet therapy with loading doses of 250 mg aspirin and 300 mg clopidogrel on admission followed by 100 mg aspirin and 75 mg clopidogrel daily. P2Y12-dependent platelet reactivity (expressed in P2Y12-Reaction Units, PRU) was assessed with VerifyNow® device on admission, daily after thrombolysis and pre-angiography.

Results

41 patients fulfilled the inclusion criteria. Median time between thrombolysis and angiography was 2,5 days (IQR 1,8-4,1). Post-treatment platelet reactivity (PPR) showed poor correlation with time on clopidogrel treatment (r2 = 0.04) and reached a maximum value of 274 ± 84 PRU during the first 24 h after thrombolysis (Day + 1 determination). After this, values showed a progressive reduction until the point of angiography (249 ± 82 PRU), without significant differences between consecutive time-points (p = 0,549).Inhibition of platelet aggregation (IPA) assessed as a percentage of P2Y12 receptor blockage was poor, increasing gradually from 0 ± 4% on admission to 11 ± 6% the day of the angiography (p = 0,001). 71,4% of patients showed PPR ≥ 208 PRU during angiography.

Conclusions

Platelet reactivity, as assessed by post-treatment P2Y12 mediated reactivity, is heightened after thrombolytic therapy during STEMI management. In this scenario, standard doses of clopidogrel did not achieve significant inhibition of ADP-mediated platelet reactivity.     

Ticagrelor, but not clopidogrel and prasugrel, prevents ADP-induced vascular smooth muscle cell contraction: a placebo-controlled study in rats

Introduction

Off-target effects of novel antiplatelet agents due to their potential clinical benefits are currently an area of intensive investigation. We aimed to compare the effects of different P2Y₁₂ antagonists on the reactivity of vascular smooth muscle cells.

Materials and methods

Wistar rats (n = 30) were pretreated with an investigated drug or placebo. Clopidogrel (50 mg/kg, n = 7), prasugrel (10 mg/kg, n = 7), ticagrelor (10 mg/kg, n = 7) or placebo (n = 9) were administered orally 12 and 2 hours before experiments. Constrictions of rat tail arteries induced with a stable analogue of adenosine diphosphate (2-MeS-ADP), phenylephrine and arginine vasopressin were measured as an increase in perfusion pressure. Effects of ticagrelor were assessed in the presence of ticagrelor (1 μM/L) added to the perfusion solution as this drug reversibly inhibits the P2Y₁₂ receptor.

Results

Pretreatment with clopidogrel and prasugrel did not inhibit 2-MeS-ADP-induced contraction while ticagrelor did. Experiments employing endothelium-deprived arteries provided similar results. Clopidogrel and prasugrel did not influence concentration-response curves in the presence of neither phenylephrine nor arginine vasopressin. The curves obtained for both vasopressors in the presence of ticagrelor and 2-MeS-ADP were shifted to the right with a significant reduction in the maximal response.

Conclusions

Oral administration of ticagrelor, in contrast to clopidogrel and prasugrel, prevents adenosine diphosphate-induced contraction of vascular smooth muscle cells in a rat model. Both the clinical significance and detailed mechanism of our findings warrant further investigation.