Cost of acute ischemic and hemorrhagic stroke in Turkey

Objective

The aim of this study is to examine the direct medical costs and outcomes of patients with stroke.

Material and methods

The records of the patients admitted with ischemic and hemorrhagic stroke to the University of Trakya, School of Medicine, Department of Neurology were reviewed retrospectively in year 2007. Direct medical costs (total costs, radiological, laboratory, medicine, and other) were calculated, additionally cost per life saved and per life-year saved were calculated for stroke patients.

Results

The study group consisted of 328 patients (169 male/159 female) and mean age was 66.5 ± 12.4 years. Length of hospital stay was 10.7 ± 7.5 days. Mortality rate was 20.4% and the mRS score of the patients was 3.2 ± 2.1. The average cost of stroke was US$ 1677 ± 2964 (29.9% medicine, 19.9% laboratory, 12.8% neuroimaging, and 38% beds and staff). Cost per life saved and per life-year saved were US$ 2108 and US$ 1070, respectively.

Conclusion

This is the first study in order to determine direct medical cost of stroke in Turkey, therefore, it may be guideline for disease-cost management of stroke.     

Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression

Background

Ketamine rapidly improves depressive symptoms in patients with treatment-resistant major depressive disorder (MDD) who do not respond to multiple standard antidepressants. However, it remains unknown whether ketamine is equally effective in patients with MDD who previously also did not respond to electroconvulsive therapy (ECT).

Methods

This study compared 17 patients with treatment-resistant MDD who previously did not respond to ECT and 23 patients with treatment-resistant MDD who had not previously received ECT. All subjects received a single open-label infusion of ketamine (0.5 mg/kg). Patients were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline (60 min before the infusion), as well as at 40, 80, 120, and 230 min after infusion.

Results

Depressive symptoms were significantly improved in the ECT-resistant group at 230 minutes with a moderate effect size (p < .001, d = 0.50, 95% C.I.: 0.21-0.80). At 230 minutes, the non-ECT exposed group showed significant improvement with a large effect size (p < .001, d = 1.00, 95% C.I.: 0.71-1.29).

Conclusion

Ketamine appears to improve depressive symptoms in patients with MDD who had previously not responded to ECT. These preliminary results encourage further investigation with a larger sample size to determine effectiveness compared to other treatment-resistant patients with MDD.     

Age, sex and first treatment of schizophrenia in a population cohort

Objective

Schizophrenia affects men more than women, but this may not be true at all ages. This study examines the incidence of first hospitalization for treatment of schizophrenia in each sex over different ages.

Methods

We compared the incidence of first admission for treatment in a cohort of 46,388 males and 43,680 females followed from birth until ages 29-41, using life tables and proportional hazards methods.

Results

Life table estimates of cumulative incidence by age 40 were 1.44% in males and 0.86% in females. For over all ages the relative risk (RR) in males was 1.6 (95% confidence limits = 1.4-1.8) compared with females. Before age 17 there was no significant difference between the sexes (RR = 0.86, 0.56-1.3). Excess risk in males was observed only from age 17 (RR = 1.7, 1.4-1.9). There was no evidence of the incidence in females catching up with that in males, during the 30s.

Conclusion

In this population, there was a significant change, over age, in the relative incidence of first hospitalization for schizophrenia between the sexes; the excess incidence in males first developed at age 17.     

MTHFR and the risk for cerebral venous thrombosis- a meta-analysis

Background

The association between methylenotetrahydrofolate reductase (MTHFR) 677TT and the increased risk of venous thrombosis is uncertain. Studies of this polymorphism in cerebral venous thrombosis (CVT) are inconclusive.

Objectives

With a systematic review, we aimed to collect all case-control studies comparing the frequency of this polymorphism in CVT patients (cases) and healthy controls.

Methods

We used the MEDLINE, Cochrane Library and the ISI web of knowledge electronic databases and reference lists of retrieved articles in order to identify published case-control studies that evaluated the presence of MTHFR 677C>T polymorphism in CVT. Two reviewers independently selected studies. We compared the frequency of 677TT between cases and controls using the Mantel-Haenszel method, a fixed and a random-effects model in the pooled data.

Results

Nine case-control studies were included. The pooled analysis included 382 patients with CVT and 1217 controls. The frequency of 677TT genotype among CVT patients was not significantly higher compared with controls (15.7% versus 14.6%; OR = 1.12, 95% confidence interval (95% CI) 0.80 to 1.58; p = 0.50). There was significant heterogeneity between studies.

Conclusions

This meta-analysis confirmed that there is currently insufficient data supporting that 677TT genotype is a risk factor for CVT. These results imply a continuing searching for the cause of CVT in patients with this polymorphism.     

Comparison of the clinical usefulness of two quantitative D-Dimer tests in patients with a low clinical probability of pulmonary embolism

Background

Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study.

Objective

Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE.

Patients and Methods

We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed.

Results

The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96- > 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-> 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p < 0.001).

Conclusion

Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.     

Modafinil reduces microsleep during partial sleep deprivation in depressed patients

Objective

Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24 h. Following the recovery night, however, a relapse into depression occurs in most patients. Recovery sleep, naps and even very short episodes of sleep (microsleep; MS) during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and stabilizes the treatment response to PSD compared to placebo.

Methods

A total of 28 patients (13 men, 15 women; age 45.1 ± 12.1 years) with a major depressive episode and a cumulative daytime microsleep of five or more minutes were investigated using a double-blind placebo-controlled study design. All patients were treated with a stable mirtazapine monotherapy. A partial SD (PSD) was performed after one week. Additional morning treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep-EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale before, during and after PSD and at follow-ups after one and two weeks.

Results

Patients treated with modafinil showed significantly reduced microsleep during PSD (11.63 ± 15.99 min) compared to the placebo group (47.77 ± 65.31 min). This suppression of MS was not associated with the antidepressive effect of PSD.

Conclusions

Compared to placebo, modafinil was efficient in reducing daytime microsleep following partial sleep deprivation but did not enhance the antidepressive effects of PSD and did not stabilize antidepressive effects over two weeks.     

Cellular origin of platelet-derived microparticles in vivo

Introduction

Microparticles (MP), presumably of platelet origin, are the most abundant microparticles in blood. To which extent such MP may also directly originate from megakaryocytes, however, is unknown. During hematopoietic stem cell transplantation, patients undergo total body irradiation which leads to an irreversible destruction of hematopoiesis.

Material and Methods

We studied the levels of “platelet-derived” MP (PMP) in 13 patients before and after total body irradiation with 12 Gy (4 Gy for 3 days, dose rate 4.5 cGy/min). PMP were isolated and double-stained with annexin V and anti-CD61. In 6 patients, we additionally analyzed MP exposing P-selectin or CD63.

Results

PMP rapidly declined upon total body irradiation, which was 2.4-fold faster than platelet disappearance. In contrast, the kinetics of MP exposing P-selectin or CD63 was comparable to platelets.

Conclusions

Since CD61-positive MP disappear faster than platelets or MP exposing P-selectin or CD63, our data indicate that MP exposing P-selectin or CD63 are likely to originate from platelets, whereas at least a major fraction of CD61-exposing MP is likely to originate from megakaryocytes in vivo.     

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.     

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.     

Accuracy of a portable international normalized ratio monitor for patients receiving a low molecular weight heparin as a bridge pending full oral anticoagulant efficacy

Background

Point of care (POC) devices measuring the international normalized ratio (INR) are accurate for patients with stable disease, but their efficiency has not been prospectively assessed during the “bridging period” when patients are receiving a low molecular weight heparin (LMWH) on top of a vitamin K antagonist (VKA) until the target INR is reached.

Methods

188 dual INR measurement using the POC (INR_POC) and the laboratory (INR_lab) at the same time were consecutively determined : 69 in patients receiving LMWH + VKA (bridging group) and 119 in patients receiving only a VKA (control group). INRpoc was compared to INR_lab.

Results

Test strip failure rate was higher in the bridging group than in the control group (29% vs 4% ; p < 0,001).In successful tests, POC accuracy was not modified by LMWH administration: the correlation coefficients between POC and lab INR values for the bridging group and the control group were 0,81 and 0,87 respectively, and the relative measure of divergence (RMD = INR_lab - INR_poc / INR_lab) was lower in the bridging group than in the control group (4 ± 7% vs 10 ± 14%; p = 0,02). Finally, clinically relevant agreement between POC and laboratory was of 90% in the bridging group and 92.1% in the control group (p = 0.6).

Conclusion

With the POC used (INRatio), in patients receiving LMWH when the POC gives a result, it is as accurate as in patients not receiving a LMWH.     

Transsphenoidal microsurgical results of female patients with prolactinomas

Objective

We investigated surgical cure rate and surgical complications of patients with macroprolactinomas who desired pregnancy to evaluate the efficacy of transsphenoidal surgery.

Methods

Surgical cure rate was investigated in 138 female patients who were under 40 years old.

Results

We found a significant correlation between serum prolactin levels and adenoma volume (r = 0.004; p < 0.0001), adenoma volume and age (r = −0.213; p < 0.03), and proliferative index of the adenoma and age (r = −0.15; p < 0.007). Seventy-seven out of 81 patients with enclosed macroadenoma were considered cured, and therefore the overall surgical cure rate was 95%. However, during long-term follow-up, recurrence of adenomas with hyperprolactinemia was seen in 5 out of 81 patients (6%), and the long-term cure rate in patients with enclosed macroadenomas was 89%. Adenomas that did not invade the cavernous sinus showed a significantly higher surgical curability and lower serum prolactin levels, and a smaller size than those adenomas that invaded the cavernous sinus.

Conclusions

The long-term surgical cure rate was found to be 89% and this success rate far surpasses the complication rate of 39% during pregnancy by dopamine agonist therapy. Thus, transsphenoidal surgery should be considered as a first-line treatment for female patients who desire pregnancy.     

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.     

Statin use in patients with nephrotic syndrome is associated with a lower risk of venous thromboembolism

Background

Nephrotic syndrome (NS) is a well-known risk factor for venous thromboembolism (VTE), however preventive measures are not routinely taken. In non-renal populations, statins are associated with lower risk of VTE. Hence, we set up this single-center retrospective cohort study to assess whether statin use influenced VTE risk in NS subjects.

Methods

We analyzed 289 consecutive patients with NS (defined by proteinuria ≥ 3.5 g/day) who were aged > 18 years at the study entry and followed for at least 6 months. Use of statins and concomitant medication were determined.

Results

Of patients with NS (59% men; mean age, 42 years), 48% used statins for at least 1 month during NS. Using univariate and time-dependent Cox regression analyses, hazard ratio for VTE in statin users versus non-users was 0.2 (95%CI, 0.1-0.7) and 0.6 (95% CI, 0.2 -2.0), respectively. Adjustments for potential confounders did not change outcomes. Three VTE events occurred in a total of 812 statin-years, corresponding to an annual incidence of 0.37% (95%CI, 0.12-1.15). In contrast, 17 VTE occurred in a total of 2106 patient-years without statin exposure, annual incidence 0.81% (95%CI, 0.50-1.30).

Conclusions

Although statistically significant, the hazard ratio of 0.2 for VTE risk in statin users versus non-users could have been biased, but the time-dependent hazard ratio of 0.6 was probably not. As the association was in the same direction for both analyses, we conclude that statin use is associated with a lower risk of VTE in patients with NS.     

Lack of association between a functional genetic variant of connexin 37 and ischemic stroke in a Taiwanese population

Introduction

Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result.

Materials and Methods

A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes.

Results

We did not find any significant association for overall stroke (p = 0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association.

Conclusions

GJA4 polymorphism is not associated with stroke risk in the Taiwanese population.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.     

A confirmatory factor analysis of the Beck Depression Inventory-II in end-stage renal disease patients

Objective

We sought to examine several competing factor structures of the Beck Depression Inventory-II (BDI) in a sample of patients with End-Stage Renal Disease (ESRD), in which setting the factor structure is poorly defined, though depression symptoms are common. In addition, demographic and clinical correlates of the identified factors were examined.

Methods

The BDI was administered to clinical sample of 460 ESRD patients attending 4 UK renal centres. Competing models of the factor structure of the BDI were evaluated using confirmatory factor analysis.

Results

The best fitting model consisted of general depression factor that accounted for 81% of the common variance between all items along with orthogonal cognitive and somatic factors (G-S-C model, CFI = .983, TLI = .979, RMSEA = .037), which explained 8% and 9% of the common variance, respectively. Age, diabetes, and ethnicity were significantly related to the cognitive factor, whereas albumin, dialysis adequacy, and ethnicity were related to the somatic factor. No demographic or clinical variable was associated with the general factor.

Conclusion

The general-factor model provides the best fitting and conceptually most acceptable interpretation of the BDI. Furthermore, the cognitive and somatic factors appear to be related to specific demographic and clinical factors.     

Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized acute medical patients in China - the RAMP study

Background

In developed countries, hospitalized patients with acute medical conditions are at significant risk for venous thromboembolism (VTE). Little is known about VTE risk and prophylaxis practices in China.

Objective

To determine the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized Chinese patients with acute medical conditions.

Methods

Multi-center, cross-sectional, observational study. Eligibility criteria: ≥ 30 years, admitted to an intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had ≥ 1 VTE risk factor/1 disease that predisposes to VTE, and provided informed consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines to assess VTE risk and the frequency of recommended VTE prophylaxis.

Results

1247 patients from 19 hospitals in 11 cities across 11 provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had > 2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU patients: 22.7%, ICU patients: 16.9%, p = 0.0117).

Limitations

Excluding some patients with VTE risk factors did not allow assessment of the prevalence of VTE risk in the acute hospital-care setting. We could not determine whether the duration of prophylaxis complied with the ACCP recommendations. Our results may not be representative of hospitals in small cities/rural areas in China.

Conclusions

The prevalence of VTE risk factors in Chinese patients was similar to that in developed countries; however, only a small proportion of eligible patients received the recommended VTE prophylaxis. Our findings highlight the need for dissemination and implementation of appropriate VTE prophylaxis guidelines in China.     

Behavioral and psychological symptoms of dementia in a pilot psychogeriatric unit: management and outcomes

Background

Behavioral and psychological symptoms in dementia (BPSD) are a major concern. The French government gave a consensual definition of reinforced intermediate-term care units for BPSD within the project “Plan Alzheimer 2008/2012”.

Objective

Our aim was to report one of the first experiences of this unit in France.

Results

Fifty-two patients (38 females, 14 males) were included, mean age 82.07 ± 7.84 (73-97). About 80% of patients were improved and there was a high discharge rate to home of about 30%. Night-time behaviors, aberrant motor behaviors and agitation were the most frequent symptoms.

Conclusion

Our study confirms that demented elderly patients greatly benefit from a specific BPSD care unit in agreement with the objective of Plan Alzheimer 2008/2012.     

Platelet protease-activated receptor 1 and membrane expression of P-selectin in pulmonary arterial hypertension

Introduction

Pulmonary arterial hypertension (PAH) is frequently associated with thrombotic events, particularly involving the pulmonary microcirculation at sites of vascular injury. We therefore decided to analyse protease-activated receptor 1 (PAR1), a key element in the activation of human platelets by thrombin, in PAH patients in stable clinical condition.

Methods

Using flow cytometry, we analyzed platelet PAR1 density, PAR1-mediated exposure of P-selectin and the formation of platelet-leukocyte aggregates in 30 PAH patients aged 11 to 78 years (median 50.5 years). The control group consisted of 25 healthy subjects with the same age range as patients.

Results

In patients, total platelet PAR1 density and uncleaved PAR1 density correlated negatively with platelet count (r² = 0.33 and r² = 0.34 respectively, p < 0.0015). In patients with a low platelet count (< 150 × 10⁹ platelets/L), both densities were increased relative to controls (82% and 33% respectively, p < 0.05). Thrombin peptide-induced platelet exposure of P-selectin was directly related to total and uncleaved PAR1 density (respectively, r² = 0.33 and r² = 0.29, p < 0.0025) and increased in subjects with low platelet count (46% versus those with normal platelet count, p < 0.05). Patients with low platelet count had decreased in vitro thrombin-induced formation of platelet-leukocyte aggregates (57% decrease versus controls, p < 0.05).

Conclusions

There seems to be a subpopulation of PAH patients with increased propensity to thrombotic events as suggested by increased platelet PAR1 expression and PAR-mediated surface exposure of P-selectin associated with decreased platelet count.