Rapid exclusion of the diagnosis of immune HIT by AcuStar HIT and heparin-induced multiple electrode aggregometry

Background

Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential but remains challenging. We have previously demonstrated, in a retrospective study, the usefulness of the combination of the 4Ts score, AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) with optimized thresholds.

Objectives

We aimed at exploring prospectively the performances of our optimized diagnostic algorithm on suspected HIT patients. The secondary objective is to evaluate performances of AcuStar HIT-Ab (PF4-H) in comparison with the clinical outcome.

Methods

116 inpatients with clinically suspected immune HIT were included. Our optimized diagnostic algorithm was applied to each patient. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) of the overall diagnostic strategy as well as AcuStar HIT-Ab (at manufacturer’s thresholds and at our thresholds) were calculated using clinical diagnosis as the reference.

Results

Among 116 patients, 2 patients had clinically-diagnosed HIT. These 2 patients were positive on AcuStar HIT-Ab, AcuStar HIT-IgG and HIMEA. Using our optimized algorithm, all patients were correctly diagnosed. AcuStar HIT-Ab at our cut-off (> 9.41 U/mL) and at manufacturer’s cut-off (> 1.00 U/mL) showed both a sensitivity of 100.0% and a specificity of 99.1% and 90.4%, respectively.

Conclusion

The combination of the 4Ts score, the HemosIL® AcuStar HIT and HIMEA with optimized thresholds may be useful for the rapid and accurate exclusion of the diagnosis of immune HIT.     

Platelet microparticle generation assay: A valuable test for immune heparin-induced thrombocytopenia diagnosis

Background

Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is essential to improve clinical outcome but remains challenging. The release of platelet microparticles (PMPs) is considered of major pathophysiological significance.

Objectives

The aim of this study was to evaluate performances of PMP generation assay (PMPGA) compared to clinical outcome to diagnose HIT. The second objective was to compare PMPGA with performances of ¹⁴C-serotonin release assay (SRA) on the same series of patients.

Methods

Sera of 53 HIT-suspected patients were retrospectively incubated with citrated-whole blood from healthy donors with 1 IU and 500 IU/ml of unfractionated heparin (UH). PMPGA was performed using FACSAria® flow cytometer. The clinical diagnosis was established by two blinded independent investigators analysing in a standardized manner the patient’s medical records. Performances of PMPGA and SRA (n = 53) were evaluated using ROC curve analysis with clinical outcome as reference.

Results

In positive HIT patients, PMPs expressing phosphatidylserine are generated with low UH concentration whereas PMP rate decreases significantly in presence of high UH concentration. Using clinical outcome as reference, sensitivity and specificity of PMPGA reached 88.9% (95% CI: 50.7-99.4) and 100.0% (95% CI: 90.0-100.0). Sensitivity and specificity of ¹⁴C-SRA were 88.9% (95% CI: 50.7-99.4) and 95.5% (95% CI: 83.3-99.2).

Conclusions

PMPGA is a rapid and reliable assay for HIT diagnosis. PMPGA showed good correlation with ¹⁴C-SRA performances and predominately with clinical outcome.     

Interleukin-10 promoter microsatellite polymorphisms influence the immune response to heparin and the risk of heparin-induced thrombocytopenia

Introduction

Heparin-induced thrombocytopenia (HIT) results from an atypical immune response with synthesis of IgG antibodies (Abs) to platelet factor 4/heparin complexes (PF4/H), and probably involves both B and T cells. We investigated whether 3 single nucleotide polymorphisms (SNPs), rs1800896 (− 1082G/A), rs1800871 (− 819C/T) and rs1800872 (− 592C/A) and the polymorphic CA repeat microsatellites IL10R [5325CA(11_15)] and IL10G [8134CA(14_29)] are associated with the synthesis of Abs to PF4/heparin and HIT.

Materials and methods

Eighty-two patients with definite HIT and two control groups were studied. The first control group (Ab^neg) consisted of 85 patients without Abs to PF4/heparin after cardiopulmonary bypass (CPB). The second control group (Ab^pos) consisted of 84 patients who had developed significant levels of PF4-specific antibodies after CPB, but without HIT.

Results

Allele frequencies of the 3 SNPs were similar in HIT patients and controls. Fourteen alleles in IL10G (G16 to G29) and 3 alleles in IL10R (R13 to R15) were defined. The short G20 allele of IL10G was more frequent in Ab^neg patients (8.2%) than in Ab^pos (2.9%) and HIT patients (3%). It thereby appeared to protect against developing Abs to PF4/heparin (OR 0.29; 95% CI [0.12-0.70], p = 0.006). Combined haplotypes cH1/cH8 comprising the short G20 + R13 alleles were less frequent in HIT (OR 0.33; 95% CI [0.11-0.97], p = 0.036), and levels of Abs to PF4 in Ab^pos patients were lower in cH1/cH8 subjects (p = 0.019).

Conclusion

These results suggest that IL10 promoter microsatellite polymorphisms might influence the immune response against PF4/heparin and the risk of HIT.     

Differences in the clinical course of heparin induced thrombocytopenia before and after the availability of HIT IgG class testing

Introduction

To determine whether the HIT IgG class platelet factor 4 (PF4) enzyme immunoabsorbant assay (EIA) influenced the duration of parenteral direct thrombin inhibitor (pDTI) therapy or bleeding risk in patients started on pDTI for a presumed diagnosis of HIT.

Materials/Methods

187 patients started on pDTI for presumed HIT were assessed in two time periods before (period 1, n = 88 patients) and after the introduction of an IgG-specific assay (period 2, n = 99 patients).

Results

Patients in period 2 were treated with pDTI therapy for a median of 5 days less (p < 0.0001) however the incidence of Grade III and IV bleeding episodes was not different. Bleeding was observed to occur early during the hospital course at a median of 2-3 days after initiation of the pDTI. The average pDTI drug acquisition cost was markedly decreased in period 2 when compared to period 1 (p < 0.0001).

Conclusions

Implementation of the IgG class HIT EIA resulted in a decrease in the number of days on a pDTI and a decrease in the average pDTI acquisition cost per patient without an observed change in serious bleeding events.     

Low prevalence of heparin-induced thrombocytopenia after cardiac surgery in Thai patients

Introduction

Heparin induced-thrombocytopenia (HIT) has been well recognized in Western countries. However, there are no data in the Thai population. We therefore investigated the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies, HIT, and its thrombotic complications in Thai patients undergoing cardiac surgery using unfractionated heparin.

Materials and methods

Seventy-three consecutive patients were prospectively enrolled in this study. Blood samples before operation and week 1, week 2, and week 3 after operation were collected from each patient for HIT antibody screening by enzyme-linked immunosorbent assay using IgG antibody specific to the PF4/heparin complex. Positive samples were further analyzed by ¹⁴C-serotonin release assay. Complete blood count was performed daily during the first week, then weekly for 3 weeks.

Results

No patient had detectable anti-PF4/heparin antibodies at baseline. Five patients sero-converted during the course of the study for anti-PF4/heparin IgG: 3 (4.1%) at week 1, 4 (5.5%) at week 2, and 5 (6.8%) at week 3 after surgery. However, none of these patients had anti-PF4/heparin antibodies that resulted in ¹⁴C-serotonin release to be considered clinically significant antibodies. Post-operative thrombocytopenia after the operation was found in 35 patients (47.9%), but was not considered to be caused by HIT. Thromboembolic events occurred in 3 patients (4.1%) during follow up; however, none of these patients had positive PF4/heparin antibody tests.

Conclusions

Our study represents the first study to examine Thai patients exposed to heparin in the context of cardiac surgery. We found a lower prevalence of positive anti-PF4/heparin antibodies and clinical HIT than previously published studies.     

New insights in heparin-induced thrombocytopenia by the use of fluid-phase assays to detect specifically platelet factor 4/heparin complex antibodies and antibody-secreting cells

Introduction

The key feature of heparin-induced thrombocytopenia (HIT) is the production of antibodies (Ab) against the platelet factor 4 (PF4)/heparin complex. These Ab are directed against neoepitopes of the PF4 tetramer, which are induced by the complex formation with heparin. To study this humoral immune response in greater detail, either in a murine immunization model or in human blood samples, reliable and specific immune assays to detect specifically Ab against the PF4/heparin complexes, but not PF4 alone are required.

Materials and Methods

We established fluid-phase enzyme-immunoassays in which the soluble biotinylated antigen, PF4/heparin, is firstly captured by specific Ab, and secondly directly detected with enzyme-conjugated streptavidin.

Results

The use of this fluid-phase principle allowed a higher specificity than the traditional solid-phase enzyme-immunoassays in terms of Ab binding to murine PF4/heparin compared to murine PF4 alone. This fluid-phase approach applied to the detection of specific murine PF4/heparin Ab-secreting cells (ASC) identified the spleen as the main lymphatic organ that contributes to the PF4/heparin Ab response in mice. IgG ASC specific for PF4/heparin are very transiently detectable in mice, which might explain why anti-PF4/heparin IgG Ab typically disappear within 100 days in humans. Furthermore, this fluid-phase approach was successfully transferred to detect human PF4/heparin-specific Ab.

Conclusion

The fluid-phase principle for the specific detection of anti-PF4/heparin IgG and IgM Ab enables new and improved assays for HIT research in men and mice. At least in mice PF4/heparin antibodies are produced by transient B cells.     

Reliability and validity of a Chinese version of the HADS for screening depression and anxiety in psycho-cardiological outpatients

Aim

The Hospital Anxiety and Depression Scale (HADS) has been used widely with cardiovascular patients. This study aims to examine the reliability and validity of a Chinese version of HADS among psycho-cardiological outpatients.

Methods

One hundred psycho-cardiological outpatients were asked to complete the Chinese version of HADS and were then interviewed according to the Mini International Neuropsychiatric Interview, Version 5 (MINI).

Results

According to the MINI, 38 outpatients were diagnosed with major depression and 15 outpatients were diagnosed with an anxiety disorder. Compared with the MINI diagnoses, the optimum cutoff value of the anxiety subscale (HADS-A) was six (6) with a sensitivity of 81.6%, specificity of 75.8%, positive predictive value (PPV) of 54.0% and negative predictive value (NPV) of 91.9%; at the optimum cutoff value of nine (9), the depression subscale (HADS-D) had a sensitivity of 80.0%, specificity of 92.9%, PPV of 52.2% and NPV of 96.1%. The Cronbach's alpha coefficients of the HADS-A and HADS-D subscales were 0.753 and 0.764, respectively. The areas under the ROC curves of the HADS-A and the HADS-D subscales, as compared to MINI diagnoses of anxiety and depression, were 0.81 (SE = 0.05, 95%CI: [0.73, 0.90]) and 0.86 (SE = 0.05, 95%CI: [0.77, 0.94]), respectively.

Conclusions

The HADS was found to be a reliable measurement tool for excluding depression and anxiety in psycho-cardiological outpatients.     

Antipsychotic prophylaxis in surgical patients modestly decreases delirium incidence — but not duration — in high-incidence samples: A meta-analysis

Objective

The objective was to examine whether prophylactic treatment with antipsychotics can decrease the incidence and severity of postsurgical delirium.

Method

A meta-analysis of existing trials comparing delirium incidence between patients given prophylactic antipsychotic and placebo was performed. Secondary outcomes were total hospital days, total days of delirium and severity. Pooled odds ratios (ORs) and mean differences were calculated using a random-effects model.

Results

Five randomized placebo-controlled trials comprising a total of 1491 patients were included. In the pooled analysis, prophylactic antipsychotic administration showed a reduction in delirium incidence (OR: 0.42; 95% confidence interval (CI): 0.24, 0.74). Among the studies reporting other outcomes, patients receiving antipsychotics prophylactically showed no differences in total hospital days (0.1; 95% CI: − 0.73, 0.94), days of delirium (− 1.17; 95% CI: − 5.22, 2.88) or delirium severity (− 1.02; 95% CI: − 6.81, 4.76).

Conclusions

Prophylactic antipsychotic treatment in surgical patients modestly decreases the incidence of delirium, but not the length of hospital stay, duration of delirium or its severity. Given the modest protective effect of antipsychotics and their potential adverse reactions, there is insufficient evidence to support its universal use as a preventive agent, though potential benefit may be seen in populations at high risk of developing delirium.     

Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: A meta-analysis

Objectives

Our meta-analysis was performed to estimate the effect of continuous positive airway pressure (CPAP) therapy on systemic inflammation in patients with obstructive sleep apnea (OSA).

Methods

A comprehensive literature search of PubMed and EMBASE was performed for literature published up to January 2013. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy.

Results

A total of 35 studies involving 1985 OSA patients were included in the meta-analysis. Each study investigated one or more inflammatory markers: 24 studies on C-reactive protein (CRP), 16 studies on IL-6, 3 studies on IL-8, and 12 studies on tumor necrosis factor α (TNF-α). The results showed that the SMD (95% confidence interval [CI]) for CRP, IL-6, IL-8, and TNF-α were 0.452 (95% CI, 0.252–0.651), 0.299 (95% CI, 0.001–0.596), 0.645 (95% CI, 0.362–0.929), and 0.478 (95% CI, 0.219–0.736) in pre- and post-CPAP therapy, respectively. The subgroup analyses seemed to support better benefits with therapy duration of ?3 months and more adequate compliance (?4 h/night).

Conclusions

CPAP therapy could partially suppress systemic inflammation in OSA patients, and substantial differences were present among the various inflammatory markers.     

Depression,anxiety, and prevalent diabetes in the Chinese population: Findings from the China Kadoorie Biobank of 0.5 million people

Objective

Despite previous investigation, uncertainty remains about the nature of the associations of major depression (MD) with type 2 diabetes mellitus (T2DM), particularly in adult Chinese, and the relevance of generalized anxiety disorder (GAD) for T2DM.

Methods

Cross-sectional data from the China Kadoorie Biobank Study, a sample of approximately 500,000 adults from 10 geographically defined regions of China, were analyzed. Past year MD and GAD were assessed using the Composite International Diagnostic Inventory. T2DM was defined as either having self-reported physician diagnosis of diabetes at age 30 or later (“clinically-identified” cases) or having a non-fasting blood glucose ≥ 11.1 mmol/L or fasting blood glucose ≥ 7.0 mmol/L but no prior diagnosis of diabetes (“screen-detected” cases). Logistic regression was used to assess the relationship between MD and GAD with clinically-identified and screen-detected T2DM, adjusting for demographic characteristics and health behaviors.

Results

The prevalence of T2DM was 5.3% (3.2% clinically-identified and 2.1% screen-detected). MD was significantly associated with clinically-identified T2DM (odds ratio [OR]: 1.75, 95% confidence interval (CI): 1.47–2.08), but not with screen-detected T2DM (OR: 1.18, 95% CI: 0.92–1.51). GAD was associated with clinically-identified (OR: 2.14, 95% CI: 1.60–2.88) and modestly associated with screen-detected (OR: 1.44, 95% CI: 0.99–2.08) T2DM. The relationship between MD and GAD with T2DM was moderated by obesity.

Conclusion

MD is associated with clinically-identified, but not screen-detected T2DM. GAD is associated with both clinically-identified and screen-detected T2DM. The relationship between MD and T2DM is strongest among those who are not obese.     

Case fatality of bleeding and recurrent venous thromboembolism during,initial therapy with direct oral anticoagulants: A systematic review

Introduction

The frequency and case fatality of venous thromboembolism (VTE) and major bleeding during the initial 3 months of therapy in those treated for symptomatic VTE with either direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA) are important clinically relevant outcomes. We sought to measure it during the initial months of anticoagulation for symptomatic VTE.

Material and Methods

We searched MEDLINE, EMBASE, and CENTRAL to identify studies that enrolled patients with acute symptomatic VTE treated with DOACs or VKA and reported data on bleeding, VTE recurrence and death. Studies were evaluated according to a priori inclusion criteria and critically appraised using established internal validity criteria. Single-proportion random-effects models were used to pool estimates.

Results

Of the 2453 citations retrieved, 5 RCTs that enrolled 24,507 patients were included. The rate of major bleeding was 1.8 (95% CI: 1.3-2.5) and 3.1 (95% CI: 2.4-3.9) per 100 patient-years in DOAC and VKA arms, respectively. The rate of VTE recurrence was 3.7 (95% CI: 2.7-4.7) and 4.1 (95% CI: 3.0-5.4) per 100 patient-years of DOAC and VKA, respectively. The case fatality rate of bleeding was significantly higher in the VKA arms 10.4% (95% CI: 6.6-15.4) compared to DOACs 6.1% (95% CI: 2.7-11.7; p value for difference = 0.029) with no statistical difference between the case fatalities for recurrent VTE. The rate of death from either definite major bleeding or definite recurrent VTE was 0.27 (95% CI: 0.16-0.40) and 0.46 (95% CI: 0.32-0.63) per 100 patient-years for DOACs and VKAs respectively, resulting in a number needed to treat of 875 for DOACs to prevent one death.

Conclusion

DOACs are attractive alternatives to VKAs for initial treatment of symptomatic VTE, with lower frequency and case fatality for major bleeding. However, the incremental safety benefit of DOACs over VKAs is small, with large numbers needed to treat.     

A clinical-laboratory approach contributing to a rapid and reliable diagnosis of heparin-induced thrombocytopenia

Introduction

Heparin-induced thrombocytopenia (HIT) remains a very challenging diagnosis. The first objective of this study was to compare the performance of the ID-H/PF4 PaGIA^® with the Asserachrom^® HPIA ELISA. The main purpose was to evaluate the diagnostic utility of the combination of the H/PF4 PaGIA^® with the clinical “4T's” score as a screening strategy.

Materials and Methods

102 patients with clinical suspicion of HIT were classified into risk groups using the 4T's score. The presence of HIT antibodies was assessed by two immunoassays and confirmed by a functional flow cytometric assay.

Results

Comparison of the ID-H/PF4 PaGIA^® with the Asserachrom^® HPIA ELISA demonstrated a comparable technical performance, being an excellent screening test to rule out HIT (negative predictive value or NPV = 100%). According to the 4T's score, HIT was excluded in all low risk patients (NPV = 100%). ELISA optical density levels were significantly different between all risk groups (P-values < 0.01). In contrast, due to the low positive predictive value (22%) and weak positive likelihood ratio (2.6), a positive ID-H/PF4 PaGIA^® result did not considerably increase the probability of HIT.

Conclusion

Our study confirms the combination of the 4T's score with the ID-H/PF4 PaGIA^® as a reliable strategy to rule out HIT. Yet, confirming positive ID-H/PF4 PaGIA^® results by flow cytometry within 1-2 h after blood sampling remains necessary. This novel clinical-laboratory approach can contribute in a rapid and reliable way to the definite diagnosis of HIT.     

A pilot study of eptifibatide for treatment of acute pain episodes in sickle cell disease

Introduction

The contribution of platelet activation to the pathogenesis of sickle cell disease (SCD) remains uncertain. We evaluated the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the αIIbβ3 receptor, in SCD patients during acute painful episodes.

Materials and Methods

In this single site, double-blind, placebo-controlled trial, eligible patients with SCD admitted for acute painful episodes were randomized to receive eptifibatide or placebo at a ratio of 2:1.

Results

Thirteen patients (SS - 10, Sβ⁰ - 2, SC - 1) were randomized to receive either eptifibatide (N = 9; 6 females; median age - 25 years) or placebo (N = 4; 3 females; median age - 31 years). In the intent-to-treat analysis, there were no major bleeding episodes in either the eptifibatide or placebo arms (point estimate of difference: 0.00, 95% CI; -0.604, 0.372). There was one minor bleeding episode in the eptifibatide arm (point estimate of difference for any bleeding: 0.11, 95% CI: -0.502, 0.494). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference: 0.11, 95% CI: -0.587, 0.495). There were no differences in the median times to discharge, median times to crisis resolution or the median total opioid use.

Conclusions

In this small study, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Adequately powered studies are required to evaluate the safety and efficacy of eptifibatide in SCD. Clinicaltrials.gov Identifier: NCT00834899.     

Parámetros de marcha en una muestra de referencia de escolares sanos españoles: descripción multivariante y asimetrías entre ciclos izquierdos y derechos

Introduction

Instrumental gait analysis is an emerging technology used increasingly to evaluate motor disorders in children. Normal reference data is necessary in order to evaluate patients, but there are few reference resources for the Spanish paediatric population.

Objective

We aim to describe the values of 16 clinically relevant gait variables in healthy Spanish schoolchildren, and identify any linear associations or left-right asymmetries.

Subjects and methods

The values of 16 gait variables were determined in schoolchildren (n = 27, aged 5-13 years) using instrumental gait analysis. We analysed asymmetries for each variable (Student's t-test for dependent samples) and calculated their confidence intervals (95% of the standardised difference in right and left means [SMD]). Values and associations between variables were represented using a heat map.

Results

Our project presents normal values tables for 16 variables in the gait cycle. Significant asymmetries were detected in the mean values for minimum hip flexion (SMD: 0.25 95% CI, 0.11-0.39) and peak hip abduction in swing (SMD: −1.05 95% CI: −1.71- − 0.27). Functional associations among gait variables are present.

Conclusions

We present a reference dataset for Spanish school-aged children in which left-right asymmetries and functional associations may be observed for different variables.     

Lifetime mania is related to post-traumatic stress symptoms in high school students exposed to the 2009 L’Aquila earthquake

Background

Bipolar patients seem to be at high risk of trauma exposure and, when exposed, of PTSD. When comorbid, PTSD has shown a negative impact on the course of the bipolar illness. Conversely, a correlation between even manic symptoms and an increased risk for suicide has also been reported in PTSD patients. The aim of this study was to investigate the relationships between lifetime mood spectrum symptoms and PTSD in a sample of earthquake survivors.

Methods

A total of 475 young adults who survived the L’Aquila 2009 earthquake, 21 months earlier, were assessed by the Moods Spectrum-Self Report (MOODS-SR) and the Trauma and Loss Spectrum Self Report (TALS-SR).

Results

Significantly higher MOODS-SR and TALS-SR domain scores were found in PTSD survivors compared to those without. The mood depressive (O.R. = 1.17, 95% CI: 1.10–1.25), cognition depressive (O.R. = 1.07, 95% CI: 1.01–1.14) and energy manic (O.R. = 1.13, 95% CI: 1.02–1.25) MOODS-SR domains were significantly associated with an increased likelihood of PTSD.

Conclusions

Our data corroborate the strong relationship between mood disorder and PTSD highlighting a relationship between lifetime depressive and manic symptoms and PTSD, with a particular impact of the latter on the number of traumatic exposures and maladaptive behaviors.     

Renal failure as a risk factor for venous thromboembolism in critically Ill patients: A cohort study

Rationale

The relationship between kidney function and venous thromboembolism (VTE) in critically ill patients is not well studied. The main objective of this study was to evaluate this relationship in patients admitted to a medical-surgical intensive care unit (ICU).

Methods

This was a retrospective study of 798 patients admitted to a tertiary-care ICU and prospectively followed for the development of clinically suspected and radiologically diagnosed deep venous thrombosis or pulmonary embolism. Patients were divided based on admission creatinine and dialysis history into five groups: normal kidney function, RIFLE classes R, I and F (combined = acute kidney injury [AKI]) and endstage renal disease (ESRD). We compared VTE prophylaxis practices and VTE incidence in these groups and evaluated renal failure as a VTE risk factor using multivariate Cox regression analysis.

Results

Of the 798 patients, 27.2% had AKI and 10.1% had ESRD. Unfractionated heparin use was similar in the five groups but enoxaparin use was less frequent in AKI (13.4%) and ESRD (3.8%) patients compared with patients with normal kidney function (39.0%). VTE occurred in 7.6% of patients with normal renal function, 7.8% AKI patients and 2.5% ESRD patients (p = 0.22). The adjusted hazard ratios for VTE compared to patients with normal kidney function were 0.35 (95% confidence interval [CI], 0.08-1.47) for RIFLE class R, 1.19 (95% CI, 0.83-1.70) for RIFLE class I, 0.82 (95% CI, 0.59-1.14) for RIFLE class F and 0.71 (95% CI, 0.49-1.02, p = 0.06) for ESRD.

Conclusions

Neither AKI nor ESRD was an independent risk factors for critically ill patients.     

Physiological changes in membrane-expressed platelet factor 4: Implications in heparin-induced thrombocytopenia

Background

Many heparin-induced thrombocytopenia (HIT) antibodies cause platelet activation in the serotonin release assay (SRA) in the absence of heparin. This in vitro observation may help unravel the mechanism of delayed-onset HIT, where seropositive patients develop thrombocytopenia and associated thrombosis after cessation of heparin.

Objective

Studies were conducted to examine the relationship between platelet environment, surface PF4 expression, and the extent of heparin-independent platelet activation in the SRA.

Methods

Ex vivo platelets were washed and labeled for SRA, then used either before or after 45 minutes of recovery at 37 °C. HIT antibody-mediated serotonin release in the absence of heparin was compared to the extent of surface staining of the platelets with fluorescent anti-human PF4 antibodies.

Results

Handling of platelets for in vitro studies resulted in transient expression of surface PF4, and it was during this interval that platelets were most sensitive to activation by HIT antibodies in the absence of heparin. Heparin-independent platelet activation was attenuated when SRA-positive specimens were retested after platelets were incubated 45 minutes at 37 °C. Surface PF4 expression was diminished on the rested platelets, compared to the same platelets labeled immediately after handling. Thus compared to rested platelets, mildly activated platelets had elevated surface PF4 expression and a higher level of HIT antibody-mediated, heparin-independent platelet activation.

Conclusion

Surface expression of PF4 reflects HIT antigen presentation, and varies with the physiological state of platelets. Thus there can be differences in HIT antibody target availability among patients which may explain the variability in consequences of HIT antibody seropositivity.     

Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Background

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE.

Materials and Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated.

Results

A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I²: 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I²: 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I²: 0%) and 0.29% (95% CI: 0.06 to 0.68%; I²: 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I²: 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management.

Conclusions

Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.     

Symptomatic thromboembolic events in patients treated with intravenous-immunoglobulins: Results from a retrospective cohort study

Aims

To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events (TEE) from intravenous immunoglobulin (IVIg) therapy according to its indications.

Methods

We performed a retrospective cohort study of patients seen at our institution and treated with IVIg over a 36-month period. Indications, comorbility and comedication associated with TEE were identified by a stepwise logistic regression analysis.

Results

Of 303 patients included with at least one infusion of IVIg over three years, TEE were identified in a total of 50 patients treated with IVIg, for an incidence of 16.9% (CI 95%: 13.0–21.6); 27 (54%) arterial (9.1%;CI 95%: 6.3–13.0%) and 23 (46%) venous TEE (7.8%; CI95%: 5.2–11.4%), overall mortality was 32%. Per indication there were more patients with autoimmune conditions, secondary immunodeficiency, dysimmune neuropathies, acute rejection of solid organ transplantation and sepsis. Patients with TEE were significantly older, were more likely to be men, they had more comorbid conditions; the doses of IVIg were high (589.4 mg/kg/day vs 387.0 mg/kg/day, p < 0.001) and differences in comedication were found. The stepwise logistic regression analysis retained high doses of IVIg (OR 3.03; CI 95%: 1.49–5.67) and diuretics therapy (OR 1.69; CI 95%: 1.06–3.97) when combined with the usual comorbid confounders.

Conclusions

The incidence of TEE from IVIg therapy remains high at one in six patients treated. The most remediable factor is a high daily IVIg load. Decreasing the daily IVIg dose together with carefully weighing diuretics therapy and comorbid risk factors may be the keys to saving lives.     

Correlates of depressive symptoms among at-risk youth presenting to the emergency department

Objective

The study's objective was to identify correlates of depressive symptoms among at-risk youth in an urban emergency department (ED).

Method

A systematic sample of adolescents (ages 14–18) in the ED were recruited as part of a larger study. Participants reporting past-year alcohol use and peer aggression self-administered a survey assessing: demographics, depressive symptoms and risk/protective factors. Logistic regression identified factors associated with depressive symptoms.

Results

Among 624 adolescents (88% response rate) meeting eligibility criteria, 22.8% (n=142) screened positive for depressive symptoms. In logistic regression, depressive symptoms were positively associated with female gender [odds ratio (OR): 2.84, 95% confidence interval (CI): 1.78–4.51], poor academic performance (OR: 1.57, 95% CI: 1.01–2.44), binge drinking (OR: 1.88, 95% CI: 1.21–2.91), community violence exposure (OR: 2.25, 95% CI: 1.59–3.18) and dating violence (OR: 2.14, 95% CI: 1.36–3.38) and were negatively associated with same-sex mentorship (OR: 0.52, 95% CI: 0.29–0.91) and older age (OR: 0.55, 95% CI 0.34–0.89). Including gender interaction terms did not significantly change findings.

Conclusions

Screening and intervention approaches for youth in the urban ED should address the co-occurrence of depressive symptoms with peer and dating violence, alcohol and nonmarijuana illicit drug use.