Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: A retrospective study

Background

Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods.

Objectives

We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis.

Methods

Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n = 81). The clinical diagnosis was established by analysing in a standardized manner the patient’s medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference.

Results

Using the recommended thresholds (1.00 AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89 AU, HIT-Ab: 9.41 AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed.

Conclusion

Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV.     

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.     

Rate and clinical impact of intra-procedural complications during coil embolisation of ruptured small (3 mm or less) cerebral aneurysms

Objective

Coiling of small (≤3 mm) cerebral aneurysms can be technically challenging and is associated with increased procedural-related morbidity and mortality. The authors report the clinical and radiological results following coiling of ruptured small cerebral aneurysms in a single-institution, and define the rates of intra-procedural rupture and thromboembolism.

Methods

A retrospective analysis was conducted on consecutive patients from 01/01/2008 to 31/12/2010 with subarachnoid haemorrhage (SAH) from ruptured cerebral aneurysms (≤3 mm) managed in a tertiary neurosurgical institution in the United Kingdom.

Results

Of the 108 patients identified, 72 patients (66.7%) underwent coil embolisation. A favourable outcome, defined as a Glasgow outcome score of 4–5, was achieved in 63 (87.5%) of these patients. Intra-procedural complications were observed in 11.1% (±7.3% 95% CI) of cases, wherein the rate of intra-procedural rupture was determined to be 8.3% (±6.4% 95% CI) and intra-procedural thromboembolism to be 2.8% (±3.8% 95% CI).

Conclusion

Although coil embolisation of small ruptured cerebral aneurysms is technically feasible and an efficacious means of treatment, it is associated with an increased rate of intra-procedural complications. This should be taken into account when embarking upon treatment of patients with ruptured small cerebral aneurysms.     

Prognostic implications of computed tomographic right ventricular dilation in patients with acute pulmonary embolism

Introduction

Whether right ventricular (RV) dilation on computerized tomography (RVD-CT) is a useful predictor for clinical outcomes of acute pulmonary embolism (PE) remains debatable. Furthermore, data regarding the best combination of prognostic markers for predicting the adverse outcome of PE are limited.

Materials and Methods

The authors retrospectively reviewed 657 consecutive patients hospitalized at a tertiary referral center with a diagnosis of PE based on multi-detector row CT scan.

Results

Patients were allocated into an adverse outcome group (11% [n = 69]) or a low risk group (89% [n = 588]). Multivariate analysis showed that RVD-CT (RV/left ventricle [LV] diameter ratio ≥ 1), high pulmonary embolism severity index (PESI) score (class IV-V), high N-terminal-pro-B-type natriuretic peptide (NT-proBNP,≥1,136 pg/ml), and elevated troponin I (≥ 0.05 ng/ml) significantly predicted an adverse outcome (odds ratio [OR] 6.26, 95% confidence interval [CI] 2.74-14.31, p < 0.001; OR 4.71, 95% CI 2.00-11.07, p < 0.001; OR 2.71, 95% CI 1.15-6.39, p = 0.023; and OR 3.00, 95% CI 1.27-7.07, p = 0.012, respectively). The addition of RVD-CT to PESI, NT-proBNP, troponin I or their combinations enhanced the positive predictive values and positive likelihood ratios of an adverse outcome.

Conclusions

RVD-CT could be an independent prognostic factor of adverse outcomes in patients with acute PE, and provides additional prognostic value when combined with other prognostic factors.     

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.     

Higher mean platelet volume determined shortly after the symptom onset in acute ischemic stroke patients is associated with a larger infarct volume on CT brain scans and with worse clinical outcome

Objective

Mean platelet volume (MPV) determined shortly after the onset of acute ischemic stroke represents the pre-stroke values. Data on its relationship to stroke severity/outcome have been conflicting. We related MPV to infarct volume on CT brain scans and risk of death/dependence 7 days and 3 months post-stroke.

Methods

MPV (within 30 h since stroke onset), infarct volume (13–83 h since stroke onset) and clinical outcomes were evaluated in 81 consecutive patients (32 men, age 52–91 years, 10 small artery occlusion, 10 large artery atherosclerosis, 29 cardioembolic, 32 multiple probable/possible etiology).

Results

Higher MPV was independently associated with larger ln-infarct volume [estimate 0.259, 95% confidence interval (CI) 0.004–0.513, P = 0.046], greater risk of death/dependence 7 days post-stroke [relative risk (RR) = 1.077, 95% CI 1.005–1.115, P = 0.036], and greater risk of death/dependence 3 months post-stroke (RR = 1.077, 95% CI 1.001–1.158, P = 0.048). Considered covariates: stroke etiology, CT scan timing, platelet count and other hematological parameters, demographic variables, history of cerebrovascular, cardiac or cardiovascular diseases, diabetes, serum chemistry, previous antiplatelet and statin use and treatments delivered after the index event.

Conclusions

Data support the view about MPV as a determinant of severity/outcome of the acute ischemic stroke.     

The role of temperament and character in the outcome of depressive mood in eating disorders

Objectives

The aims were to see which temperament and character dimensions were associated with depression, mainly with its outcome at two-year follow up in eating disorders (EDs).

Methods

Participants (N = 151) were 44 Anorexia nervosa (AN), 55 Bulimia nervosa (BN) and 52 Eating disorders not otherwise specified (EDNOS) patients. The Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI), Rosenberg Self Esteem Questionnaire (RSE), Eating Disorder Inventory (EDI-2) and Temperament and Character Inventory (TCI) were administered.

Results

Depression at the beginning (t0) was severe in 22% of the cases. Harm Avoidance and Novelty Seeking had an effect on depressed mood at t0, mediated by Ineffectiveness. Responsibility (SD1) was associated with scores on the BDI at two-year follow up (β = −0.37, 95% CI −2.6, −0.6, p < 0.01).

Conclusion

The evaluation of personality dimension in EDs has therapeutic and prognostic implications: To enhance self-efficacy and self-directness is crucial for good clinical outcome.     

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.     

Impact of CYP2C19 polymorphism on clinical outcome following coronary stenting is more important in non-diabetic than diabetic patients

Objective

The aim of this study was to examine the impact of CYP2C19 genotype on clinical outcome in coronary artery disease (CAD) patients with or without diabetes mellitus (DM).

Methods

CYP2C19 polymorphism and DM are associated with increased risk of cardiovascular events during antiplatelet therapy following stent implantation. Platelet reactivity during clopidogrel therapy and CYP2C19 polymorphism were measured in 519 CAD patients (males 70%, age 69 years) treated with stent placement. Patients were divided into two groups; DM (n = 249), and non-DM (n = 270), and clinical events were evaluated according to the carrier state, which included at least one CYP2C19 loss-of-function allele.

Results

The level of platelet reactivity and incidence of cardiovascular events were significantly different between Carriers and non-Carriers of the non-DM (platelet reactivity: 4501 +/− 1668 versus 3691 +/− 1714AUmin, P < 0.01; events, 32/178 versus 2/92, P < 0.01, respectively), however, there was no difference in clinical outcome in the DM group (events, 34/168 versus 14/81, respectively, P = 0.57). Multivariate analysis identified CYP2C19 loss-of-function allele carriage as an independent predictor of cardiovascular events in non-DM, but not in DM (non-DM, HR 7.180, 95% CI, 1.701 to 30.298, P = 0.007; DM, HR 1.374, 95% CI, 0.394 to 4.792, P = 0.618).

Conclusion

The impact of CYP2C19 polymorphism on clinical outcome seems to be more significant in non-DM compared with DM in patients with coronary stents.     

HLA class II alleles and multiple sclerosis in Tunisian patients

Objective

The aim of our study was to investigate the association of HLA-DRB1 and -DQB1 alleles with multiple sclerosis (MS) in a Tunisian population and their effect on age at onset and disease severity.

Methods

58 MS patients and 105 healthy controls were genotyped for HLA class II alleles by PCR-SSP technique.

Results

An association of MS with HLA-DRB1*15 was found (14.7% vs 3.8%, OR (95% CI) = 4.34 (1.69–11.39), p_c = 2.5 × 10⁻³) after Bonferroni's correction. Moreover, the DRB1*15–DQB1*06 (13.8% vs 2.8%, OR (95% CI) = 5.44 (1.92–17.41), p_c = 1.1 × 10⁻³) and DRB1*04–DQB1*04 (8.6% vs 1.9%, OR (95% CI) = 4.86 (1.36–21.62), p_c = 0.028) haplotypes were found to confer a susceptibility to multiple sclerosis.

Conclusion

To our knowledge, this is the first study performed to analyze the association of HLA-DRB1/DQB1 alleles on MS susceptibility in Tunisia. The modern Tunisian gene pool shows some degree of heterogeneity and reflects a significant gene flow from Mediterranean regions.     

Significance of triphasic waves in patients with acute encephalopathy: A nine-year cohort study

Objective

Triphasic waves (TWs) are a frequent electroencephalography (EEG) finding in encephalopathy, yet their origin and prognostic significance are not well understood. The aim of this study was to determine the clinical and EEG characteristics in encephalopathic patients with TWs. We hypothesized that specific EEG characteristics are predictive of outcome.

Methods

Consecutive adult encephalopathic patients with TWs on EEG and neuroimaging were included. EEG analysis included semiquantitative evaluation of TWs, background activity, and EEG reactivity. The study endpoint was death.

Results

Over a nine-year period, 105 patients with TWs were included. Common abnormalities on neuroimaging were white matter lesions (60%) and cerebral atrophy (59%). Pathologic conditions included infections (56%), renal (50%) and liver insufficiency (12%), and respiratory failure (20%). Mortality was 20%. Absent EEG background reactivity and respiratory failure were independently associated with death (OR 3.73, 95%CI 1.08–12.80, p = 0.037 and OR 6.47, 95%CI 1.98–21.12, p = 0.02).

Conclusions

These results suggest that TWs are a marker of structural brain disease coupled with toxic-metabolic perturbations, and that etiologies or underlying pathologies were not predictive for outcome while non-reactive EEG was independently associated with death.

Significance

In contrast to clinical, EEG and neuroimaging findings, non-reactive EEG patterns predicted death in encephalopathic patients with TWs.     

Red Blood Cell Distribution Width (RDW) and long-term survival in patients with ST Elevation Myocardial Infarction

Introduction

High RDW values are associated with adverse prognosis in many clinical conditions including short and medium term outcome of patients with ST Elevation Myocardial Infarction (STEMI). The aim of the present study was to evaluate the association between RDW and long term mortality in STEMI patients undergoing primary angioplasty (PPCI).

Material and methods

A cohort of 535 STEMI patients undergoing PPCI were divided into two groups (RDW > 14%, RDW ≤ 14%) using CHAID and CART methods. The association between RDW and 5-year all-cause mortality was assessed using Cox’s proportional hazards analysis.

Results

A total of 37 patients died during follow up of 5 years (mean: 1059, median: 1013, range 2–2130 days). RDW > 14% was associated with increased risk of all-cause mortality (HR = 5, CI 95% 2.7– 9.9, p < 0.001). In multivariate analysis, RDW > 14 remained significantly associated with increased risk for all-cause mortality (HR = 3.8, CI 95% 1.8– 7.99, p < 0.001). Patients with RDW above 14% did not have lower ejection fraction, higher CPK or more conventional risk factors.

Conclusion

RDW value above 14 is independently associated with increased long term all-cause mortality in patients with STEMI undergoing PPCI.     

Two years outcome of isolated distal deep vein thrombosis

Background

Isolated distal deep vein thrombosis (IDDVT) is frequently found in symptomatic outpatients, but its long term outcome is still uncertain.

Aims

To assess IDDVT long term outcome and the impact of IDDVT characteristics on outcome.

Methods

In a prospective, single center study we enrolled symptomatic outpatients in whom IDDVT was detected by whole-leg compression ultrasonography. Patients with provoked IDDVT were treated with low molecular weight heparins (LMWH) for 30 days while those with unprovoked IDDVT received with vitamin K antagonists (VKA) for three months. The primary end-point was the rate of the composite of pulmonary embolism (PE), proximal deep vein thrombosis (DVT), and IDDVT recurrence/extension during 24 month follow-up.

Results

90 patients (age 61 ± 18, male 48.9%) were enrolled. Risk factors for thrombosis were reduced mobility (34.4%), obesity (25.3%), surgery (15.6%), and previous DVT (15.6%) and cancer in 8 patients (8.9%). Eighty-eight patients were treated (56 with LMWH and 32 with VKA). During follow-up (median 24 ± 2 months), 17 events were recorded, which included 3 PE (two in cancer patients), 4 proximal DVTs (one in cancer patient) and 10 IDDVT. Male sex (HR 4.73 CI95%: 1.55-14.5; p = 0.006) and cancer (HR 5.47 CI95%: 1.76-17.6; p = 0.003) were associated with a higher risk of complications, whereas IDDVT anatomical characteristics, anticoagulant therapy type, and provoked IDDVT were not.

Conclusions

The risk of recurrent venous thromboembolism after IDDVT may be relevant in male patients or in patients with active cancer. Larger studies are needed to address this issue.     

Intravenous rt-PA in patients with ischaemic stroke and renal dysfunction

Objective

Renal dysfunction (RD) increases risk for ischaemic stroke (IS). The impact of RD on the effects of iv-thrombolysis in the Caucasian population has not been fully determined.

Aims

To evaluate the associations between RD and the outcome of iv-thrombolysis in Caucasian patients with IS.

Methods

The observational, multicentre study included 404 patients with IS who were treated with iv-thrombolysis. RD was defined as estimated glomerular filtration rate ≤60 ml/min/1.73 m². Outcome was assessed with modified Rankin Score at 3 months after the stroke onset.

Results

Medians baseline NIHSS score did not differ between groups of patients with and without RD (12.0 vs. 11.0 pts, p = 0.33). Unfavourable outcome was found in 52.1% of patients with and in 41.2% of patients without RD (p = 0.05), mortality was higher in patients with RD (29.9% vs. 14.3%, p < 0.001), and the presence of haemorrhagic transformation (HT) did not differ between the groups (17.1% vs. 17.1% respectively, p = 0.996). A multivariate analysis showed no impact of RD on the unfavourable outcome (OR 0.98; 95%CI 0.88–1.10), mortality (OR 0.92; 95%CI 0.81–1.05) or presence of HT (OR 1.03; 95%CI 0.90–1.18).

Conclusions

We found no impact of RD on the safety and efficacy of iv-thrombolysis in Caucasian patients with IS.     

Diabetes and psychiatric illness in the total population of Stockholm

Objective

Concomitant psychiatric disorders in people with diabetes affect morbidity and mortality. We aimed to study psychiatric morbidity in people with diabetes and the general population using administrative health care data in Stockholm County.

Methods

The study population included all living persons who resided in Stockholm County, Sweden, on January 1, 2011 (N = 2,058,408). Subjects with a diagnosis of diabetes were identified with data from all consultations in primary health care, specialist outpatient care and inpatient care during the time span 2009–2013. As outcome, information was obtained on all consultations due to any psychiatric diagnosis as well as, specifically, schizophrenia, bipolar disorders, depression, and anxiety disorders, in 2011–2013. Analyses were performed by age group and gender. Age-adjusted odds ratios (ORs) with 95% confidence intervals (95% CI) for women and men with diabetes, using individuals without diabetes as referents, were calculated.

Results

Age-adjusted OR for all psychiatric diagnoses among people with diabetes was 1.296 (95% CI 1.267–1.326) for women and 1.399 (95% CI 1.368–1.432) for men. The greatest excess risk was found for schizophrenia, with OR 3.439 (95% CI 3.057–3.868) in women and 2.787 (95% CI 2.514–3.089) in men, with ORs between 1.276 (95% CI 1.227–1.327) and 1.714 (95% CI 1.540–1.905) for the remaining diagnoses.

Conclusion

The prevalence of psychiatric disorders is elevated in people with diabetes, which calls for preventive action to be taken to minimize suffering and costs to society.     

The impact of childhood trauma on depression: Does resilience matter? Population-based results from the Study of Health in Pomerania

Objective

Data suggests that traumatic experiences at early age contribute to the onset of major depressive disorder (MDD) in later life. This study aims at investigating the influence of dispositional resilience on this relationship.

Methods

Two thousand and forty-six subjects aged 29–89 (SD = 13.9) from a community based sample who were free of MDD during the last 12 months prior to data collection were diagnosed for Lifetime diagnosis of MDD by the Munich-Composite International Diagnostic Interview (M-CIDI) according to DSM-IV criteria. Childhood maltreatment (CM) and resilience were assessed with the Childhood Trauma Questionnaire (CTQ) and the Resilience-Scale (RS-25).

Results

Both CM (OR = 1.03, 95% CI [1.02, 1.04], P < .000) and resilience (OR = 0.98, 95% CI [0.98, 0.99], P < .000) were associated with MDD later in life. The detrimental effects of low resilience on MDD were not only especially prominent in subjects with a history of CM (OR = 3.18, 95% CI [1.84, 5.50], P < .000), but also effective in subjects without CM (OR = 2.62, 95% CI [1.41, 4.88], P = .002).

Conclusions

The findings support the clinical assumption that resilient subjects may be partly protected against the detrimental long-term effects of child abuse and neglect.     

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.     

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.     

Who are at risk for thromboembolism after arthroplasty? A systematic review and meta-analysis

Background

Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.

Methods

We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.

Results

Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p = 0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p = 0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p = 0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.

Conclusion

This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.     

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.