Which factors are associated with bone marrow oedema suspicious of axial spondyloarthritis as detected by MRI in the sacroiliac joints and the spine in the general population?

OBJECTIVE: Identify factors associated with presence and extension of spinal and sacroiliac joints (SIJ)-MRI lesions suggestive of axial spondyloarthritis (axSpA) in a population-based cohort (Study of Health in Pomerania) aged <45 years. METHODS: Spinal (sagittal T1/T2) and SIJ (semicoronal STIR sequences) MRIs were evaluated by two trained blinded readers. The presence (yes/no) and extension (Berlin MRI Score) of bone marrow oedema (BME) were captured. Degenerative spinal lesions were excluded and discrepancies resolved by consensus. Cross-sectional associations between clinical factors and presence/extension of BME were analysed by logistic/negative binomial regression. Record linkage of claims data was applied to identify participants with axSpA. RESULTS: MRIs of 793 volunteers were evaluated. The presence of SIJ-BME (odds ratio) was strongly associated delivery during the last year (4.47, 1.49-13.41). For SIJ-BME extension, associations (incidence rate ratios, 95% CI) were found for delivery ((during last year) 4.52, 1.48-13.84), human leucocyte antigen (HLA)-B27+ (2.32, 1.30-4.14), body mass index (25-30 vs <25 kg/m²; 1.86 (1.19-2.89)) and back pain ((last 3 months) 1.55, 1.04-2.31), while for spinal BME, associations were found for age per decade (1.46, 1.13-1.90) and physically demanding work (1.46, 1.06-2.00). Record linkage was available for 694 (87.5%) participants and 9/694 (1.3%) had a record of axSpA (ICD M45.09). CONCLUSION: These population-based data support the hypothesis of mechanic strain contributing to BME in the general population aged <45 years and the role of HLA-B27+ as a severity rather than a susceptibility factor for SIJ-BME.

Frequency of MRI changes suggestive of axial spondyloarthritis in the axial skeleton in a large population-based cohort of individuals aged <45 years.

OBJECTIVE: To investigate the frequency of bone marrow oedema (BME) and fatty lesions (FL) suggestive of axial spondyloarthritis (axSpA) on MRI of the spine and sacroiliac joints (SIJ) in a general population sample. METHODS: As part of a community-based cohort project (Study of Health in Pomerania), volunteers underwent spinal (sagittal T1/T2) and SIJ (semicoronal short tau inversion recovery) MRI examinations. Two calibrated readers evaluated the images to detect BME in SIJ and vertebral corners (VC) and FL in VC suggestive of axSpA using Assessment of SpondyloArthritis international Society definitions. RESULTS: MRIs of 793 volunteers (49.4% males, mean age 37.3±6.3 years, 8.4% human leucocyte antigen-B27+) aged <45 years were evaluated. SIJ BME was seen in 136 (17.2%), VC BME in 218 (27.5%) and FL in 645 (81.4%) volunteers. SIJ BME in ≥1, ≥3 and ≥5 SIJ quadrants was seen in 136 (17.2%), 7 (0.9%) and 1 (0.1%) volunteers, respectively. In VC, BME≥1, ≥3 and ≥5 lesions were seen in 218 (27.5%), 38 (4.8%) and 6 (0.8%) volunteers, respectively, while FL≥1, ≥3 and ≥5 were seen in 645 (81.3%), 351 (44.3%) and 185 (23.3%) volunteers, respectively. Logistic regression analysis showed that BME and FL in VC were related to increasing age: OR 1.33, 95% CI 1.02 to 1.72, and OR 1.73, 95% CI 1.32 to 2.27, per decade increase, respectively. CONCLUSIONS: In this large population-based study, a high frequency of inflammatory and fatty MRI lesions suggestive of axSpA was found, especially in the spine. This indicates a limited value of such MRI findings for diagnosis and classification of axSpA. The increasing frequency with age suggests that mechanical factors could play a role.

The association of intensive care with utilization and costs of outpatient healthcare services and quality of life.

BACKGROUND: Little is known about outpatient health services use following critical illness and intensive care. We examined the association of intensive care with outpatient consultations and quality of life in a population-based sample. METHODS: Cross-sectional analysis of data from 6,686 participants of the Study of Health in Pomerania (SHIP), which consists of two independent population-based cohorts. Statistical modeling was done using Poisson regression, negative binomial and generalized linear models for consultations, and a fractional response model for quality of life (EQ-5D-3L index value), with results expressed as prevalence ratios (PR) or percent change (PC). Entropy balancing was used to adjust for observed confounding. RESULTS: ICU treatment in the previous year was reported by 139 of 6,686 (2,1%) participants, and was associated with a higher probability (PR 1.05 [CI:1.03;1.07]), number (PC +58.0% [CI:22.8;103.2]) and costs (PC +64.1% [CI:32.0;103.9]) of annual outpatient consultations, as well as with a higher number of medications (PC +37.8% [CI:17.7;61.5]). Participants with ICU treatment were more likely to visit a specialist (PR 1.13 [CI:1.09; 1.16]), specifically internal medicine (PR 1.67 [CI:1.45;1.92]), surgery (PR 2.42 [CI:1.92;3.05]), psychiatry (PR 2.25 [CI:1.30;3.90]), and orthopedics (PR 1.54 [CI:1.11;2.14]). There was no significant effect regarding general practitioner consultations. ICU treatment was also associated with lower health-related quality of life (EQ-5D index value: PC -13.7% [CI:-27.0;-0.3]). Furthermore, quality of life was inversely associated with outpatient consultations in the previous month, more so for participants with ICU treatment. CONCLUSIONS: Our findings suggest that ICU treatment is associated with an increased utilization of outpatient specialist services, higher medication intake, and impaired quality of life.

Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling.

Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

Prevalence of Fatty Liver Disease and Hepatic Iron Overload in a Northeastern German Population by Using Quantitative MR Imaging.

Purpose To quantify liver fat and liver iron content by measurement of confounder-corrected proton density fat fraction (PDFF) and R2* and to identify clinical associations for fatty liver disease and liver iron overload and their prevalence in a large-scale population-based study. Materials and Methods From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift-encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed. On the basis of previous histopathologic calibration, participants were stratified according to their liver fat and iron content as follows: none (PDFF, ≤5.1%; R2*, ≤41.0 sec-1), mild (PDFF, >5.1%; R2*, >41 sec-1), moderate (PDFF, >14.1%; R2*, >62.5 sec-1), high (PDFF: >28.0%; R2*: >70.1 sec-1). Prevalence of fatty liver diseases and iron overload was calculated (weighted by probability of participation). Clinical associations were identified by using boosting for generalized linear models. Results Median PDFF was 3.9% (range, 0.6%-41.5%). Prevalence of fatty liver diseases was 42.2% (1082 of 2561 participants); mild, 28.5% (730 participants); moderate, 12.0% (307 participants); high content, 1.8% (45 participants). Median R2* was 34.4 sec-1 (range, 14.0-311.8 sec-1). Iron overload was observed in 17.4% (447 of 2561 participants; mild, 14.7% [376 participants]; moderate, 0.8% [20 participants]; high content, 2.0% [50 participants]). Liver fat content correlated with waist-to-height ratio, alanine transaminase, uric acid, serum triglycerides, and blood pressure. Liver iron content correlated with mean serum corpuscular hemoglobin, male sex, and age. Conclusion In a white German population, the prevalence of fatty liver diseases and liver iron overload is 42.2% (1082 of 2561) and 17.4% (447 of 2561). Whereas liver fat is associated with predictors related to the metabolic syndrome, liver iron content is mainly associated with mean serum corpuscular hemoglobin. © RSNA, 2017 Online supplemental material is available for this article.

Current smoking and reduced gray matter volume-a voxel-based morphometry study.

Nicotine modulates prefrontal processing when tested with functional imaging. Previous studies on changes in regional brain volumes in small samples, reporting different life-time exposure to nicotine, identified reduced volume in smokers in prefrontal areas but reported controversial results for other areas. We investigated the association of cigarette smoking and regional gray and white matter volume by using voxel-based morphometry (VBM) for T1-weighted high-resolution magnetic resonance imaging in 315 current-smokers and 659 never-smokers from the representative Study of Health in Pomerania (SHIP). Our study showed that in current-smokers smoking is significantly associated with gray matter volume loss in the prefrontal cortex, the anterior cingulate cortex, the insula, and the olfactory gyrus. White matter volumes were not relevantly reduced in current-smokers. In current-smokers, we found associations of gray matter loss and smoking exposure (pack-years) in the prefrontal cortex, the anterior and middle cingulate cortex, and the superior temporal and angular gyrus, which however did not stand corrections for multiple testing. We confirmed associations between smoking and gray matter differences in the prefrontal cortex, the anterior cingulate cortex and the insula in the general population of Pomerania (Germany). For the first time, we identified differences in brain volumes in the olfactory gyrus. Other cerebral regions did not show significant differences when correcting for multiple comparisons within the whole brain. The regions of structural deficits might be involved in addictive behavior and withdrawal symptoms, whereas further investigations have to show if the observed atrophies were caused by smoking itself or are preexisting differences between smoking and non-smoking individuals.

Potentially relevant incidental findings on research whole-body MRI in the general adult population: frequencies and management.

OBJECTIVES: To report the frequencies of potentially relevant incidental findings in the general adult population and to develop a protocol for their management in whole-body magnetic resonance imaging (wb-MRI). METHODS: A total of 2,500 adult subjects (1,271 women, 1,229 men; mean age 53 years) from the population-based Study of Health in Pomerania underwent standardised wb-MRI. Additionally, 1,129 participants received contrast-enhanced cardiac MRI, 619 men received MR angiography and 544 women received MR mammography. Two independent residents performed first-line reading. A third reader resolved disagreements. An interdisciplinary advisory board decided about disclosure. RESULTS: There were 1,330 incidental findings of potential clinical relevance in 904 subjects (36.2 %). Nine findings (0.4 %) required immediate referral. In total, 1,052 findings (79.1 %) were confirmed by the advisory board and disclosed to 787 participants (31.5 %). The abdominal organs (6.8 %), the urinary tract (6.8 %) and the skeletal system (6.0 %) were affected most often. While 383 findings (36.4 %) were indicated as benign and 62 (5.9 %) as malignant, most abnormalities, 607 (57.7 %), were of an unclear nature. CONCLUSIONS: Potentially relevant incidental findings are very common in wb-MRI research but the nature of these findings remains unclear in most cases. This requires dedicated management to protect subjects' welfare and research integrity.

Normal breast parenchyma: contrast enhancement kinetics at dynamic MR mammography--influence of anthropometric measures and menopausal status.

PURPOSE: To study T1 baseline signal intensity (SI) and contrast material enhancement kinetics of normal breast parenchyma by using dynamic contrast-enhanced (DCE) magnetic resonance (MR) mammography and to determine the influence of anthropometric measures and menopausal status on the variability of these features. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Between June 2008 and September 2011, 345 women (age range, 26-81 years; mean age, 51.3 years ± 11.6 [standard deviation]) underwent DCE MR mammography, with T1-weighted three-dimensional MR images (repetition time msec/echo time msec, 8.86/4.51; flip angle, 25°) acquired with a 1.5-T whole-body MR unit before and 1, 2, 3, 4, and 5 minutes after a gadobutrol bolus injection of 0.1 mmol per kilogram of body weight. Regions of interest were traced manually, and T1 SI of parenchyma was recorded. The influence of different predictors of T1 baseline SI and contrast enhancement was studied by using random-effects models. RESULTS: T1 baseline SI varied considerably between women, with a mean of 167.7 ± 49.2 (71.4-424.7 [range]) and 175.9 ± 48.9 (51.8-458.3) in the right and the left breast, respectively (P < .01). T1 baseline SI increased linearly with age (P < .0001) and body weight (P < .0001). After contrast material delivery, relative percentage of enhancement was 8.1%, 13.8%, 18.2%, 22.1%, and 24.6% at 1, 2, 3, 4, and 5 minutes, respectively, but varied considerably between women. Contrast enhancement was 9.3% in the lowest quintile and 47.4% in the highest. Contrast enhancement increased with body weight (P < .01) but decreased in postmenopausal women (P < .01). Women with higher baseline T1 SI tended to have a higher contrast enhancement slope. CONCLUSION: Anthropometric measures and menopausal status contribute to a large variability in contrast enhancement of normal breast parenchyma. This might influence the interpretation of contrast enhancement kinetics of breast lesions and current strategies for determining contrast medium dose for breast MR imaging.

Contrast enhancement kinetics of normal breast parenchyma in dynamic MR mammography: effects of menopausal status, oral contraceptives, and postmenopausal hormone therapy.

OBJECTIVES: To investigate effects of menopausal status, oral contraceptives (OC), and postmenopausal hormone therapy (HT) on normal breast parenchymal contrast enhancement (CE) and non-mass-like enhancing areas in magnetic resonance mammography (MRM). METHODS: A total of 459 female volunteers (mean age 49.1 ± 12.5 years) underwent T1-weighted 3D MRM 1-5 min after bolus injection of gadobutrol. Quantitative analysis was performed in normal breast parenchyma by manually tracing regions of interest and calculating percentage CE. Semiquantitative analysis was performed in non-mass-like enhancing areas, and signal intensity changes were characterised by five predefined kinetic curve types. The influence of OC (n = 69) and HT (n = 24) on CE was studied using random effects models. RESULTS: Breast parenchymal enhancement was significantly higher in premenopausal than in postmenopausal women (P < 0.001). CE decreased significantly with the use of OC (P = 0.01), while HT had negligible effects (P = 0.52). Prevalence of kinetic curve types of non-mass-like enhancement differed strongly between pre- and postmenopausal women (P < 0.0001), but was similar in OC users and non-OC users (P = 0.61) as well as HT users and non-HT users (P = 0.77). CONCLUSIONS: Normal breast parenchymal enhancement and non-mass-like enhancing areas were strongly affected by menopausal status, while they were not affected by HT use and only moderately by OC use. KEY POINTS: Breast parenchymal enhancement at MR mammography is stronger in premenopausal than postmenopausal women. The prevalence of strong enhancing non-mass-like areas is greater before menopause. Such enhancing non-mass-like areas may impair lesion detection in premenopausal women. Breast parenchymal enhancement is only marginally affected by hormone use. Discontinuation of hormone use before MR mammography may be unnecessary.

Subjects with sonographical hepatic steatosis should be excluded from studies to establish upper reference levels of serum transaminases.

BACKGROUND AND AIMS: Correct upper reference limits (URL) of serum liver enzyme activities are used to select individuals in whom further diagnostic procedures for suspected liver disorders are warranted and to compare the prevalence and incidence of increased serum liver enzyme levels within and among populations. We sought to establish URL in a general adult population by not only generating a disease-free population but also further excluding subjects with ultrasonographical diagnosis of hepatic steatosis. METHODS: We used data from 4,242 subjects (2,154 women) aged 20-79 years recruited for the population-based Study of Health in Pomerania. A reference population was selected comprising 1,953 subjects (1,129 women). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT) were measured photometrically. RESULTS: The exclusion of 630 subjects with hepatic steatosis and 20 subjects with equivocal data on liver ultrasound from the reference population predominantly affected the URL for serum ALT and GGT levels in younger age groups. URL for serum ALT, AST and GGT levels were 1.00 µmol/L/s (60 U/L), 0.55 µmol/L/s (33 U/L) and 1.11 µmol/L/s (67 U/L), respectively, in men as well as 0.57 µmol/L/s (34 U/L), µmol/L/s (25 U/L) and µmol/L/s (39 U/L), respectively, in women. CONCLUSIONS: URL for serum liver enzyme activities are higher than recommended previously. Creating a reference population for establishing URL for serum liver enzyme activities should include liver ultrasound in order to exclude subjects with subclinical hepatic steatosis.

Subclinical hyperthyroidism and blood pressure in a population-based prospective cohort study.

OBJECTIVES: There is current controversy on the association between subclinical hyperthyroidism and hypertension. Data from cohort studies have not been available yet. The present study was designed to longitudinally investigate possible associations of subclinical hyperthyroidism with blood pressure, pulse pressure and the risk of hypertension. METHODS: We used data from the population-based, prospective cohort Study of Health in Pomerania and included 2910 subjects (1469 women) aged 20-79 years with completed 5-year examination follow-up. Subjects with increased serum TSH levels or overt hyperthyroidism were excluded. Serum TSH levels below 0.25 mIU/l with free triiodothyronine and free thyroxine levels within the reference range were defined as subclinical hyperthyroidism. Blood pressure was measured according to standard methods. RESULTS: Multivariable analyses adjusted for age, sex, overweight, obesity, smoking status and time between the examinations did not reveal any statistically significant association between subclinical hyperthyroidism and any of the blood pressure-related variables in the whole study population. Although the 5-year hypertension incidence was higher in subjects with subclinical hyperthyroidism compared with those without (31.4 vs 19.2%; risk ratio 1.64; 95% confidence interval (CI) 1.17-2.28, P=0.006), both groups did not differ with respect to the risk of hypertension, after analyses were adjusted for confounders (relative risk 1.23, 95% CI 0.91-1.68, P=0.182). Analyses yielded similar results in subjects without thyroid disease and in those who took no antihypertensive medication. CONCLUSION: Subclinical hyperthyroidism is not associated with changes in blood pressure, pulse pressure or incident hypertension.

Regional differences in the prevalence of left ventricular hypertrophy within Germany.

BACKGROUND: There are considerable regional disparities in the prevalence of cardiovascular risk factors within Germany. We undertook this study to investigate differences in the prevalence of left ventricular hypertrophy (LVH) between northeast and southwest Germany. METHODS: Data from two population-based studies, Kooperative Gesundheitsforschung im Raum Augsburg (KORA) conducted in southwest and Study of Health in Pomerania (SHIP) conducted in northeast Germany, were utilized. The study population comprised 2,516 women and men (835 from KORA and 1,681 from SHIP) aged 45-74 years who had no history of myocardial infarction. Echocardiograms were obtained according to standard protocols. Left ventricular mass (LVM), left ventricular mass indexed for body height, and left ventricular hypertrophy were used as dependent variables in multivariable analyses. RESULTS: SHIP participants had higher LVM and left ventricular mass index values compared with KORA participants. These differences remained after analyses were adjusted for major confounders including obesity and hypertension. Consequently, there were higher proportions of LVH in SHIP compared with KORA across all 10-year age groups. Multivariable logistic regression revealed that the odds for LVH in participants living in northeast Germany were higher in women and men, respectively, by 1.57 (95% confidence interval: 1.18-2.09) and 1.68 (95% confidence interval: 1.25-2.27) than in participants living in southwest Germany. Potential methodological differences between studies do not seem to account for these findings. CONCLUSION: There is a higher prevalence of LVH in northeast compared with southwest Germany. Regional disparities in hypertension and overweight only partly explain this difference.

Extended recruitment efforts minimize attrition but not necessarily bias.

OBJECTIVES: There has been a debate about the effect of extended recruitment efforts on attrition and bias. The aims of the present study are (1) to investigate the effectiveness of extensive multimode recruitment procedures; (2) to study their effect on attrition and bias; and (3) to determine the potential predictors of attrition. STUDY DESIGN AND SETTING: We used data from the longitudinal population-based study of health in Pomerania. RESULTS: Using multimode recruitment methods, we reached a follow-up response proportion of 83.6%. In-person contacts at home turned out to be an effective recruitment tool. Sociodemographic and health characteristics of late respondents and converted nonrespondents were most distinct from early respondents but not necessarily indicative of nonrespondents. Analyzing attrition bias, extended recruitment efforts produced an effect only for sociodemographic characteristics but not for health-related indicators. The strongest predictors for attrition from the regression model were late recruitment at baseline, unemployment, low educational level, female sex, and smoking habit. CONCLUSION: Extended recruitment efforts appeared justified in terms of response maximization. However, enhanced response proportions may not necessarily minimize bias. In our analysis, aiming for a high-response proportion in terms of health-related indicators had no effect, because late respondents did not differ from early respondents.

Does precontemplation represent a homogeneous stage category? A latent class analysis on German smokers.

The authors examined the subtype structure of smokers classified in the precontemplation stage of change within the transtheoretical model. From a general practice-based sample of 1,499 daily smoking patients from Germany (participation rate 80%), they used a subgroup of 929 smokers who were classified in the precontemplation stage and applied latent class analysis, using the pros and cons of nonsmoking and smoking cessation self-efficacy as the defining variables. Cross-sectional validation of the emerging classes was based on smoking behavior and processes of change variables. For longitudinal validation, generalized estimation equation analyses were used on motivational and abstinence criteria from 6-, 12-, 18-, and 24-month follow-ups. A 4-class model best represented the data. Three subtypes (labeled progressive, immotive, and disengaged pessimistic) were similar to clusters identified in U.S. studies. The 4th (disengaged optimistic), by contrast, was reminiscent of a type that had previously only emerged in a Dutch study. Cross-sectional and longitudinal validation results confirmed the distinctiveness and predictive power of the classes. The findings highlight the importance of tailoring interventions for smoking behavior change to the needs of different subgroups of precontemplating smokers.

Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

Immune heparin-induced thrombocytopenia can occur in patients receiving clopidogrel and aspirin.

Platelet adenosine diphosphate (ADP) receptors may play a role in potentiating platelet activation induced by IgG from patients with immune heparin-induced thrombocytopenia (HIT), as shown by previous studies using the ADP receptor antagonists AR-C66096 and ticlopidine. Consistent with these observations, we found that platelet activation by HIT sera is also significantly reduced in patients receiving clopidogrel, an ADP receptor antagonist prodrug now in wide clinical use. Despite these in vitro and ex vivo findings, we observed two patients develop acute HIT while receiving both clopidogrel and aspirin: both patients' sera tested strongly positive in a heparin-dependent washed platelet activation assay (100% serotonin release) and PF4/heparin-enzyme-immunoassay (2.594 and 2.190 absorbance units). Both patients also developed HIT-associated clinical sequelae (acute systemic reaction postintravenous heparin bolus; thrombotic stroke) in association with their episode of HIT. We conclude that combined therapy with aspirin and clopidogrel does not necessarily protect against clinical HIT, at least in patients with HIT antibodies that have strong platelet-activating characteristics.