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Objective: Life expectancy in patients suffering from affective disorders is considerably diminished. We investigated whether skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, mediates the association between affective disorders and excess mortality. Methods: Included were 81,041 participants of the Lifelines cohort study. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed with the Mini-International Neuropsychiatric Interview. SAF was assessed as mediator in Cox proportional hazards models for all-cause or natural-cause mortality. Results: Mortality was increased in cases with major depression compared to controls (36.4 vs. 22.5 per 100,000 person years). Partial mediation by SAF of the association between affective disorders and mortality was shown (9.0-10.5%, P

Background: Oxidative stress may be a mechanistic link between affective disorders (depressive and anxiety disorders) and somatic disease. Advanced glycation end products are produced under the influence of oxidative stress and in the skin (measured by skin autofluorescence [SAF]) serve as marker for cumulative oxidative stress. Aim of study was to determine whether SAF is associated with presence of affective disorders. Methods: Participants in the Lifelines cohort study who had completed the Mini-International Neuropsychiatric Interview for affective disorders and a SAF-measurement were included. Cross-sectional associations between SAF and presence of the following psychiatric disorders were investigated through logistic regression analyses adjusted for sociodemographic factors, cardiometabolic parameters, and somatic morbidities: major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia. Results: Of 81,041 included participants (41.7% male, aged 18–91 years), 6676 (8.2%) were cases with an affective disorder. SAF was associated with presence of affective disorders (OR=1.09 [95%CI 1.07–1.12], P

Hereditary angioedema is characterized by recurrent and unpredictable episodes of subcutaneous and mucosal swelling that can be life threatening. IONIS-PKK-LRx is a ligand-conjugated antisense oligonucleotide designed for receptor-mediated delivery to hepatocytes. In a compassionate-use pilot study, two patients with severe bradykinin-mediated angioedema were initially administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKKRx, for 12 to 16 weeks, after which they received IONIS-PKK-LRx at a dose of 80 mg every 3 to 4 weeks for 7 to 8 months. Treatment was accompanied by a reduction in the angioedema attack rate. (Funded by Amsterdam UMC.).

Severe hypertriglyceridemia is a major risk factor for acute pancreatitis. In exceptional cases, it is caused by plasma components inhibiting lipoprotein lipase activity. This phenomenon is predominantly associated with autoimmune diseases. Here, we report a case of severe hypertriglyceridemia due to a transient reduction in lipoprotein lipase activity following an episode of COVID-19 in an otherwise healthy 45-year-old woman. The lipoprotein lipase activity of the patient was markedly reduced compared with a healthy control and did recover to 20% of the healthy control’s lipoprotein lipase activity 5 months after the COVID-19 episode. Mixing tests substantiated reduced lipolytic capacity in the presence of the patient’s plasma at presentation compared with a homozygous lipoprotein lipase-deficient control, which was no longer present at follow-up. Western blotting confirmed that the quantity of lipoprotein lipase was not aberrant. Fibrate treatment and a strict hypolipidemic diet improved the patient’s symptoms and triglyceride levels.

Low levels of C1 inhibitor, the main inhibitor of the classic complement system, result in paroxysmal angioedema attacks that can be incapacitating or even life-threatening in affected individuals. Molecular defects in the gene for C1 inhibitor cause hereditary angioedema. In recent years, new insights in the pathways leading to angioedema due to a deficiency of C1 inhibitor have been gathered. Bradykinin, which is formed upon activation of the kallikrein-kinin system under insufficient regulation by C1 inhibitor, plays a crucial role. Whereas C1 inhibitor also occupies a central mediatory role in other plasma systems, such as the contact activation system of coagulation and the fibrinolytic plasminogen-plasmin system, a C1 inhibitor deficiency may also cause enhanced activation of these pathways. Novel therapeutic modalities for treatment and prevention of hereditary angioedema are now available, such as different forms of C1 inhibitor concentrate and novel agents that interfere in the kallikrein-kinin system.

Congenital deficiency of C1 inhibitor, the main inhibitor of the classic complement system pathway, leads to paroxysmal angioedema (hereditary angioedema) that can be debilitating or life‐threatening for affected patients. In the past few years many new insights on the pathogenesis of angioedema formation in the presence of low levels of C1 inhibitor has been accumulated. There is a central role for bradykinin that is released upon activation of the kallikrein‐kinin system that is insufficiently controlled by adequate levels of C1 inhibitor. As C1 inhibitor also possesses a central regulatory role of other plasma systems, including the contact activation system of coagulation and the plasminogen‐plasmin system that governs endogenous fibrinolysis, it is interesting to observe the effects of C1 inhibitor deficiency on activation of these systems and relevance for hemostasis in vivo and thrombo‐embolic disease. Interestingly, and despite significant activation of these pathways, C1 inhibitor deficiency is not at all associated with a hemorrhagic tendency or prothrombotic state. New therapeutic options for treatment of C1 inhibitor efficiency have become available in recent years, including various forms of C1 inhibitor concentrate. Restoration of C1 inhibitor levels in patients with hereditary angioedema has not resulted in thrombotic complications or any other relevant disorder associated with the hemostatic system.

Background: Skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, is cross-sectionally associated with affective disorders. Prospective studies of oxidative stress markers will help to clarify the pathophysiological role of oxidative stress. Methods: Data of a population-based cohort study were used. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed at baseline and at 5-year follow-up with the Mini-International Neuropsychiatric Interview. Associations between SAF at baseline and incidence and persistence/recurrence of affective disorders were assessed with logistic regression. Results: Of 43,267 participants with no disorder at baseline, 2885 (6.7%) developed an incident disorder during follow-up. In 1360 of 3648 participants (37.3%) with an affective disorder at baseline, a persisting/recurrent disorder was present at follow-up. A modest association existed between SAF and incident affective disorders (OR=1.07 [95%CI 1.03–1.12], P

In patients with diabetes, metabolic disorders disturb the physiological balance of coagulation and fibrinolysis, leading to a prothrombotic state characterized by platelet hypersensitivity, coagulation disorders and hypofibrinolysis. Hyperglycemia and insulin resistance cause changes in platelet number and activation, as well as qualitative and/or quantitative modifications of coagulatory and fibrinolytic factors, resulting in the formation of fibrinolysis-resistant clots in patients with diabetes. Other coexisting factors like hypoglycemia, obesity and dyslipidemia also contribute to coagulation disorders in patients with diabetes. Management of the prothrombotic state includes antiplatelet and anticoagulation therapies for diabetes patients with either a history of cardiovascular disease or prone to a higher risk of thrombus generation, but current guidelines lack recommendations on the optimal antithrombotic treatment for these patients. Metabolic optimizations like glucose control, lipid-lowering, and weight loss also improve coagulation disorders of diabetes patients. Intriguing, glucose-lowering drugs, especially cardiovascular beneficial agents, such as glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter inhibitors, have been shown to exert direct anticoagulation effects in patients with diabetes. This review focuses on the most recent progress in the development and management of diabetes related prothrombotic state.

INTRODUCTION: Although quality of life (QoL) is recognized as an important indicator of the course of a disease, it has rarely been addressed in studies evaluating the outcome of care for patients with pulmonary embolism (PE). This study primarily aimed to evaluate the QoL of patients with acute PE in comparison to population norms and to patients with other cardiopulmonary diseases, using a generic QoL questionnaire. Secondary, the impact of time period from diagnosis and clinical patient characteristics on QoL was assessed, using a disease-specific questionnaire.METHODS: QoL was assessed in 109 consecutive out-patients with a history of objectively confirmed acute PE (mean age 60.4 ± 15.0 years, 56 females), using the generic Short Form-36 (SF-36) and the disease specific Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL). The score of the SF-36 were compared with scores of the general Dutch population and reference populations with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), a history of acute myocardial infarction (AMI), derived from the literature. Scores on the SF-35 and PEmb-QoL were used to evaluate QoL in the short-term and long-term clinical course of patients with acute PE. In addition, we examined correlations between PEmb-QoL scores and clinical patient characteristics.RESULTS: Compared to scores of the general Dutch population, scores of PE patients were worse on several subscales of the SF-36 (social functioning, role emotional, general health (PCONCLUSION: Our study demonstrated an impaired QoL in patients after treatment of PE. The results of this study provided more knowledge about QoL in patients treated for PE.

Summary. Background: Nowadays, large numbers of patients are tested for thrombophilia, even though the benefits of this strategy remain unclear. A potential disadvantage of this predominantly genetic testing is the psychological impact, including fear, depression and worry. Objectives: To systematically review studies that determined the nature and extent of the psychological impact of testing for thrombophilia. Patients/methods: We searched the MEDLINE data base (1966–2008), the EMBASE data base (1985–2008) and the PsychInfo data base (1806–2008) for relevant trials, without language restrictions. Bibliographies of relevant articles were scanned for additional articles. We reviewed all relevant studies that focused on the psychological impact of testing for thrombophilia. Only full papers of studies that included 15 patients or more were considered eligible for this review. Two reviewers independently extracted data and assessed quality. Results: Six studies fulfilled the eligibility criteria. As these studies varied appreciably in methodology, the pooling of data was not possible. Studies of psychological impact of genetic testing for thrombophilia report few negative results, although most assessments were limited to short-term follow-up, or lacked methodological accuracy. Conclusions: No valid conclusions can be drawn about the psychological impact of genetic testing in patients based on the current available literature. Given the large number of patients that are being exposed to testing for thrombophilia, and the uncertain benefits, there is an urgent need for more uniformity in the measurement of the psychological impact of thrombophilia testing.

In the last decades, the knowledge on the etiology of venous thromboembolism (VTE) has increased tremendously. In approximately half of patients presenting with VTE, one or more thrombophilic defects can be identified. This has led to widespread testing for thrombophilia, despite the fact that, at present, it is unclear whether this should have therapeutic consequences. Here we review the currently established hereditary and acquired thrombophilic defects, and focus on the pros and cons of testing in the setting of VTE. Thrombophilia is defined as a disorder associated with an increased tendency to venous thromboembolism (VTE). Thrombophilia can be acquired, such as in patients with cancer, or congenital, in which case a defect in the coagulation system is hereditary. Egeberg was the first to use the term thrombophilia in 1965, when he described a Norwegian family that had a remarkable tendency to VTE, based on a deficiency of antithrombin. Since then, various laboratory abnormalities, both hereditary and acquired, have been discovered that increase the risk of VTE. This article reviews the currently established thrombophilic abnormalities and discusses the potential usefulness and implications of testing for thrombophilia.

Background The PEmb-QoL is a validated 40-item questionnaire to quantify health-related quality of life in patients having experienced pulmonary embolism (PE). It covers six health dimensions: frequency of complaints, activities of daily living limitations, work-related problems, social limitations, intensity of complaints, and emotional complaints. Originally developed in Dutch and English, we sought to prospectively validate the psychometric properties of a French version of the PEmb-QoL. Methods We performed a forward and backward translation of the English version of the PEmb-QoL into French. French-speaking consecutive adult patients with an acute, objectively confirmed PE admitted to the emergency department of a Swiss university hospital between 08/2009 and 09/2011 were recruited telephonically. We used standard psychometric tests and criteria to evaluate the acceptability, reliability, and validity of the French version of the PEmb-QoL. We also performed an exploratory factor analysis. Results Overall, 102 patients were enrolled in the study. The French version of the PEmb-QoL showed good reliability (internal consistency, item–total and inter-item correlations), reproducibility (test-retest reliability), and validity (convergent, discriminant) in French-speaking patients with PE. The exploratory factor analysis suggested three underlying dimensions: limitations in daily activity (items 4b-m, 5a-d), symptoms (items 1a-h and 7), and emotional complaints (items 9a-f and j). Conclusion We successfully validated the French version of the PEmb-QoL questionnaire in patients with PE. Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of life after PE in French-speaking patients. Electronic supplementary material The online version of this article (doi:10.1186/s12955-014-0174-4) contains supplementary material, which is available to authorized users.

Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in a retrospective controlled cohort. Methods All pregnant women who received therapeutic doses of LMWH between 1995 and 2008 were identified in the Academic Medical Center, Amsterdam, The Netherlands. The controls were women registered for antenatal care in the same hospital who did not use LMWH during pregnancy, matched by random electronic selection for age, parity and delivery date to LMWH users. The incidence of PPH (blood loss >500 ml), severe PPH (blood loss >1000 ml) and median blood loss were compared in two cohorts of LMWH users and non-users. Results The incidence of PPH was 18% in LMWH users (N=95) and 22% in non-users (N=524) (RR 0.8; 95% CI 0.5 to 1.4). The incidence of severe PPH was 6% in both groups (RR 1.2; 0.5 to 2.9). The median amount of blood loss differed only in normal vaginal deliveries. It was 200 ml in LMWH users and 300 ml in non-users (difference −100 ml; 95% CI −156 to −44). Conclusion Therapeutic doses of LMWH in pregnancy were observed not to be associated with a clinically meaningful increase in the incidence of PPH or severe PPH in women delivered in this hospital, although this observation may be confounded by the differential use of strategies to prevent bleeding. A randomised controlled trial is necessary to provide a definite answer about the optimal dose of LMWH in pregnancy., Article summary Article focus To compare the incidence of PPH (ie, blood loss >500 ml in the first 24 h of delivery) in two cohorts of pregnant women who were treated with therapeutic doses of LMWH and those who were not. To compare the incidence of severe PPH (blood loss >1000 ml) in two cohorts of pregnant women who were treated with therapeutic doses of LMWH and those who were not. To compare the median blood loss in two cohorts of pregnant women who were treated with therapeutic doses of LMWH and those who were not. Key message Therapeutic doses of LMWH in pregnancy were not associated with a clinically meaningful increase in the incidence of PPH (RR 0.8; 95% CI 0.5 to 1.4) or severe PPH (RR 1.2; 0.5 to 2.9) in women delivered in our hospital. The median amount of blood loss differed only in normal vaginal deliveries. It was lower in LMWH users (200 ml) than in non-users (300 ml) (difference −100 ml; 95% CI −156 to −44). Strength and limitation of this study This is the largest cohort of pregnancies treated with high doses of LMWH. Although this was a controlled cohort study, it is likely that strategies to decrease the risk of PPH differed between women who were treated with LMWH and controls.

Summary. Background: Factor V Leiden (FVL) increases the risk of venous thrombosis and pregnancy loss in carriers. Nevertheless, this relatively old mutation is prevalent in Caucasion populations, which could be explained by positive selection pressure. Men with FVL have previously been found to have higher fecundity (the time between marriage and first pregnancy). Whether this is caused by increased sperm counts in men with FVL is unknown. Objectives: To assess whether men with factor V Leiden have increased sperm counts. Patients/methods: We performed a prospective cohort study among 1139 consecutively included male partners of subfertile couples presenting at our university hospital for fertility workup between January 2000 and July 2007. All potential candidates who gave informed consent were included, irrespective of their fertility workup. In this retrospective analysis, we excluded participants with known causes of spermatogenic function or azoospermia. Subsequently, we genotyped all participants and compared sperm counts between FVL carriers and non-carriers. Results: We identified 37 FVL carriers and 921 non-carriers. FVL carriers had higher total sperm counts and total motile sperm counts than non-carriers: 236 × 106 (95% CI 158–292 × 106) vs. 163 × 106 (95% CI 147–178 × 106) and 81 × 106 (95% CI 54–105 × 106) vs. 52 × 106 (95% CI 48–57 × 106), respectively. Conclusions: To our knowledge, this is the first study that indicates that an increased incidence of a genotype may be controlled by increased sperm counts. However, the finding that men with FVL had higher total (motile) sperm counts was not statistically significant and needs confirmation in other studies.

Background Tests for thrombophilia are being performed on a large scale in people after venous thromboembolism (VTE) even though the benefits of testing are still subject to debate. The most important benefit would be a reduction in the risk of recurrent VTE due to the use of additional prophylactic measures. This is an update of a review first published in 2009. Objectives The objective of this review was to assess the benefit of testing for thrombophilia after VTE in terms of risk reduction of recurrent VTE. Search methods For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 21 2012) and CENTRAL (2012, Issue 5). The authors searched MEDLINE and EMBASE. Selection criteria Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the rate of recurrent VTE in participants with VTE who were tested for thrombophilia with the rate in participants with VTE who were not tested were eligible. Data collection and analysis We planned to extract data from identified studies using data extraction forms. Main results No studies were included because no RCTs or CCTs could be identified. Authors' conclusions There are currently no randomized controlled trials or controlled clinical trials that have assessed the benefit(s) of testing for thrombophilia on the risk of recurrent VTE.

Background: Patients with (undiagnosed) diabetes mellitus, impaired glucose tolerance or stress-induced hyperglycemia may be at greater risk for venous thrombosis and present with relative hyperglycemia during the thrombotic event. Objectives: To assess whether venous thrombosis is associated with hyperglycemia at diagnosis. Patients/methods: We performed a case-control study, derived from a cohort of consecutive patients referred for suspected deep vein thrombosis. Cases were patients with confirmed symptomatic venous thrombosis of the lower extremity. Controls were randomly selected in a 1:2 ratio from individuals in whom this diagnosis was excluded. We measured plasma glucose levels upon presentation to the hospital. Results: In total, 188 patients with thrombosis and 370 controls were studied. The glucose cut-off levels for the first to fourth quartiles were as follows: first quartile

Abstract 2971 Poster Board II-947 Introduction: Women with antiphospholipid syndrome (APS) are at increased risk of recurrent miscarriage. Remarkably, the outcome of a successive pregnancy in women with APS and recurrent miscarriage is merely unknown. Patients and methods: We performed a cohort study including all women with 2 or more consecutive miscarriages who attended the recurrent miscarriage clinic of Liverpool Women's Hospital, Liverpool, UK between 1988 and 2006. All women underwent a systematic diagnostic work up including testing for APS. Women with proven APS (according to the SAPPORO criteria) were studied, and outcomes were compared to women with unexplained recurrent miscarriage. We excluded all women from couples with other reasons for recurrent miscarriage. Results: 737 women were included, of whom 220 (30%) had APS. Mean age (32 years) and obstetric history (mean number of prior losses: 3) did not differ between women with and without APS. Of women with APS, 148 (67%) had a successful pregnancy outcome as compared to 324 women without APS (63%), OR=1.2 (95%CI 0.9 to 1.7). No differences were found for birth weight, gestational age, and intra-uterine growth retardation. Women with APS who received aspirin and heparin more often had a successful pregnancy 53/67 (79%) as compared to women without treatment 26/44 (59%); OR=2.6 (95%CI 1.0 to 6.6). Combined use of aspirin and heparin was not associated with an increased success rate in women without APS: 25/43 (58%) vs 204/305 (67%); OR=0.7 (95%CI 0.3-1.4). Conclusions: The prognosis of a successive pregnancy in women with recurrent miscarriage and APS was comparable to women with unexplained recurrent miscarriage. However, the combined use of heparin and aspirin was associated with a significantly increased chance of a successful pregnancy in women with APS. Disclosures: No relevant conflicts of interest to declare.