Economy class syndrome: what is it and who are the individuals at risk?

Abstract The term 'economy class syndrome' refers to the occurrence of thrombotic events during long-haul flights that mainly occur in passengers in the economy class of the aircraft. This syndrome results from several factors related to the aircraft cabin (immobilization, hypobaric hypoxia and low humidity) and the passenger (body mass index, thrombophilia, oral contraceptives or hormone replacement therapy, cancer), acting together to predispose to excessive blood coagulation, which can result in venous thromboembolism. Several risk factors, both genetic and acquired, are associated with venous thromboembolism. The most important genetic risk factors are natural anticoagulant deficiencies (antithrombin, protein C and protein S), factor V Leiden, prothrombin and fibrinogen gene mutations and non-O blood group individuals. Acquired risk factors include age, pregnancy, surgery, obesity, cancer, hormonal contraceptives and hormone replacement therapy, antiphospholipid syndrome, infections, immobilization and smoking. People who have these risk factors are predisposed to hypercoagulability and are more susceptible to suffer venous thromboembolism during air travel. For these individuals, a suitable outfit for the trip, frequent walks, calf muscle exercises, elastic compression stockings and hydration are important preventive measures. Hence, it is essential to inform about economic class syndrome in an attempt to encourage Brazilian health and transport authorities to adopt measures, in partnership with the pharmaceutical industry, to prevent venous thromboembolism.

Economy class syndrome: what is it and who are the individuals at risk?

The term 'economy class syndrome' refers to the occurrence of thrombotic events during long-haul flights that mainly occur in passengers in the economy class of the aircraft. This syndrome results from several factors related to the aircraft cabin (immobilization, hypobaric hypoxia and low humidity) and the passenger (body mass index, thrombophilia, oral contraceptives or hormone replacement therapy, cancer), acting together to predispose to excessive blood coagulation, which can result in venous thromboembolism. Several risk factors, both genetic and acquired, are associated with venous thromboembolism. The most important genetic risk factors are natural anticoagulant deficiencies (antithrombin, protein C and protein S), factor V Leiden, prothrombin and fibrinogen gene mutations and non-O blood group individuals. Acquired risk factors include age, pregnancy, surgery, obesity, cancer, hormonal contraceptives and hormone replacement therapy, antiphospholipid syndrome, infections, immobilization and smoking. People who have these risk factors are predisposed to hypercoagulability and are more susceptible to suffer venous thromboembolism during air travel. For these individuals, a suitable outfit for the trip, frequent walks, calf muscle exercises, elastic compression stockings and hydration are important preventive measures. Hence, it is essential to inform about economic class syndrome in an attempt to encourage Brazilian health and transport authorities to adopt measures, in partnership with the pharmaceutical industry, to prevent venous thromboembolism.

The unexpected beneficial role of smoking in preeclampsia.

We have recently investigated the association between the risk of developing PE and clinical, hemostatic, inflammatory and genetic parameters of 108 severe preeclamptic women. A multivariate logistic regression analysis was performed to assess what variables are independent risk factors for PE. Univariate analysis was performed including the variables in age, smoking condition, multiple pregnancy, blood group, phenotypes and alleles of IL-4, IL-5, IL-10, IL-6, IL-8, IL-12, IL-1ß, IFN-γ, TNF-α, and the plasma levels of FVII, FVIIa, FVIIa-AT, FVIII, FVW, ADAMTS13, D-Di, PAI-1, ADMA. Those variables whose P<0.20 (smoking, multiple pregnancy, blood group, phenotype IL-6, IFN-γ allele, IL-10 allele and FVII) were selected to the multivariate logistic regression. In the final model, only FVII, IFN-γ allele and smoking were independently associated to severe PE (P<0.0001, P<0.0001 and P=0.008, respectively). Increased FVII plasma levels and IFN-γ "T" allele were associated to an increased probability of developing PE (OR 1.001, 95% CI [1.001-1.002], and OR 4.81 95% CI [2.42-9.60], respectively). On the other hand, smoker status was associated with a 4.72 decreased chance of PE occurrence (OR 4.72, 95% CI [1.51-14.75]). In this article we also reviewed the studies that investigate the risk of PE in pregnant women who smoked, as well as the effect of tobacco extract in cells or animal models. The hypotheses proposed to explain the biological mechanism by which smoking during pregnancy reduces the risk of PE was also discussed.

Clinical applicability of reticulated platelets.

BACKGROUND: Reticulated platelets (RPs), immature platelets newly released from the bone marrow into the circulation, have a high content of ribonucleic acid and are larger and more active in thrombus formation. OBJECTIVE: This review compiles articles that evaluated RP in order to establish their clinical significance. DISCUSSION: RPs increase when platelet production rises and decrease when production falls. As such, the measurement of circulating RPs allows the assessment of thrombocytopenia, i.e., bone marrow production or peripheral destruction. CONCLUSION: RPs are a promising laboratory tool for evaluation of idiopathic thrombocytopenia (differentiating hypoproduction from accelerated platelet destruction), chemotherapy and after stem cell transplantation (predicting platelet recovery) and thrombocytosis (estimating platelet turnover). Additional randomized and well controlled clinical studies are required to clearly establish the significance of circulating RPs in other clinical conditions.

Preeclampsia: integrated network model of platelet biomarkers interaction as a tool to evaluate the hemostatic/immunological interface.

BACKGROUND: Preeclampsia (PE) is associated with platelet activation, which may be involved in its pathogenesis promoting coagulation and mediating inflammation. We investigated whether the platelet activation status together with the frequency of platelet-leukocyte aggregates/PLA and monocyte tissue factor/TF expression could be used as laboratorial biomarkers for PE diagnosis and prognosis. METHODS: Ninety-seven women were evaluated including severe PE/sPE (N=15), mild PE/mPE (N=20), normotensive pregnant/NP (N=31) and non-pregnant women/nonP (N=31). Platelet markers were analyzed by flow cytometry. RESULTS: Platelet counts and CD41a expression by platelets were lower in NP and sPE vs nonP. The expression of CD61 was lower during pregnancy. Altered balance of platelet marker expression was also observed in NP and sPE vs nonP. No significant differences in the PLA and TF expression by monocytes were observed among the groups. There are several correlations between platelet activation markers, especially in sPE, which suggest a relevant role of the hemostatic/immunological cross-talk in this disease. CONCLUSIONS: PE is not associated with increased platelet activation markers. It cannot rule out a role of platelet activation in the PE pathophysiology. Despite those correlations, we did not find a putative laboratorial biomarker that could be useful by itself for PE diagnosis and prognosis.

Antiphospholipid syndrome: a clinical and laboratorial challenge.

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by the presence of a heterogeneous family of antibodies that bind to plasma proteins with affinity for phospholipid surfaces. The two major protein targets of antiphospholipid antibodies are prothrombin and ß2-glycoprotein I (ß2GPI). APS leads to aprothrombotic state, and it is characterized by the occurrence of arterial, venous or microvascular thrombosis or recurrent fetal loss. The diagnosis of APS is based on a set of clinical criteria and the detection of lupus anticoagulant (LA), anticardiolipin antibodies (ACA) or anti-ß2GPI in plasma. Although laboratory tests are essential for APS diagnosis, these tests have limitations associated with the robustness, reproducibility and standardization. The standardization of diagnostic tests for detection of APLAs has been a challenge and a variety of results have been obtained using different commercial kits and in-house techniques. An increased sensitivity of the ELISA kits for detection of ACA effectively has contributed to APS diagnosis. However, the lack of specificity associated with a high number of false-positive results is a clinical and laboratorial challenge, since such results may lead to mistaken clinical decisions, such as prescription of oral anticoagulant, leading to the risk of hemorrhaging. Furthermore, clinicians are often unfamiliar with these tests and have difficulty interpreting them, requiring interaction between clinical and laboratory professionals in order to ensure their correct interpretation.

Antiphospholipid syndrome: a clinical and laboratorial challenge / Síndrome do anticorpo antifosfolípide: um desafio clínico e laboratorial

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by the presence of a heterogeneous family of antibodies that bind to plasma proteins with affinity for phospholipid surfaces. The two major protein targets of antiphospholipid antibodies are prothrombin and β2-glycoprotein I (β2GPI). APS leads to aprothrombotic state, and it is characterized by the occurrence of arterial, venous or microvascular thrombosis or recurrent fetal loss. The diagnosis of APS is based on a set of clinical criteria and the detection of lupus anticoagulant (LA), anticardiolipin antibodies (ACA) or anti-β2GPI in plasma. Although laboratory tests are essential for APS diagnosis, these tests have limitations associated with the robustness, reproducibility and standardization. The standardization of diagnostic tests for detection of APLAs has been a challenge and a variety of results have been obtained using different commercial kits and in-house techniques. An increased sensitivity of the ELISA kits for detection of ACA effectively has contributed to APS diagnosis. However, the lack of specificity associated with a high number of false-positive results is a clinical and laboratorial challenge, since such results may lead to mistaken clinical decisions, such as prescription of oral anticoagulant, leading to the risk of hemorrhaging. Furthermore, clinicians are often unfamiliar with these tests and have difficulty interpreting them, requiring interaction between clinical and laboratory professionals in order to ensure their correct interpretation.

A síndrome do anticorpo antifosfolípide (SAAF) é uma trombofilia autoimune adquirida, caracterizada pela presença de uma família heterogênea de anticorpos que se ligam a proteínas plasmáticas com afinidade, por superfícies fosfolipídicas. As duas principais proteínas-alvo dos anticorpos antifosfolípides (AAF) são a protrombina e a β2-glicoproteína 1 (β2GP1). A SAAF está associada a um estado protrombótico e é clinicamente caracterizada pela ocorrência de trombose arterial, venosa ou microvascular ou perda fetal recorrente. O diagnóstico da SAAF é baseado em um conjunto de critérios clínicos e na detecção plasmática de anticoagulante lúpico (AL), anticorpo anticardiolipina (ACA) ou antiβ2GP1. Embora os testes laboratoriais sejam de fundamental importância para o diagnóstico da SAAF, eles apresentam limitações associadas à robustez, à reprodutibilidade e à padronização. A padronização de testes diagnósticos para a pesquisa de AAF tem sido um desafio, pois uma variedade de resultados pode ser obtida utilizando diferentes kits comerciais e técnicas in-house. Um aumento da sensibilidade dos kits de ELISA para a detecção do ACA contribuiu efetivamente para o diagnóstico da SAAF. No entanto, a falta de especificidade, associada a um número elevado de resultados falso-positivos, é um desafio clínico e laboratorial, uma vez que tais resultados podem levar a decisões clínicas erradas, como a prescrição de anticoagulante oral, levando ao risco de hemorragia. Além disso, os clínicos muitas vezes não estão familiarizados com esses testes e têm dificuldade em interpretá-los, sendo necessária a interação da clínica e dos profissionais do laboratório para assegurar sua correta interpretação.

Assessment of L-arginine asymmetric 1 dimethyl (ADMA) in early-onset and late-onset (severe) preeclampsia.

Preeclampsia (PE) is characterized by hypertension and proteinuria. It has been classified in early or late according to gestational age at the onset of disease. Endothelial dysfunction plays a crucial part in its pathogenesis. NO is a potent vasodilator and ADMA is its endogenous inhibitor. We have assessed maternal ADMA levels. ADMA were increased in early [0.66 µmol/L] versus late sPE [0.47 µmol/L] (P=0.001) and versus normotensive pregnant [0.48 µmol/L] (P=0.001). Our findings suggest that high ADMA levels in early sPE could compromise NO synthesis contributing to endothelial dysfunction, leading to impaired placentation and the onset of this disease.

Preeclampsia: are platelet count and indices useful for its prognostic?

INTRODUCTION: Preeclampsia (PE) is characterized by hypertension and proteinuria after the 20th week gestation. The aim of this study was to investigate whether platelet count (PC) and platelet indices (mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT)) could predict severe form of preeclampsia (sPE). METHODS: Three groups were evaluated; G1-pregnant with sPE (N = 29); G2-normotensive pregnant (N = 28) and Group 3: non-pregnant women (N = 30). Platelet parameters were obtained using the same automatic blood cells count. Statistical analysis was performed by analysis of variance, t-test, and receiver operating characteristic (ROC) curve. P ≤ 0.05 was considered significant. RESULTS: Lower PC and PCT were observed in sPE comparing to normal pregnant (P = 0.031 and 0.035, respectively) and to non-pregnant women (P < 0.001 and 0.004, respectively). PDW was higher in sPE comparing to normotensive pregnant (P = 0.028) and to non-pregnant women (P < 0.001). MPV was higher in sPE comparing to normotensive pregnant and non-pregnant women (P = 0.05 and P < 0.001, respectively). Analysis from the ROC curve and its areas for each variable showed that the parameters have regular diagnostic significance, except for PCT, considered as not good for this purpose. CONCLUSION: PC emerges as a good candidate for sPE diagnosis, since it is a simple and habitually done method, with lower cost and greater accessibility in the clinical laboratory. Further studies evaluating sequential PC and platelet indices throughout pregnancy are necessary to clarify the role of platelet parameters in PE development and severity.

Preeclampsia and ABO blood groups: a systematic review and meta-analysis.

Preeclampsia (PE) is a multifactorial pregnancy-specific syndrome which represents one of the leading causes of maternal mortality worldwide. Inherited thrombophilia have been investigated as risk factor for the development of PE and it is currently known that ABO blood group may impact haemostatic balance, having the non-O blood groups (A, B or AB) subjects increased risk for thrombus formation, as compared to those of group O. We performed a systematic review of the literature for published studies investigating whether ABO blood groups could influence PE developing. A sensitive search of four databases identified 45 unique titles. The retrieved papers were assessed independently by authors and a rigorous process of selection and data extract was conduct. Methodological quality of the included studies was also evaluated. Two studies met eligibility criteria. As a main finding of our systematic review, an association between the AB blood group and the occurrence of PE was detected based on two original studies. Considering the role of ABO blood groups on the hemostatic process and thrombus formation, special attention should be given to pregnant patients carrying the AB blood group in order to prevent the syndrome and improve prognosis.