Ana Paula Salles Moura Fernandes

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.

Sensitive and Specific Serodiagnosis of Leishmania infantum Infection in Dogs by Using Peptides Selected from Hypothetical Proteins Identified by an Immunoproteomic Approach

ABSTRACT In Brazil, the percentage of infected dogs living in areas where canine visceral leishmaniasis (CVL) is endemic ranges from 10 to 62%; however, the prevalence of infection in dogs is probably higher than figures reported from serological studies. In addition, problems with the occurrence of false-positive or false-negative results in the serodiagnosis of CVL have been reported. The present work analyzed the potential of synthetic peptides mapped from hypothetical proteins for improvement of the serodiagnosis of Leishmania infantum infection in dogs. From 26 identified leishmanial proteins, eight were selected, considering that no homologies between these proteins and others from trypanosomatide sequence databases were encountered. The sequences of these proteins were mapped to identify linear B-cell epitopes, and 17 peptides were synthesized and tested in enzyme-linked immunosorbent assays (ELISAs) for the serodiagnosis of L. infantum infection in dogs. Of these, three exhibited sensitivity and specificity values higher than 75% and 90%, respectively, to differentiate L. infantum-infected animals from Trypanosoma cruzi-infected animals and healthy animals. Soluble Leishmania antigen (SLA) showed poor sensitivity (4%) and specificity (36%) to differentiate L. infantum-infected dogs from healthy and T. cruzi-infected dogs. Lastly, the three selected peptides were combined in different mixtures and higher sensitivity and specificity values were obtained, even when sera from T. cruzi-infected dogs were used. The studys findings suggest that these three peptides can constitute a potential tool for more sensitive and specific serodiagnosis of L. infantum infection in dogs.

Mutations in methylenetetrahydrofolate reductase and in cysthationine beta synthase: is there a link to homocysteine levels in peripheral arterial disease?

Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase (CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed 39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development.

PAI-1 and D-dimer in type 2 diabetic women with asymptomatic macrovascular disease assessed by carotid Doppler.

Asymptomatic diabetic patients with different degrees of macrovascular complications can present different hemostatic changes. At this study, plasminogen activator inhibitor-1 (PAI-1) and D-dimer were evaluated in 12 women without diabetes and 64 type 2 diabetic women. All patients were classified into 3 different categories according to the carotid intima-media thickness (IMT) assessed by Doppler: 25 with <1 mm (normal), 15 with >1 mm and without plaque (intermediate), and 24 with stenosis lower than 50% of the vessel lumen (plaque). The results showed increased plasma D-dimer in type 2 diabetic women with carotid plaque when compared to the other groups. High levels of PAI-1 were observed in all the 3 groups of diabetic women when compared to women without diabetes. Our results suggest that high levels of PAI-1 in type 2 diabetic women are only associated with diabetes and are not associated with macrovascular progression; however, it seems that D-dimer plasma levels are associated with carotid plaque.

Resistance of dialyzed patients to erythropoietin

Resistance to recombinant human erythropoietin is a common condition in dialyzed patients with chronic kidney disease and is associated with more hospitalizations, increased mortality and frequent blood transfusions. The main cause of hyporesponsiveness to recombinant human erythropoietin in these patients is iron deficiency. However, a high proportion of patients does not respond to treatment, even to the use of intravenous iron, which indicates the presence of other important causes of resistance. In addition to the iron deficiency, the most common causes of resistance include inflammation, infection, malnutrition, inadequate dialysis, and hyperparathyroidism, although other factors may be associated. In the presence of adequate iron stores, other causes should be investigated and treated appropriately.

Comparison of discriminative indices for iron deficiency anemia and β thalassemia trait in a Brazilian population

Abstract To discriminate iron deficiency anemia (IDA) from β thalassemia trait (βTT), several indices obtained from modern blood count analyzers have been reported. Discrimination power of seven indices to differentiate between IDA and βTT, such as Green and King Index (GKI), RDW Index (RDWI), Srivastava Index (SRI), Mentzer Index (MI), Shine and Lal Index (SLI), Ehsani Index (EI), and Sirdah Index (SI), were evaluated. These indices were applied on 47 patients with βTT and on 289 patients with IDA, as confirmed by gold standard tests. Sensitivity, specificity, positive and negative predictive values, efficiency, area under receiver-operating characteristics curve (AUC), and Youdens Index (YI) were calculated. GKI and RDWI showed the highest reliability, as they had the largest AUCs (0.919, 0.912, respectively) and Youdens Index (70.4, 74.6, respectively). Conversely, SLI presented a less satisfactory performance (AUC = 0.786 and YI = 6.6). Data taken together suggest the superiority of GKI and RDWI to discriminate between IDA and βTT.

Type 2 diabetes : assessment of endothelial lesion and fibrinolytic system markers

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.

Alterações do sistema hemostático nos pacientes com diabetes melito tipo 2

Diabetes has acquired an epidemic character due to the large increase in the number of individuals affected over recent decades. Diabetes-related mortality is associated with thrombotic events, especially cardiovascular. In general, patients with diabetes present symptoms of hypercoagulability and hypofibrinolysis. However, the mechanisms that trigger hemostatic abnormalities in diabetic patients are not clear. The aim of this paper was to address the most frequent changes of the hemostatic system in diabetic patients described in the literature. Diabetics have abnormalities of the endothelium, platelets, clotting factors, natural anticoagulants and the fibrinolytic system; all these changes are directly and/or indirectly caused by hyperglycemia. Thus, analytes such as von Willebrand factor, factor VIII, fibrinogen and D-dimer are markers that should be interpreted differently in diabetic patients. Laboratory evidence of hemostatic abnormalities in diabetic patients supports clinical observations that diabetes is a state of hypercoagulability and hypofibrinolysis. Strategies for clinical intervention and medications are not well established considering the results of the hemostatic markers.

O hemograma nas anemias microcíticas e hipocrômicas: aspectos diferenciais

O diagnostico diferencial das anemias microciticas e clinicamente importante. Na tentativa de tornar esse diagnostico menos oneroso e mais eficiente, o uso de parâmetros dos contadores automaticos tem sido sugerido. O objetivo deste estudo foi avaliar a eficiencia diagnostica de alguns parâmetros do hemograma na diferenciacao das anemias microciticas. Foram comparados os parâmetros hematologicos de 395 pacientes portadores de anemia ferropriva, anemia de doenca cronica ou talassemia menor. O numero de hemacias apresentou os maiores valores combinados de sensibilidade e especificidade na diferenciacao dessas anemias. Em conclusao, a contagem de hemacias pode ser util no diagnostico diferencial de anemias microciticas.

Avaliação da anticoagulação natural em pacientes com diabetes mellitus tipo 2

BACKGROUND: Hemostatic abnormalities have been associated with vascular complications in patients with type 2 diabetes (DM2). Efficiency of the natural anticoagulation mechanism mediated by proteins C (PC), S (PS) and antithrombin (AT) depends on intact endothelial cells, so the evaluation of these proteins may contribute to a better understanding of the natural anticoagulation status, considering that they inhibit the state of hypercoagulability. OBJECTIVES: The aim of this study was to measure AT, PC and PS levels and the cofactors, factors V (FV) and VIII (FVIII), in subjects with and without DM2 and hypertension (HAS). MATERIAL AND METHOD: 16 healthy subjects (controls), seven patients with DM2, 12 with hypertension (HAS) and 18 with DM2 associated to HAS (DM2 + HAS) were included in this study for natural anticoagulation evaluation. RESULTS: HAS group showed increased levels of AT compared with controls. DM2 + HAS group showed increased levels of PC. For PS and FVIII, no difference was observed among groups. Nevertheless, the increase of FV was observed in DM2 + HAS group, while DM2 group did not show increase. CONCLUSION: AT increase is not yet well known for all conditions. Previous studies have already described PC increase in normoalbuminuric patients with DM2, however its cause is also unknown. FV increase observed in DM2 + HAS group suggests that HAS should contribute to this increase. As FVIII is an acute phase protein the data for FVIII may indicate that assessed subjects had no important inflammatory condition.