Danyelle Romana Alves Rios

Pre-eclampsia: Relationship between coagulation, fibrinolysis and inflammation

Pre-eclampsia (PE) is a multi-system disorder of human pregnancy, characterised by hypertension and proteinuria. Although the pathogenesis of PE is not fully understood, predisposition to endothelial dysfunction is thought to play a crucial part. Despite intensive research there is no reliable test for screening purposes or to inform decision making towards effective treatment for PE. Understanding the link between PE, abnormal haemostatic activation and inflammation may help to elucidate some of the patho-physiology of the disease; primary preventative measures and targeted therapies at an early stage of the disease could then be considered. In the present paper we discuss potential causal links between PE, haemostasis and inflammation. The potential implications of such interaction on the pathogenesis of PE are also addressed.

Hemostatic changes in patients with end stage renal disease undergoing hemodialysis

Patients undergoing hemodialysis may show both thrombotic complications and bleeding abnormalities. Hemostatic changes in patients on hemodialysis may result from alterations in vessel wall integrity and platelet function, and reduced blood flow in the native arteriovenous fistula. Vascular complications represent 20-25% of all hospitalizations of patients on hemodialysis. Literature survey revealed that changes in the hemostatic system may play a major role in vascular complications observed in these patients. Thus, it is essential to investigate hemostatic alterations in patients on hemodialysis so that adequate regimes for anticoagulant therapy could be implemented. In this review we discuss hemostatic abnormalities in end stage renal disease patients undergoing hemodialysis.

Inflammation, neoangiogenesis and fibrosis in peritoneal dialysis

Peritoneal dialysis (PD) is a form of renal replacement therapy used in patients with end stage renal disease (ESRD). It is based on using the peritoneum as a semipermeable membrane through which ultrafiltration (UF) and diffusion occur. Despite several benefits, PD has long-term complications, including inflammation, neoangiogenesis and fibrosis. Several inflammatory molecules can be found in the dialysate of PD patients including: interleukins (IL), tumor necrosis factor α (TNF-α) and C-reactive protein (CRP). Angiogenesis results in increased effective surface area exchange. Consequently, the glucose-driven osmotic pressure of the peritoneal dialysis fluid (PDF) is significantly reduced leading to UF failure (UFF). Several factors are implicated in the development of peritoneal fibrosis (PF) in PD patients. The most important factor is the conventional bio-incompatible PD solution, which contains high concentration of glucose and glucose degradation products (GDP). Although there are several studies elucidating the mechanisms leading to UFF in PD patients, more studies needed to be developed in this area and more research is required to find mechanisms to delay or to minimize the occurrence of many deleterious changes in peritoneal membrane (PM) during PD.

Acquired Pelger–Huët: What does it really mean?

Pelger-Huët anomaly (PHA) is a benign inherited condition characterized by hyposegmentation of the neutrophils nucleus and excessive chromatin clumping. An acquired neutrophil dysplasia similar to PHA has been described in hematological diseases and in some clinical conditions. It has been known as acquired or pseudo PHA. Although some hypotheses have been proposed to explain this phenomenon, the mechanism of nuclear change is still unclear. Only the laboratory and clinical data combined will yield a better understanding on the need for follow-up and management of patients in the appropriate cases. In addition, a possible cause of pseudo PHA must always be investigated to add insights to the full understanding of this abnormality. Whether this neutrophil phenomenon has clinical implications remains to be elucidated. It is clear that only a small number of patients under drugs (immunosuppressive and others) may present these neutrophil abnormalities. Most of them do not show this phenomenon and we are unable to explain the different responses in drug users. Whether these patients display a predisposition for developing bone marrow or other diseases in the future, it is a very intriguing matter and only a follow-up will solve this question.

Hemodialysis vascular access thrombosis: The role of factor V Leiden, prothrombin gene mutation and ABO blood groups.

BACKGROUND Vascular access thrombosis increases morbidity in hemodialysis (HD) patients. The aim of this study was to investigate the association between HD vascular access thrombosis and mutations in the prothrombin and factor V Leiden (FV) genes and ABO blood system. METHODS This cross-sectional study included 195 patients with end stage renal disease (ESRD) on HD for more than six months. HD patients were allocated into two groups according to the occurrence (cases, N=46) or not (controls, N=149) of previous vascular access thrombosis. FV and prothrombin gene mutations were investigated by polymerase chain reaction and ABO blood group phenotyping was performed by the indirect technique. Univariate analysis detected the variables with a trend to be associated with thrombosis and was followed by multivariate analysis to define independent predictors of vascular access thrombosis. RESULTS FV Leiden mutation and ABO blood group were not associated with vascular access thrombosis, whereas G20210A mutation in the prothrombin gene was significantly higher in patients with vascular access thrombosis and independently associated with this complication (OR=12.0; CI 95%=1.8-83.5; p=0.012). CONCLUSIONS G20210A mutation emerges as an important genetic factor predisposing to vascular access thrombosis. The definition of risk factors for thrombosis will certainly enable a rational approach for HD patients.

Increased Levels of sENG and sVCAM-1 and Decreased Levels of VEGF in Severe Preeclampsia

BACKGROUND Preeclampsia (PE) is characterized by hypertension and proteinuria after the 20th week in pregnant women who have had no previous symptoms. Clinically, it is important to diagnose the severe form of the disease, in which blood pressure is much higher. Imbalance between angiogenic and antiangiogenic factors, as well as changes in adhesion molecules seem to contribute to the endothelial dysfunction and PE clinical manifestations. The aim of this study was to assess plasma levels of the angiogenic factors (free vascular endothelial growth factor (VEGF) and soluble endoglin (sEng)) and adhesion molecules (soluble forms of intercellular adhesion molecule-1 (sICAM-1) and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1)) in severe PE (sPE), in order to clarify the circulating profile of these factors. METHODS Sixty women with sPE (34 with early sPE and 26 with late sPE), and 60 normotensive pregnant were enrolled in this study. Free VEGF, sICAM-1, sVCAM-1, and sEng plasma levels were determined by ELISA. RESULTS Increased sEng and sVCAM-1 and decreased free VEGF plasma levels were found in women with sPE, compared with normotensive pregnant group. However, no significant difference was observed comparing early and late sPE. CONCLUSION Our data confirm the imbalance in changes in angiogenic and antiangiogenic factors, as well changes in adhesion molecule (sVCAM-1) in PE. These findings give support to the hypothesis that circulating angiogenic proteins and endothelial dysfunction may have an important biologic role in PE. Data from prospective, longitudinal studies producing serial determinations of these molecules throughout pregnancy are needed to better understanding the relevance of these markers in PE diagnosis and prognosis.

Peritoneal dialysis and inflammation

Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal disease (ESRD) patients. Despite being a lifesaving treatment, the rate of mortality in patients under PD is elevated, mainly due to the chronic peritoneal dysfunction which is characterized by inflammation, peritoneal fibrosis and neoangiogenesis. The inflammatory process is trigged and modulated by the type of the peritoneal dialysis solutions (PDSs) used during PD. Currently, different PDSs are commercially available: (i) the conventional solutions; (ii) solutions of neutral pH containing low concentration of glucose degradation products (GDPs); (iii) solutions with icodextrin; and (iv) solutions containing taurine. Therefore, the aim of this review is to describe the different types of peritoneal dialysis solutions used during PD and their relationship with systemic and intraperitoneal inflammation. Some studies suggested that solutions of neutral pH containing low concentration of GDPs, icodextrin and taurine have better biocompatibility and lower influence on the inflammatory process compared to the conventional one. On the other hand, the studies, in general, were performed with a small population and for a short period of time. Therefore, further well-designed and -controlled clinical trials with larger number of individuals are required in order to better understand the role of different peritoneal dialysis solution types in the development of inflammation in patients with chronic peritoneal dialysis. Accordingly, studies that are more well-designed, well-controlled and with a larger number of patients are needed to explain and define the role of different types of PDS in the inflammation development in patients with chronic peritoneal dialysis.

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 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.

Point-of-care test (POCT) INR: hope or illusion?

In the last decade, point-of-care tests were developed to provide rapid generation of test results. These tests have increasingly broad applications. In the area of hemostasis, the international normalized ratio, INR point-of-care test (POCT INR), is the main test of this new proposal. This test has great potential benefit in situations where the quick INR results influences clinical decision making, as in acute ischemic stroke, before surgical procedures and during cardiac surgery. The INR POCT has the potential to be used for self-monitoring of oral anticoagulation in patients under anticoagulant therapy. However, the precision and accuracy of INR POCT still need to be enhanced to increase effectiveness and efficiency of the test. Additionally, the RDC / ANVISA Number 302 makes clear that the POCT testing must be supervised by the technical manager of the Clinical Laboratory in the pre-analytical, analytical and post-analytical. In practice, the Clinical Laboratory does not participate in the implementation of POCT testing or release of the results. Clinicians have high expectation with the incorporation of INR POCT in clinical practice, despite the limitations of this method. These professionals are willing to train the patient to perform the test, but are not legally responsible for the quality of it and are not prepared for the maintenance of equipment. The definition of who is in charge for the test must be one to ensure the quality control.

Cytokine Signature in End-Stage Renal Disease Patients on Hemodialysis

Hemodialysis is a modality of blood filtration in which accumulated toxins and water are removed from the body. This treatment is indicated for patients at the end stage of renal disease. Vascular access complications are responsible for 20–25% of all hospitalizations in dialyzed patients. The occurrence of thrombosis in the vascular access is a serious problem that may severely compromise or even make the hemodialysis impossible, which is vital for the patient. The aim of this study was to investigate inflammatory profile in patients undergoing hemodialysis as well as the association between these alterations and vascular access thrombosis. A total of 195 patients undergoing hemodialysis have been evaluated; of which, 149 patients had not experienced vascular access thrombosis (group I) and 46 patients had previously presented this complication (group II). Plasma levels of cytokines including interleukin (IL-) 2, IL-4, IL-5, IL-10, TNF-α, and IFN-γ were measured by cytometric bead array. Our results showed that patients with previous thrombotic events (group II) had higher levels of the IL-2, IL-4, IL-5, and IFN-γ when compared to those in group I. Furthermore, a different cytokine signature was detected in dialyzed patients according to previous occurrences or not of thrombotic events, suggesting that elevated levels of T-helper 1 and T-helper 2 cytokines might, at least in part, contribute to this complication.