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Article ; Online: Clinical applications of immunoglobulin

Marcia Cristina Zago Novaretti / Carla Luana Dinardo

Revista Brasileira de Hematologia e Hemoterapia, Vol 33, Iss 3, Pp 221-

update

2011 Volume 230

Abstract: Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious ...

Abstract	Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia), Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.
Keywords	Immunoglobulin ; intravenous ; Plasma ; Purpura ; thrombocytopenic ; idiopathic ; Guillain-Barre syndrome ; Immune system diseases ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2011-06-01T00:00:00Z
Publisher	Associação Brasileira de Hematologia e Hemoterapia e da
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunoglobulin

Marcia Cristina Zago Novaretti / Carla Luana Dinardo

Revista Brasileira de Hematologia e Hemoterapia, Vol 33, Iss 5, Pp 377-

production, mechanisms of action and formulations

2011 Volume 382

Abstract: Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the ... ...

Abstract	Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs). There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented.
Keywords	Immunoglobulins ; intravenous ; Plasma ; Hemoderivate drugs ; Antibodies ; Immune system ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	630
Language	English
Publishing date	2011-10-01T00:00:00Z
Publisher	Sociedade Brasileira de Hematologia e Hemoterapia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Study of possible clinical and laboratory predictors of alloimmunization against red blood cell antigens in cancer patients

Carla Luana Dinardo / Glaucia Munemasa Ito / Luciana Ribeiro Sampaio / Alfredo Mendrone Junior

Revista Brasileira de Hematologia e Hemoterapia, Vol 35, Iss 6, Pp 414-

2013 Volume 416

Abstract: Background: The inflammatory background of patients influences the process of alloimmunization against red blood cell antigens. Proof of this statement to clinical practice is still lacking. Objective: The aim of this study was to verify whether factors ... ...

Abstract	Background: The inflammatory background of patients influences the process of alloimmunization against red blood cell antigens. Proof of this statement to clinical practice is still lacking. Objective: The aim of this study was to verify whether factors related to disease severity and inflammatory status of cancer patients can predict alloimmunization. Methods: This was a case-control study in which alloimmunized oncologic patients treated between 2009 and 2012 were compared with a non-alloimmunized control group regarding the severity of the disease (metastasis/performance status/body mass index) and C-reactive protein levels. Results: The groups did not differ significantly in terms of C-reactive protein, Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status, presence of metastasis and body mass index. Conclusion: It is not possible to predict alloimmunization in cancer patients based on severity of illness and inflammatory markers. Strategies of screening patients by phenotyping blood based on these criteria are not justified.
Keywords	Oxidative stress ; Beta-thalassemia ; Lipid peroxidation ; Beta-globins ; Thiobarbituric acid reactive substances ; Mutation ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Sociedade Brasileira de Hematologia e Hemoterapia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transfusion of older red blood cell units, cytokine burst and alloimmunization

Carla Luana Dinardo / Frederico Leon Arrabal Fernandes / Luciana Ribeiro Sampaio / Ester Cerdeira Sabino / Alfredo Mendrone Jr

Revista Brasileira de Hematologia e Hemoterapia, Vol 37, Iss 5, Pp 320-

a case-control study

2015 Volume 323

Abstract: BACKGROUND: Experimental data have shown that the transfusion of older red blood cell units causes alloimmunization, but the clinical applicability of this statement has never been properly assessed in non-sickle cell patients. It has been hypothesized ... ...

Abstract	BACKGROUND: Experimental data have shown that the transfusion of older red blood cell units causes alloimmunization, but the clinical applicability of this statement has never been properly assessed in non-sickle cell patients. It has been hypothesized that older units have higher numbers of cytokines, increasing the risk of alloimmunization related to antigen-presenting events. The goal of this study was to evaluate the association between the transfusion of older red blood cell units subjected to bedside leukodepletion and alloimmunization.METHODS: All patients submitted to transfusions of bedside leukodepletion red blood cell units proven to have become alloimmunized in one oncologic service between 2009 and 2013 were enrolled in this study. A control group was formed by matching patients without alloimmunization in terms of number of transfusions and medical specialty. The median age of transfused units, the percentage of transfused red blood cell units >14 days of storage in relation to fresher red cell units (≤14 days of storage) and the mean age of transfused units older than 14 days were compared between the groups.RESULTS: Alloimmunized and control groups were homogeneous regarding the most relevant clinical variables (age, gender, type of oncological disease) and inflammatory background (C-reactive protein and Karnofsky scale). The median age of transfused red blood cell units, the ratio of older units transfused compared to fresher units and the mean age of transfused units older than 14 days did not differ between alloimmunized and control patients (17 vs. 17; 68/32 vs. 63.2/36.8 and 21.8 ± 7.0 vs. 21.04 ± 7.9; respectively).CONCLUSION: The transfusion of older red blood cell units subjected to bedside leukodepletion is not a key risk factor for alloimmunization. Strategies of providing fresh red cell units aiming to avoid alloimmunization are thus not justified.
Keywords	Alloimmunization ; Old blood ; Antibodies ; Cytokines ; Transfusion ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2015-10-01T00:00:00Z
Publisher	Sociedade Brasileira de Hematologia e Hemoterapia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prophylactic strategies for acute hemolysis secondary to plasma-incompatible platelet transfusions

Cinthia Silvestre Landim / Francisco Carlos Almeida Gomes / Bernardete Martin Zeza / Alfredo Mendrone-Júnior / Carla Luana Dinardo

Revista Brasileira de Hematologia e Hemoterapia, Vol 37, Iss 4, Pp 217-

correlation between qualitative hemolysin test and isohemagglutinin titration

2015 Volume 222

Abstract: OBJECTIVE: Brazilian legislation has recently suggested the use of the qualitative hemolysin test instead of isohemagglutinin titers as prophylaxis for acute hemolysis related to plasma-incompatible platelet transfusions. The efficacy of this test in ... ...

Abstract	OBJECTIVE: Brazilian legislation has recently suggested the use of the qualitative hemolysin test instead of isohemagglutinin titers as prophylaxis for acute hemolysis related to plasma-incompatible platelet transfusions. The efficacy of this test in preventing hemolytic reactions has never been evaluated while isohemagglutinin titers have been extensively studied. The main objective of this study was to evaluate the correlation between the results of these two tests. The impact of each type of prophylaxis on the platelet inventory management and the ability of the qualitative hemolysin test to prevent red cell sensitization after the transfusion of incompatible units were also studied.METHODS: A total of 246 donor blood samples were evaluated using both isohemagglutinin titers and the qualitative hemolysin test, and the results were statistically compared. Subsequently, 600 platelet units were tested using the hemolysin assay and the percentage of units unsuitable for transfusion was compared to historical data using isohemagglutinin titers (cut-off: 100). Moreover, ten patients who received units with minor ABO incompatibilities that were negative for hemolysis according to the qualitative hemolysin test were evaluated regarding the development of hemolysis and red cell sensitization (anti-A or anti-B).RESULTS: Isohemagglutinin titration and the results of qualitative hemolysin test did not correlate. The routine implementation of the qualitative hemolysin test significantly increased the percentage of platelet units found unsuitable for transfusions (15-65%; p-value <0.001). Furthermore the qualitative hemolysin test did not prevent red blood cell sensitization in a small exploratory analysis.CONCLUSION: Qualitative hemolysin test results do not correlate to those of isohemagglutinin titers and its implementation as the prophylaxis of choice for hemolysis associated with plasma-incompatible platelet transfusions lacks clinical support of safety and significantly affects platelet inventory management.
Keywords	Platelet transfusion ; Hemolysis ; ABO blood-group system ; Blood group incompatibility ; Hemolysin proteins ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	796
Language	English
Publishing date	2015-08-01T00:00:00Z
Publisher	Sociedade Brasileira de Hematologia e Hemoterapia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quality of life scores differs between genotypic groups of patients with suspected hereditary hemochromatosis

Paula Fernanda Silva Fonseca / Rodolfo Delfini Cançado / Flavio Augusto Naoum / Carla Luana Dinardo / Guilherme Henrique Hencklain Fonseca / Sandra Fatima Menosi Gualandro / José Eduardo Krieger / Alexandre Costa Pereira / Pierre Brissot / Paulo Caleb Junior Lima Santos

BMC Medical Genetics, Vol 19, Iss 1, Pp 1-

2018 Volume 5

Abstract: Abstract Background Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical ... ...

Abstract	Abstract Background Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical and magnetic resonance imaging (MRI) assessment, and genetic testing. Questionnaires, such as SF-36 (short form health survey), have been increasingly used to assess the impact of diseases on the patient’s quality of life (QL). In addition, different genotypes are identified as results of genetic tests in patients with suspected primary iron overload. In the present study, our aim was to evaluate whether domains of QL are different according to genotypic groups in patients suspected of HH. Methods Seventy-nine patients with primary iron overload were included and two genotypic groups were formed (group 1: homozygous genotype for the HFE p.Cys282Tyr mutation; group 2: other genotypes). Results Group 1 had higher means of plasma transferrin saturation (86 ± 19%) and serum ferritin (1669 ± 1209 ng/mL) compared to group 2 (71 ± 12%, 1252 ± 750 ng/mL, respectively; p = 0.001). Four domains were significantly different among groups 1 and 2: physical functioning (p = 0.03), bodily pain (p = 0.03), vitality (p = 0.02) and social functioning (p = 0.01). Conclusions Our main finding was that patients with p.Cys282Tyr homozygosity had a worse QL scenario assessed by SF-36, compared with patients with iron overload without the same genotype. Being aware of this relationship between genotypes and QL might be helpful in the overall management of patients suspected of hereditary hemochromatosis.
Keywords	Hereditary hemochromatosis ; Quality of life ; Short form health survey ; SF-36 ; Internal medicine ; RC31-1245 ; Genetics ; QH426-470
Subject code	610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Smoking and Female Sex

Carla Luana Dinardo / Hadassa Campos Santos / André Ramos Vaquero / André Ricardo Martelini / Luis Alberto Oliveira Dallan / Adriano Mesquita Alencar / José Eduardo Krieger / Alexandre Costa Pereira

PLoS ONE, Vol 10, Iss 12, p e

Independent Predictors of Human Vascular Smooth Muscle Cells Stiffening.

2015 Volume 0145062

Abstract: Aims Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been ... ...

Abstract	Aims Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been investigated. This study's objective was to evaluate if the arterial rigidity risk factors aging, African ancestry, female sex, smoking and diabetes mellitus are associated with VMSC stiffening in an experimental model using a human derived vascular smooth muscle primary cell line repository. Methods Eighty patients subjected to coronary artery bypass surgery were enrolled. VSMCs were extracted from internal thoracic artery fragments and mechanically evaluated using Optical Magnetic Twisting Cytometry assay. The obtained mechanical variables were correlated with the clinical variables: age, gender, African ancestry, smoking and diabetes mellitus. Results The mechanical variables Gr, G'r and G"r had a normal distribution, demonstrating an inter-individual variability of VSMC viscoelasticity, which has never been reported before. Female sex and smoking were independently associated with VSMC stiffening: Gr (apparent cell stiffness) p = 0.022 and p = 0.018, R2 0.164; G'r (elastic modulus) p = 0.019 and p = 0.009, R2 0.184 and G"r (dissipative modulus) p = 0.011 and p = 0.66, R2 0.141. Conclusion Female sex and smoking are independent predictors of VSMC stiffening. This pro-rigidity effect represents an important element for understanding the vascular rigidity observed in post-menopausal females and smokers, as well as a potential therapeutic target to be explored in the future. There is a significant inter-individual variation of VSMC viscoelasticity, which is slightly modulated by clinical variables and probably relies on molecular factors.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is there justification for universal leukoreduction?

Alfredo Mendrone Jr. / Antonio Fabron Jr. / Dante Langhi Jr. / Dimas Tadeu Covas / Carla Luana Dinardo / Eugênia Amorim Ubiali / José Francisco Comenalli Marques Jr. / José Orlando Bordin / Marilia Rugani

Revista Brasileira de Hematologia e Hemoterapia, Vol 36, Iss 4, Pp 237-

2014 Volume 237

Keywords	Internal medicine ; RC31-1245 ; Medicine ; R
Language	English
Publishing date	2014-07-01T00:00:00Z
Publisher	Sociedade Brasileira de Hematologia e Hemoterapia
Document type	Article ; Online
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Article ; Online: Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis

Carla Luana Dinardo / Paulo Caleb Junior Lima Santos / Isolmar Tadeu Schettert / Renata Alonso Gadi Soares / Jose Eduardo Krieger / Alexandre Costa Pereira

Genetics Research International, Vol

2013 Volume 2013

Keywords	Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Genetics ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Non-HFE hemochromatosis

Paulo Caleb Júnior de Lima Santos / Carla Luana Dinardo / Rodolfo Delfini Cançado / Isolmar Tadeu Schettert / José Eduardo Krieger / Alexandre Costa Pereira

Revista Brasileira de Hematologia e Hemoterapia, Vol 34, Iss 4, Pp 311-

2012 Volume 316

Abstract: Hereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. ...

Abstract	Hereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.
Keywords	Hemochromatosis ; Iron overload ; Iron metabolism disorders ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Sociedade Brasileira de Hematologia e Hemoterapia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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