Guilherme Henrique Hencklain Fonseca

HEMOPHAGOCYTIC SYNDROME ASSOCIATED WITH HEPATITIS A: CASE REPORT AND LITERATURE REVIEW

Virus-Associated Hemophagocytic Syndrome (VAHS) is a severe hematological disorder related to some viral infections. It is an illness characterized by persistent fever, pancytopenia, splenomegaly, hyperferritinemia and, the most important, hemophagocytosis observed in the bone marrow, liver and/or lymph nodes. VAHS associated with hepatitis A virus infection is rarely described, despite the high incidence of this viral infection in the population in general. There is no consensus in the literature regarding the optimal treatment of VAHS. In this article the clinical features, presumed pathogenesis, diagnostic criteria and treatment of VAHS are discussed, including description of cases of VAHS related to hepatitis A virus infection found in the medical literature.

Two new mutations in the HIF2A gene associated with erythrocytosis

Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen‐sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis‐associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor‐2α (HIF‐2α), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met‐535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe‐540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF‐2α with both VHL and PHD2. Am. J. Hematol. 2012.

Complicações cardiopulmonares das doenças falciformes

The lung is a major target organ for acute and chronic complications in sickle cell disease. Acute chest syndrome is the second most common cause of hospital admission resulting in considerable morbidity and mortality. The mainstay of successful treatment remains high quality supportive care. Fluid management, analgesia, oxygenation, bronchodilators, incentive spirometry and judicious use of transfusion therapy are essential elements of supportive care management. Pulmonary hypertension (PHT) has emerged as one of the most frequent and serious complications in these patients. The pulmonary artery pressure should be evaluated periodically by echocardiography. If the PHT diagnosis is positive the use of hydroxiurea, anticoagulation, transfusions and oxygen therapy should be considered. Cardiac manifestations are common including enlargement of the heart, myocardial ischaemia, ventricular dysfunction and cor pulmonale. The management of these complications follows the current guidelines.

First case of immune-mediated haemolytic anaemia associated to imatinib mesylate.

Abstract: Imatinib mesylate is a specific inhibitor of protein tyrosine kinase activity secondary to bcr‐abl, mostly indicated for the treatment of patients with Philadelphia chromosome positive chronic myeloid leukaemia (CML). Generally, the undesirable effects of imatinib administration observed in clinical trials were of mild‐to‐moderate degree, and no haemolysis has been associated with this drug. We report here a case of immune‐mediated haemolytic anaemia associated to imatinib mesylate successfully treated with prednisone in a patient with CML. Laboratory investigation showed anaemia [haemoglobin (Hb) of 59 g/L], reticulocyte of 61 × 109/L and a positive direct antiglobulin test. Anti‐drug in vitro studies revealed a positive result with gel microcolumn assay by an adsorption mechanism. Seventy‐four days after prednisone therapy, the patients Hb level was of 110 g/L with negative direct antiglobulin test and drug in vitro studies. This case demonstrated that patients treated with imatinib mesylate can present immune‐mediated haemolysis and adequate management of this event can be done maintaining the drug and associating corticosteroids.

Resultados maternos e perinatais em gestações complicadas por doenças falciformes

PURPOSE: the aim of this study was to describe perinatal and maternal outcomes of pregnancies complicated by sickle cell disease (SCD), comparing to pregnancies of women with sickle cell trait (SCT). METHODS: this was a retrospective cohort study, covering the period from March 2001 to April 2008, which included all pregnant women with SCD (n=42) followed up at a university hospital in the Southeast region of Brazil. The maternal and perinatal outcomes were compared to those of pregnant women with SCT (n=56) who were followed up at the same service. RESULTS:SCD-SS was diagnosed in 42 (82.4%) pregnant women and SC in 9 (17.6%). Mean (±SD) maternal age was significantly lower in the SCD group (26.0 years) compared to SCT women (28.7±7.1 years; p=0.018). The following maternal complications were more common among women with SCD in comparison to SCT: urinary tract infection (25.5 versus 8.9%; p=0.04), pneumonia (23.5 versus 1.8%; p=0.002), pulmonary hypertension (15.7 versus 0%; p=0.002), and blood transfusion during delivery or postpartum (33.3 versus 5.4%; p=0.001). Adverse perinatal outcome was more frequent in the SCD group compared to the SCT group: prematurity (49 versus 25%, p=0.01); mean gestational age at delivery (35.2 versus 37.9 weeks, p<0.001); fetal distress (56.9 versus 28.6%, p=0.006); birth weight <2,500 g (62.7 versus 17.9%, p<0.001); mean birth weight (2,183 versus 2,923 g, p<0.001), and small for gestational age infants (29.4 versus 10.7%, p=0.029). Two maternal deaths (3.9%) occurred in the group with SCD. CONCLUSION: Pregnant women with SCD are at greater risk for maternal morbidity and for adverse perinatal outcomes than women with SCT.

Cohort study of adult patients with haemoglobin SC disease: clinical characteristics and predictors of mortality.

Haemoglobin (Hb) SC disease is the second most common subtype of sickle cell disease and is potentially fatal. This study aimed to determine the clinical characteristics, outcome and predictors of mortality in HbSC disease patients, and to compare these findings with patients followed‐up in different centres. Clinical, laboratory and outcome data were collected from a cohort of adult patients with HbSC disease followed between 1991 and 2103. Cox regression multivariate analysis was used to determine predictors of mortality. One hundred and fifty‐five patients were followed‐up over 20 years: 9% died and 70·8% had at least one complication. The most common complications were: painful crises (38·3%), retinopathy (33·8%), cholelithiasis (30·3%), osteonecrosis (24·8%) and sensorineural hearing disorders (9·7%). Frequency of chronic complications was similar in most studies. In multivariate analysis, hearing disorders remained an independent predictor of mortality (Odds Ratio 9·26, 95% confidence interval 1·1–74·8; P = 0·03). It was concluded that patients with HbSC disease receive a late diagnosis and there is remarkable similarity between the studies conducted in different centres around the world. Sensorineural hearing disorders were an independent predictor of mortality, suggesting that it may be useful to implement routine diagnostic screening.

Temporomandibular joint arthritis in sickle cell disease: a case report

We report a rare case of aseptic arthritis in the temporomandibular joint of a patient with sickle cell anemia. A 22-year-old woman with sickle cell disease, in the 18th week of gestation, was referred by her hematologist to investigate a sudden mouth opening limitation and severe pain on her left cheek. The patient received a standard pain assessment protocol, clinical examination, and complementary exams (complete blood count, hemoglobin electrophoresis, blood solubility test, panoramic radiograph, and magnetic resonance imaging [MRI]). The blood results were consistent with a sickle cell crisis and the MRI showed an inflammatory process around the left temporomandibular joint. Treatment with opioid analgesics and blood transfusion provided good results. Sickle cell anemia is a disease that can cause arthritis of the temporomandibular joint, and although it is rare, clinicians should be attentive to the differential diagnosis in patients with this disease.

Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure.

Background Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown. Objective We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF. Methods Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients. Results Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001). Conclusion These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.

Acute chest syndrome in pregnant women with hemoglobin SC disease

discomfort, hypotension, and shortness of breath (oxygen saturation 90%). An emergency cesarean was performed. Placental abruption was detected, and a stillborn weighing 1,630 g was delivered. The laboratory test results showed hemoglobin electrophoresis of S 51%, C 47.5%, and F 1.5%, hemoglobin 8.4 g/dL, white blood cell count (WBCC) 34.3x10 9 /L, platelet count 142,000/mm 3 , alanine aminotransferase (ALT) 35 U/L, aspartate aminotransferase (AST) 54 U/L, total bilirubin 1.5 mg/dL, and lactate dehydrogenase (LDH) 791 U/L. The patient was transferred to the ICU immediately post-cesarean, where examination revealed that the uterus was contracted and without abnormal bleeding. At the fifth hour post-partum, she presented with bradycardia and hypotension. An intravenous infusion of vasoactive drugs and broad-spectrum antibiotics were administered. A red blood cell transfusion was performed. At the eighth hour post-partum, she was hemodynamically unstable, and echocardiography was used to diagnose diffuse hypokinesis of the right ventricle with dilatation of the right chambers. At the tenth hour post-cesarean, she presented with cardiovascular shock, bradycardia, hypotension, and cardiac arrest. The autopsy revealed bone marrow pulmonary emboli.

Massive autoimmune hemolysis documented by monocyte monolayer assay in a multiply transfused patient using reticulocytes isolated by simple centrifugation in microhematocrit tubes: ASSAY TO DOCUMENT AUTOIMMUNE HEMOLYSIS

A 34-year-old man who was positive for the human immunodeficiency virus was admitted to the hospital with intense anemia and hemodynamic instability. His hemoglobin concentration at admission was 1 g/dL, and he had a mean corpuscular volume of 110 fL/cell and an absolute reticulocyte count of 12,000/mm. He received urgent transfusion of 5 units of Images of the Monocyte Monolayer Assay performed to picture the autoimmune RBC destruction. (A) Negative control. (B,C) The patient’s results reveal that the RBCs gathered inside the macrophages in an aspect resembling a pearl necklace.