Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis.

The cell adhesion molecule P-selectin plays a key role in the pathogenesis of a vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the double-blind, placebo-controlled phase 2 SUSTAIN study, crizanlizumab (humanized, anti-P-selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of VOC with crizanlizumab vs placebo. This post hoc descriptive analysis evaluated the proportion of patients who did not experience a VOC during the study in the following subgroups: VOCs in the year prior to study entry (2-4/5-10), SCD genotype (HbSS/non-HbSS), and concomitant hydroxyurea use (yes/no). More patients were VOC event-free in the crizanlizumab 5 mg/kg arm than in the placebo arm, including those with more frequent prior VOCs (ie, 5-10; 28.0% vs 4.2%), the HbSS genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%). Further analyses of secondary endpoints demonstrated that crizanlizumab treatment significantly increased time-to-first VOC vs placebo in these subgroups. The rates of treatment-emergent adverse events were similar between treatment arms across all subgroups. This post hoc analysis of SUSTAIN shows that in patients with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS genotype, crizanlizumab treatment increases the likelihood of patients being VOC event-free and delays time-to-first VOC.

Length of treatment and dose as determinants of mutagenicity in sickle cell disease patients treated with hydroxyurea.

Hydroxyurea (HU) is an antineoplastic drug widely used in the clinical management of patients with sickle cell disease (SCD), and many questions related with its use remain unresolved. Given the severity of SCD, HU benefits, although not thoroughly confirmed, seem to outweigh its potential carcinogenicity. This study aimed to assess the genotoxicity associated with HU dose and treatment length by evaluating mutagenicity in patients with SCD treated with HU (SCHU) using the cytokinesis-block micronucleus assay (CBMN) in white cells. The study was conducted with 35 individuals in the SCHU group and 34 controls matched according to age, sex and smoking habit. CBMN results showed an increase (p=0.032) in the number of micronuclei (MN), but not of nucleoplasmic bridges (NPB) or nuclear buds (NBUD) in the SCHU group. The increased frequency of MN in the SCHU group was significantly correlated with treatment length and final HU dose, which confirms that patients with SCD treated with HU should be carefully monitored to reduce the risk of carcinogenicity.

Cirurgia e anestesia na doença falciforme / Anesthesia and surgery in sickle cell disease

Pacientes com doença falciforme (DF) que serão submetidos a procedimentos anestésicos e cirúrgicos demandam cuidados específicos. Condições comumente associadas a estes procedimentos, como hipóxia, acidose, hipotermia, infecção e hipovolemia, podem ter conseqüências deletérias especialmente graves no paciente com DF. Há uma tendência ao aumento da eritrofalciformação e dos fenômenos vaso-oclusivos, o que pode levar à síndrome torácica aguda, episódio álgico agudo, priapismo, acidente vascular cerebral dentre outras complicações diretamente relacionadas à DF. Para minimizar o risco destas complicações, recomenda-se que pacientes com DF tenham avaliação pré-operatória multidisciplinar, atenção especial à hidratação e oxigenação, escolha de procedimentos cirúrgicos menos invasivos e cuidados pós-operatórios intensivos. Mesmo com a adoção destes cuidados, a incidência de complicações cirúrgicas em pacientes com DF é especialmente alta, estimada em 25 por cento a 30 por cento. O objetivo desta revisão é abordar as principais condições cirúrgicas associadas à DF e os cuidados perioperatórios que devem ser tomados neste grupo de pacientes.

Individuals with sickle cell disease (SCD) have special perioperative concerns that must be considered before their anesthesia and surgery. During the perioperative period, these individuals are at risk for vaso-occlusive events, including acute chest syndrome, pain crises, priapism and stroke because they are exposed to hypoxia, acidosis, hypothermia, infections and hypovolemia. Several suggestions to reduce risk have been made, including a structural multidisciplinary approach, paying special attention to hydration and oxygenation, postoperative respiratory care and selection of less aggressive or extensive surgical procedures. Even with meticulous care, approximately 25 percent to 30 percent of individuals with SCD will have a postoperative complication. This article provides readers with information about the role of surgery in SCD and the measures that should be taken to ensure patients are well cared for in the perioperative period.

Prevalência de talassemias e hemoglobinas variantes em pacientes com anemia não ferropênica / Prevalence of thalassemias and variant hemoglobins in patients with non-ferropenic anemia

Para estabelecer a freqüência de hemoglobinopatias e talassemias em pacientes com anemia não ferropênica foram estudados 58 casos de pacientes comprovadamente com anemia não ferropênica e 235 controles obtidos de pessoas sem anemia. Todas as amostras foram obtidas do Hospital de Clínicas de Porto Alegre (HCPA), RS, Brasil. As técnicas realizadas foram eletroforese em acetato de celulose, pH alcalino, pesquisa citológica de Hb H, HPLC, hemograma e ferritina. A análise dos dados realizada no grupo de pacientes com anemia não ferropênica demonstrou que 63,8 por cento eram portadores de alguma forma de anemia hereditária: 25,9 por cento de talassemia alfa heterozigota, 32,8 por cento de talassemia beta heterozigota, 3,4 por cento de heterozigose para hemoglobina S (Hb AS) e 1,7 por cento de homozigose para hemoglobina C (Hb CC). No grupo dos controles, foram identificados 14,1 por cento de anemias hereditárias, sendo destas 11,5 por cento de talassemia alfa, 0,9 por cento de talassemia beta, 1,3 por cento de heterozigose para hemoglobina S (Hb AS) e 0,4 por cento de heterozigose para hemoglobina C (Hb AC). Os resultados obtidos permitem concluir que a prevalência de talassemias e hemoglobinas variantes no grupo controle é coincidente com a descrita na literatura. Entretanto, a excepcional prevalência dessas hemopatias hereditárias em pessoas com anemia não ferropênica deve ser divulgada entre médicos e serviços de saúde dada a sua importância no diagnóstico definitivo de anemia e dos corretos procedimentos terapêuticos.

Long-term follow-up of kidney allografts in patients with sickle cell hemoglobinopathy

Although sickle cell anemia and sickle cell disease produce a variety of functional renal abnormalities they uncommonly cause end stage renal failure. Renal transplantation has been a successful alternative for the treatment of the rare terminal chronic renal failure with outcomes comparable with non-sickle recipients. This approach, however, has not been often described on patients with renal failure associated with SC hemoglobinopathy. Here we report the outcomes of two patients with chronic renal failure due to SC hemoglobinopathies who underwent renal transplantation. At the time of the transplantation they were both severely anemic and had frequent vasoocclosive pain crises. Both patients evolved with good allograft function, near normal hematological parameters, and very rare pain crisis, thirteen and eight years after transplant. These cases illustrate that terminal renal failure due to SC hemoglobinopathy can be successfully managed by renal transplantation and satisfactory long-term results are achievable not only in terms of renal allograft function but also of their hematological condition

Genetic aspects of Schistosoma mansoni infection severity

A variabilidade genética em 13 sistemas proteicos foi investigada em uma amostra de 61 pacientes com hepatosplenomegalia (H) esquistossomótica e 61 com a forma intrestinal (I) doença, provenientes de uma regiäo endêmica (Catolandia, estado da Bahia). Foi verificada apenas uma diferença significante nas distribuiçöes genotípicas de pacientes H e I. Os homozigotos GLO*1/GLO*11 têm uma incidência relativa da forma hepatosplênica 4 vezes maior e os heterozigotos GLO*1/GLO*2 3 vbezes maior do que os homozigotos GLO*2/GLO*2