Diverse Clinical manifestations in Sickle Cell Anemia: study in District Amravati, MS India.

Background: Sickle cell disease refers to group of genetic disorder characterized by the predominance of hemoglobin S. Changes in the coagulation system seem to play an important role in the clinical manifestations of this disorder. Objective: This study aimed to determine the change in PT and APTT test in Sudanese pregnant women with sickle cell anemia. Material and methods: Fifty pregnant women with SCA with different age and different trimester, admitted to Mohammed Alamin Hamid hospital for children, were included case control study. Eleven healthy and pregnant women without SCA. Blood sample from three group were collected and investigated for PT and APTT. Results: The study revealed that in comparison with control mean PT (P=0.000) and APTT (p=0.000) high significant , in comparison with pregnant without SCA mean PT (P=0.000) and APTT (p=0.000) high significant ,no significant in comparison between all trimester mean PT (P=0.168) APTT (P=0.757) ,high significant in comparison with treatment mean PT(P=0,0000) APTT (P=0.000) ,in comparison with duration of disease and age mean PT(P=0.043) low significant with age APTT (P=0.558) no significant. Conclusion: The study concluded that these is hypercoagulable state in pregnant women with SCA indicated by prolongation in PT and APTT.

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Association of MBL2 polymorphism with Leg Ulcers Development in Sickle Cell Anemia Patients

Blood ◽

10.1182/blood.v124.21.4912.4912 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4912-4912

Author(s):

Marcos André Cavalcanti Bezerra ◽

Isabela Cristina Farias ◽

Diego Arruda Falcão ◽

Igor de Farias Domingos ◽

Luana Laranjeira Prado ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Clinical Manifestations ◽

Monogenic Disease ◽

Prior History ◽

Leg Ulcers ◽

Immune Disorder ◽

History Of ◽

Mbl Deficiency

Abstract Leg ulcers are the most common clinical manifestations of sickle cell anemia (SCA), a monogenic disease with huge clinical diversity among patients. They affect 8% to 10% of SCA patients, reaching a percentage greater than 50% in patients residing in tropical areas. These ulcers occur due to vascular occlusion, tissue hypoxia, hemolysis and genetic factors, presenting a slow healing, high recurrence rate and huge susceptibility to infection. Recently, some studies have shown a positive relationship between the complement system and the development of some vascular diseases and injuries such as leg ulcers in non-SCA patients. Mannan-binding lectin (MBL) is an important component of the humoral innate immune system, and MBL possesses several characteristics indicating that it may play an essential role in wound healing; modulating inflammation and contributing to the clearance of microorganisms and apoptotic cells. In a recent study of chronic leg and foot ulcer patients, serum MBL levels were significantly different between wounds of different etiologies, with chronic venous leg ulcers patients having a higher frequency of MBL deficiency. Polymorphisms in the MBL2 are associated with a reduction in the MBL protein serum levels, increasing risk of developing leg ulcers and also the maintenance of these wounds, compromising the integrity of the immune defence and its response to potential invading pathogens. Here, we aimed to determine the frequency of polymorphisms in the promoter region -221 (Y / X) and -550 (H / L) and exon 1 of the MBL2 and assess the clinical impact of these variants in a northeastern Brazilian SCA population who presented leg ulcers. Two-hundred seventy-five unrelated SCA patients were included. According the leg ulcers presence, the total cohort was classified in patients presenting current or prior history of leg ulcers (n=100) and SCA patients above 18 years with no history of leg ulcers (n=175). Molecular analysis was performed by qPCR. Our population was in Hardy-Weinberg equilibrium. The allelic frequency of haplotypes associated with high MBL production (HYA, LYA) was 54.5% for cases and 62.9% in controls. The genotypes related to low MBL production (HYO, LYO) in cases and controls was 27.5% and 18.6%, respectively. The frequency of genotype related to intermediate MBL production (LXA) was 18% in cases and 18.5% in controls. We had no statistically significant results when we analyzed only the polymorphisms (P>0.05). However, the phenotypic analysis between high and low MBL production revealed that patients with leg ulcers have lower MBL protein levels (P=0.019). We focused specifically on a possible role of MBL deficiency on healing complications, based on the facts that MBL deficiency is the most common immune disorder, and that a common causality for prolonged healing of these ulcers is infection or colonization by bacteria. In our study, MBL deficiency appears to increase the risk of developing leg ulcers in SCA patients. Disclosures No relevant conflicts of interest to declare.

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Phytomedicines and Nutraceuticals: Alternative Therapeutics for Sickle Cell Anemia

The Scientific World JOURNAL ◽

10.1155/2013/269659 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 24

Author(s):

Ngozi Awa Imaga

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Globin Gene ◽

Alternative Therapy ◽

Clinical Manifestations ◽

Base Substitution ◽

Beta Globin ◽

Inherited Disease ◽

Gene Encoding

Sickle cell anemia is a genetically inherited disease in which the “SS” individual possesses an abnormal beta globin gene. A single base substitution in the gene encoding the humanβ-globin subunit results in replacement ofβ6 glutamic acid by valine, leading to the devastating clinical manifestations of sickle cell disease. This substitution causes drastic reduction in the solubility of sickle cell hemoglobin (HbS) when deoxygenated. Under these conditions, the HbS molecules polymerize to form long crystalline intracellular mass of fibers which are responsible for the deformation of the biconcave disc shaped erythrocyte into a sickle shape. First-line clinical management of sickle cell anemia include, use of hydroxyurea, folic acid, amino acids supplementation, penicillinprophylaxis, and antimalarial prophylaxis to manage the condition and blood transfusions to stabilize the patient's hemoglobin level. These are quite expensive and have attendant risk factors. However, a bright ray of hope involving research into antisickling properties of medicinal plants has been rewarding. This alternative therapy using phytomedicines has proven to not only reduce crisis but also reverse sickling (in vitro). The immense benefits of phytomedicines and nutraceuticals used in the management of sickle cell anemia are discussed in this paper.

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STUDIES ON CONGENITAL HEMOLYTIC SYNDROMES

PEDIATRICS ◽

10.1542/peds.23.3.462 ◽

1959 ◽

Vol 23 (3) ◽

pp. 462-475

Author(s):

Marion E. Erlandson ◽

Irving Schulman ◽

Carl H. Smith

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Pediatric Patients ◽

Clinical Manifestations ◽

Adult Patients ◽

Present Series ◽

Risk Of Infection ◽

Laboratory Examination ◽

Careful Observation ◽

Compensation Index

Four adult patients were studied in whom classic congenital spherocytic anemia was evident clinically and by laboratory examination. Anemia, as determined by total volume of erythrocytes, was marked although concentrations of hemoglobin were only slightly low. Rates of destruction and production of erythrocytes were markedly accelerated. Six pediatric patients with minimal clinical manifestations but definite laboratory evidence of congenital spherocytosis were evaluated. Anemia, in terms of total volume of erythrocytes, was present in all patients despite normal concentrations of hemoglobin in some patients. A potential for future severe clinical manifestations was shown to be present in five of six children by the demonstration of marked hemolytic defects equivalent to the hemolytic defects present in adult patients with classic congenital spherocytic anemia. In the present series of patients with congenital spherocytosis in whom concentrations of hemoglobin were normal or slightly low, values for the total volume of erythrocytes and the compensation index were similar to values in patients with intermediate (homozygous) thalassemia and in many patients with sickle cell anemia. Abnormally low values for total volume of erythrocytes and compensation index were present in four patients in whom the rate of destruction of erythrocytes was less than six times normal. Rates of production of erythrocytes were less than six times normal in the majority of patients studied. This is contrary to a previous concept of the capacity for erythropoietic compensation in such patients. These values imply that some factor(s) which has not as yet been identified regulates the rate of erythropoiesis in these patients. Studies of four family groups of patients with congenital spherocytosis demonstrated the absence of any specific familial pattern of manifestations of the disease. It has been suggested that management of children with minimal symptoms resulting from the presence of this disease consists of careful observation, splenectomy being deferred until late in childhood to avoid a maximal risk of infection after splenectomy. It has also been suggested that splenectomy be performed before the age of 10 years in order to avoid the complication of gallstones, and that splenectomy be performed at an even earlier age if persistent severe symptoms are present. The existence of a truly mild hemolytic defect was demonstrated in only 1 of the 10 patients studied. It would seem that splenectomy is not indicated in this unusual patient.

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Superoxide Inhibits ADAMTS-13 Activity and Regulates Sickle Cell Adhesion.

Blood ◽

10.1182/blood.v106.11.2342.2342 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2342-2342

Author(s):

Prasenjit Guchhait ◽

Miguel A. Cruz ◽

Jing-Fei Dong ◽

José A. López

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Clinical Manifestations ◽

Chronic Phase ◽

Cell Disease ◽

Ample Evidence ◽

Enhanced Production ◽

Sickle Erythrocytes ◽

Erythrocyte Adhesion

Abstract The major clinical manifestations of sickle cell anemia are due to a vaso-occlusive process that leads to severe pain crises, tissue infarction, and in some instances, death. The pathophysiology of vaso-occlusion is extremely complex, the proximate cause appearing to be an increase in the adhesive interaction between sickle erythrocytes and vascular endothelium. There is ample evidence that it is the highest molecular weight forms of VWF, the ultra-large multimers (ULVWF), expressed on endothelium support sickle erythrocyte adhesion most potently. We postulate that variation in the activity of the plasma metalloprotease, ADAMTS-13, which processes ULVWF to the VWF form normally found in plasma will be an important determinant of the propensity for individuals with sickle cell anemia to develop vaso-occlusive crises. It has also been postulated that increased production of reactive oxygen species (ROS) also contributes to the pathology of sickle cell disease. ROS have been implicated in diverse cellular processes, acting through oxidation of cysteine residues. ADAMTS-13 is a cysteine-rich protein; we therefore hypothesized that its function could be affected by ROS. We measured ADAMTS-13 activity in the plasmas of sickle cell disease patients, both in the “steady state” and at various times during vaso-occlusive crises. We used three assays: a static assay that measures the ability of patient plasma to reduce the size of endothelial-derived ULVWF, a static assay that assesses the ability of patient plasma to cleave a recombinant VWF A2 fragment, and an assay performed under flow that evaluates the ability of patient plasma to cleave ULVWF attached to the surfaces of histamine-stimulated human umbilical vein endothelial cells (HUVECs). Five of nine patients with sickle cell anemia had significantly lower ADAMTS-13 activity than measured in normal controls during the chronic phase of the illness, some with activity measuring below 50% of normal levels. We also evaluated activity in two patients during acute vaso-occlusive crisis. Both patients had levels on the day of hospitalization that were indistinguishable from the levels found in patients with thrombotic thrombocytopenic purpura. Recovery of activity correlated with clinical recovery, to the point that in both cases activity was normal upon hospital discharge. We then compared superoxide generation facilitated by sickle erythrocytes with that generated by normal erythrocytes and found, as others have a significantly higher generation by sickle erythrocytes. We also found that superoxide (produced using a hypoxanthine-xanthine oxidase system) significantly decreased the activity of both plasma and recombinant ADAMTS-13 in vitro. Superoxide was also able to stimulate release of ULVWF and cell-membrane expression from cultured HUVEC. These results suggest that the enhanced production of superoxide in patients with sickle cell disease plays an important role in promoting erythrocyte adhesion to the endothelium by both stimulating release of ULVWF and inhibiting its cleavage by ADAMTS-13.

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