scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter

To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2705-2705
Author(s):  
Jonathan R. Lindner ◽  
Michael Widlansky ◽  
Melinda D. Wu ◽  
Jillian Dargatz ◽  
Leanne M. Harmann ◽  
...  

Abstract Background: Outcome measures for therapeutic studies in patients with sickle cell disease (SCD) are poor.Abnormal microvascular blood flow (MBF), the basis for tissue ischemia and injury associated with vaso-occlusion, would be an optimal outcome measure for SCD studies. Ideally, a modality to measure blood flow in SCD would non-invasively quantify microvascular tissue perfusion rather than assess conduit arterial flow through large vessels. Limitations of existing techniques to measure blood flow prevent their widespread use in clinical trials of patients with SCD. Contrast-enhanced ultrasound (CEU) is a non-invasive and portable technique that uses standard ultrasound equipment to measure microvascular perfusion and functional capillary patency. The primary objective of this study was to determine whether CEU is able to detect differences in the MBF of skeletal muscle: 1) before and after infusion with the adenosine A2A receptor (A2AR) agonist regadenoson, and 2) between steady state and vaso-occlusive crisis (VOC). Methods: CEU measurements were obtained in forearm skeletal muscle in adult HbSS patients. Two measures are used to calculate MBF: 1) velocity of RBCs through capillaries and 2) volume of blood perfused in an area of tissue. MBF is the product of RBC velocity and volume of blood. In one study cohort, MBF was measured in steady-state patients during a 24-hour infusion of regadenoson (1.44 µg/kg/hour). CEU perfusion imaging was obtained at baseline, 6 and 24 hours after initiation of regadenoson. In the second study cohort, CEU measurements were obtained within the same patient during a hospital admission for VOC and at steady state. MBF was expressed in terms of a ratio to baseline flow (pre-regadenoson) in cohort 1 and as a ratio of VOC to steady-state flow for cohort 2. Results: CEU measurements were obtained in13 patients administered regadenoson, and 7 patients at steady state and during VOC. Median age (range) of all patients studied was 24 years (20-45) and 55% were female. During regadenoson infusion, there was a median increase in skeletal muscle MBF of 29% at 6 hours (ratio 1.29, IQR 0.81) and 9% at 24 hours (ratio 1.09, IQR 1.40). Increase in MBF during regadenoson administration was largely due to higher RBC velocity (6 hours ratio: 1.24, IQR 0.88; 24 hours: ratio 1.12 IQR 0.85). There was a median decrease of 40% in skeletal muscle blood flow during VOC compared to steady state (ratio 0.60, IQR 0.27). Similarly, a decrease in RBC velocity accounted for most of the reduction in MBF in VOC compared to steady state (ratio 0.63, IQR 0.35). Conclusion: CEU measures of skeletal muscle MBF increased during a 24-hour infusion of regadenoson and decreased in VOC compared to steady state. Changes in RBC velocity, as opposed to the volume of blood perfused, accounted for most of the differences in MBF seen during regadenoson infusion and VOC. Alterations in rheology or vascular tone could explain these changes. These data provide additional evidence for the A2AR agonist regadenoson as a therapeutic modality for patients with SCD and suggest that CEU is a valid measure of blood flow in VOC. Taken together, the findings of this preliminary study demonstrate that CEU, a non-invasive, portable technique to measure MBF, could be used as an objective outcome measure for therapeutic studies in SCD. Disclosures Field: NKTT: Consultancy, Research Funding. Off Label Use: IND for regadenoson for treatment of VOC in sickle cell disease.


Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 79-85
Author(s):  
Oluwagbemiga Oluwole Ayoola ◽  
Rahman Ayodele Bolarinwa ◽  
Chidiogo Chukwunweike Onwuka ◽  
Bukunmi Michael Idowu ◽  
Adeniyi Sunday Aderibigbe

BackgroundEndothelial dysfunction (ED), as ascertained by brachial artery flow-mediated dilation (FMD), is a known feature of sickle cell disease (SCD), which is present both in crisis and in steady state. The assessment of FMD was introduced to examine the vasodilator function. Our objective was to establish the relationship between ED determined by FMD, biomarkers of renal dysfunction, and biomarkers of disease severity in SCD subjects asymptomatic of renal disease.MethodsWe enrolled 44 patients with homozygous SCD in steady state and 33 age- and sex-matched controls between 2013 and 2014 in a tropical tertiary hospital. Ultrasonographic FMD of the right brachial artery, renal arterial Doppler, complete blood count, creatinine, fetal hemoglobin, soluble P-selectin, and cystatin C (Cys-C) levels were determined. Using the median FMD value of the control group, the SCD subjects were further classified into two groups for comparison.ResultsThe median FMD in SCD subjects of 3.44 (IQR, 0.00–7.08) was significantly lower than that of controls, which was 5.35 (IQR, 3.60–6.78; P=0.04). There was negative correlation between FMD and Cys-C levels (r=−0.372; P=0.01) along with renal artery resistivity index (RARI; r=−0.307; P=0.04) in SCD subjects. Additionally, Cys-C level was significantly higher in SCD subjects with FMD<5.35.ConclusionsBrachial artery FMD was significantly lower in SCD subjects compared with a control group. Cys-C and RARI show a negative correlation with FMD, indicating that renal function is related to ED in SCD.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4918-4918
Author(s):  
Magda Oliveira Seixas Carvalho ◽  
Carvalho Luís André ◽  
Mauri­cio Batista Carvalho ◽  
Larissa Carneiro Rocha ◽  
Valma Maria Lopes Nascimento ◽  
...  

Abstract Sickle cell disease (SCD) has heterogeneous clinical picture and there are several pathway involved in SCD pathogenesis, and chronic inflammation and hemolysis are important hallmarks of the disease. Based on such points, there is a search for prognostic markers to establish possible sub-genotypes of the disease. The present study investigated the alpha-1 antitrypsin (AAT) levels, a serum glycoprotein inhibitor of proteases responsible for trigger inflammatory reactions, describing its associations with SERPINA1 gene polymorphisms, hematological and chemistry biomarkers, and clinical history in a group of SCD children in steady-state. The study was approved at FIOCRUZ research board and followed the principle of Declaration of Helsinki. A total of 356 steady state unrelated SCD patients were included at the present study and a control group (CG) compound by 100 unrelated healthy individuals sex and age matched with the patients group, which were from the same geographical origin. Patients age ranging 13.96+9.91 years of age, the AAT levels higher than the 50th percentile (158.0 mg/mL) had significantly lower red blood cells (RBC) count (p=0.003), hemoglobin (Hb) (p=0.0002) and hematocrit (Hct) (0.0002) concentration, and higher white blood cells (WBC) (p=0.004) and neutrophils (p=0.0001) counts, and higher C-reactive protein (CRP) levels (p<0.0001), and lower urea levels (p=0.0003). AAT had significant negative correlation with RBC (r=-0.205, p=0.0001), Hb (r=-0.203, p=0.0001), Hct (r=-0.256, p<0.0001), high density lipoprotein cholesterol (HDL-C) (r=-0.205, p=0.0001), urea (r=-0.184, p=0.0005), creatinine (r=-134, p=0.012), and albumin (r=-0.135, p=0.011), and significant positive correlation with WBC (r=0.18, 0.0007), neutrophils (r=0.2297, p<0.0001), HbS (r=0.2874), total bilirubin (r=0.137, p=0.01), direct bilirubin (r=0.136, p=0.001), indirect bilirubin (r=0.115, p=0.032), lactate dehydrogenase (r=0.159, p=0.003), ferritin (r=0.1353, 9=0.011), CRP (r=0.355, p<0.0001). Patients with higher levels of AAT had clinical history of more than three infection episodes (OR=1.71, CI:1.05-2.65, p=0.02), gallstones presence (OR=1.75, CI:1.03-2.97, p=0.02), and received more blood therapy (OR=2.35, CI:1.51-3.65, p=0.0001).The SERPINA1 gene polymorphisms were analyzed in 126 SCD patients and 100 CG individuals, the protease inhibitor (Pi)*MM or wide type genotype was find in 115 (91.3%) of SCD patients and 92 (92%) of CG; the PI*SS genotype was find in 2 (1.6%) SCD patients and in none individual of the CG; the PI*MS genotype was find in 9 (7.1%) SCD patients and in 6 (6%) CG individuals; and the PI*MZ genotype was find in 2 (2%) CG individuals. Ours results suggest that the AAT may be considerer as a marker of SCD patients’ outcome, once increased levels is related to stress situation, anti-inflammatory and inhibitory proteases properties and may act as a physiological and cytoprotective regulator influencing the severity of SCD. Our results related to SERPINA1 genotypes emphasize the role of the mutant allele in decrease the AAT production what may represent a risk factor. Additional studies should be carried out in order to investigate mechanisms throughout the AAT can induce several important events in the SCD pathogenesis. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Maysaa Ali Hassan Ali ◽  
Elharam Ibrahim Abdallah ◽  
Alaa Eltayeb Omer ◽  
Lienda Bashier Eltayeb

Background: Patients with Sickle Cell Disease (SCD) have been found to have an aberrant coagulation profile. One of the primary elements hypothesized to contribute to the vaso-occlusive crisis that characterizes sickle cell disease is coagulopathy (SCD) Material and Methods: A total of 150 children were enrolled as follows, 50 children with Sickle Cell Anemia (SCA) in steady-state, 50 in crisis, and 50 with Hb AA genotype as control. 5 ml of Venous blood was collected. The platelets count was performed using Sysmex KX21N, the electrical impedance principle. The Mean Platelet Volume (MPV) is derived from the impedance platelet size distribution curve. STAGO PT31039352) semi-automated machine was used for estimation of PT, and APTT. Result: children with SCA have significantly a prolonged PT, and APTT compared with children with normal hemoglobin genotype (P. value < 0.001) the mean of PT was (16.64, and 12.6) respectively, and APTT (41.45 and 37.94) consequently. A significant increase in platelet count between patients with SCA when compared with control (p. value 0.02), however a significant prolonged in APTT when compared to steady-state (P. value 0.005). MPV among children with crises when compared with steady-state revealed a significant result (p. value 0.006) the mean of MPV in steady-state = 6.79 while the mean of MPV in crisis = 7.09. Conclusion: children with sickle cell anemia had a longer coagulation profile and marked variation in platelet count, which may increase the risk of thrombosis or bleeding.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4930-4930
Author(s):  
Peter B. Soh ◽  
Abdul H. Siddiqui

Abstract Background Stroke and splenic sequestration are known complications associated with sickle cell disease in children. The cerebral blood flow velocity measured by transcranial doppler ultrasonography (TCD) is a screening tool to identify patients who are at increased risk of stroke. Children with critical time-average maximum velocity (TAMV) are started on chronic blood transfusion program to prevent stroke. Iron overload, inhibitor development and risk of infection are some of the complications associated with chronic blood transfusions. The objective of this study was to assess the changes in cerebral blood flow and the need for chronic blood transfusions after splenectomy performed in children with splenic sequestration. Methods A retrospective chart review of sickle cell disease children splenectomized between 1999 and 2014 at the University of South Alabama was performed. In addition to demographic data, results of routine screening TCDs for up to 15 years were obtained and compared to pre-splenectomy TCDs by using the paired t-test. We also compared the TAMV and blood counts in splenectomized and non-splenectomized patients of the same sickle cell disease variant that were age- and sex-matched. The cases were also compared to a non-splenectomized cohort control group comprising of children with sickle cell disease using the independent t-test. Results A total of 40 patients (36 with Hemoglobin SS disease and 4 with S-Beta Thalassemia Zero) received splenectomy during the study period at a mean age of 2.5 years (1.5 to 18 years). The mean TAMV before splenectomy was 129 cm/sec, which increased to 157 cm/sec and decreased back to 137 cm/sec at two and five years post-splenectomy, respectively. When comparing these changes using the paired t-test, the difference was not statistically significant. Four (10%) of these patients needed to be started on chronic blood transfusions due to critical TCDs. Another patient had a critical TCD before splenectomy and was continued on chronic transfusions post-splenectomy. The mean TAMV in our sickle cell patients without splenectomy at age 14 years was 123 cm/sec (n=107). Five (4.7%) of these patients were receiving chronic blood transfusions for critical TCDs. The odds ratio of having a critical TCD in splenectomized patients versus non-splenectomized patients was 2.3:1. The TAMV in patients at 2 years post-splenectomy was 157 cm/sec compared to 139 cm/sec in age- and sex-matched non-splenectomized controls (p = 0.035). The mean platelet count prior to splenectomy was 301/m3. It increased to 536/m3 one year post-splenectomy and remained elevated at 510/m3 four years post-splenectomy. The differences in platelet counts were statistically significant. The mean platelet count in non-splenectomized patients at 14 years of age was 387/m3. Prevalence of treatment with Hydroxyurea was 45% (18 patients) in splenectomized patients and 18% (19 patients) in the non-splenectomized control group. Conclusion We conclude that the mean cerebral blood flow velocity was increased after splenectomy. When comparing cases to matched controls, the biggest difference in TAMVs was found at two years post-splenectomy. Splenectomy is effective in preventing life threatening sequestration events. However, in our patient cohort, the risk of requiring chronic blood transfusions for a critical TCD (≥200 cm/s) doubled after splenectomy. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 7 (2) ◽  
pp. 17 ◽  
Author(s):  
Charles Antwi-Boasiako ◽  
Gifty Dankwah ◽  
Robert Aryee ◽  
Charles Hayfron-Benjamin ◽  
Eric Donkor ◽  
...  

Oxidative stress plays a very significant role in the pathophysiology of sickle cell disease (SCD) and associated complications. Oxidative stress, which is often experienced by SCD patients as a result of continuous production of reactive oxygen species (ROS), may lead to endothelial dysfunction and acute inflammation. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), often play a protective role. The current study aimed at determining the oxidative profile of persons with SCD at a tertiary hospital in Ghana. This was a case-control study involving 90 patients with SCD (34 HbSS patients at steady state, 30 HbSC at steady state, 15 HbSS with vaso-occlusive crisis, 11 HbSC with vaso-occlusive crisis), and 50 HbAA control group. Whole blood samples were collected from the study participants and analyzed for full blood counts. The blood samples were assayed for SOD and CAT as a measure of antioxidant defense, while lipid peroxidation was quantified as malondialdehyde (MDA). The results showed that the levels of SOD and CAT were significantly lower in SCD patients as compared to the control group. Patients with HbSS vaso-occlusive crisis had the lowest levels of SOD and CAT. The difference in SOD levels between HbSS at steady state and HbSC with vaso-occlusive crisis was, however, not significant (p = 0.228). The MDA level was significantly higher in SCD patients compared to the control group. This study concludes that the levels of various antioxidant enzymes (erythrocyte SOD and erythrocyte CAT) and oxidative marker (MDA) and are altered in SCD patients.


2014 ◽  
Vol 6 (1) ◽  
pp. e2014044 ◽  
Author(s):  
Adel Abd elhaleim Hagag ◽  
Ghada Elmashad ◽  
Aml Ezzat Abd El-Lateef

Abstract: Background: Sickle cell disease has a worldwide distribution. Vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease. Thrombospondin (TSP1) and Placenta growth factor (PlGF) have been reported to be involved in sickle cell diseases (SCD). Objective: The aim of this study is to assess TSP1 and PlGF levels in SCD patients. Patients and methods: This study was carried out in forty patients with sickle cell anemia who were attendants to Hematology units, Pediatric Departments, Tanta and Elmenofia University Hospital in the period between December 2011 and December 2013 including twenty patients with sickle cell anemia during vaso-occlusive crisis (twelve males and eight females) and twenty patients with sickle cell disease out of crisis (ten males and ten females). Also this study included twenty healthy children of matched age and sex as a control group. Serum TSP1 and PlGF levels were analyzed by ELISA. Results: Mean serum TSP1 levels were significantly higher in SCA patients with crisis than SCA patients out of crisis and were significantly higher in SCA patients with or without crisis compared to controls. Mean serum Placenta growth factor levels were significantly higher in SCA patients with crisis than SCA patients out of crisis and were significantly higher in SCA patients with or without crisis compared to controls. Conclusions: TSP1and PlGF concentration may be useful VOC markers in SCD patients. Recommendation: Further studies should be conducted to determine the exact point before VOC, when serum TSP1 and PIGF levels begin to increase. This requires monitoring of the TSP1 and PIGF levels in sickle cell patients out of crisis, showing how rapidly these levels increase just before VOC development.


Author(s):  
Kingsley Akaba ◽  
Ofem Enang ◽  
Bassey Okon Bassey ◽  
Oluwakorede Babatope ◽  
Omolabake Riman

Background: Sickle cell disease (SCD) is often associated with liver disease. The constant state of haemolysis, multiple blood transfusion, viral hepatitis, hepatic sinusoidal congestion, haemosiderosis and cholestasis, are all conditions which may eventually evolve into liver disease. Sickle cell disease is a heterogeneous group of disorders that is usually associated with an autosomal recessive structural haemoglobin disorder. Biochemical abnormalities have been associated with SCD and it is usually more pronounced in vaso occlusive crises; an acute bone crisis and common painful complication of SCD, than in steady state. Aim: The aim of the study was to assess some biochemical parameters in relation to SCD patients in our environment with a view to improving the monitoring and management of these patients.  Methodology: The study was a comparative hospital based research carried out at the University of Calabar Teaching Hospital (UCTH), Calabar, South-South Nigeria. Liver function tests were carried out on 60 SCA both in steady state and in crisis and also on 50 apparently healthy adults.  The data collected were analyzed using statistical data for social sciences (SPSS) Version 22 for windows. Pearson linear correlation and simple inferential statistical methods were employed for data analysis, a P ≤ 0.05 was considered to be statistically significant. Result: The serum concentrations of AST, ALT, ALP, LDH, Total and conjugated bilirubin were seen to be elevated in VOC compared to in steady state and with the apparently healthy control group. The AST/ALT ratio was also observed to be elevated in VOC as compared with the steady state and the control. Significant product moment correlation was observed in the biochemical parameters both in steady state and in VOC. Conclusion: The findings of this study revealed marked changes in the biochemical parameters of the liver in VOC than in steady state. It will be recommended that routine evaluation and proper interpretation of liver enzymes is paramount in early detection of liver pathology in SCD.


Author(s):  
Ofonime Lawrence Effiong ◽  
John C. Aneke ◽  
Ifeyinwa Maryann Okafor ◽  
Clara Ngozi Soronnadi ◽  
Iniobong Eno Abasibom

Background: The experience of painful episodes of ill health caused by sequelae of erythrocytes sickling, impaired blood flow, hypercoagulation and vaso-occlusion is one of the hallmarks of sickle cell disease. Preventing painful episodes and promoting the physical wellbeing of persons with sickle cell disease is usually a major objective in the management of the condition. The purpose of this study is to investigate capillary blood flow and D-Dimer activities in people with sickle cell anaemia.Methods: A total of 90 subjects (27 males and 63 females) participated in the study, the study comprised of 34 HbSS patients, three were in crisis and thirty-one in steady state, 9 sickle cell carriers (HbAS) and 47 HbAA were control subjects. The haemoglobin phenotype was determined using haemoglobin electrophoresis at alkaline pH (8.6), speed of capillary blood flow was estimated using vascular Doppler ultrasonographic technique and D-Dimer was determined using ELISA method.Results: Results obtained showed that there was a significant variation (p=0.042) in the mean levels D-Dimer among the groups. There was however no significant variations (p>0.05) in the other parameters among the groups. A post hoc analysis of mean D-Dimer in sickle cell patients, sickle cell carriers and controls showed that the sickle cell patients had significantly higher D-Dimer levels compared with controls.Conclusions: Sickle cells patients in steady state had higher D-Dimer levels compared with controls and sickle cell patients in crisis had lower speed of capillary blood flow when compared to sickle cell patients in steady state and controls.


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