scholarly journals Cortical Thinning and White Matter Loss in Sickle Cell Anemia Despite Chronic Exchange Transfusion Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4169-4169
Author(s):  
Olubusola Oluwole ◽  
Tales Santini ◽  
Joseph Mettenburg ◽  
Tamer Ibrahim ◽  
Enrico M Novelli
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Brain Atrophy ◽  
Exchange Transfusion ◽  
Cerebral Atrophy ◽  
Acquisition Time ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Prospective Longitudinal

Abstract Neurovascular complications are a common and major cause of morbidity and mortality in patients with sickle cell disease (SCD). Prior studies have demonstrated cortical thinness (Kim et al. 2016) as well as reduced cerebral volume in children with SCD (Kawadler et al. 2013) when compared to age-matched controls. There is very limited data regarding cerebral volume in adults with SCD. Recently, our group showed that adults with SCD have reduced cerebral volumes when compared to race and age-matched controls (Santini et al. 2021a). A prior prospective study by Nitkunan et al. 2011. demonstrated brain atrophy rate of −0.914%±0.8% in older adults (mean 68 years old) with Small Vessels Disease, which is about twice the rate of healthy controls. Transfusion therapy has been effective in the primary and secondary prevention of strokes and silent infarcts in SCD. Automated erythrocytapheresis (exchange transfusion), in particular, is the most aggressive disease modifying-treatment in SCD, by rapidly diluting sickle hemoglobin and replacing it with normal hemoglobin. We hereby present a case of a 42 -year-old woman with sickle cell anemia (HbSS) who developed accelerated loss of cerebral volume within a three-year period despite chronic exchange transfusion therapy. The patient underwent brain MRI in 2016 and 2019 as part of an NIH-funded, prospective, longitudinal study of the neuroradiological correlates of cognitive dysfunction in SCD. Past medical history is notable for prior right hemispheric stroke for which she was placed on chronic exchange transfusion monthly with the goal of reducing HbS to <30%. T1-weighted images were acquired at 7T MRI using a customized RF coil (Santini et al. 2021b) and with the following parameters: 3D MPRAGE, TE/TI/TR = 2.17/1200/3000 ms, resolution 0.75 mm isotropic, total acquisition time = 5 min. The extent of atrophy was estimated using the longitudinal analysis as part of the Freesurfer package (version 7.1.1) and ITK-snap (version 3.8.0). The pre-exchange HbS was reliably maintained <30% throughout the observation period, during which the patient did not develop new strokes or neurological complications. Unfortunately, in spite of the patient's excellent adherence with the treatment and the achievement of the target HbS values, we observed progression of cerebral atrophy of 2.47% in volume in the hemisphere contralateral to the stroke between the two time points. The differences are also visible in the raw data (Figure 1). Chronic exchange transfusion is the most aggressive preventive treatment for the neurological sequelae of sickle cell disease. This case demonstrates an accelerated brain atrophy, suggesting that this treatment may not be fully protective against progressive cerebral atrophy. Unfortunately, the mechanism of brain atrophy in SCD is not fully understood. More longitudinal studies are needed to assess cortical changes and cerebral volume changes as this can lead to further understanding of their pathophysiology and to the development of therapeutic options to arrest the progression of cerebrovascular disease in this population. Figure 1 Figure 1. Disclosures Novelli: Novartis Pharmaceuticals: Consultancy.

Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy

2021 ◽  
pp. 103304
Author(s):  
Susanna A. Curtis ◽  
Balbuena-Merle Raisa ◽  
John D. Roberts ◽  
Jeanne E. Hendrickson ◽  
Joanna Starrels ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Exchange Transfusion ◽  
Adult Patients ◽  
Cell Disease ◽  
Transfusion Therapy

scholarly journals How I treat and manage strokes in sickle cell disease

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3401-3410 ◽  
Author(s):  
Adetola A. Kassim ◽  
Najibah A. Galadanci ◽  
Sumit Pruthi ◽  
Michael R. DeBaun
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Management Strategies ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Hematopoietic Stem ◽  
Neuro Imaging

Abstract Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD.

A Randomized Trial of the Safety and Benefit of Transfusion Vs. Standard Care In the Prevention of Sickle Cell-Related Complications In Adults: a Preliminary Report From the Phase II NHLBI Comprehensive Sickle Cell Centers (CSCC) Study of Neuropsychological Dysfunction and Neuroimaging Abnormalities In Neurologically Intact Adult Patients with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3221-3221 ◽  
Author(s):  
Elliott Vichinsky ◽  
Lynne Neumayr ◽  
Jeffrey I Gold ◽  
Michael W Weiner ◽  
Jeffrey Kasten ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adverse Events ◽  
Randomized Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Preliminary Report ◽  
Standard Care ◽  
Neurocognitive Function ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Abstract 3221 Background: Most adult sickle cell anemia patients have received transfusion therapy. However, prospective studies evaluating the efficacy of transfusions in preventing sickle cell-related complications are lacking. The Phase II Neuropsychological Adult Sickle Cell Anemia Study is a randomized trial of chronic transfusion vs. standard of care in patients with abnormal neurocognitive function in order to determine the safety and benefits of transfusion therapy on neurocognitive function. A secondary goal of the study is to evaluate the benefit of chronic transfusion on the frequency and severity of acute sickle cell events; this is a preliminary report of this specific aim. Methods: Eligibility required normal neurological exam, WAIS III PIQ score ≤ 90, hemoglobin ≤ 9 g/dL, hemoglobin SS electrophoresis, and age between 21 and 55 years. Patients were randomly assigned to receive either standard care or transfusions. The transfusion goal was to maintain a hemoglobin of 2 g/dL rise over baseline with matched red cells for D, C/c, E/e, and Kell antigens. The protocol required simple transfusions at approximately 4 week intervals. Chelation therapy was not part of the study design. Patients underwent serial clinical and laboratory evaluations with central analysis of all clinical and transfusion events and complications. Laboratory testing of subjects in the transfusion arm included quantitative hemoglobin S/A, hemoglobin concentration, ferritin levels, and red cell antibody screening; a full hematology/chemistry panel was performed for all subjects at baseline, the study mid-point, and at the end of the study. Results: There were 20 patients in the transfusion arm (TX arm) with a mean age of 29 years vs. 16 patients in the standard care arm (SC arm) with a mean age of 30.5 years. The baseline data in the TX arm was similar to the SC arm: hemoglobin 7.8 vs. 8.0 g/dL; hematocrit 22.6% vs. 23.1%; hemoglobin F 10.5% vs. 12.5%. Thirty-five percent of patients randomized to the TX arm had a history of acute chest syndrome (ACS) vs. 31% in the SC arm; 30% of patients in the TX arm were on hydroxyurea compared to 50% in the SC arm. The TX arm patients have received an average of 5.6 transfusions (2 units per transfusion) with only one subject requiring an acute transfusion (5%); in contrast, 4 SC arm patients (25%) were transfused for acute events for a total of 7 units (average 1.8 per patient). The transfusion therapy improved the average hematologic status of patients: hemoglobin S% decreased from 85% to 32% (p=0.0003); hemoglobin and hematocrit increased from 7.6 to 9.4 g/dL (p=0.0052) and 22% to 28%, (p=0.007), respectively. Bilirubin declined from 3.6 to 2.4 mg/dL (p=0.042). In contrast, only bilirubin showed a significant decrease in the SC arm. In the TX arm, serum ferritin rose an average of 1318 to 2368 (p=.001); there was no change in liver function. There were no clinical transfusion reactions in the 120 study transfusions (360 units); however, one patient on routine screening reported a transient anti-D antibody without clinical or laboratory changes. Clinical Results: Adverse events were higher in the SC arm. Total number of adverse events in the TX arm were 23 (1.2 per person) vs. 66 in (4.1 per person) in the SC arm. There were 5 hospitalizations in the TX arm and 21 in the SC care arm, with a median number of hospitalized days per hospitalization of 5.0 and 6.0 respectively. The total number of serious events was 6 in the TX arm (0.3 per person) vs. 23 in the SC arm (1.4 per person). The total number of vaso-occlusive events in the TX arm were 14 (0.7 per person) vs. 57 (3.6 per person) in the SC arm. Acute pulmonary events occurred in 25% (4 patients) of the SC arm vs. none in the TX arm. Conclusions: This is preliminary data from the first prospective randomized study of the safety and efficacy of transfusion therapy in adults with SCD. We demonstrate the safety of transfusion therapy. Compared to standard therapy, transfusions improve or stabilize critical laboratory markers, decrease serious sickle cell anemia-related adverse events, and decrease in hospitalizations. Increase in ferritin is an expected outcome in transfused patients since chelation was not a part of this transfusion protocol. On completion of the study, the potential benefits of transfusion therapy on sickle cell disease morbidity including neurocognitive function will be reported. Disclosures: Field: Novartis Pharm: Honoraria.

Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4767-4767
Author(s):  
Giovanna Graziadei ◽  
Alessia Marcon ◽  
Martina Soldarini ◽  
Ilaria Gandolfi ◽  
Luisa Ronzoni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Clinical Complications ◽  
Significant Difference ◽  
The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

Exchange Transfusion In Adult Patients With Sickle Cell Disease With Refractory Vaso-Occlusive Crises

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4689-4689 ◽  
Author(s):  
Padmini Moffett ◽  
Bryan K Moffett
Keyword(s):  
African American ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Exchange Transfusion ◽  
Iron Chelation ◽  
Adult Patients ◽  
Cell Disease ◽  
Psychological Burden ◽  
Ed Visits

Sickle cell disease occurs in 1/500 African-American births. Pain is one of the most common complications of sickle cell disease and is associated with depression, anxiety, decreased quality of life and poor sleep patterns. Vaso-occlusive crises resulting in three or more hospitalizations per year occur in 48% of patients with sickle cell disease (Annals of Emergency Medicine - May 2009 (Vol. 53, Issue 5, Pages 587-593). Hydroxyurea has been shown to ameliorate the frequency of painful vaso-occlusive crises in sickle cell anemia (Charache et al, Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia NEJM. 1995), unfortunately many eligible patients are not treated due to psychosocial reasons and fear of teratogenicity or malignancy or have painful crisis refractory to hydroxyurea. A panel of experts has suggested that RBC exchange transfusion in these patients may decrease ED visits and subsequent hospitalizations based on anecdotal evidence [Best practices for transfusion for pateitns with sickle cell disease. T Wun, K Hagel. Hematology Review 2009, July 1; 1(22); e22]. We present the case of a 31 year old African-American male with Hgb S/beta thalassemia + with complications of sickle cell disease including Parvovirus B19 induced aplastic anemia, iron overload secondary to multiple simple transfusions, multiple vaso-occlusive crises as well as a left lower extremity ulcer precipitated by treatment with hydroxyurea. He was treated with folic acid as well as deferasirox for iron chelation. He began PRBC exchange transfusions every 6 weeks in March of 2011. In the one year prior to exchange transfusion initiation he had 13 ED visits and 4 hospitalizations for vaso-occlusive crises. After initiation of exchange transfusions he had 11 ED visits and 2 hospitalizations for vaso-occlusive crises the following year. An elevated WBC is associated with poor outcomes in sickle cell disease (Miller et al Predictors of adverse outcomes in children with sickle cell disease. N Engl J Med 2000). His average WBC level was 13 x 109/L, which decreased to 11 x 109/L after initiation of exchange transfusion. The patient underwent extended typing for E,C, and Kell RBC antigens to minimize development of antibodies. Though monthly exchange transfusions are costly and carry the attendant risk of antibody formation, this may be offset by reducing the financial and psychological burden of frequent hospitalizations for management of refractory vaso-occlusive crises. Exchange transfusion may also ameliorate the cost associated with long-term iron chelation. Further investigation is warranted to determine whether a program of monthly exchange transfusions can curtail ED visits and hospitalizations in adult patients with sickle cell disease and multiple, refractory vaso-occlusive crises. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Physiological properties and characteristic reactions of hydroxyurea

2020 ◽  
Vol 22 (100) ◽  
pp. 94-102
Author(s):  
O. G. Demchuk ◽  
M. R. Hrytsyna ◽  
L. O. Kobryn ◽  
M. B. Kalytovska ◽  
B. V. Gutyj
Keyword(s):  
Sickle Cell Disease ◽  
Life Expectancy ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Genetic Disorder ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Erythroid Precursors ◽  
Hb S

As it was mentioned in the previous paper, we observed the mechanism of action the interesting drug, first synthesized back in 1869 for the first time, called Hydroxyurea. A century later, phase I and II trials began to test its safety in humans with solid tumors. It was first approved by the FDA in 1967 for the treatment of neoplastic diseases and is presently approved for the treatment of melanoma, resistant chronic myelocytic leukemia (CML), and recurrent, metastatic testicular and ovarian cancer. Sickle cell disease is a genetic disorder that decreases life expectancy by 25 to 30 years. Individuals are diagnosed with sickle cell disease if they have one of several genotypes that result in at least half of their hemoglobin being hemoglobin S (HbS). Sickle cell anemia refers specifically to the condition associated with homozygosity for the Hb S mutation (Hb SS). Several other hemoglobin mutations, when occurring with an Hb S mutation, cause a similar but often milder disease than sickle cell anemia. In addition to reduced life expectancy, patients with sickle cell disease experience chronic pain and reduced quality of life. Painful crises, also known as vaso-occlusive crises, are the most common reason for emergency department use and hospitalization, and acute chest syndrome is the most common cause of death. Prior to the approval of hydroxyurea for use in sickle cell disease, patients with this condition were treated only with supportive therapies. These measures included penicillin in children to prevent pneumococcal disease, routine immunizations, and hydration and narcotic therapy to treat painful events. Red blood cell transfusions increase the blood’s oxygen carrying capacity and decrease the concentration of cells with abnormal hemoglobin, but chronic transfusion therapy predictably leads to iron overload and alloimmunization. Therapies such as hydroxyurea that raise fetal hemoglobin (Hb F, α2γ2) levels are promising because they effectively lower the concentration of Hb S within a cell, resulting in less polymerization of the abnormal hemoglobin.Hydroxyurea’s efficacy in sickle cell disease is generally attributed to its ability to raise the levels of Hb F in the blood; however, the mechanisms by which it does so are unclear. Early studies suggested that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, resulting in the recruitment of early erythroid precursors with an increased capacity to produce HbF.

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
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

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.

Transfusion therapy for cerebrovascular abnormalities in sickle cell disease

1976 ◽  
Vol 88 (3) ◽  
pp. 382-387 ◽  
Author(s):  
Marie Olivieri Russell ◽  
Herbert I. Goldberg ◽  
Linda Reis ◽  
Shlomo Friedman ◽  
Robert Slater ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Transfusion Therapy
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