An Evidence-Based Approach to the Treatment of Adults with Sickle Cell Disease

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Richard Lottenberg ◽  
Kathryn L. Hassell
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Enzyme Inhibitor ◽  
Controlled Trial ◽  
Acute Chest Syndrome ◽  
Evidence Based ◽  
Clinical Expertise ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Treatment And Prevention

Abstract The application of evidence-based medicine to the management of adults with sickle cell disease (SCD) is currently primarily driven by clinical expertise and patient preference, as there is a paucity of randomized controlled trial (RCT) data to guide decision-making. A summary of SCD management principles in the areas of health care maintenance, transfusion therapy, treatment and prevention of painful episodes, acute chest syndrome, stroke, renal disease, contraception and pregnancy, and priapism is predominantly based on the authors’ interpretation of available observational studies as well as the opinions of experts in SCD. RCTs impacting current practices address use of hydroxyurea to prevent painful episodes and acute chest syndrome, intensity of pre-operative transfusion, transfusion during pregnancy, and angiotensin-converting enzyme inhibitor therapy for proteinuria, but most issues in adult SCD care have not been rigorously studied and management may not be appropriately extrapolated from pediatric data. While challenging clinical problems need to be addressed by RCTs, there is also the need for development of practice guidelines using formal methodological strategies. This brief review is not a substitute for the process but provides a literature-based approach to making treatment decisions when caring for adults with SCD.

Sickle crisis in the critically ill

2016 ◽  
Author(s):  
Shilpa Jain ◽  
Mark T. Gladwin
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Systemic Infection ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Ischaemia Reperfusion Injury ◽  
Transfusion Therapy

Sickle cell disease crises are precipitated by an acute occlusion of microvessels, which can lead to end organ ischaemia reperfusion injury and acute haemolysis. Acute fat emboli syndrome, acute lung injury (the acute chest syndrome), acute pulmonary hypertension, and cor pulmonale, haemorrhagic and occlusive stroke, and systemic infection represent the most common life-threatening complications observed in current ICU practice. General principles of management in all patients admitted to the critical care unit are hydration, antibiotics, pain control, and maintenance of oxygenation and ventilation. Red blood cell transfusion therapy is the treatment of choice for most complications of sickle cell disease requiring intensive care management. Transfusion of sickle negative, leukoreduced red blood cells, phenotypically matched for Rhesus and Kell antigens is the minimum standard of care in sickle cell disease patients as they have a high incidence of red blood cell alloimmunization.

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.

scholarly journals Iron Overload in Sickle Cell Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Radha Raghupathy ◽  
Deepa Manwani ◽  
Jane A. Little
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Organ Damage ◽  
Endothelial Damage ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Treatment And Prevention ◽  
Oxygen Carrying Capacity

In sickle cell disease transfusions improve blood flow by reducing the proportion of red cells capable of forming sickle hemoglobin polymer. This limits hemolysis and the endothelial damage that result from high proportions of sickle polymer-containing red cells. Additionally, transfusions are used to increase blood oxygen carrying capacity in sickle cell patients with severe chronic anemia or with severe anemic episodes. Transfusion is well-defined as prophylaxis (stroke) and as therapy (acute chest syndrome and stroke) for major complications of sickle cell disease and has been instituted, based on less conclusive data, for a range of additional complications, such as priapism, vaso-occlusive crises, leg ulcers, pulmonary hypertension, and during complicated pregnancies. The major and unavoidable complication of transfusions in sickle cell disease is iron overload. This paper provides an overview of normal iron metabolism, iron overload in transfused patients with sickle cell disease, patterns of end organ damage, diagnosis, treatment, and prevention of iron overload.

Chronic Transfusion Therapy for Children With Sickle Cell Disease and Recurrent Acute Chest Syndrome

2005 ◽  
Vol 27 (3) ◽  
pp. 158-161 ◽  
Author(s):  
Jane Hankins ◽  
Michael Jeng ◽  
Sylvia Harris ◽  
Chin-Shang Li ◽  
Tiebin Liu ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy

Contemporary Management and Prevention of Vaso-Occlusive Crises (VOCs) in Adults With Sickle Cell Disease

2021 ◽  
pp. 089719002110266
Author(s):  
Salome Bwayo Weaver ◽  
Dhakrit Rungkitwattanakul ◽  
Divita Singh
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
English Language ◽  
Sub Saharan Africa ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Treatment And Prevention ◽  
Sub Saharan ◽  
Contemporary Management ◽  
Sickle Cell Crises

Sickle cell disease (SCD) is a hematological disorder that primarily affects individuals of African descent from sub-Saharan Africa and along the mediterranean. The main complications leading to hospitalizations include vaso-occlusive crises (VOCs) and acute chest syndrome (ACS). Therefore, the main objective of this paper was to identify and evaluate evidence-based management and prevention of VOCs in patients with SCD. A literature search of PubMed, Medline Cochrane and Google Scholar database (January 1985 to April 2020) was performed using the following search terms “vaso-occlusive crises”, “sickle cell disease”, “hydroxyurea”, “L-glutamine”, “voxelotor”, “crizanlizumab”, “treatment” and “prevention” as well as a combination of these terms. All English-language interventional studies assessing the efficacy and safety of VOC outcomes were evaluated. Literature was excluded if published in a language other than English or if it was a review article. A total of 69 articles were identified and there were 7 articles that met the search criteria. Majority of the studies focused on mean and median annual rates of VOCs as primary outcomes while median time to first sickle cell crises, median rates of hospitalizations etc were evaluated as secondary outcomes. After reviewing the literature, many patients with VOCs will still benefit from hydroxyurea therapy since long term efficacy data and cost is still a concern for the newer agents including L-glutamine, voxelotor and crizanlizumab. Other factors such as cost or compliance may also be taken into consideration when making recommendations for therapy.

scholarly journals A cautionary note regarding hydroxyurea in sickle cell disease

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1124-1128
Author(s):  
EP Vichinsky ◽  
BH Lubin
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Course ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
History Of ◽  
Hbf Level

Hydroxyurea can increase fetal hemoglobin (HbF) and improve the clinical course of sickle cell disease (SCD) patients. However, several issues of hydroxyurea therapy remain unresolved, including differences in patients' drug clearance, predictability of drug response, reversibility of sickle cell disease-related organ damage by hydroxyurea, and the efficacy of elevated HbF. We treated two patients with hydroxyurea for periods of 1 to 4 years, monitoring clinical course and laboratory parameters at regular intervals. The first patient (patient A) had a history of chronic pain and extensive hospitalizations. The second patient (patient B) had a history of stroke and refused to continue with chronic transfusion therapy and chelation. Both patients showed a fivefold to tenfold increase in HbF (5% to 25%, 3% to 31%). However, patient A developed an acute chest syndrome, despite an HbF level of 20%. After red blood cell transfusions for hypoxia, the HbF level decreased to 5%. When hydroxyurea dosage was increased, pancytopenia developed and was not resolved until 2 months after hydroxyurea was discontinued; Patient B developed a cerebral hemorrhage on hydroxyurea; he died shortly thereafter. His HbF level was 21% before death. We noted an increase in HbF and a general improvement in the two patients. However, both experienced major SCD-related complications despite HbF levels over 20%. Our findings also suggest that the progressive vascular changes associated with SCD are unlikely to be dramatically affected by increased HbF levels. Because neither the efficacy nor the toxicity of hydroxyurea have been thoroughly investigated, physicians should be cautious in prescribing hydroxyurea for patients with SCD before completion of the National Clinical Trial.

Transfusion therapy for sickle cell disease: a balancing act

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 439-446 ◽  
Author(s):  
Stella T. Chou
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Perioperative Complications ◽  
Iron Chelation ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Oral Agents ◽  
Blood Group Typing

AbstractTransfusion therapy is a key intervention in decreasing morbidity and mortality in patients with sickle cell disease (SCD). Current indications for acute and chronic transfusion therapy have significantly increased the number of RBC units transfused to patients with SCD worldwide. This review summarizes transfusion management for the treatment or prevention of neurologic and perioperative complications, acute chest syndrome, and acute anemia associated with SCD. Despite the recognized benefits of transfusion therapy, it is not without the risks of iron overload, alloimmunization, and delayed hemolytic transfusion reactions. Transfusional iron overload management includes automated RBC exchange, noninvasive imaging to monitor iron burden, and iron chelation with parenteral or oral agents. Although limited and extended RBC antigen matching reduces antibody formation, the prevalence of RBC alloimmunization in patients with SCD remains high. Recent studies demonstrate that RH genetic diversity in patients with SCD contributes to Rh alloimmunization, suggesting that even more refined RBC matching strategies are needed. Advances in molecular blood group typing offer new opportunities to improve RBC matching of donors and recipients and can be of particular benefit to patients with SCD.

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 Indications for transfusion in the management of sickle cell disease

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 696-703
Author(s):  
Hyojeong Han ◽  
Lisa Hensch ◽  
Venée N. Tubman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Perioperative Complications ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Frequent Use ◽  
Clinical Scenarios ◽  
Conclusive Data

Abstract The transfusion of red blood cells (RBCs) is a crucial treatment for sickle cell disease (SCD). While often beneficial, the frequent use of transfusions is associated with numerous complications. Transfusions should be offered with specific guidelines in mind. Here we present updates to the indications for transfusion of RBCs in SCD. We review recent publications and include expert perspectives from hematology and transfusion medicine. For some clinical indications, such as ischemic stroke, the role of transfusion has been well studied and can be applied almost universally. For many other clinical scenarios, the use of transfusion therapy has less conclusive data and therefore must be tailored to individual needs. We highlight the roles of RBC transfusions in preventing or mitigating neurological disease, in reducing perioperative complications, in managing acute chest syndrome, and in optimizing pregnancy outcomes in SCD. We further highlight various transfusion techniques and when each might be considered. Potential complications of transfusion are also briefly discussed.

Encephaloduroarteriosynangiosis (EDAS) For Patients With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 999-999
Author(s):  
Jeffrey D. Lebensburger ◽  
Christina J. Bemrich-Stolz ◽  
Christoph Griessenauer ◽  
Lee Hilliard ◽  
Thomas H. Howard ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Case Series ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Indirect Revascularization

Abstract Introduction Regular blood transfusion therapy is the standard care for secondary prevention of strokes in sickle cell disease (SCD). Despite regular blood transfusion therapy approximately 45% of the children with strokes will have progressive neurological disease (overt strokes or new silent cerebral infarcts) with an incidence of overt strokes of 3.2 events/100 patient-years (95% confidence interval, 1.3-6.5) (Hulbert, Blood 2011). Limited additional therapeutic options exist for these patients. Encephaloduroarteriosynangiosis (EDAS) is a neurosurgical procedure to improve cerebral blood flow by transposing scalp arteries onto the surface of the brain. Five previously published series reported a total of 41 EDAS or indirect revascularization procedures on patients with SCD aged 3-22 yrs. Three of 41 patients (7%) had a stroke at 24 hours, 5 days and three weeks following EDAS/indirect revascularization. Additionally, one patient developed TIA 12 months later, two patients developed intracranial hemorrhage, and one patient died from a pulmonary embolus during an episode of acute chest syndrome 48 months post-EDAS. To date, the incidence of complications and efficacy of EDAS procedure in stroke prevention has not been well established. Objectives To examine the incidence of overt stroke pre and post-EDAS for patients on chronic transfusion. Methods We studied a pediatric cohort with history of HbSS and SB0 thalassemia on chronic transfusion for CNS injury who underwent EDAS at the University of Alabama at Birmingham. The incidence of overt stroke pre- and post-EDAS was reviewed. All pre-transfusion hemoglobin and percent Hemoglobin S levels were recorded from the time of their first recorded abnormal MRI. To determine the acute complications of EDAS, we reviewed the peri-operative hospital records at the time of EDAS, post-EDAS emergency room visits and chronic transfusion clinic visits post EDAS. Results A total of 13 patients on chronic transfusion for secondary stroke prevention underwent 17 EDAS procedures for recurrent stroke, progressive vascular disease, or neurologic change including psychosis and decline in neuropsychometric scores. The mean time to EDAS was 80 months (median 56) from their first abnormal MRI in the medical records. The patients’ mean pre-transfusion hemoglobin level was 9.4 g/dL and mean HbS was 29.5%. All participants (n=13) maintained a mean pre-transfusion HbS < 40%; 62% (8/13) participants maintained a mean HbS <30% (two patients with elevated HbS were transitioned to hydroxyurea as part of a clinical trial). Prior to EDAS, three patients had a new overt stroke during 81 patient years.(3.7 strokes per 100 pt yrs) One of 17 EDAS procedures was complicated by an acute stroke one month after the procedure. No additional strokes occurred in these patients during 34 patient years.(3 strokes per 100 pt yrs) One child developed a chronic subdural hematoma one month post-EDAS requiring burr hole drainage; this patient had a complete recovery. Conclusion This case series represents the largest cohort of EDAS procedures for children with SCD, and in combination with the literature, suggests that patients with progressive CNS disease may benefit from EDAS. A multicenter retrospective case series should be completed to identify risk factors for progression status post an EDAS procedure followed by a clinical trial to determine the effectiveness of the procedure versus regular blood transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

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