Reassessing the Need for Pre-Operative Transfusions in Sickle Cell Disease Patients with a High Baseline Hemoglobin

Abstract Background: Patients with sickle cell disease (SCD) are more likely to require surgical procedures, and to have post-operative complications compared to the general population. The TAPS trial demonstrated that pre-operative transfusion is associated with a 3.8-fold reduction in peri-operative complications in patients with SCD. Pre-operative exchange transfusion has not been shown to have benefit over simple top-up transfusion. Patients with SCD may have baseline hemoglobin levels higher than the usual 60-80 g/L for a variety of reasons including; non-hemoglobin SS genotype SCD, co-inheritance of deletion(s) in alpha globin genes, hereditary persistence fetal hemoglobin, and hydroxyurea (HU) use. It is less clear whether patients with pre-operative hemoglobin levels > 90 g/L would also benefit from pre-operative transfusions. Previous studies of pre-operative transfusions in SCD have largely not captured these patients, in part due to low HU uptake at the time of the study and exclusion of non-hemoglobin SS SCD. We conducted a retrospective cohort study to assess the role of pre-operative transfusion in patients with SCD and a high baseline hemoglobin. Methods: 1304 patients seen at The Hospital for Sick Children, Toronto between 2007 and 2017 were assessed for eligibility. Patients were included if they: had a baseline hemoglobin ≥ 90 g/L, were 1-18 years of age at the time of surgery, had a diagnosis of hemoglobin SS, SC, Sβ+-thalassemia or Sβ0-thalassemia SCD subtypes, and had a low or medium risk elective surgery under a general anesthetic. Surgeries were classified according to the Co-operative Study of Sickle Cell Disease. Post-operative complications were defined as one or more of the following within 30 days of surgery: fever, vaso-occlusive crisis (VOC), infection, bleeding requiring transfusion, acute chest syndrome (ACS), stroke, intensive care admission (ICU), emergency room visit after discharge, readmission to hospital after discharge, or death. The incidence of postoperative complications for those with a baseline hemoglobin ≥90 g/L was compared between those who received a transfusion and those who did not. To estimate the adjusted effect of pre-operative transfusion on the risk of developing post-operative complications, a multi-variable logistic regression model was fitted using the change-in-estimate procedure, where variables with the strongest influence on the crude (unadjusted) estimate were included as model covariates (i.e. key confounders). Results: 117 patients with a hemoglobin ≥90 g/L underwent a total of 137 procedures. The most frequent procedures included were: tonsillectomies/adenoidectomies (26), cholecystectomies (25), splenectomies (20), and umbilical hernia repairs (11). There were 22 procedures (16%) where a pre-operative transfusion was administered. All patients received simple top-up transfusions. Of these, 11 (50%) encountered at least one post-operative complication. In contrast, 22/115 (19.1%) procedures without a pre-operative transfusion experienced a post-operative complication. There was an increased risk of post-operative complications in the group that was transfused (p=0.003, OR=4.2, 95% CI 1.6-11). Adjusting for two key confounders identified during the modeling process (splenectomy and prior ACS), pre-operative transfusion was again found to be associated with an increased risk of post-operative complications (p=0.017, OR=3.6, 95% CI 1.2-9.2). The characteristics of these patients and the incidence and distribution of post-operative complications are shown in Table 1. Conclusion: Patients with SCD and a baseline hemoglobin ≥90 g/L who receive a pre-operative top-up transfusion have an increased risk of post-operative complications compared to those who are not transfused. In low and medium risk surgeries, a policy of withholding transfusions for such patients may be considered. Prospective studies validating these findings are needed. Disclosures No relevant conflicts of interest to declare.

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Lead Neuropathy and Sickle Cell Disease

PEDIATRICS ◽

10.1542/peds.54.4.438 ◽

1974 ◽

Vol 54 (4) ◽

pp. 438-441

Author(s):

Gerald Erenberg ◽

Steven S. Rinsler ◽

Bernard G. Fish

Keyword(s):

Case Report ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Lead Poisoning ◽

Cell Disease ◽

Hemoglobin S ◽

Increased Risk ◽

Rare Manifestation ◽

Poisoning In Children

Four cases of lead neuropathy in children with hemoglobin S-S or S-C disease are reported. Neuropathy is a rare manifestation of lead poisoning in children, and only ten other cases have been well documented in the pediatric literature. The last previous case report of lead neuropathy was also in a child with hemoglobin S-S disease. The neuropathy seen in the children with sickle cell disease was clinically similar to that seen in the previously reported cases in nonsicklers, but differed in both groups from that usually seen in adult cases. It is, therefore, postulated that children with sickle cell disease have an increased risk of developing neuropathy with exposure to lead. The exact mechanism for this association remains unknown, but in children with sickle cell disease presenting with symptoms or signs of peripheral weakness, the possibility of lead poisoning must be considered.

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A case of severe multi-system disease in a sickle cell SC patient caused by parvovirus B19 infection

Journal of Clinical Images and Medical Case Reports ◽

10.52768/2766-7820/1314 ◽

2021 ◽

Vol 2 (5) ◽

Author(s):

Mohamed Almuqamam ◽

◽

Swetha Madhavarapu ◽

Nataly Apollonsky ◽

◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Parvovirus B19 ◽

Acute Infection ◽

Organ Injury ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Splenic Sequestration ◽

Increased Risk ◽

Parvovirus B19 Infection

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.

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Review of Sickle Cell Disease and Spinal Pathology

Global Spine Journal ◽

10.1177/2192568218799074 ◽

2018 ◽

Vol 9 (7) ◽

pp. 761-766 ◽

Cited By ~ 1

Author(s):

Hayeem L. Rudy ◽

David Yang ◽

Andrew D. Nam ◽

Woojin Cho

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Vertebral Osteomyelitis ◽

Compression Fracture ◽

Symptomatic Therapy ◽

Cell Disease ◽

Blood Disorder ◽

Increased Risk ◽

Adequate Hydration ◽

Surgical Treatments

Study Design:Sickle cell disease (SCD) is a relatively common blood disorder that has profound implications on the musculoskeletal system and particularly the spine; however, there is a paucity of data in the literature discussing this important topic.Objectives:(1) To elucidate common spinal pathologies affecting patients with SCD, as well as the medical and surgical treatments available for these patients. (2) To discuss indications for surgical management of spinal complications of SCD and important for orthopedic surgeons when taking patients with SCD to the operating room.Methods:A narrative review of the literature was performed.Results:Patients with SCD have a significantly higher risk of developing spinal pathologies including vertebral osteomyelitis, compression fracture, vertebral vaso-occlusive crises, and osteoporosis, among others. In addition, patients with sickle cell disease are particularly susceptible to developing perioperative and post-operative complications including surgical site infection, implant malfunction, and vertebral body compression fracture. Postoperatively patients with SCD are prone to developing complications and adequate hydration is necessary in order to reduce complications of SCD.Conclusions:Several spinal pathologies may arise secondary to SCD and distinguishing these pathologies from one another may be challenging due to similarities in symptoms and inflammatory markers. Although most patients with SCD can benefit from conservative treatment involving rest, symptomatic therapy, antibiotic therapy, and/or orthosis, surgical intervention may be indicated in certain cases. It is preferable to avoid surgery in patients with SCD due to an increased risk of complications such as wound infection and vaso-occlusive crisis.

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Sickle cell trait and the risk of venous thromboembolism among blacks

Blood ◽

10.1182/blood-2006-11-057604 ◽

2007 ◽

Vol 110 (3) ◽

pp. 908-912 ◽

Cited By ~ 142

Author(s):

Harland Austin ◽

Nigel S. Key ◽

Jane M. Benson ◽

Cathy Lally ◽

Nicole F. Dowling ◽

...

Keyword(s):

Venous Thromboembolism ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Odds Ratio ◽

Sickle Cell Trait ◽

Coagulation System ◽

Cell Disease ◽

Hemoglobin C ◽

Increased Risk ◽

S Allele

Abstract People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case–control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.

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Haemoglobinopathies

10.1093/med/9780199642489.003.0172 ◽

2013 ◽

Cited By ~ 2

Author(s):

David Rees

Keyword(s):

Bone Marrow ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Lupus Erythematosus ◽

Single Gene ◽

Globin Genes ◽

Globin Chain ◽

Cell Disease ◽

Increased Risk ◽

Marrow Expansion

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.

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Identification of Clinical and Laboratory Parameters Associated with the Development of Acute Chest Syndrome during Vaso-Occlusive Episodes in Children with Sickle Cell Disease: A Preliminary Step before Assessing Specific and Early Treatment Strategies

Journal of Clinical Medicine ◽

10.3390/jcm8111839 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1839

Author(s):

Madhi ◽

Kamdem ◽

Jung ◽

Carlier-Gonod ◽

Biscardi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Pain Score ◽

Sickle Cell ◽

Multivariate Model ◽

Red Blood Cell Transfusion ◽

Predictive Score ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Laboratory Parameters ◽

Increased Risk

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

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Perioperative Endocarditis Management in a Patient with Homozygous Sickle Cell Disease

The Thoracic and Cardiovascular Surgeon Reports ◽

10.1055/s-0038-1676962 ◽

2019 ◽

Vol 08 (01) ◽

pp. e1-e4 ◽

Cited By ~ 1

Author(s):

Malgorzata Gozdzik ◽

Sergio Mariotti ◽

Michele Genoni ◽

Alicja Zientara

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Heart Surgery ◽

Open Heart Surgery ◽

Cell Disease ◽

Coagulase Negative Staphylococci ◽

Right Heart ◽

Double Valve Replacement ◽

Increased Risk ◽

Homozygous Sickle Cell Disease

Background Homozygous sickle cell disease (SCD) compounded with bacterial endocarditis makes open-heart surgery a multidisciplinary challenge. Case description A 45-year-old African male patient with homozygous SCD presented with right heart decompensation, tricuspid regurgitation, and endocarditis of the aortic valve. Blood coulters were positive for coagulase-negative staphylococci. An emergent double valve replacement was successfully performed involving a multidisciplinary team. Conclusion Homozygous SCD is associated with an increased risk of preoperative vaso-occlusive complications. Surgery with cardiopulmonary bypass can be performed, if hypothermia, hypoxia, acidosis, or low-flows are being avoided. Due to the lack of data, the adequate approach is still intuitive and requires standardization.

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Allocation of Treatment Responsibility and Adherence to Hydroxyurea Among Adolescents With Sickle Cell Disease

Journal of Pediatric Psychology ◽

10.1093/jpepsy/jsz061 ◽

2019 ◽

Vol 44 (10) ◽

pp. 1196-1204 ◽

Cited By ~ 1

Author(s):

Susan E Creary ◽

Avani C Modi ◽

Joseph R Stanek ◽

Deena J Chisolm ◽

Sarah H O’Brien ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Shared Responsibility ◽

Prescription Data ◽

Cell Disease ◽

Electronic Prescription ◽

Appointment Adherence ◽

Increased Risk ◽

Complete Treatment ◽

Caregiver Involvement

Abstract Objective Adolescents with sickle cell disease (SCD) are at increased risk for complications. Hydroxyurea is a medication that can ameliorate risk but to benefit, adolescents must adhere to treatment. Study aims were to describe how adolescents and their caregivers decided who was responsible for treatment tasks, to describe adolescents’ and caregivers’ responsibility for these tasks, and to examine if hydroxyurea adherence was associated with younger adolescent age, less discrepancy between adolescents’ and caregivers’ reports of adolescent responsibility, and higher caregiver involvement. Methods Twenty-nine dyads completed treatment responsibility measures. A combination of laboratory and electronic prescription data were used to determine hydroxyurea adherence and electronic medical records were used to determine appointment adherence. Results Few dyads agreed or planned how to complete treatment tasks. Adolescents shared responsibility with caregivers for medication-taking tasks. Adolescents perceived caregivers and caregivers perceived adolescents were overall responsible for treatment, especially for appointment tasks. Half of adolescents were adherent to hydroxyurea and half were adherent to appointments but medication adherence was not associated with age, discrepancy between adolescents’ and caregivers’ responses, or caregiver involvement. Conclusions Despite frequent hydroxyurea and appointment nonadherence, few adolescents and caregivers plan how to manage adolescents’ SCD treatment or perceive they are overall responsible. Future studies are needed to determine the factors that influence these perceptions and if increasing adolescent and caregiver treatment planning improves adherence and clinical outcomes.

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Pulmonary hypertension in sickle cell disease: diagnosis and management

Hematology ◽

10.1182/asheducation-2014.1.425 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 425-431 ◽

Cited By ~ 7

Author(s):

Kenneth I. Ataga ◽

Elizabeth S. Klings

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Disease Diagnosis ◽

Adult Patients ◽

Heart Catheterization ◽

Cell Disease ◽

Risk Of Death ◽

Increased Risk ◽

High Prevalence

Abstract The increased survival of patients with sickle cell disease (SCD) into adulthood is associated with an increased incidence of multiorgan dysfunction and a progressive systemic and pulmonary vasculopathy. The high prevalence of an elevated tricuspid regurgitant jet velocity and its association with an increased risk of death in adult patients is well established. However, there has been controversy regarding the prevalence of pulmonary hypertension (PH) and its association with mortality in SCD. Multiple recently published reports demonstrate that PH as diagnosed by right heart catheterization is common in adult SCD patients, with a prevalence of 6%–11%. Furthermore, PH is associated with an increased risk of death in SCD patients. In this chapter, we provide evidence for the high prevalence of PH in SCD and its association with mortality and make recommendations for its evaluation and management. Finally, we provide the rationale for screening for this life-threatening complication in adult patients with SCD.

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Berkeley Sickle Mice Demonstrate CD8- and NK1.1-Dependent Increased Rejection of Allogeneic Hematopoietic Stem Cell Transplants.

Blood ◽

10.1182/blood.v106.11.2332.2332 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2332-2332

Author(s):

Leslie Kean ◽

Kelly Hamby ◽

Jennifer Perry ◽

Christian Larsen ◽

David Archerq

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Sickle Cell Disease ◽

Hematopoietic Stem Cell ◽

Sickle Cell ◽

Cell Disease ◽

Hematopoietic Stem ◽

Cell Immunity ◽

Increased Risk

Abstract While hematopoietic stem cell transplantation (HSCT) represents the only curative therapy for sickle cell disease, sickle patients undergoing HSCT face many complications, including an increased risk of graft rejection compared to non-sickle patients. We have used the Berkeley sickle mouse model to study the potential mechanisms underlying this increased risk of rejection. Using a CD28/CD40 costimulation-blockade-based non-myeloablative HSCT regimen, we transplanted Berkeley sickle mice with fully allogeneic SJL bone marrow. While the vast majority (>85%, n=25) of control C57BL/6 animals became stably chimeric and immunologically donor-tolerant with this transplant regimen, sickle mice were much more prone to reject the transplant (~20% graft acceptance, n=25). Both CD8+ cells and NK1.1+ cells were found to contribute to this rejection, as depletion of either of these cell populations led to a marked increase in the percent of engrafted mice (>85% graft acceptance, n=15–25), while depletion of CD4+ cells led to the opposite effect, with 0% (n=25) animals engrafted in this depletion cohort. The increased propensity of HSCT rejection in the Berkeley sickle mice may, in part, be explained by the presence of increased numbers of donor-reactive T cells (5–10-fold compared to C57BL/6 controls) in naïve sickle mice, despite their lack of exposure to donor antigens, and their housing in a Specific-Pathogen-Free environment. We speculate that these increased numbers of anti-donor T cells may occur as a result of heightened inflammation in the context of active sickle cell disease, which could lead to increased expansion and persistence of a T cell repertoire containing anti-donor heterologous T cell immunity. This heterologous immunity may have a profound effect on the success of HSCT for sickle cell disease, especially when non-myeloablative regimens are employed.

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