Sickle Cell Anemia

2017 ◽  
Author(s):  
Eboni I Lance ◽  
Andrew W. Zimmerman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Cells ◽  
Marrow Transplant ◽  
Neurologic Complications ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Hematological Disorder ◽  
History Of ◽  
Underlying Mechanisms

Sickle cell disease is a genetic hematological disorder involving red blood cells that become deformed when stressed. Patients with homozygous hemoglobin SS disease often have multiple systemic and neurologic complications, particularly stroke. Intellectual disability is commonly seen in the population, in patients with and without a history of stroke, attributed to different underlying mechanisms of brain injury. Autism is rare and not described in sickle cell disease in the literature to date. Many treatments (chronic transfusion therapy, hydroxyurea, bone marrow transplant) are in trials at this time to see if risk of stroke and other neurologic complications can be reduced (ClinicalTrials.gov identifiers: NCT01425307, NCT01389024, NCT00152113).

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.

scholarly journals Silent Cerebral Infarcts and Cerebral Aneurysms Are Prevalent in Adults with Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2712-2712
Author(s):  
Adetola A. Kassim ◽  
Sumit Pruthi ◽  
Matthew Day ◽  
Michael R. DeBaun ◽  
Lori C. Jordan
Keyword(s):  
Sickle Cell Disease ◽  
Cerebral Aneurysm ◽  
Sickle Cell ◽  
Cerebral Aneurysms ◽  
Cell Disease ◽  
Cerebral Infarcts ◽  
Transfusion Therapy ◽  
History Of ◽  
The Brain ◽  
Saccular Aneurysms

Abstract Introduction: Neurologic complications are a major cause of morbidity in sickle cell disease (SCD). The cumulative cerebral risk for neurological complications in sickle cell anemia has been estimated around 50% by age 14 (Bernaudin et. al, 2011;Blood 4:1130-40). Silent cerebral infarcts (SCI), is the most commonly recognized cause of neurological injury, associated with cognitive difficulties (King et al, Am J Hematol 2014;89:162-7) found in 20-40% of children with SCD, more common in genotype SS or Sβ0 thalassemia. The prevalence of SCI has not been well studied in adults. The prevalence of intracranial saccular aneurysms by radiographic and autopsy series is estimated to be 3.2% in a population without comorbidity, a mean age of 50 years, and a 1:1 gender ratio. (Valk et al, Lancet Neurol 2011; 10: 626–36) while other investigators found a 1.8% prevalence and no increased incidence with age (Vernooij et al NEJM 2007;357:1821-8). The goal of this study was to assess the prevalence of neurologic morbidity, including SCI, overt stroke, and cerebral aneurysm, in a large cohort of adults with SCD. We hypothesized the SCI would be more prevalent in adults compared to children with SCD. Methods: Due to the high prevalence of cerebral infarcts in children with SCD, we elected to obtain as part of routine clinical practice, a MRI and magnetic resonance angiography (MRA) of the brain in adults with SCD in our Hematology clinic. As standard care if SCIs are seen, neurocognitive testing is recommended, and based on this testing and MRI results, appropriate patients are referred for vocational rehabilitation service. All MRIs and MRAs were reviewed by 2 board certified neuroradiologists and consensus findings were recorded including presence of cerebral infarcts, intracerebral hemorrhage, aneurysms and cerebralvasculopathy. All adults with SCD were followed by a single hematologist and were asked about neurological symptoms. Medical records were reviewed to see if stroke like symptoms had been reported. If no symptoms were reported and no abnormalities were documented on neurological examination, then infarcts were judged to be silent. Results: The study population included 94 adults with SCD (80% HbSS or Hb Sβ0 thalassemia; 11% HbSC, and 9% other), 51% males, median age 26 years, interquartile range (22-36 years) who had MRI of the brain and 88 had MRA of the brain. Of these, 91 MRIs were of sufficient quality to assess for the presence or absence of infarcts. Infarcts were present in 58% (53 individuals) with multiple infarcts in 40% (37 patients); infarcts were overt/symptomatic in 13% (12) and silent in 45% (41). Hemorrhages were present in 8 patients (9%) and of these, 7 of 8 also had infarcts present on MRI. MRI and MRA of the brain were felt of adequate quality to assess for vascular disease or aneurysm in 79 patients. Of these 7.5% (6 of 79 patients) had moyamoya vasculopathy and 7.5% (6 of 79 patients) had saccular aneurysms with no overlap between groups. All of the adults with moyamoya vasculopathy had overt strokes. The aneurysms were incidental findings and all were <5mm in size. Patients were referred to Neurosurgery for evaluation of aneurysmal lesions. Amongst the 12 adults with a history of overt stroke, 67% were on therapy (50% on hydroxyurea therapy; 17% on chronic blood transfusion therapy), 42% (5 of 12) received aspirin for stroke and 1 patient was already on warfarin for history of systemic thrombosis at the time of stroke. Conclusions: Silent cerebral infarctions are common in adults with SCD. Silent cerebral infarcts were present in 45% and over strokes had occurred in 13% of adults with SCD. Our aneurysm prevalence of 7.5% in a younger cohort (median age 26 years) suggests that adults with SCD may have a higher prevalence of cerebral aneurysms than the general population. Further study is warranted to assess whether SCD should be considered a comorbidity that confers a higher risk of cerebral aneurysm in adults. The optimal strategies for primary and secondary stroke prevention and to mitigate against the progressive cerebral vasculopathy in adults with SCD are still being debated. Disclosures No relevant conflicts of interest to declare.

Moyamoya Disease Predicts Progression of Cerebral Vasculopathy in Patients with Sickle Cell Disease Despite Chronic Transfusion Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2071-2071 ◽  
Author(s):  
Alyssa M Schlenz ◽  
Michael U Antonucci ◽  
Rebecca Cafiero ◽  
Nina-Serena Burkett ◽  
Julie Kanter
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Moyamoya Disease ◽  
Stroke Prevention ◽  
Conflicts Of Interest ◽  
The Body ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Moya Moya Disease ◽  
History Of

Abstract Introduction: Patients with sickle cell disease (SCD) develop multi-organ complications due to hemolysis, inflammation, and vascular occlusion that results in small vessel obstruction throughout the body. In the brain, however, large cerebral vessels are also damaged resulting in occlusion or stenosis and subsequent development of abnormal collateral vasculature and moyamoya disease. Chronic red cell transfusion (CRCT) therapy significantly reduces the risk of stroke in children with abnormal transcranial doppler (TCD) studies and is also effective in reducing stroke recurrence in those with a history of overt or silent stroke; however, it is unclear if CRCT halts or reverses the progression of vasculopathy. The present study evaluated cerebrovascular stenosis and moya moya disease as risk factors for progression of vasculopathy over time in a cohort of patients with SCD who were started on CRCT therapy as children for stroke prevention. Methods: A retrospective cohort study (with IRB approval) was used to evaluate cerebrovascular changes in patients on CRCT.Patients were included in the study if they had received CRCT for stroke prevention for at least 12 months and had at least two serial magnetic resonance imaging and angiography (MRI/MRA) studies for review. For the imaging analysis, the patient's MRI/MRA closest to the initiation of CRCT (i.e. baseline imaging) was compared to the most recent imaging available by a neuro radiologist who was blind to the patient's clinical history. Additional demographic information included the patient's current age, gender, indication for CRCT, years on CRCT, and laboratory results for pre-transfusion % hemoglobin S (HbS). Results: Forty patients with SCD (current age: M = 16.48, SD = 5.10; 23 male, 17 female) were included. Average duration of CRCT therapy was 9.96 years (SD = 5.67) and average pre-transfusion HbS levels were 42.52% (SD = 9.88). Patients were initiated on therapy due to: overt stroke (n = 19), silent stroke (n = 2), and abnormal TCD (n = 20). Of the 20 patients initiated on therapy due to abnormal TCD, 7 were found to have abnormal MRI at baseline consistent with silent stroke. One of these patients was also found to have co-occurring moyamoya disease, despite no evidence of prior overt stroke. At baseline, 45% (n = 18) of patients had abnormal MRA and 25% (n = 10) had moyamoya disease. Progression of vasculopathy occurred in 15% (n = 6) of patients, all of whom had a history of moya moya disease at baseline (5 patients with overt stroke and 1 with silent stroke). Of the remaining 3 patients with moya moya disease at baseline, 2 remained stable with no improvement and 1 demonstrated improvement on MRA. For patients with abnormal MRA, but no history of moya moya disease (n = 9), 5 demonstrated improvement (2 patients with silent stroke and 3 with overt stroke). Conclusions: Progression of vasculopathy was common among patients with baseline moyamoya disease despite CRCT. Also notable, however, was improvement in vasculopathy (as defined by reduction of stenosis) in 6 patients, the majority of whom had not developed moyamoya prior to the initiation of CRCT suggesting that more mild vasculopathy can be reversed with early intervention. Patients with moya moya disease warrant ongoing annual assessment as they may require vascular bypass to prevent further worsening. Future large, multi-site investigations are needed to identify improved biomarkers and further understand characteristics of patients who demonstrate improvement versus progression of vasculopathy on CRCT. Disclosures No relevant conflicts of interest to declare.

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

Abstract 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.

Limitations of Clinical Trials in Sickle Cell Disease: A Case Study of the Multi-center Study of Hydroxyurea (MSH) Trial and the Stroke Prevention (STOP) Trial

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 482-488 ◽  
Author(s):  
Michael R. DeBaun ◽  
Joshua J. Field
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Stop Trial ◽  
History Of ◽  
Secondary Analyses ◽  
Multi Center Study ◽  
Center Study

AbstractIn the past two decades, two landmark randomized controlled trials (RCT) have been completed among individuals with sickle cell disease (SCD), the Multi-center Study of Hydroxyurea (MSH) trial and the Stroke Prevention (STOP) trial. The MSH trial tested the hypothesis that hydroxyurea will reduce the frequency of painful episodes for adults with hemoglobin SS who had a history of 3 or more painful episodes per year. The STOP trial tested the hypothesis that among children with hemoglobin SS and an elevated transcranial Doppler (TCD) velocity measurement, blood transfusion therapy would decrease the risk of an initial stroke. After completion, both trials have defined standard care for individuals with hemoglobin SS. The purpose of this review is to examine the limitations of the MSH and STOP trials. In the context of these trials, we will examine the effects of narrow inclusion criteria that primarily include participants with hemoglobin SS and secondary analyses that are prone to false-positive results. In addition, we describe how after publication of these two trials use of hydroxyurea and TCD assessment has drifted towards a standard practice without evidence of therapeutic efficacy among groups that were excluded from the trials. Finally, we suggest that rigorously conducted RCTs or at the minimum multicenter observation studies with strong methodology should be performed in these excluded subgroups to confirm a benefit of hydroxyurea or TCD measurement.

scholarly journals Sudden Death in Sickle Cell Disease: An Autopsy Diagnosis

2017 ◽  
Vol 3 (4) ◽  
pp. 113-115
Author(s):  
Nanditha Sheshanna ◽  
Gurpreet Sethi ◽  
Sumitha M Prakash
Keyword(s):  
Sickle Cell Disease ◽  
Sudden Death ◽  
Red Blood Cells ◽  
Blood Vessels ◽  
Sickle Cell ◽  
Blood Cells ◽  
Cell Disease ◽  
High Prevalence ◽  
Autopsy Diagnosis ◽  
History Of

ABSTRACT Sickle cell disease is a common hereditary hemoglobinopathy with high prevalence in the central and northeastern regions of India. A 24-year-old male patient with 3 days’ history of fever was brought dead to the hospital. Morphology showed clogging of blood vessels with sickled red blood cells (RBCs) in all the organs, and an autopsy diagnosis of sickle cell disease was made. As the cause may not be obvious in many cases, most patients remain undiagnosed. It is important to note the circumstances of death, gross finding, and histopathology, with hemoglobin electrophoresis if available, during autopsy to arrive at the diagnosis. This case is presented here to highlight this fact and draw attention to its pathology. How to cite this article Sheshanna N, Sethi G, Raj JA, Prakash SM, Surhonne SP. Sudden Death in Sickle Cell Disease: An Autopsy Diagnosis. J Med Sci 2017;3(4):113-115.

IHP-Loaded Red Blood Cells as Preventive Therapy In Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1625-1625
Author(s):  
Vanessa Bourgeaux ◽  
Yannick Campion ◽  
Emeline Aufradet ◽  
Cyril Martin ◽  
Yann Godfrin
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Platelet Counts ◽  
Hypoxic Conditions ◽  
Hypotonic Lysis

Abstract Abstract 1625 Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin S (HbS) that polymerizes under hypoxic conditions leading to sickled-shape red blood cells (RBCs). Vaso-occlusive crisis (VOC) is one of the major clinical manifestations of the disease, very painful for patients and causing irreversible organ damages. RBC exchange is commonly used as preventive and curative treatment of the disease. However, the therapeutic action of RBC exchange only relies on the removal of HbS-containing RBCs (SS-RBCs) and their transient replacement by normal RBCs (AA-RBCs). Recent works have shown that sickled reticulocytes, activated platelets and leukocytes play a critical role in the onset of VOC. They aggregate with endothelial cells creating local hypoxia, enhancing sickling and thus capillary blockade. Oxygen deprivation that occurs in venous capillaries may widely contribute to the severity of the occlusion. Therefore, increasing the oxygenation level in capillaries could help to prevent SS-RBCs from sickling and avoid crisis. This may be possible by transfusing patients with AA-RBCs loaded with Inositol HexaPhosphate (IHP), an allosteric effector that binds tightly to hemoglobin. The resulting suspension (IHP-RBCs) has the ability to increase oxygen release by 2 to 3 fold compared to normal AA-RBCs. The objective of the present study was to evaluate in vivo the benefit of using IHP-RBCs treatment in SCD. We used BERK transgenic mouse model that fully mimics human SCD in childhood with specific features of splenomegaly, reticulocytosis and leukocytosis. IHP-RBCs were prepared by loading IHP into murine C57BL6J RBCs using reversible hypotonic lysis method. RBCs subjected to reversible hypotonic lysis but without IHP were used as control suspension. Study was designed with repeated RBC exchanges scheduled every 2 weeks. First RBC exchange using IHP-RBCs or control suspension was performed on 6–7 week-old mice followed by 2 further injections. Mice were sacrificed one week after last RBC exchange and critical hematological parameters (reticulocyte, leukocyte, platelet counts and sickled cells) as well as serum inflammation markers were used as readouts to evaluate the risk of VOC. The first study was performed in normoxic conditions. After the therapy, approximately 42% of mouse RBCs had been replaced by IHP-RBCs or control suspension. Strong reduction of spleen weight (50%) and circulating sickled RBCs was observed in both cases due to the dilution of SS-RBCs. Interestingly, IHP-RBCs treatment enabled to significantly lower reticulocytes (18% vs 31%), leukocytes (5.3 vs 8.4 103/μl) and platelet counts (1057 vs 1518 103/μl) compared to not treated mice. Additionally, Serum Amyeloid Protein (SAP), an inflammation marker analogous of human C-Reactive Protein was also significantly reduced with IHP-RBCs (450 vs 750 μg/ml) indicating lowered severity of inflammation. The analysis of VCAM and HIF-1 factors in both spleen and lungs were very low in both treated and not treated mice. Further experiments demonstrated that hypoxic stress is needed to induce significative inflammation at the organ level. The study will thus be repeated in hypoxic conditions to evaluate the effect of IHP-RBCs treatment on organ damaging. We had in a previous study demonstrated in vitro the ability of IHP-RBCs to reduce sickling of human SS-RBCs (Bourgeaux et al, Transfusion, in press). The present in vivo study brings new evidence of the therapeutic potential of IHP-RBCs with the observation of a significant reduction of VOC risk factors and SAP level in treated mice. These results strongly support the fact that loading IHP into AA-RBCs may improve the effectiveness of conventional transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

Increased Pre-Transfusion Reticulocytosis Among Chronically Transfused Sickle Cell Disease Patients Is Associated With More Severe Cerebral Vasculopathy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1163-1163
Author(s):  
Megha Kaushal ◽  
Ross M. Fasano ◽  
Colleen Byrnes ◽  
Naomi L.C. Luban ◽  
Emily Riehm Meier ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Sickle Cell Disease ◽  
Magnetic Resonance Angiography ◽  
Sickle Cell ◽  
Control Group ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Blood Samples ◽  
History Of ◽  
The Mean

Abstract Chronic red blood cell transfusion therapy is indicated for primary and secondary stroke prevention in children with sickle cell disease (SCD). The main transfusion goal is achievement of pre-transfusion sickle hemoglobin (HbS) levels of 30%. Unfortunately, there continues to be a population of patients with a history of stroke who have progressive vasculopathy and/or secondary stroke, despite chronic transfusion therapy. Predictive markers for vasculopathy and cerebral events are needed to identify patients at risk for disease progression. Increased reticulocytosis was previously associated with other sickle cell disease complications, and adherent reticulocytes may contribute to the vascular pathology. The objective of this study was to explore the hypothesis that pre-transfusion reticulocytosis may serve as a disease severity marker for cerebral vasculopathy among chronically transfused children with sickle cell disease. After obtaining consent and assent, reticulocytosis was studied in a cohort of pediatric sickle cell patients treated with chronic transfusions (n=33, ages 2-17 years). The group was stratified into three groups: group 1 with an abnormal transcranial doppler (TCD) study in the absence of magnetic resonance angiography (MRA) detected vasculopathy [TCD(+), MRA(-), n=14], group 2 with a history of a stroke in the absence of MRA-detected vasculopathy [Stroke(+), MRA(-), n=5], and group 3 with a history of abnormal TCD or stroke and more severe vasculopathy detected by magnetic resonance angiography [MRA(+), n=14]. Pre-transfusion blood samples were analyzed within 72 hours of collection. Steady-state blood samples were also examined from a control group of pediatric SCD patients (>6 years of age) with normal TCD studies who were receiving supportive care in the absence of chronic transfusions or hydroxyurea (n=7). Hematologic data, including automated complete blood counts, absolute reticulocyte counts (ARC) with reticulocyte maturity were obtained. In addition, a flow cytometric approach was developed to further examine and quantitate reticulocyte subsets based upon staining with thiazole orange combined with CD36, CD45, CD49d, CD71, and CD235. The pre-transfusion HbS levels were not statistically different among the three transfused groups ([TCD(+), MRA(-)]: 30.2 ± 11.8%; [Stroke(+), MRA(-)]: 28.4 ± 3.3%; [MRA(+)]: 33.3 ± 9%, p>0.3). The high levels of reticulocytosis in the pre-transfusion samples were similar to those measured in the control group (ARC: 451 ± 126 K/uL in the chronically transfused cohort; ARC: 369 ± 94 K/uL in the control group, p=0.11). Pre-transfusion reticulocytosis was detected in every chronically transfused subject (ARC range 151-701 K/ul). The mean ARC in the [TCD(+), MRA(-)] group was not significantly different from the [Stroke(+), MRA(-)] group (411 ± 135 K/uL and 396 ± 97 K/uL respectively, p=0.82). However, the mean ARC in the [MRA(+)] group (512 ± 107 K/uL) was significantly higher than the control group, the [TCD(+), MRA(-)] group and the [Stroke(+), MRA(-)] group (p<0.05). The increased ARC in the MRA(+) group included higher absolute numbers of circulating reticulocytes at all stages of maturation including the immature reticulocyte subset [CD36(+), CD71(+)] that was detected in every sample. These data suggest that reticulocytosis with the release of immature CD36(+), CD71(+) cells into the peripheral blood remains as a characteristic feature of pediatric SCD even among chronically transfused patients. More severe vasculopathy, detected by MRA, was associated with significantly higher levels of pre-transfusion reticulocytosis. As such, reticulocytosis should be explored further as a marker or a potential contributor to more severe vasculopathy among chronically transfused children with SCD. Disclosures: No relevant conflicts of interest to declare.

Increased Procoagulant Activity of Red Blood Cells from Patients with Homozygous Sickle Cell Disease and β-Thalassemia

1996 ◽  
Vol 76 (03) ◽  
pp. 322-327 ◽  
Author(s):  
Dominique Helley ◽  
Amiram Eldor ◽  
Robert Girot ◽  
Rolande Ducrocq ◽  
Marie-Claude Guillin ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Annexin V ◽  
Mean Value ◽  
Procoagulant Activity ◽  
Dependent Manner ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease

SummaryIt has recently been proved that, in vitro, red blood cells (RBCs) from patients with homozygous β-thalassemia behave as procoagulant cells. The procoagulant activity of β-thalassemia RBCs might be the result of an increased exposure of procoagulant phospholipids (i. e. phosphatidylserine) in the outer leaflet of the membrane. In order to test this hypothesis, we compared the catalytic properties of RBCs of patients with β-thalassemia and homozygous sickle cell disease (SS-RBCs) with that of controls. The catalytic parameters (Km, kcat) of prothrombin activation by factor Xa were determined both in the absence and in the presence of RBCs. The turn-over number (kcat) of the reaction was not modified by normal, SS- or (3-thalassemia RBCs. The Km was lower in the presence of normal RBCs (mean value: 9.1 µM) than in the absence of cells (26 µM). The Km measured in the presence of either SS-RBCs (mean value: 1.6 µM) or β-thalassemia RBCs (mean value: 1.5 pM) was significantly lower compared to normal RBCs (p <0.001). No significant difference was observed between SS-RBCs and p-thalassemia RBCs. Annexin V, a protein with high affinity and specificity for anionic phospholipids, inhibited the procoagulant activity of both SS-RBCs and (3-thalassemia RBCs, in a dose-dependent manner. More than 95% inhibition was achieved at nanomolar concentrations of annexin V. These results indicate that the procoagulant activity of both β-thalassemia RBCs and SS-RBCs may be fully ascribed to an abnormal exposure of phosphatidylserine at the outer surface of the red cells.

scholarly journals To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

2021 ◽  
pp. 1-5
Author(s):  
Justin E. Juskewitch ◽  
Craig D. Tauscher ◽  
Sheila K. Moldenhauer ◽  
Jennifer E. Schieber ◽  
Eapen K. Jacob ◽  
...  
Keyword(s):  
Pregnant Woman ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pregnancy Termination ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Childbearing Age ◽  
Procedural Complications ◽  
History Of ◽  
Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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