Vaso-occlusive Complications Research Articles

Inpatient palliative care use by patients with sickle cell disease: a retrospective cross-sectional study

ObjectiveSickle cell disease (SCD) is a highly morbid condition notable for recurrent hospitalisations due to vaso-occlusive crises and complications of end organ damage. Little is known about the use of...

Transcranial doppler as screening method for sickling crises in children with sickle cell anemia: a latin America cohort study

BackgroundSickle cell anemia (SCA) is the leading cause of childhood stroke. We aimed to evaluate whether altered cerebral flow velocities, as measured by transcranial Doppler (TCD), are associated with vaso-occlusive complications in addition to stroke in pediatric SCA patients.MethodsWe evaluated 37 children aged between 2 and 16 years with SCA who underwent screening for TCD between January 2012 and October 2018. Genotypic profiles and demographic data were collected, TCD examinations were performed during follow-up, and the presence of sickling crises was compared. Survival analyses were performed using simple frailty models, in which each predictor variable was analyzed separately in relation to the occurrence of a sickling crisis.ResultsThe variables related to sickle cell crises in the univariate analysis were peak systolic velocity (PSV) in the middle cerebral artery (MCA), hazard ratio (HR) 1.01 (1.00—1.02) p = 0.04; end-diastolic velocity (EDV) in the MCA, HR 1.02 (1.01—1.04) p = 0.01; time average mean maximum velocity (TAMMV) in the basilar artery (BA), HR 1.02 (1.00—1.04) p = 0.04; hemoglobin, HR 0.49 (0.38—0.65) p < 0.001; hematocrit, HR 0.78 (0.71—0.85) p < 0.001; leukocyte counts, HR 1.1 (1.05—1.15) p < 0.001; platelets counts, HR 0.997 (0.994—0.999) p = 0.02; and reticulocyte numbers, HR 1.14 (1.06—1.23) p < 0.001.ConclusionsOur results indicate PSV and EDV in the MCA and TAMMV in the BA as markers of risk for the occurrence of sickling crises in SCA.

Complications lithiasiques chez les patients drépanocytaires

Chronic haemolysis exposes patients with sickle cell disease (SCD) to the development of black pigment gallstones, which can trigger biliary complications. In order to avoid these complications, elective cholecystectomy is recommended in France for all SCD patients with detected gallstones. However, all surgeries, and especially abdominal surgeries, entail an increased risk of vaso-occlusive complications in the peri- and post-operative periods, the most dreadful one being the acute chest syndrome. Preoperative transfusion has been shown in several studies to reduce acute postoperative complications, but exposes the patient to definitive alloimmunization, or even delayed post- transfusion haemolysis, justifying a recent trend towards transfusion sparing. The conditions for avoiding transfusion for a simple and frequent surgery such as cholecystectomy are based on a benefit- risk balance, and must be discussed on a case-by-case basis by the SCD specialist. In particular, it seems fully justified to perform prophylactic preoperative transfusion in patients with a history of recent vaso-occlusive crisis or acute chest syndrome (within 6 months preoperatively), and those operated on in an emergency setting, who are particularly at risk of postoperative events.

Barriers to Therapeutic Use of Hydroxyurea for Sickle Cell Disease in Nigeria: A Cross-Sectional Survey.

Background: Sickle cell disease, the inherited blood disorder characterized by anemia, severe pain and other vaso-occlusive complications, acute chest syndrome, disproportionate hospitalization, and early mortality, has significant financial, social, and psychosocial impacts and drains individuals, families, and health systems globally. Hydroxyurea could improve the health of the 300,000 individuals born each year with sickle cell disease in sub-Saharan Africa; however, challenges to adoption and adherence persist. This study assessed the barriers to therapeutic use of hydroxyurea for sickle cell disease within the Nigerian healthcare system, specifically from the level of the patient, provider, and health system. Methods: We used purposive sampling to recruit participants from 13 regions in Nigeria. A cross-sectional survey was administered to physicians (n = 70), nurses or counselors (n = 17), and patients or their caregivers (n = 33) at 13 health centers. Findings were mapped onto the appropriate Consolidated Framework for Implementation Research (CFIR) domains. Results: This study was able to identify factors that mapped onto the inner setting, outer setting, and characteristics of individuals domains of CFIR. The majority of physicians (74.3%) prescribe hydroxyurea, and half stated hydroxyurea is the standard of care. Among clinicians, barriers included limited knowledge of the drug, as well as low self-efficacy to prescribe among physicians and to counsel among nurses; perceived side effects; perceived patient preference for traditional medicine; cost for patient and expense of accompanying laboratory monitoring; and limited availability of the drug and equipment for laboratory monitoring. Among patients and caregivers, barriers included lack of knowledge; perceived side effects; cost; religious beliefs of disease causation; and lack of pediatric formulation. Conclusions: Findings suggest that patient, provider, and health systems-level interventions are needed to improve hydroxyurea uptake among providers and adherence among patients with sickle cell disease in Nigeria. Interventions such as patient education, provider training, and policy change could address the disproportionate burden of sickle cell disease in sub-Saharan Africa and thus improve health equity.

In Vitro Red Blood Cell Segregation in Sickle Cell Anemia

Red blood cells in sickle cell anemia (sRBC) are more heterogeneous in their physical properties than healthy red blood cells, spanning adhesiveness, rigidity, density, size, and shape. sRBC with increased adhesiveness to the vascular wall would trigger vaso-occlusive like complications, a hallmark of sickle cell anemia. We investigated whether segregation occurs among sRBC flowing in micron-sized channels and tested the impact of aggregation on segregation. Two populations of sRBC of different densities were separated, labeled, and mixed again. The mixed suspension was flowed within glass capillary tubes at different pressure-drops, hematocrit, and suspending media that promoted or not cell aggregation. Observations were made at a fixed channel position. The mean flow velocity was obtained by using the cells as tracking particles, and the cell depleted layer (CDL) by measuring the distance from the cell core border to the channel wall. The labeled sRBC were identified by stopping the flow and scanning the cells within the channel section. The tube hematocrit was estimated from the number of fluorescence cells identified in the field of view. In non-aggregating media, our results showed a heterogeneous distribution of sRBC according to their density: low-density sRBC population remained closer to the center of the channel, while the densest cells segregated towards the walls. There was no impact of the mean flow velocity and little impact of hematocrit. This segregation heterogeneity could influence the ability of sRBC to adhere to the vascular wall and slow down blood flow. However, promoting aggregation inhibited segregation while CDL thickness was enhanced by aggregation, highlighting a potential protective role against vaso-occlusion in patients with sickle cell anemia.

Causes and Circumstances of Death: Analysis in 266 Sickle Cell Adult Patients

IntroductionSickle cell disease is a genetic disease with acute and chronic complications. Pediatric mortality has decreased in recent decades with the introduction of systematic antibiotic therapy, preventive management of cerebral vasculopathy and therapeutic education of families. However, in the absence of cohort follow-up at birth, life expectancy, which is a different concept from age at death, cannot be assessed.In this retrospective, monocentric study, we describe causes and circumstances of death, acute chronic complications, long-term treatments and baseline biology of these patients. It seems important to analyze the risks of morbidity and mortality in order to decide on the necessary preventive measures.Material and method:Records of patients deceased between 2000 and 2020, from the national referral center (Henri Mondor Hospital), were retrospectively reviewed. The referral center follows 3500 patients. All deaths reported to the hospital, by families, other hospitals and health professionals were retrieved from computerized records. Deaths published by the INSEE (National Institute of Statistical and Economical study) from 2000 to December 2020 were accessible and compared with our databases to identify all our deceased patients. All patients with a medical record in our center were included for the study. Patients who had never visited our center were excluded.Results:During this period 226 patients including 128 women and 138 men are recorded. Genotypes for these patients were 204(76%) SS, 41 (15%) SC, 14(5%) Sβ°thalassemia and 7 (2%) Sβ+thalassemia. The median age at death was 41 years with an IQR [32-51]. 186 (70%) patients were hospitalized, 129 (70%) of whom were admitted to intensive care. 36 (13%) patients died at home, including 15 with opioid addiction and 5 patients with psychiatric pathology, and 4 patients on dialysis. This information was not available for 44 (16%) patients.The causes of death were vaso-occlusive complications with multivisceral failure in 44 cases, 42 sepsis, among which there were 11 renal failures, 9 of which were dialyzed. 5 patients died of COVID 19. Cerebral hemorrhage and neurological accident occurred in 22 cases, 4 of which were known to have macrovasculopathy. 25 patients died of a direct complication of renal failure, of which 17 were dialysed, 8 pre-dialysed and 3 transplanted. Acute liver failure in 16 cases, 10 precapillary pulmonary hypertension, 14 DHTR, 10 end-stage heart failure were noted. Two road accidents, 2 suicides, 1 dementia are repoted. For 51 cases, there was no information on the cause or circumstance of death. The causes of death according to genotype is on Table 1.Concerning the chronic complications, 94/266 (35%) patients had significant chronic organ damage. Sixteen patients had required renal or liver transplantation in their history. End-stage organ damage was frequent, 42 had end-stage renal failure, 21 had major liver failure, of which five were transplanted and 16 were awaiting transplantation. Twenty-one patients had known heart failure, 10 of which were associated with end-stage renal disease. Ten patients were followed for significant precapillary pulmonary hypertension.Transfusion difficulties due to a history of DHTR were found for 33 patients. Fourteen patients had an opioid addiction. Nine patients were pregnant and nine had received corticosteroids.Discussion:Causes of death have changed and chronic organ failure is the leading cause of death, especially in patients with kidney, liver and heart disease. This study does not calculate life expectancy, but there was an increase in age at death of about 1/4 of the patients who were between 51 and 81 years old.The management of sickle cell disease has progressed in recent years and new therapies are being proposed. Prevention of the development of these complications is one of the new challenges, especially for renal disease, which is associated with premature mortality. DHTR and cerebral hemorrhage, Covid-19 are new entities and DHTR was probably underdiagnosed in previous publications. Pregnancy remains a period at risk, for which surveillance should be reinforced. The analysis is ongoing and correlations are currently being investigated between different parameters to find risk factors for mortality. [Display omitted] DisclosuresHabibi: Novartis: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria, Research Funding. Audard: Addmedica: Consultancy. Michel: Novartis: Consultancy; Amgen: Consultancy; Rigel: Honoraria; Alexion: Honoraria; UCB: Honoraria; Argenx: Honoraria. Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci: INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; GBT: Consultancy; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; Hemanext: Consultancy; Emmaus: Consultancy; Fabre Foundation: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Addmedica: Consultancy, Other: Lecture fees, Research Funding.

Plasma Concentration of 12-Hydroxyeicosatetraenoic Acid, Single Nucleotide Polymorphisms of 12-Lipooxygenase Gene and Vaso-Occlusion in Sickle Cell Disease.

Background and Novel Aspect of this Work: In the light of previous findings that inflammation predisposes to intercellular adhesion and microvascular occlusion in sickle cell disease (SCD), this study investigated the relationship between the number of vaso-occlusive events in SCD, plasma levels of the pro-inflammatory molecules 12-Hydroxyeicosatetraenoic acid (12-HETE), TNF-α and IL-1β; and single nucleotide polymorphisms (SNPs) in the gene 12-Lipooxygenase (ALOX-12), which encodes the enzyme 12-Lipoxygenase that catalyzes the biosynthesis of 12-HETE. Objective: To evaluate the relationship between vaso-occlusion in SCD and plasma concentrations of 12-HETE, TNF-α, and IL-1β; and single nucleotide polymorphisms (SNPs) in ALOX-12 gene. Participants and Methods: In 50 HbSS patients, the numbers of vaso-occlusive crisis requiring hospital treatment in the previous 1 year and the vaso-occlusive complications of SCD developed to date (e.g stroke) were added to obtain the vaso-occlusive events (VOE) score. In the HbSS patients and 30 healthy sibling control persons, plasma concentrations of 12-HETE, TNF-α and IL-1β were measured by ELISA, the ALOX12 SNPs rs2073438 and rs1126667 detected by DNA sequencing, and the accrued data statistically analyzed. Results: Compared to SCD patients with VOE score 0–1, those with scores ≥3 had higher plasma levels of 12-HETE (p < 0.0001) and TNF-α (p = 0.19), but not IL-1β (p = 0.27). VOE score showed strong direct correlation with plasma level of 12-HETE (r = 0.65, p < 0.0001), but not with TNF-α nor IL-1β. Neither VOE score nor plasma concentration of 12-HETE showed any relationship with the ALOX12 SNPs rs2073438 and rs1126667. Conclusion: The strong direct correlation of VOE score with plasma concentration of 12-HETE suggests that the clinical relevance of this pro-inflammatory molecule in SCD-associated vaso-occlusion needs to be evaluated in further studies.

Anti-tubercular therapy alone for treatment of isolated tubercular retinal vasculitis.

To compare the time to resolution of perivascular infiltrates in tubercular retinal vasculitis (TRV) between anti-tubercular therapy (ATT) alone, and in combination with systemic corticosteroids. Observational retrospective cohort study in a tertiary eye centre in eastern India. Patients with TRV who were treated with anti-tubercular therapy (ATT) alone (Group A), or in combination with systemic corticosteroids (Group B) were included in the study. Eyes with additional inflammatory signs (cystoid macular oedema, vitritis ≥2+, optic disc oedema) were excluded. Resolution was defined as complete disappearance of perivascular infiltrates on seven-field fundus photographs. Descriptive statistics were used for demographic data. A linear mixed effects model was applied to adjust for intereye correlations, in patients with bilateral disease. The primary outcome measure was time to resolution of perivascular infiltrates. Secondary outcome measure was need for laser or surgical intervention for management of complications of TRV. Fifty eyes of 39 patients (Group A 21/18 and Group B 29/21) were included. Both groups had similar demographics and severity of vasculitis. All patients had complete resolution of TRV. On adjusting for intereye correlation, the mean difference in time to resolution between the two groups (Group A, 3.24 [95% CI 2.69-3.77] months, and Group B, 4.76 [95% CI 3.52-5.99] months) was not statistically significant (0.96 weeks [-0.52 to 2.45] p = 0.21). Vaso-occlusive complications and healing patterns were similar in both groups. ATT alone, may be sufficient for resolution of perivascular infiltrates, in TRV without additional inflammatory signs.

Arteriolar Bottle-Necks in the Lung Are the Site of Pulmonary Thrombo-Embolism

Acute Pulmonary Thrombo-Embolism (PTE) is a major vaso-occlusive pulmonary complication associated with high morbidity. Despite advances in diagnosis and treatment, the pathophysiology of PTE remains incompletely understood and anticoagulant therapy is the only available treatment. Based on computed tomography in humans and accumulation of radiolabeled platelets in mice, PTE is believed to be primarily triggered by embolic platelet aggregates arriving from the venous circulation and sequestering in the pulmonary arterioles. However, new clinical evidence suggest that in situ pulmonary arteriole micro-thrombosis may also promote PTE. Studies that can visualize PTE in real time in vivo in mice are highly warranted to identify different mechanisms contributing to PTE. Improved understanding of the biophysical, cellular and molecular mechanism would enable development of new therapies for PTE.ADP, collagen or thrombin were administered intravascularly (IV) to wild type (WT) mice and the pulmonary microcirculation was studied using multi-photon-excitation (MPE) enabled quantitative intravital fluorescence lung microscopy (qFILM). Fluorochrome-conjugated anti-mouse CD49b Ab and dextran was administered IV for in vivo staining of circulating platelets and visualization of blood vessels. Time series of qFILM images were collected at baseline and immediately following IV administration of ADP, collagen or thrombin. Images were analyzed to identify PTE, which was defined as occlusion of blood vessels with platelet aggregates leading to loss of blood flow.ADP (0.5-2.5 mg/kg), collagen (0.2-0.5 mg/kg) and thrombin (250-500 U/kg) triggered dose-dependent PTE in mice. Remarkably, large embolic platelet aggregates were observed to arrive in the pulmonary arterioles and occlude the arteriolar bottle-necks located at the junction of pulmonary arterioles and capillaries. The occlusion of arteriolar bottle-necks led to stasis of blood flow in the arteriole and the down-stream capillaries. Surprisingly, unlike collagen or thrombin, ADP induced PTE was transient and resolved over a time period of 10 min. However, thrombin (500 U/kg) and collagen (0.5 mg/kg) triggered stable emboli within the arteriolar bottle-necks.We introduce an intravital microscopy approach to probe agonist-dependent platelet aggregation in the lung microcirculation of live mice. We provide the first real-time visual in vivo evidence establishing that PTE indeed involves entrapment of embolic platelet aggregates in the pre-capillary pulmonary arterioles. Our model has potential application in investigating the molecular determinants of pulmonary thrombosis in diverse pulmonary disorders as well as evaluating efficacy of new antithrombotic drugs. DisclosuresNo relevant conflicts of interest to declare.

English

BACKGROUND Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C variants are considered as potential genetic risk factors for vaso-occlusive complications in sickle cell disorder (SCD). The purpose of the study was to determine the interaction of the combined haplotypes on the clinical presentations in children with sickle cell disorder. METHODS A cross-sectional study was conducted on 249 children, confirmed for sickle cell disorder. Clinical details and frequencies of clinical episodes in the past one year were noted and a severity index number was allotted to each child and evaluated for their relationship with the combined haplotypes of C677T and A1298C single nucleotide polymorphisms genotyped by real-time PCR. RESULTS The frequency for 677T / 1298A haplotype was 46.4 % and that of 677C / 1298C was 12.4 %. The three variant combined haplotypes had higher plasma homocysteine values than the wild 677C / 1298A haplotypes (P &lt; 0.001). Clinical events like vasoocclusive crisis (VOC), homocysteinemia, hospitalization frequency and SI were found significantly related among the children in sickle cell trait (SCT) group (P &lt; 0.001) but not so in SCD group. Chances for anemia was 1.93 times more in presence of dual variant alleles (95 %CI: 0.95 to 3.92, P = 0.07) in SCT. The 677T / 1298C haplotype accounted for higher SI was 7.85 times more than the wild haplotypic children even in SCT children and 1.67 times in SCD children. CONCLUSIONS Presence of the variant haplotypes had significant implication on crisis events in children with sickle cell trait and make them more prone for the clinical severity. A preliminary allelic screening might be helpful in them. KEY WORDS Dual Variant Alleles, Heterozygous, Homozygous, MTHFR, Variant Haplotypes

POS-403 VARIATIONS IN THE THROMBIN GENERATION PROFILE AND CLOTTING FACTOR LEVELS IN THE PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS

Chronic kidney disease (CKD) patients are at high risk of cardiovascular disorders and thrombosis. CKD-V patients undergoing maintenance hemodialysis exhibit varying degrees of hemostatic dysregulation. Endogenous thrombin potential (ETP) is important to the pathogenesis of vaso-occlusive complications. This study investigated ETP and its relevance to circulating coagulation factor levels in CKD-V patients.

Fetal Hemoglobin in Sickle Hemoglobinopathies: High HbF Genotypes and Phenotypes.

Fetal hemoglobin (HbF) usually consists of 4 to 10% of total hemoglobin in adults of African descent with sickle cell anemia. Rarely, their HbF levels reach more than 30%. High HbF levels are sometimes a result of β-globin gene deletions or point mutations in the promoters of the HbF genes. Collectively, the phenotype caused by these mutations is called hereditary persistence of fetal hemoglobin, or HPFH. The pancellularity of HbF associated with these mutations inhibits sickle hemoglobin polymerization in most sickle erythrocytes so that these patients usually have inconsequential hemolysis and few, if any, vasoocclusive complications. Unusually high HbF can also be associated with variants of the major repressors of the HbF genes, BCL11A and MYB. Perhaps most often, we lack an explanation for very high HbF levels in sickle cell anemia.

Genetic Association of Clinical Complications for Genes Differentially Expressed in Reticulocytes of Sickle Cell Anemia

Introduction Sickle cell anemia (SCA) is characterized by hemolysis, a tissue hypoxia-driven increase in erythropoietin production, and a marked reticulocytosis reflecting stress erythropoiesis. Reticulocytes in SCA constitute 4-15% or more of peripheral red blood cells. Sickle reticulocytes express adhesion molecules that are normally cleared by exosome shedding, including α4β1 integrin, which is thought to contribute to vaso-occlusive crises by binding to vascular endothelial cell vascular cell adhesion molecule 1. Our recent study of the reticulocyte transcriptome in SCA versus healthy African Americans, using RNA-Seq, revealed differential genes that were implicated in a broad range of biological processes including terminal erythroid differentiation, the unfolded protein response, and altered membrane systems. In this study, we assessed the genetic association of these differential genes with disease complications relevant to sickle reticulocytes. Methods We analyzed vaso-occlusive complications including episodic severe pain and chronic avascular necrosis. We also analyzed hemolysis and anemia measured by a hemolysis index and hemoglobin concentration, respectively. The patient cohort combined 525 adolescent and adult patients from Walk PHaSST and 377 pediatric patients from PUSH. Genomic DNA isolated from peripheral blood mononuclear cells of Walk-PHaSST and PUSH patients were genotyped using Illumina Human 610-Quad SNP array and the genotypes were phased and imputed to 1000 genomes phase 3 data. Single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) &amp;gt;0.01 and imputation r2&amp;gt;0.7 were tested for gene-wise genetic association using SKAT. For severe pain and avascular necrosis, the covariates included age, gender, β globin genotype severity (HHbSS and HbSβ0-thalassemia versus HbSC and HbSβ+-thalassemia), and population stratification. For hemolysis and hemoglobin concentration, the covariates included age, gender, β globin genotype severity, alpha thalassemia, hydroxyurea treatment, recent blood transfusion, and population stratification. Results A total of 111 genes were analyzed. These genes were classified into 13 functional categories based on published research (transcription, post-transcription, translation, histone modification, cell cycle arrest, mitophagy, metabolism, iron homeostasis, antioxidative system, unfolded protein response, membrane skeleton and structural proteins, membrane adhesion molecules and blood group antigens, and membrane transporters). For each functional class, the number of significant gene-wise associations the functional class contains was compared to the number of significant associations from the other classes combined. Defining significance of gene-wise association at nominal P=0.05, we found that the "Unfolded protein response" contained more significant gene-wise associations with severe pain than the other functional classes (one-sided Fisher's exact test P=0.046), driven by genes FUCA1 (alpha-L- fucosidase) and CLN8 (associated with endoplasmic reticulum function). "Membrane skeleton and structural proteins" showed a trend of enrichment for hemolysis (P=0.057), driven by genes MYO5B and CD2AP, and for avascular necrosis (P=0.075), driven by genes MYLK, CAVIN2 and PALLD. Defining the significance of gene-wise association at a less stringent nominal P=0.1, "membrane adhesion molecules and blood group antigens" showed a trend of enrichment in association with severe pain (P=0.097), driven by genes GYPA, ITGA4 and ITGB1, the latter two encoding α4β1 integrin subunits which are abnormally present on the reticulocyte membrane and have been implicated in sickle vaso-occlusion. Regional scans revealed the SNPs with the most significant associations within these genes. Discussion Our results reveal enrichment of genetic association with vaso-occlusive and hemolytic complications in gene functional categories that showed altered expression in sickle reticulocytes. Future study is needed to validate these associations. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy.

Roleof Allogeneic Stem Cell Transplant (ASCT) in Patients (Pts) with Relapsed/Refractory (R-R) Acute Lymphoblastic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (INO) in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) with or without Blinatumomab (Blina): Results from a Phase 2 Study

Roleof Allogeneic Stem Cell Transplant (ASCT) in Patients (Pts) with Relapsed/Refractory (R-R) Acute Lymphoblastic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (INO) in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) with or without Blinatumomab (Blina): Results from a Phase 2 Study

Contemporary Practice Patterns of Tyrosine Kinase Inhibitor Use Among Older Patients with Chronic Myeloid Leukemia in the United States

Contemporary Practice Patterns of Tyrosine Kinase Inhibitor Use Among Older Patients with Chronic Myeloid Leukemia in the United States

Higher Hemoglobin Levels Achieved with Voxelotor Are Associated with Lower Vaso-occlusive Crisis Incidence: 72-Week Analysis from the HOPE Study

Higher Hemoglobin Levels Achieved with Voxelotor Are Associated with Lower Vaso-occlusive Crisis Incidence: 72-Week Analysis from the HOPE Study

Parathyroid Hormone Profile In Sickle Cell Disease In School Aged Children

Background: Sickle cell disease (SCD) is group of hemoglobinopathies associated with hemolytic anemia and vasoocclusive complications. All forms of SCD are inherited in an autosomal recessive fashion. Parathyroid hormone plays an essential role in calcium and phosphorus homeostasis, which is achieved by its action on target organs (intestine, bone and kidney), leading to normal bone formation and mineralization and normal physiological concentration of calcium and phosphorus. Objectives: This study aimed to detect the effect of sickle cell disease on parathyroid hormone and consequently on serum calcium (S.Ca), phosphorus (ph), alkaline phosphatase (alk.Ph) and magnesium (Mg) on patients with sickle cell anemia. Subjects and Methods: Forty children known as sickle cell disease patients, twenty of them were SCD (HbSS) (11 males and 9 females). The other twenty were known SC trait (10 males and 10 females). The ages of the children ranged from 5 to 15 years old. All were in non-crises state in routine Outpatient Clinic visits, compared to twenty apparently healthy, age matched and with normal hemoglobin from Atfal Masr Hospital as control. Neither patients nor control received calcium supplementation before the study. Results: The results indicated that sickle cell patients and sickle cell trait patients had hypocalcaemic tendency associated with supernormal parathyroid hormone level and implied impaired calcium absorption from intestine leading to disturbed calcium metabolism, which might contribute in skeletal changes seen in sickle cell patients. Conclusion: We found that there was statistically significant decrease in serum Ca levels accompanied with increase in serum PTH, ph, alk Ph and Mg levels in SCD and Sickle cell trait patients compared to control group.

Pregnancy Outcomes among Patients with Sickle Cell Disease in Brazzaville.

Introduction Sickle cell disease (SCD) is one of the most common genetic diseases in the world. It combines, in its homozygous form, chronic hemolytic anemia, vasoocclusive complications, and susceptibility to infections. It is well known that the combination of pregnancy and sickle cell disease promotes the occurrence of complications that are sometimes fatal for the mother and/or the fetus. Objective The objective of the current study was to compare pregnancy outcomes among women with SCD with those of women without the diagnosis of SCD. Materials and methods. It was a case-control study carried out in four maternity hospitals in Brazzaville in 2 years (July 2017–June 2019). It concerned 65 parturients with SS homozygous SCD. The mode of childbirth and maternal and perinatal morbidity and mortality were compared with those of 130 non-sickle cell pregnant women. Results The average age was 27 years for SCD women and 31 years for non-SCD women. The average gestational age at delivery was 35 weeks for SCD women and 38 weeks for non-SCD women. From the logistic regression analysis using the comparison group as the reference group, there was excessive risk in SCD compared to non-SCD of infection (29.3% vs. 4.6%, OR = 21.7, 95% CI [7.6–62.7]; p=0.001), cesarean (63% vs. 35.4%, OR = 3.1, 95% CI [1.6–5.7]; p=0.001), prematurity (75.4% vs. 30.8%, OR = 8, 95% CI [3.0–23.2]; p=0.001), low birth weight (52.3% vs. 16.1%, OR = 4.7, 95% CI [2.4–9.4]; p=0.001), neonatal requiring admission to the intensive care unit (40.3% vs. 17.5%, OR = 3.2, 95% CI [1.6–6.3]; p=0.01), and neonatal death (21.5% vs. 4.8%, OR = 4.3, 95% CI [1.5–12.2]; p=0.01). Conclusion The risk of pregnancy in patients with homozygous sickle cell anemia remains high, on both the maternal and fetal sides.

Hemoglobin S/Hemoglobin Quebec-Chori Presenting as Sickle Cell Disease: A Case Report

Sickle cell disease is a homozygous hemoglobinopathy with vaso-occlusive complications secondary to abnormal sickling of red blood cells under stressful conditions such as hypoxia. Children with sickle cell trait have a heterozygous genetic state, typically without symptoms. An 8-year-old boy diagnosed with sickle cell trait was found to have multiple complications consistent with sickle cell disease, including pain crises, osteomyelitis, and priapism. Over a 6-year period, he underwent routine laboratory evaluations without a definitive diagnosis. The diagnosis of a compound heterozygous state of hemoglobin S/hemoglobin Quebec-Chori was eventually made on the basis of mass spectrometry and confirmed with hemoglobin subunit beta gene sequencing. Expanding diagnostic evaluation in patients with abnormal clinical presentations is vital to making the correct diagnosis and hence earlier institution of appropriate management of rare hemoglobinopathies.

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis.

Background Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. Results Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1β, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. Conclusion In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1β, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1β and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.