scholarly journals FOETAL HAEMOGLOBIN AND DISEASE SEVERITY IN NIGERIAN CHILDREN WITH SICKLE CELL ANAEMIA.

2017 ◽  
Vol 9 (1) ◽  
pp. e2017063 ◽  
Author(s):  
Oluwagbemiga Adeodu ◽  
Morenike Akinlosotu ◽  
Samuel Adegoke ◽  
Saheed Oseni
Keyword(s):  
Disease Severity ◽  
Sickle Cell ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Foetal Haemoglobin ◽  
Nigerian Children ◽  
Moderate Disease ◽  
History Of ◽  
The Mean ◽  
Hbf Level

Background: Foetal haemoglobin (HbF) is a major modifying factor influencing sickle cell disease (SCD) severity. Despite this, HbF estimation is not routinely done in Nigeria. Relationship between HbF and SCD severity among affected children is also poorly studied.Methods: In this descriptive cross-sectional study, we determined the relationship between steady state HbF levels and disease severity of Nigerian children aged 1 – 15 years with homozygous SCD. For each child, the socio-demographic characteristics and SCD clinical severity were determined. The latter was assessed based on the frequency of significant painful episodes, blood transfusion, and hospitalization in the preceding 12 months; lifetime cummulative incidence of SCD-related complications; degree of splenic and hepatic enlargement; current haematocrit and leucocyte count, as previously described. Foetal haemoglobin levels were quantified with high performance liquid chromatography.Results: The mean HbF level of the 105 children with SCA was 9.9 ± 6.0%. Male had significantly lower mean HbF levels than females, 8.0 ± 5.6% vs. 12.2 ± 5.8% (p < 0.001). None of the children had severe disease. However, those with moderate disease had significantly lower mean foetal haemoglobin levels than those with mild disease (7.7 ± 5.6% vs. 10.8 ± 6.0% respectively). The mean HbF level was also significantly lower in children who had history of acute chest syndrome and stroke compared to those without these complications,   p = 0.002 and 0.010 respectively.Conclusion: Children with SCA who had moderate disease and those with history of life threatening complications such as stroke and acute chest syndrome had significantly low HbF. Therefore it is recommended that facilities for early quantification of foetal haemoglobin and HbF inducement be made available in order to reduce the morbidity and mortality among these children.

Severity of Sickle Cell Disease: Modeling Interrelationships among Hemolysis, Pulmonary Hypertension and Risk of Death.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 786-786
Author(s):  
Paola Sebastiani ◽  
Vikki G. Nolan ◽  
Clinton T. Baldwin ◽  
Maria M. Abad-Grau ◽  
Ling Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Risk Of Death

Abstract A single point mutation in the β hemoglobin gene causes sickle cell disease (SCD), but patients have extremely variable phenotypes. Hemolysis-related complications include pulmonary hypertension (PHT), priapism, stroke and leg ulceration; blood viscosity and sickle vasoocclusion are associated with painful episodes, acute chest syndrome and osteonecrosis. Predicting who is at highest risk of death would be useful therapeutically and prognostically. Applying Bayesian network modeling that describes complex interactions among many variables by factorizing their joint probability distribution into modules, to data from 3380 SCD patients, we constructed a disease severity score (DSS: 0, least severe; 1, most severe), defining severity as risk of death within 5 years. A network of 24 variables described complex associations among clinical and laboratory complications of SCD. The analysis was validated in 140 patients whose SCD severity was assessed by expert clinicians and 210 adults where severity was also assessed by the echocardiographic diagnosis of PHT and death. Information about PHT allowed a comparison of the DSS with the tricuspid regurgitant jet velocity (TRJV), an objective marker of PHT and an independent risk factor for death. DSS and three indices of clinical severity (severity ranking of individuals by expert clinicians; objective measurement of the presence and severity of PHT; risk of prospective death) were correlated. Among living subjects, the median score was 0.57 in 135 patients without PHT, 0.64 in 40 patients with mild PHT and 0.86 in 15 patients with severe PHT. The difference in average score between living patients with and without PHT is significant. The same increasing trend was noticeable in the subjects who died during follow-up: 0.60 in subjects without PHT; 0.68 in subjects with mild PHT; 0.79 in subjects with severe PHT. The utility of the DSS is also supported by the ability to assign a score to subjects for whom the TRJV cannot be measured. Surprisingly, besides known risk factors like renal insufficiency and leukocytosis, we identified the intensity of hemolytic anemia and clinical events associated with hemolytic anemia as contributing to risk for death. Priapism, an excellent reflection of the hemolytic anemia-related complications of SCD, is associated with PHT and its association with death was unexpected. Laboratory variables predictive of disease severity included LDH and reticulocytes that reflect the intensity of hemolytic anemia. Elevated systolic blood pressure increased the odds of death by 3.4, consistent with hypertension as a marker of early death in SCD. Subjects with sickle cell anemia are at greatest risk compared with subjects with sickle cell anemia-α thalassemia and with subjects with HbSC disease. Our model suggests that the intensity of hemolytic anemia, estimated by LDH, reticulocyte count and AST, and shown previously to be associated with PHT, priapism, leg ulceration and possibly stroke, is an important contributor to death. This model can be used to compute a personalized measure of disease severity that might be useful for guiding therapeutic decisions and designing clinical trials.

Combining Fetal Hemoglobin and Reticulocytosis to Index Clinical Severity of Sickle Cell Disease in Children.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2556-2556
Author(s):  
Emily Riehm Meier ◽  
Colleen Byrnes ◽  
Maxine Weissman ◽  
Pierre Noel ◽  
Naomi L.C. Luban ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Supportive Care ◽  
Disease Severity ◽  
Sickle Cell ◽  
Fetal Hemoglobin ◽  
Treatment Decisions ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
F Cells

Abstract Abstract 2556 Poster Board II-533 Predictors of disease severity during infancy or childhood in patients with sickle cell disease (SCD) are needed to guide treatment decisions with therapies that have known toxicities [transfusion, hydroxyurea (HU), bone marrow transplant]. Erythrocyte fetal hemoglobin (HbF) expression levels above 20% reduce sickle hemoglobin (HbS) polymerization and decrease hemolysis. As a result of the decreased hemolysis, the survival of erythrocytes is prolonged, and the overall level of erythropoiesis is reduced. To determine if clinical markers of increased HbF production and decreased erythropoiesis may be combined to score disease severity, we developed a Fetal Hemoglobin-Reticulocytosis Index (FRI) defined as: [HbF (%) × non-transfused F-cells (%)] / [Absolute Reticulocyte Count (K/uL)]. For these studies, red cell lysates were analyzed by high power liquid chromatography (HPLC) to estimate HbA, HbS, and HbF fractions. F-cells were analyzed by flow cytometry using antibodies directed against HbF, while transfused cells were labeled with antibodies directed against HbA. Dual staining with both antibodies provided a method for accurately distinguishing transfused and non-transfused F-cells (NT F-cells). A minimum of 10,000 cells was analyzed in all samples. Absolute reticulocyte counts (ARC) were determined using a Sysmex XE 2100 hematology analyzer (Sysmex America, Mundelein, IL). Preliminary studies revealed FRI values near 100 at one month of age followed by a rapid drop before the age of 4 years. Blood from children between the ages of 4 and 21 years was also studied to determine if FRI correlates with therapeutic regimen. FRI values for three groups were compared: those treated with chronic transfusion (n=19, mean FRI=0.72±1.04), HU (n=19, mean FRI=5.61±6.24), versus supportive care alone that did not include recent transfusions (n=42, mean FRI=2.70 ±4.85). When the FRI values from each of these groups were placed in rank order, the slope of the line increased sharply from a linear to an exponential shape near the FRI value of 2. To determine if the FRI=2 inflection may be indicative of reduced disease severity, the number of SCD events were determined in the 42 study subjects treated with supportive care. Overall, twenty-eight (66.7%) patients had an FRI<2, and fourteen (33.3%) patients had an FRI≥2. Among those patients, SCD events were tallied (listed in descending order according to number of events): painful crises requiring hospitalization (FRI<2, n=128; FRI≥2, n=25), pneumonia /acute chest syndrome (FRI<2, n=74; FRI≥2, n=18), splenic sequestration (FRI<2, n=14; FRI≥2, n=0), conditional transcranial Doppler [(TCD), FRI<2, n=13; FRI≥2, n=1), silent stroke (FRI<2, n=4; FRI≥2, n=2), bacteremia (FRI<2, n=2; FRI≥2, n=1), cholecystectomy (FRI<2, n=3; FRI≥2, n=0), and nephropathy (FRI<2, n=1; FRI≥2, n=0). None of the supportive care group had an overt stroke, abnormal TCD, sickle cell retinopathy, or priapism. Age adjusted analysis showed that the FRI≥2 group had significantly fewer total events per year [events/year: FRI<2 (0.70±0.52) vs. FRI≥2 (0.38 ± 0.36), p=0.02]. These data suggest that combining the clinical parameters of fetal hemoglobin production and reticulocytosis provides a simple index for SCD severity. Based upon this retrospective data, prospective studies are underway to determine if the FRI decline during infancy or FRI levels in childhood are useful to predict clinical severity and treatment decisions in SCD patients. 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

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 Sickle Cell Disease Related Outcomes in Patients Evaluated for COVID-19 Infections in South Carolina

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Laurence Noisette ◽  
Mamatha Mandava ◽  
Mathew Gregoski ◽  
Shayla Bergmann
Keyword(s):  
South Carolina ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Presentation ◽  
Self Report ◽  
Mortality Data ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
History Of ◽  
The Mean

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), first identified in Wuhan, China, was declared a pandemic by WHO in March 2020 due to its high transmission rate. Due to the diffuse vasculo-endothelial damage, individuals with Sickle Cell Disease (SCD) are at risk to develop severe clinical complications, if infected with coronavirus 19 (COVID-19).[1] Given this risk, a systematic evaluation of individuals with SCD presenting with COVID19 infection is paramount to identify the variable clinical manifestations and complications encountered in children and adults with SCD. Methods: A retrospective chart review was conducted from January to June 2020 at the Medical University of South Carolina. We included individuals with sickle cell disease of all genotypes, from 0 to 65 years of age found to be positive for COVID19 by polymerase chain reaction (PCR). Patients' past medical history, clinical presentations, admissions, treatment, complications, and mortality data were reviewed. The data was collected with REDCap@ and descriptive data analysis was conducted per SPSS@. Results: Of the identified 23 patients with SCD who tested positive for COVID during the time specified, 19 (82.6%) had Hgb SS genotype, two had Hgb SC (9%) and two Hgb Sβ+ thalassemia (9%) with similar incidence in both genders (47.8% male and 52.2 % female). All patients were African American. The mean age was 26.13+/-11.53 years. In the last three years they had admissions for pain at a mean of 4.29 +/- 5 and admissions for acute chest syndrome 1+/- 2.2. Six participants (26.1%) had history of mild asthma. Two (8.7%) had pulmonary hypertension. No participants had a history of silent stroke. One participant had history of ischemic stroke, three (13%) had history of pulmonary embolism, and six (26.1%) had deep vein thrombosis (DVT). A variable clinical presentation was noted in our population (Table 1). Of the 23, only nine (39%) required admission of which only one met criteria for intensive care (4.3%) requiring respiratory support with high flow nasal canula. All participants recovered well with the mean length of admission 4.36+/- 3.8 days. Treatment included supportive care including transfusion support, two (8.7%) needed simple transfusion, two (8.7%) needed exchange transfusion. Regarding the laboratory values, coagulations studies were noted to be elevated among all those obtained, but overall limited values were obtained. (Table 2) Thus far no complications of stroke, thrombosis, or pulmonary emboli are noted in the patients positive for COVID in sickle cell disease at our institution. No deaths were reported. Conclusion: Our population reflects what has been described thus far in other cohorts regarding patient demographics, clinical presentation and evolution of disease. Missing laboratory results is most likely due to the mild severity which did not require further clinical evaluation. The absence of VTE/PE may be explained by the low rate of ICU admissions. A similar ICU admission rate of 13% in the same age group as our population was described in a study conducted in France with 83 patients. [2] Compared to a study conducted in Detroit, Michigan, our population underwent comparable rates of transfusions with 3 patients compared to 4 in our population, again most likely due to the mild severity. [3] Our results reflect only MUSC's testing sites and we are dependent on patient's self-report which may not represent our entire population. To address this issue, as part of the Sickle Cell South Carolina network, we are partnering with two other institutions to assess SARS-Cov-2 infection in South Carolina. SARS-CoV-2 pandemic has brought to light many disparities encountered in the American health care system. It is premature to evaluate the immediate and long-term ramifications of COVID19 in individuals with sickle cell disease, due to which we plan to continue to monitor for the next 2 years. References 1. Hussain, F.A., et al.,COVID-19 Infection in Patients with Sickle Cell Disease.Br J Haematol, 2020. 2. Arlet, J.B., et al.,Prognosis of patients with sickle cell disease and COVID-19: a French experience.Lancet Haematol, 2020. 3. Balanchivadze, N., et al.,Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease. One Center Urban Experience, Detroit, MI, USA.Hemoglobin, 2020: p. 1-6. Disclosures Gregoski: National Institutes of Health under Grant Number UL1 TR001450:Current Employment.

scholarly journals The First Two Years of Life in Sickle Cell Anemia Infants: Results of a Comprehensive Longitudinal Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 688-688
Author(s):  
Valentine Brousse ◽  
Sara El Hoss ◽  
Naim Bouazza ◽  
Cecile Arnaud ◽  
Francoise Bernaudin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Disease Severity ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Neonatal Screening ◽  
Research Funding ◽  
Clinical Event ◽  
Acute Chest Syndrome ◽  
Hbf Level

Abstract Background and hypothesis: Infancy is a critical time during which the first complications of sickle cell anemia (SCA) emerge. Very early prognostic factors of severity are needed to select high-risk children to offer precisely tailored therapy. Our hypothesis was that clinical, biological or genetic parameters measurable soon after birth (3 to 6 months of age) could predict severe outcomes in the first two years of life in SCA infants. Methods: Infants with SCA were offered to participate in a prospective study (ClinicalTrials.gov: NCT01207037) that included clinical and laboratory assessment at enrollment (3-6 months) and at 12, 18 and 24 months of age. The prognostic performance of conventional and SCA-specific biomarkers (notably erythroid adhesion markers, dense cells, ektacytometry indices) on disease severity was assessed using Cox's proportional hazard regression models. The disease severity was defined as time to first occurrence of either acute splenic sequestration (ASS), vaso occlusive (VOC) event requiring hospitalization, transfusion, conditional or abnormal Trans Cranial Doppler, acute chest syndrome and death. Hazard ratios (HRs) were calculated with 95% Cis. Results: Fifty-seven infants (55 SS; 2 Sβ°; 54.4% males), diagnosed through neonatal screening, were included in the study at a mean age of 4.4 ± 1 months and longitudinally assessed with a median follow-up of 19.4 months (range 3.1-23.2). Only 1 of 57 infants had experienced a SCA-related event prior to enrolment (dactilytis). At inclusion, clinical examinations were unremarkable except for pallor found in 15 (26,3%) and none of the infants had an enlarged or palpable spleen. Growth parameters were normal. Main biological characteristics were a mild hemolytic anemia (Hb 9.3 ±1.3 g/dL; reticulocytes count: 151.2 ±76 x 109/L), increased HbF level (3.8 ±1.3 g/dL. or 41.4 ±11.7%) and presence of dense red cells (23.1 % ±10.8). Genetic analysis showed one alpha globin deletion in 18 (32.1%) and a balanced distribution of beta globin haplotypes: 16 (30.8%), 18 (34.6%) and 18 (34.6%) in the favorable (SEN/SEN, BEN/SEN, CAM/SEN or SEN/ATYP), unfavorable (CAR/CAR, CAM/CAR, CAR/ATYP or BEN/CAR) and intermediate category (other) respectively. During the 2 years duration of the study, 44 of 57 (77%) infants required 157 hospital admissions, median (range): 2 (1-12) per patient. Infection was a leading cause of hospitalization although no serious adverse event related to pneumococcal infection was noted. Eight (14%) children experienced an episode of ASS at a median (range) age of 13.4 months (7.8- 15.9) while 13 infants (22.8%) experienced at least one VOC event at a median age of 12.7 months (7-22.5), with 6 experiencing ≥ 2 episodes. Nineteen infants (33.3%) required at least one transfusion with 10 (17.6%) requiring more than 2. Altogether, 22 (38.6%) infants of this cohort experienced a SCA-related severe clinical event by 24 months of age. The Kaplan Meier estimate of the 24-month event-free rate was 54.4% (95% CI, 39.7 to 74.5%) (Figure). Univariate analysis of potential prognostic markers at inclusion showed that higher HbF % and concentration were the strongest protective parameters for ASS in particular and for all severe outcomes, except for VOC (p &lt; 0.001). Unfavorable haplotypes were also associated with severe outcome (HR (95% CI) 4.73 (1.31-17.01), p=0.017). Protective factors for VOC were higher Hb level (threshold &gt; 8 g/dL) and low % of circulating dense cells (p=0.04 and 0.02, respectively). In a multivariate analysis, Hb level ≥ 8 g/dL and HbF ≥ 2.8 g/dL proved to be two independent prognostic factors of a SCA-related severe event (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43) respectively). Interestingly, absolute neutrophil or reticulocyte counts, level of expression of known potentially pathogenic erythroid adhesion markers (CD36, Lu/B-CAM, ICAM-4/LW), % of red dense cell, or deformability parameters failed to be prognostic factors of specific complications or overall severity in this very young cohort. Conclusion: HbF and Hb levels measured between 3 and 6 months of age in SCA infants predict the risk of subsequent severe clinical outcome in the next 2 years. These events are frequent even in a high-income setting where neonatal screening is implemented. These findings further support the early use of HbF inducers such as hydroxyurea in high-risk infants to sustain a protective HbF level. Figure 1 Figure 1. Disclosures Brousse: Add Medica: Membership on an entity's Board of Directors or advisory committees. De Montalembert: Novartis: Consultancy, Honoraria, Research Funding; Addmedica: Consultancy, Honoraria, Research Funding.

scholarly journals Oxidative stress markers and disease severity among children with Sickle Cell Anaemia

2019 ◽  
pp. 193-202
Author(s):  
OS Smith ◽  
SA Adegoke ◽  
MA Akinlosotu ◽  
OA Ajose
Keyword(s):  
Oxidative Stress ◽  
Disease Severity ◽  
Sickle Cell ◽  
Sickle Cell Anaemia ◽  
Stress Index ◽  
Oxidative Stress Markers ◽  
Mild Disease ◽  
Stress Markers ◽  
Moderate Disease ◽  
The Mean

Background: Sickle cell anaemia has been associated with oxidative stress. Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) are cumulative markers of oxidative stress. Objective: To evaluate the serum levels of oxidative stress markers in children with sickle cell anaemia (SCA) and determine the relationship between these markers and disease severity. Method: One hundred and fifty-six children, comprising 78 with SCA, aged 1 - 15 years and 78 age- and sex-matched Haemoglobin AA controls were studied. Serum TOS, OSI, and TAC were determined using ELISA kits. The severity of the SCA was determined using clinical and laboratory parameters. Result: Children with SCA had lower mean serum TAC (0.83±0.31UAE) than controls (1.19±0.24UAE) with p<0.001. However, the mean serum TOS and OSI of children with SCA was higher than among the controls (13.33±4.64U/ml vs. 9.70±2.72U/ml and 20.95±16.75 vs. 8.68±3.76 respectively) with p<0.001. SCA subjects with mild disease had higher mean serum TAC (0.91 ± 0.27UAE) than those with moderate disease (0.54±0.27UAE) (p<0.001). On the other hand, the mean TOS and OSI were lower in children with mild disease compared to those with moderate disease (12.64±4.32U/ml vs. 15.63±5.07U/ml, p = 0.016 and 16.26±10.25 vs. 36.61±23.89 p<0.001 respectively). Sickle cell disease severity score had negative correlation with TAC (r = -0.60, p < 0.001) but positive correlation with TOS (r = 0.3, p = 0.008) and OSI (r = 0.6, p < 0.001). Conclusion: Children with SCA had lower TAC but higher TOS and OSI than matched controls. Oxidative stress markers had a significant relationship with SCD severity.

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.

scholarly journals Optimizing management of sickle cell disease in patients undergoing surgery

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 405-410
Author(s):  
Charity I. Oyedeji ◽  
Ian J. Welsby
Keyword(s):  
Sickle Cell Disease ◽  
Disease Severity ◽  
Sickle Cell ◽  
Surgical Complications ◽  
Acute Chest Syndrome ◽  
Surgical Team ◽  
Cell Disease ◽  
History Of ◽  
Baseline Hemoglobin

Abstract Individuals with sickle cell disease (SCD) are likely to be referred for surgery at some point in their lifetime due to a high incidence of musculoskeletal and intrabdominal complications such as avascular necrosis and gallbladder disease. Preoperative optimization is a multidisciplinary process that involves a hematologist with SCD expertise, an anesthesiologist, and the surgical team. The type and risk classification of the surgery, disease severity, medications, baseline hemoglobin, transfusion history, and history of prior surgical complications are often documented. Clinicians should consider perioperative risk assessment that includes determining the patient's functional status and cardiovascular risk and screening for obstructive sleep apnea. Many patients will require preoperative transfusion to reduce the risk of postoperative complications such as acute chest syndrome and vaso-occlusive pain crises. The hematologist should consider the patient's preoperative transfusion requirements and ensure that the surgical team has an appropriate plan for postoperative observation and management. This often includes follow-up laboratory studies, a postoperative pain management plan, and venous thromboembolism prophylaxis. The transfusion plan should be patient-specific and take into account the SCD genotype, baseline hemoglobin, disease severity, risk classification of the surgery, and history of prior surgical complications. In the intraoperative and postoperative period, dehydration, hypothermia, hypotension, hypoxia, and acidosis should be avoided, and incentive spirometry should be utilized to minimize complications such as acute chest syndrome. In this review we discuss preoperative, intraoperative, and postoperative strategies to optimize patients with SCD undergoing surgery.

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.

scholarly journals The Effect of Anterior Uterocervical Angle on Primary Dysmenorrhea and Disease Severity

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Mefkure Eraslan Sahin ◽  
Erdem Sahin ◽  
Yusuf Madendag ◽  
Ilknur Col Madendag ◽  
Ahter Tanay Tayyar ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Pain ◽  
Longitudinal Axis ◽  
Primary Dysmenorrhea ◽  
Uterine Corpus ◽  
Significant Family History ◽  
Significant Difference ◽  
History Of ◽  
Secondary Dysmenorrhea ◽  
The Mean

Background. Primary dysmenorrhea, defined as painful menstrual cramps originating in the uterus without underlying pathology, is a gynecological disease that affects quality of life and school success. Our goal was to determine the effect of anterior uterocervical angle on primary dysmenorrhea and disease severity. Methods. A total of 200 virgin adolescents, 16 to 20 years of age, were included in the study. The Andersch and Milsom scale was used to determine dysmenorrhea severity. Those with pathologies causing secondary dysmenorrhea were excluded from the study. Study subjects were grouped based on severity of pain. Demographic characteristics and uterocervical ultrasonographic measurements were compared among groups. Results. Of the 200 participants enrolled in the study, 50 were healthy controls and 150 had primary dysmenorrhea. Those with primary dysmenorrhea had a significant family history of primary dysmenorrhea compared with controls (P<0.001). Age (P=0.668), body mass index (P=0.898), menarche age (P=0.915), and length of menstrual cycles (P=0.740) were similar in all groups. The uterine corpus longitudinal axis, uterine corpus transverse axis, and uterine cervix longitudinal axis were also similar (P=0.359, P=0.279, and P=0.369, resp.). The mean uterocervical angle was 146.8 ± 6.0 in controls and 143.3 ± 7.3 in those with mild pain with no significant difference between the groups. In those with moderate pain, the mean uterocervical angle was 121.2 ± 7.3 compared with 101 ± 9.2 in those with severe pain, which was a significant difference. Additionally, there was also a significant difference in the uterocervical angle among those with mild, moderate, and severe pain (P<0.001). Conclusion. Our results indicate that a narrower anterior uterocervical angle is associated with primary dysmenorrhea and disease severity.

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