Asthma Is Associated with Acute Chest Syndrome, but Not an Increase Rate of Hospitalization for Pain among Children with Sickle Cell Anemia: A Retrospective Cohort Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3406-3406
Author(s):  
Francoise Bernaudin ◽  
Robert C. Strunk ◽  
Annie Kamdem ◽  
Cecile Arnaud ◽  
Ping An ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Therapeutic Intervention ◽  
Retrospective Cohort ◽  
Inhaled Corticosteroids ◽  
Medical Center ◽  
Acute Chest Syndrome ◽  
Thoracic Pain ◽  
Transfusion Therapy

Abstract Introduction In this study, we sought to validate the previous findings that asthma increases the incidence of acute chest syndrome (ACS) and pain in children with sickle cell anemia (SCA). Methods A retrospective cohort was comprised of children with SCA evaluated for at least six months from a single medical center. Asthma was defined as being present when the first wheezing episode was heard by a physician after the age of 2 years or after 3 episodes of bronchiolitis before the age of 2 years. ACS was defined as a recent abnormal X-ray of the lungs associated with fever, respiratory signs or thoracic pain. A painful episode was defined as pain that resulted in hospitalization. Therapeutic intervention (hydroxyurea, blood transfusion therapy or transplant) was uniformly applied to all children with three or more episodes of pain that required hospitalization within a 12 month period. Patient years were accumulated from birth until death, lost to follow up, last visit to the center or a therapeutic intervention, whichever came first. Results A total of 297 children with SCA were evaluable for a doctor diagnosis of asthma for a total of 1,805 patient-years. The mean length of follow-up was 6.1 patient-years. A doctor diagnosis of asthma was present in 8.4% (25 of 297). Among the children with asthma 75% (19 of 25) were consistently prescribed a beta 2 agonist or inhaled corticosteroids. After adjustment for the effect of age, asthma was significantly associated with ACS event (p = 0.03) but pain was not (>0.05). Conclusion Among children with SCA, asthma is associated with an increased incidence of ACS, but not pain that required hositalization. The absence of an association between asthma and pain may be related to uniform therapeutic intervention for children with repetitive painful episodes that require hospitalizations coupled with active treatment for asthma in most of the children.

Stroke in Sickle Cell Anemia After Excellent Response to Hydroxyurea.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4622-4622
Author(s):  
Ubaldo Martinez ◽  
Samir K. Ballas
Keyword(s):  
Atrial Septal Defect ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Septal Defect ◽  
Acute Chest Syndrome ◽  
Excellent Response ◽  
Blood Exchange ◽  
Atrial Shunt ◽  
The Right

Abstract Abstract 4622 Introduction Strokes occur in about 10% of children with sickle cell anemia (SS) less than 10 years old. These strokes are usually ischemic in nature. Stroke due to SS in adults is less common and is usually hemorrhagic in nature. We wish to report an unusual adult patient with SS and excellent response to HU who developed a stroke that was unrelated to SS. Case Report and Results A 35-year-old female with sickle cell anemia had mitral valve prolapse and migraine headaches presented 2 days after developing abrupt bilateral blurry vision, left facial numbness and weakness of her left leg. Her SS has been complicated by acute chest syndrome, bilateral hip avascular necrosis and frequent painful crises prior to hydroxyurea (HU) therapy. She was enrolled in the multicenter study of hydroxyurea (MSH) in SS and has been on 2500mg of HU per day for the past 13 years. She had an excellent response to HU with no recurrent acute chest syndrome and decreased need for blood transfusion. After starting HU, the frequency of crises requiring hospital admission decreased from 1 admission every 1 to 2 months to less than 1 admission per year except when hydroxyurea was discontinued for pregnancy. Her fetal hemoglobin increased from 6.1 % before HU to a maximum of 45%. Her MCV increased from 96 fl to a maximum of 132 fl and Hb from 8.0 g/dl to 9.8 g/dl Her exam was remarkable for left lower extremity weakness which was more pronounced proximally. All cranial nerves were intact and there was normal sensation bilaterally. CT scan of the brain showed three foci of hypodensity and MRI of the brain showed increased signal on T2, FLAIR and diffusion weighted images within the frontoparietal deep white matter consistent with infarction in the border zone of the middle cerebral artery (MCA)-anterior cerebral artery (ACA). MR angiography of the intracerebral and extracerebral vessels demonstrated focal narrowing of the right MCA at the trifurcation suggesting an embolic cause. Common causes of stroke were ruled out with routine studies. Her hemoglobin electrophoresis after admission but before blood exchange transfusion showed HbS of 55% and HbF of 45%. She underwent exchange transfusion 2 days after admission and was started on chronic blood exchange transfusions with the assumption that she had ischemic stroke due to SS. Initial transthoracic echocardiogram with contrast injection did not show an atrial shunt. Follow-up transesophageal echocardiogram after discharge showed a secundum atrial septal defect with a defect size of 1.4 cm. Right heart catheterization was performed and the pulmonary flow to systemic flow (Qp/Qs) was 1.7:1. An Amplatzer atrial septal defect (ASD) closure device was deployed with transesophageal echocardiographic guidance and a large thrombus was removed from the right atrium. At the patient's request exchange red cell transfusions were discontinued. The patient has continued treatment with hydroxyurea and aspirin. Conclusions Young patients with cryptogenic stroke have a much higher prevalence of atrial shunts and in particular patent foramen ovale than patients with other forms of stroke and therefore a cause-effect association is suggested. Young adults with stroke should be evaluated for common and reversible causes of stroke including paroxysmal emboli. Transesophageal echocardiography is the gold standard for diagnosing atrial shunts. Strokes in patients younger than age 55 are related to paroxysmal emboli and have a risk of recurrence of approximately 30% within one year. High risk features for stroke recurrence with an atrial shunt include hypercoagulable states, large opening and presence of an atrial septal aneurysm. Optimal management of patients with a stroke and an atrial shunt is unknown. Options include surgical closure, percutaneous device closure, anticoagulation and antiplatelet therapy. Patients with sickle cell disease and stroke should receive long term blood transfusions to reduce HbS below 30% if the stroke is felt to be related to sickle cell disease vasculopathy. The patient described with SS had a stroke and had an atrial septal defect that was repaired. The MRI/MRA findings are consistent with paroxysmal emboli. The patient is receiving treatment with hydroxyurea and aspirin having discontinued red cell exchange transfusions and at two years of follow-up has not had a recurrent stroke. Disclosures: No relevant conflicts of interest to declare.

Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4767-4767
Author(s):  
Giovanna Graziadei ◽  
Alessia Marcon ◽  
Martina Soldarini ◽  
Ilaria Gandolfi ◽  
Luisa Ronzoni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Clinical Complications ◽  
Significant Difference ◽  
The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

The Eveluation of Pulmonary Functions in Children with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4628-4628
Author(s):  
Cem Kurt ◽  
Ilgen Sasmaz ◽  
Bulent Antmen ◽  
Yurdanur Kilinc ◽  
Sadi Kurdak ◽  
...  
Keyword(s):  
Patient Group ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Exercise Test ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Healthy Children ◽  
Diffusion Test ◽  
Pulmonary Functions

Abstract Abstract 4628 Aim In this study we evaluated to pulmonary functions and determined relations of these findings with clinical parameters in children with sickle cell anemia (SCA) who were at follow up in our pediatric heamatology clinic. Materials and Methods 24 children with sickle cell anemia and 9 healthy children as control group include to the study. Complete blood count, hemoglobin electrophoresis and biochemical values were eveluated for both groups. At pulmonology department, the carbonmonoxide diffusion test performing for both groups. At the same day spirometric respiratory function evaluation and exercise test performed both groups at department of sports physiology. The data recieved are compared statistics. Results HbS, HbF, SGPT, ferritin, total bilirubine, direkt bilirubine and Fe++ values were high at patient group (p<0.05). Hemoglobin and hematocrit values were low at patient group according to control group as expected (p<0.05). The number of SCA patient who had one-three venoocclusive crises (VOC) were 14 (58.3%), patient who had three or more VOC were 7 (29.2%) and patient who had no VOC were 3 (12.5%). The number of patient who had acute chest syndrome (ACS) were 5 (20.9%) and 19 patients had no ACS (79.1%). Ýmpaired isole carbonmonoxide diffusion test was established at the 62.5% of the patient's. At patient group, spirometric FEV1 and MEF25 measurement were found lower than the control group (p<0.05). At exercise test VO2/HR rate were lower for patient group (p<0.05). VE/VO2 rate (p=0.023) and R (p=0.016) measurement were found higher. Conclusion Pulmonary gas transfer was found difficult in patients with SCA. Respiratory airways established obstructed in spirometric evaluation. Obstructive defficiensies have to be follow up. Oxygen pulse and respiratory exchange rates were determined low and more oxygen usage was observed for aerobic metabolic activity. With these results, ýt can be say that chronic inflamation process at lung due to oxygen radicals and hipoksemia in sickle cell patients, the aerobic respiratory load was increased. Disclosures: No relevant conflicts of interest to declare.

Hydroxyurea Reduces Conversion From Conditional to Abnormal TCD Velocities In Children with Sickle Cell Anemia (SCA)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 270-270 ◽  
Author(s):  
Jennifer Rothman ◽  
Shelly Burgett ◽  
Russell E. Ware ◽  
Courtney Thornburg
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Normal Range ◽  
Original Cohort ◽  
Transfusion Therapy ◽  
Hydroxyurea Treatment ◽  
The Mean ◽  
Flow Velocities

Abstract Abstract 270 The use of transcranial Doppler ultrasound (TCD), a non-invasive imaging technique, is now clearly established for detecting high risk of stroke in children with sickle cell anemia (SCA). Children with TCD flow velocities ≥200 cm/s have a 10% risk of primary stroke per year. For these children, chronic blood transfusions (CBT) are recommended and have been shown to reduce the risk of primary stroke by up to 90%. The incidence of stroke has decreased to 0.06–0.17 per 100 patient-years since the institution of TCD screening (Fullerton et al. Blood 2004; Enningul-Egham et al., J Pediatr 2010). Although patients with conditional TCDs (flow velocities 170–199 cm/s) have an estimated stroke risk of 2–5% annually, and their rate of conversion from conditional to abnormal is 23% over an 18 month period (Hankins JS et al., BJH 2008), there are no clinical guidelines for primary stroke prevention in this group. We previously conducted a prospective cohort study of hydroxyurea in 37 children with SCA and TCD velocities >140 cm/sec, and demonstrated that TCD velocities decreased significantly after starting hydroxyurea (Zimmerman et al., Blood 2007; NCT00402480). In order to determine if hydroxyurea provided sustained reductions in TCD velocities, we conducted a retrospective review of these 37 children in this original cohort who had elevated TCD velocities and long-term hydroxyurea treatment. The following data were abstracted from the medical record between April 2000 and September 2009: treatment with hydroxyurea and CBT; adherence with treatments; stroke and non-stroke neurological events; and TCD time-averaged mean velocities (TAMV) immediately prior to initiation of hydroxyurea and at the end of extended follow-up. The primary outcome was comparison of pre and post TCD TAMV using a paired t-test. The mean age of enrollment on the original study was 6.8 years (1.8-14.8) and the mean age at follow-up was 12.9 years (5.3-18.5). The mean follow-up was 5.8 years (0.8-8.5) with an overall follow up of 215.1 patient years. Twenty males and 17 females were enrolled. The mean hydroxyurea dose was 25.2 ± 5.6 mg/kg/day, with one patient discontinuing therapy after 15 months. At follow-up, the mean hemoglobin was 8.9 ± 1.2 g/dL and mean HbF was 16 ± 7.2%. Sustained decreases were observed in both the right MCA (164.8 ± 25.5 cm/s to 124.9 ± 35 cm/s, p<0.001) and left MCA (167.9 ± 25.2 cm/s to 126.9 ± 30 cm/s, p<0.001) for all 37 patients. For the 15 patients with conditional TCD velocities at enrollment, 13 had maximal TAMV that reverted to and were sustained in the normal range (185.8 ± 10.0 cm/s to 132.9 ± 14.5 cm/s, p<0.001). Two converted to abnormal TCD velocities at 1.6 years and 4.5 years for a conversion rate of 13%; one was non-adherent but the other was adherent with hemoglobin of 10.8 g/dL and HbF of 23.5%. These two patients were started on CBT and remain stroke free. There were no primary stroke events observed in the 15 subjects with conditional TCD velocities over a total of 78.1 patient years. Of the 5 patients who had abnormal TCD velocities on enrollment and whose parents refused CBT, 1 patient had a stroke after 0.8 years of hydroxyurea therapy. This was the only patient who continued to have abnormal TCD velocities at MTD, 7 months after starting hydroxyurea. The remaining 4 patients continued to have TCD velocities in the normal range off transfusion therapy over 26.3 patient years. Overall, these data illustrate that treatment with hydroxyurea at MTD in children with SCA and elevated TCD velocities resulted in significantly lower and sustained improvements in TCD velocities. Additionally, for children with conditional TCD velocities, hydroxyurea resulted in a lower than expected conversion to abnormal values, thereby sparing many children from CBT without any noted increase risk of stroke. Hydroxyurea did not, however, protect fully against stroke in one patient who had persistently abnormal TCD velocities and therefore CBT remains the standard of care in this population until larger randomized trials are conducted. Further studies are required to evaluate hydroxyurea for primary stroke prevention in children prior to conversion to abnormal TCD and in children who already have abnormal TCD. The currently funded TCD With Transfusions Changing to Hydroxyurea (TWiTCH) clinical trial, which is scheduled to begin enrollment in late 2010, will help answer this important clinical question. Disclosures: Off Label Use: Hydroxyurea is used to reduce complications of sickle cell anemia.

Prognostic Significance of Early Vaso-Occlusive Complications in Children Who Have Sickle Cell Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3176-3176
Author(s):  
Charles T. Quinn ◽  
Elizabeth P. Shull ◽  
Naveed Ahmad ◽  
Zora R. Rogers ◽  
George R. Buchanan
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Strong Predictor ◽  
Prognostic Significance ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Disease Modifying Therapy ◽  
Pain Crisis ◽  
Disease Modifying

Abstract Sickle cell anemia (SS) is a phenotypically variable disease whose course is difficult to predict. The Cooperative Study of Sickle Cell Disease (CSSCD) found that dactylitis in the 1st year of life predicted adverse outcomes in later childhood. We aimed to determine whether early vaso-occlusive complications, including dactylitis, were prognostic in the Dallas Newborn Cohort. We studied all cohort members with SS or sickle-β0-thalassemia who were &lt;1 yr of age at their first clinic visit, ≥5 yrs of age at last follow-up, and who had complete records. We defined 3 potential “early” (occurring in the first 3 yrs of life) predictors: any hospitalization for (1) pain crisis (non-dactylitis), (2) dactylitis, or (3) acute chest syndrome (ACS). We studied the associations of these predictors with the following “late” (occurring on or after the 3rd birthday) outcomes: death of any cause; overt stroke; use of hydroxyurea (HU), chronic transfusion (CT), or stem cell transplantation (SCT); and mean number of hospitalizations for late pain crisis and ACS. Late pain and ACS episodes were enumerated for each patient between the 3rd birthday and the last clinical encounter or the start date of a disease-modifying therapy (HU, CT, or SCT), whichever was first. Mean number of pain and ACS events was analyzed for the late follow-up period in total and in 2-yr intervals. Outcomes up to age 20 were included. Two-sided Fisher exact and t-tests were used appropriately. There were 264 subjects (256 SS; 54.9% male). Mean age at first visit was 4.1±2.3 mos (±S.D.) and mean follow-up was 12.1±4.3 yrs. The following early hospitalizations occurred: 53 subjects (20.1%) had pain crisis; 16 (6.1%) had dactylitis, and 85 (32.9%) had ACS. There were 5 deaths and 30 overt strokes. Sixty-six subjects were treated with HU (37), CT (40), and/or SCT (1). We found that subjects who had early pain, dactylitis, or ACS (compared with those who did not) were not more likely to die (1.7 vs. 2.1%; P&gt;0.99) or have a stroke (12.2 vs. 10.3%; P=0.69). However, the use of a disease-modifying therapy was more common among subjects who had early pain (37.7 vs. 19.9%; P=0.01) and ACS (37.6 vs. 16.2%; P&lt;0.001), but not dactylitis (18.8 vs. 23.6%; P&gt;0.99). This prediction held only for HU use when the treatments (HU, CT, or SCT) were analyzed separately. Subjects who experienced early pain or ACS had on average a 2.2-fold (P=0.02) or 2.1-fold (P=0.01), respectively, higher number of late pain crises between ages 3 and 11, but not beyond (all P&gt;0.05). Dactylitis did not predict a higher number of late painful events at any age (all P&gt;0.05). Likewise, neither early pain nor dactylitis was associated with a higher number of hospitalizations for late ACS (all P&gt;0.05). However, subjects who had early ACS had a 1.7 to 3.6-fold higher mean number of ACS events throughout all late age groups (all P&lt;0.05). In summary, early hospitalization for pain, dactylitis, or ACS did not predict death or stroke. Early pain and ACS were associated with use of HU in later childhood, but not CT or SCT. Early pain and ACS predicted an increased number of hospitalizations for pain until age 11, but not beyond. Early ACS was a strong predictor of recurrent ACS throughout childhood. Notably, we found that hospitalization for dactylitis had no particular prognostic significance, unlike the CSSCD. In conclusion, the prognostic significance of early vaso-occlusive complications is limited.

Extended, Flexible Program Matching Red Cell Antigens for Patients with Sickle Cell Anemia Provides for Both Chronic and Intermittent Transfusions.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2899-2899
Author(s):  
Daniel R. Ambruso ◽  
Michele LaSalle-Williams ◽  
Tuan Le ◽  
Laura Cole ◽  
Kathy Hassell ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Perfect Match ◽  
Clinical Situation ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Blood Group Antigens ◽  
Red Cell ◽  
Transfusion Therapy ◽  
Antibody Screen

Abstract Introduction: Transfusion of packed red cells (PRBCs) remains the major treatment of severe complications in sickle cell anemia. Patients may require acute, intermittent transfusions for some problems while other, more severe complications are treated with chronic transfusion (≥ 6 months) regimens to replace and suppress production of sickle cells. One of the main complications of transfusion therapy is production of red cell alloantibodies which significantly increases the risk of subsequent transfusions and limits the timely provision of appropriate blood products. Since 1978, we have provided sickle cell patients with extended matching of PRBCs to reduce the rate of alloimmunization. The flexibility of the program is adapted to meet both acute and chronic needs of the patient population. Methods: Records of patients with sickle hemoglobinopathies enrolled in the Colorado Sickle Cell Treatment and Research Center between December 31, 1993 and January 1, 2006 were reviewed under a protocol approved by the COMIRB at UCDHSC. At enrollment, serologic testing was completed on patients for the following blood group antigens: ABO; Rhesus (C,c,D,E,e); Kell (K,k); Duffy (Fya,Fyb); Kidd (Jka,Jkb); Lewis (Lea,Leb); and MNS (M,N,S,s). Donors were typed for the same antigens. For all transfusions, a perfect match was sought. When exact matches at all loci could not be found, mismatches were allowed when necessary for Fyb and MNS because of lower risk of sensitization and for Le because of infrequent hemolytic transfusion reactions. Antibody screens were completed as part of crossmatch technique at the time of each transfusion by standard methods. When an antibody screen was positive, standard antiglobulin and enzyme techniques and cell panels were used to identify the antibody. For the purposes of this study, information about patients with sickle cell anemia, complications, numbers and types of transfusions were reviewed. Results: Over the past 13 years, a total of 6,978 transfusions were provided to 104 patients (mean 68, range 1–519). In this group, 90 patients (86.5%) had HbSS, 11 (10.6%) had HbSC, and 3 (2.9%) had HbS β-thalassemia. Indications for transfusions included vaso-occlusive crisis, aplastic crises, splenic sequestration, and preparation for surgery, acute chest syndrome, stroke and priapism. Fifty-two patients (50%) received simple transfusions only while 33 (32%) had only PRBC exchange and 19 (18%) required both modalities. Of the total group, 42 (40%) were on chronic transfusions and 11 (10%) had both intermittent and chronic transfusions. The protocol and system for delivering matched PRBCs was flexible enough that even when red cells were needed for intermittent transfusions in 62 (60%) patients, delivery of the products was easily accomplished. In only 8 patients receiving 13 units of PRBCs was the clinical situation so urgent that non-antigen matched units was required. Conclusion: PRBCs with extended antigen matching were provided to our population of patients with sickle cell anemia. The program provided blood components for both intermittent and chronic transfusion schemes with very few patients having such urgent conditions that they required products without extended matching.

Impact of Hydroxyurea On Peri-Operative Management and Outcomes in Children with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2567-2567
Author(s):  
Masanori Hayashi ◽  
Agustin Calatroni ◽  
Brittany Herzberg ◽  
Courtney Thornburg
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Operative Management ◽  
Wilcoxon Test ◽  
Categorical Variables ◽  
Acute Chest Syndrome ◽  
Transfusion Therapy ◽  
Significant Difference ◽  
Operative Complications ◽  
Post Operative Complications

Abstract Abstract 2567 Poster Board II-544 Surgical procedures in children with sickle cell anemia (SCA) can be complicated by vasoocclusive events (VOE) such as acute chest syndrome (ACS) and pain. Peri-operative management requires a multidisciplinary approach to provide appropriate pre-operative intravenous hydration and intra- and post-operative monitoring. Transfusion therapy has been controversial. Our institution previously described a low incidence of complications in children who received serial transfusions over 3-4 weeks prior to surgery. Subsequently, an increasing number of children have been prescribed hydroxyurea (HU) to prevent SCA complications. In general, children on HU at our institution only receive a single top-off transfusion the day prior to surgery if their hemoglobin is less than 10 g/dL. We hypothesized that children in the HU group would have a lower number of serial transfusion compared to the non-HU group and that there would be no difference in complications or days to discharge between the two groups. We conducted a single-institution retrospective cohort study of children with SCA, who were age less than 18 years and underwent at least one surgical procedure at Duke University Medical Center between January 1, 2003 and April 30, 2008. Data were abstracted from electronic and written medical records. Descriptive statistics were used to characterize the cohort. Wilcoxon test was used to compare continuous variables and Pearson test was used to compare categorical variables between the non-HU and HU groups. Fifty-three subjects were included (Table 1). The non-HU group was significantly younger than the HU group, but children in the non-HU group were significantly more likely to be transfused pre-operatively, primarily with serial transfusions or erythrocytopheresis, compared to the HU group. One subject in the non-HU group developed a pre-operative delayed hyperhemolytic transfusion reaction. Post-operative complications are detailed in Table 1; the overall rate was low. Two subjects in the HU group developed acute chest syndrome despite pre-operative transfusion; one episode was likely related to underlying asthma and poor response to hydroxyurea; the second was likely related to pain and hypoventilation after laparoscopic splenectomy and tonsillectomy/adenoidectomy. Overall, there were no significant differences in complications and no significant difference in days to discharge between the two groups. In summary, children with SCA on HU may safely undergo surgery without significantly reducing their percent HbS. Nonetheless, attention should still be made towards multidisciplinary effort to reduce intra- and post-operative complications, and clinicians should consider response to HU, pulmonary status and type of surgery when planning peri-operative management in children with SCA on HU. Disclosures: Off Label Use: hydroxyurea in young children.

Hydroxyurea Treatment of Young Children with Sickle Cell Anemia: Safety and Efficacy of Continued Treatment – the BABY HUG Follow-up Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 7-7 ◽  
Author(s):  
Zora R. Rogers ◽  
Billie Fish ◽  
Zhaoyu Luo ◽  
Rathi V. Iyer ◽  
Courtney D. Thornburg ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hospital Admissions ◽  
Controlled Trial ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Follow Up Study ◽  
Hydroxyurea Treatment ◽  
The Impact

Abstract Abstract 7 BABY HUG [Clinical Trials #NCT00006400], an NIH-NICHD sponsored randomized placebo-controlled trial showed that hydroxyurea (HU) administered to 9–18 month old children with sickle cell anemia (SCA) provides substantial clinical benefit. Benefits include a decrease in pain crises, acute chest syndrome events, need for transfusion and hospital admission; hematologic improvement include higher total and fetal hemoglobin concentration, larger red cell size, and lower WBC counts with toxicity limited to transient reduction in absolute neutrophil count (ANC) [Lancet 2011; 377:1663–72]. The parent or guardian of all 176 children who completed at least 18 months of randomized treatment were offered participation in an initial observational BABY HUG Follow-Up Study and 163 (93%) consented to participate. Clinical and laboratory data were collected every 6 months by structured abstraction of the medical record regarding use of clinically prescribed HU (dose escalation recommended), blood counts, clinical imaging, and sickle cell-related events. At the time of enrollment the family did not know their child's randomized study treatment assignment; 133 (82%) initially chose clinical prescription of open-label HU. Acceptance of HU has remained high through 36 months of follow-up; during each 6 month data collection period 68–75% of participants reported having taken HU. Only 2 patients have left the study (due to relocation) and more than 93% of expected data have been collected. Preliminary analyses as of May 2011, including 417 patient years (pt-yrs) of follow up, demonstrate that in comparison to participants not taking HU, children who continue to take HU have statistically lower rates of pain crises requiring emergency department (ED) visits, episodic transfusions, and hospital admissions for any reason, including acute chest syndrome or febrile illness (see table). The substantial decrease in acute chest syndrome episodes is similar to the effect demonstrated with HU use in the randomized BABY HUG trial in younger infants and consistent with published trials detailing the benefit of HU therapy in older children and adults. The decrease in the rate of admission for febrile events in HU-treated patients is also comparable to that in the randomized trial, but the reason for this benefit is uncertain. There was no difference in hospitalization rates for painful events including dactylitis. Two patients in the non-HU group had a stroke. There were no differences between groups in the frequency of a palpable spleen or rate of acute splenic sequestration crises. Through 36 months of follow up children taking HU had persistently higher hemoglobin and MCV, and lower WBC and ANC than those not taking HU. Results of these analyses including growth and development assessments will enhance our understanding of the impact of HU use in children with SCA starting at a very young age. The accruing data from the BABY HUG Follow-Up Study demonstrate a continuation of the substantial benefits of early HU therapy with no discernable additional toxicities. Ongoing follow up of this cohort is essential to fully define these benefits as children grow, and to observe for late toxicity.Event Rate per 100 pt-yrsHUNo HUp valueED visit for Pain Crisis28.853.60.004Episodic Transfusion18.334.00.010Hospital Admission (any cause)74.9133.20.001Acute Chest Syndrome (admission)9.522.30.0001Febrile Illness (admission)30.764.3<.001Pain Crisis (admission)18.630.40.102 Disclosures: Off Label Use: Hydroxyurea is not indicated for treatment of children with sickle cell disease. Use of this medication was for clinical indications and not mandated by this observational study.

scholarly journals Physiological properties and characteristic reactions of hydroxyurea

2020 ◽  
Vol 22 (100) ◽  
pp. 94-102
Author(s):  
O. G. Demchuk ◽  
M. R. Hrytsyna ◽  
L. O. Kobryn ◽  
M. B. Kalytovska ◽  
B. V. Gutyj
Keyword(s):  
Sickle Cell Disease ◽  
Life Expectancy ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Genetic Disorder ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Erythroid Precursors ◽  
Hb S

As it was mentioned in the previous paper, we observed the mechanism of action the interesting drug, first synthesized back in 1869 for the first time, called Hydroxyurea. A century later, phase I and II trials began to test its safety in humans with solid tumors. It was first approved by the FDA in 1967 for the treatment of neoplastic diseases and is presently approved for the treatment of melanoma, resistant chronic myelocytic leukemia (CML), and recurrent, metastatic testicular and ovarian cancer. Sickle cell disease is a genetic disorder that decreases life expectancy by 25 to 30 years. Individuals are diagnosed with sickle cell disease if they have one of several genotypes that result in at least half of their hemoglobin being hemoglobin S (HbS). Sickle cell anemia refers specifically to the condition associated with homozygosity for the Hb S mutation (Hb SS). Several other hemoglobin mutations, when occurring with an Hb S mutation, cause a similar but often milder disease than sickle cell anemia. In addition to reduced life expectancy, patients with sickle cell disease experience chronic pain and reduced quality of life. Painful crises, also known as vaso-occlusive crises, are the most common reason for emergency department use and hospitalization, and acute chest syndrome is the most common cause of death. Prior to the approval of hydroxyurea for use in sickle cell disease, patients with this condition were treated only with supportive therapies. These measures included penicillin in children to prevent pneumococcal disease, routine immunizations, and hydration and narcotic therapy to treat painful events. Red blood cell transfusions increase the blood’s oxygen carrying capacity and decrease the concentration of cells with abnormal hemoglobin, but chronic transfusion therapy predictably leads to iron overload and alloimmunization. Therapies such as hydroxyurea that raise fetal hemoglobin (Hb F, α2γ2) levels are promising because they effectively lower the concentration of Hb S within a cell, resulting in less polymerization of the abnormal hemoglobin.Hydroxyurea’s efficacy in sickle cell disease is generally attributed to its ability to raise the levels of Hb F in the blood; however, the mechanisms by which it does so are unclear. Early studies suggested that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, resulting in the recruitment of early erythroid precursors with an increased capacity to produce HbF.

Sign in / Sign up

Export Citation Format

Share Document