Long-term follow-up of pediatric sickle cell disease patients with abnormal high velocities on transcranial Doppler

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.     

MRI/MRA evaluation of sickle cell disease of the brain

Sickle cell disease is a major cause of pediatric stroke. Understanding the disease that affects the brain as infarctions, both clinically apparent and silent, requires an understanding of how the blood vessels are affected, the way in which both the brain and the blood vessels are imaged by MRI and MRA and the mechanism of injury.     

TCD in sickle cell disease: an important and useful test

Sickle cell disease is associated with a high risk of stroke in the early years of childhood. The risk of a secondary stroke can be significantly reduced through chronic blood transfusions. Prevention of the first stroke (primary prevention) was made possible through the use of transcranial Doppler (TCD) US and demonstrated in a randomized clinical trial called the stroke prevention trial in sickle cell anemia (STOP). TCD results were classified as normal, conditional, abnormal or inadequate based on velocity readings in specific arterial segments. The MCA and ICA were carefully searched to find the highest velocity, and this was used to stratify patients as to stroke risk. Those with abnormal or high-risk TCD received either monthly blood transfusions or no transfusions, and those randomized to transfusion had a much better outcome in terms of stroke (one stroke, versus ten in the control group) and also fewer other medical problems while transfused. TCD screening is recommended for SCD patients to begin at 24 months of age and should be repeated every 6–12 months during early childhood. Transcranial Doppler imaging (TCDI) can be easier to use and learn and with a few adjustments can provide equivalent predictive power. Currently, TCD is the only recommended method for treatment selection for primary-stroke prevention. MRI and MRA can provide important information on the status of the brain and the blood vessels and, when abnormal, indicate greater risk. Although TCD cannot predict all strokes, TCD and TCDI offer an opportunity to apply an effective therapy for patients in this risk group and reduce many first-time strokes.     

经颅多普勒超声在儿童脑血管疾病筛查和诊断中的应用

经颅多普勒超声是研究脑底动脉血流动力学的一种无创性超声检测技术,在成人脑血管疾病筛查和诊断中发挥着重要作用,然而经颅多普勒超声在儿科的应用并不普遍,且未能被儿科医生普遍了解.本文从经颅多普勒超声在儿科脑血管疾病筛查和诊断中的作用进行综述.     

Cerebrovascular accidents in sickle cell disease. Risk factors and blood transfusion influence

This study presents a series of 34 sickle cell patients with one or more cerebrovascular accidents (CVA). Risk factors were studied in a subgroup of 19 patients whose clinical and biological characteristics were compared to those of a group of 444 sickle cell patients without CVA. The only risk factor discovered was a past history of purulent meningitis, which was significantly more frequent in sickle cell patients than in those without CVA (P<0.0001). No biological or radiological factor affecting the risk of recurrence was found. The risk of recurrence, neurological defects or death after subsequent CVA justify long-term transfusion treatment in patients presenting with a second CVA. However our study shows that 10 patients who were not transfused after their first CVA had no recurrences, (median follow up = 7.9 years; 2–18 years), providing a basis for discussion on the indications of long-term transfusion therapy for sickle cell patients presenting with their first CVA.D. Bachir (Creteil), J. Badoual (Paris), H. Bataille (Pointe-A-Pitre), P. Beauvais (Paris), P. Begue (Paris), M. Belloy (Paris), E. Vilmer (Paris), J.J. Benichou (Kremlin Bicetre), F. Boccara (Paris), T. Cynober (Kremlin Bicetre), J. Elion (Paris), J. Feingold (Paris), M. Guilloud-Bataille (Paris), F. Galacteros (Creteil), R. Girot (Paris), K. Bouzid (Rowba), D. Labie (Paris), A. Lambilliotte (Lille), S. Lemerle (Creteil), M. Malou (Annaba), M. Montalembert (Paris), M. Nathanson (Bondy), G. Noseda (Paris), C. Olivier (Colombes), E. Questiaux (Aulnay Sous Bois), B. Quinet (Paris), Ph. Reinert (Creteil), J. Rosa (Creteil), G. Tchernia (Kremlin Bicetre), D. Vanhaeke (Paris), B. Vignes (Montmorency), P. Zamet (Montmorency)     

Cholelithiasis in children with sickle cell disease

Abdominal ultrasonography was performed on 305 children with sickle cell disease (SCD) (285 SS and 20 S-beta-thalassemia) to establish the prevalence of cholelithiasis in Saudi children with SCD. Their ages ranged from 1 to 18 years (mean 10.45 years). Gallstones were demonstrated in 60 children, giving a prevalence of 19.7%. An additional 50 patients (16.4%) had only biliary sludge. The youngest patient with gallstones was 3 years old. There was a correlation between the presence of gallstones and increasing age. Patients with gallstones were also found to have higher serum bilirubin levels, but their hemoglobin, hematocrit, reticulocyte count, hemoglobin S, and hemoglobin F levels were not significantly different from those of patients without gallstones.     

经颅超声多普勒在PICU的临床应用

经颅超声多普勒(transcranial Doppler ultrasonography,TCD)可以无创、实时监测脑血流变化,在神经系统疾病中,尤其是神经危重症的诊治中应用广泛.在创伤性脑损伤、颅内压增高、脑血管痉挛、中风、脑血管功能障碍、中枢神经系统感染、脑死亡等疾病的临床诊断和治疗中,TCD均可以发挥重要作用:一方面可以明确患儿的脑灌注情况,监测患儿对治疗的反应,指导治疗,提示预后;另一方面,通过分析脑血流的变化情况,可以分析疾病潜在的病理生理机制,提高对疾病的认识.本文就TCD对PICU神经危重症患儿的临床应用作一概述,从而加深对TCD的认识,为神经危重症患儿的监测和治疗提供更多帮助.     

Pneumonia in young children with homozygous sickle cell disease: risk and clinical features

The incidence and clinical features of pneumonia have been examined in children with homozygous sickle cell (SS) disease and in age/sex matched control children with a normal haemoglobin (AA) genotype followed in a cohort study of sickle cell disease from birth.Survival curve analysis indicated a similar incidence of pneumonia in the two genotypes up to the ages of 8 months after which pneumonia became significantly more prevalent in SS disease, the relative risk exceeding a factor of four by 4 years of age. Children with SS disease were also more prone to multiple episodes. Comparison of clinical features in the two genotypes yielded no difference in sex or seasonal involvement, or in the results of bacteriological and radiological investigations. Children with SS disease and pneumonia had an increased frequency and increased duration of hospital admission, and mortality was confined to this group.It is concluded that children with SS disease have an increased prevalence of single and multiple attacks of pneumonia and that these events run a more serous clinical course than in control children.Abbreviations SS sickle cell disease - AA normal haemoglobin genotype     

Intra-individual variation in blood flow velocities in cerebral arteries of children with sickle cell disease

BACKGROUND: Children with sickle cell disease (SCD) are at elevated risk of stroke. Risk increases with blood flow velocity in selected cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, and use of TCD to screen these patients is widely recommended. Interpretation of TCD results should be based on knowledge of intra-individual variation in blood flow velocity, information not currently available for sickle cell patients. PROCEDURES: Between 1995 and 2002, 4,141 subjects, 2-16 years old, with homozygous SCD or Sbeta0-thalasemmia and no history of stroke were screened with TCD, including 2,018 subjects screened in one clinical trial (STOP), 1,816 screened in another (STOP 2), and 307 screened in an interim ancillary prospective study. The 812 subjects with >or=2 examinations<6 months apart were selected for analysis, including 242 (29.8%) subjects with normal average velocities (i.e., <170 cm/sec), 350 (43.1%) subjects with conditional velocities (i.e., 170-199 cm/sec), and 220 (27.1%) subjects with abnormal velocities (i.e., >or=200 cm/sec). The intra-subject standard deviation of TCD velocity was estimated from the difference between velocities at the first two interpretable examinations on each subject. RESULTS: An intra-subject standard deviation of 14.9 cm/sec was obtained. Seven (0.9%) subjects had unusually large and unexplained differences between velocities at the two examinations (range of absolute differences: 69-112 cm/sec). CONCLUSIONS: While stroke risk is well demonstrated to increase with increasingly abnormal TCD velocity, given the relatively large intra-subject variability, one TCD examination is generally not sufficient to characterize stroke risk in this patient population.     

Laparoscopic splenectomy and/or cholecystectomy for children with sickle cell disease

Background  In 1991, Delaitre reported the first laparoscopic splenectomy (LS). Since then LS has become the procedure of choice to treat hematological diseases requiring splenectomy. The Eastern province of Saudi Arabia is known to have a high incidence of hemoglobinopathies including sickle cell disease (SCD), which is known to be associated with complications necessitating splenectomy and/or cholecystectomy. This report describes our experience with LS and/or laparoscopic cholecystectomy (LC) for children with SCD. Patients and methods  The medical records of all children with SCD who had LS and/or LC were retrospectively reviewed for age, sex, indication for splenectomy, operative time, hospital stay, and post-operative complications. The results were compared to a similar group of children with SCD who had open splenectomy (OS) and/or open cholecystectomy (OC). Results  Over a period of 3.5 years (January 2005 and June 2008), a total of 45 children had LS with or without LC, 30 (66.7%) of them had SCD. Their age ranged from 2 to 12 years (mean 7 years). There were 16 males and 14 females. In all, LS was done because of recurrent splenic sequestration crisis except one who had a large spleen with multiple infarcts that was causing abdominal pain. The operative time ranged from 1.5 to 9 h (mean 2.75 h). Their hospital stay ranged from 3 to 9 days (mean 4.5 days). There was no mortality. Two patients (6.7%) required conversion to OS due to a large-sized spleen and severe adhesions in one and uncontrolled intra-operative bleeding in the other. The results were compared to a group of 120 children with SCD who had OS only (88) and OS with OC (32). From 1994 to 2006, a total of 55 children had LC only, 47 (26 M:21 F) of them (85.5%) had SCD. Their age ranged from 4 to 15 years (mean 11.4 years). The indications for cholecystectomy were: biliary dyspepsia (20), biliary colic (35), acute cholecystitis (5), obstructive jaundice (5), asymptomatic (6), and biliary pancreatitis (1). There was no mortality, but one (2.1%) required conversion to OC because of severe adhesions and another underwent postoperative exploration because of bleeding from an accessory cystic artery. The results were compared to a similar group of 27 children with SCD who underwent OC. Conclusions  With good peri-operative management, LS is feasible and safe in children with SCD and can be done concomitantly with cholecystectomy. Currently, it requires more operative time than the open approach. This is specially so for children with SCD who are known to have a large spleen with severe adhesions. It is, however, superior to OS with regard to duration of hospital stay, cosmetic appearance, post-operative complications, and post-operative recovery. LC is also safe in children with SCD. When compared with OC, it is associated with less post-operative complications, a shorter hospital stay, better cosmetic appearance and a faster recovery.     

Secondary benefit of maintaining normal transcranial Doppler velocities when using hydroxyurea for prevention of severe sickle cell anemia

In a retrospective cohort study, we tested the hypothesis that when prescribing hydroxyurea (HU) to children with sickle cell anemia (SCA) to prevent vaso‐occlusive events, there will be a secondary benefit of maintaining low transcranial Doppler (TCD) velocity, measured by imaging technique (TCDi). HU was prescribed for 90.9% (110 of 120) of children with SCA ≥5 years of age and followed for a median of 4.4 years, with 70% (n = 77) receiving at least one TCDi evaluation after starting HU. No child prescribed HU had a conditional or abnormal TCDi measurement. HU initiation for disease severity prevention decreases the prevalence of abnormal TCDi velocities.     

Acute chest syndrome in children with sickle cell disease

Acute chest syndrome (ACS) is an acute pulmonic process in patients with sickle cell disease. We prospectively studied 50 patients with ACS admitted to the Pediatric Medical Ward during one year period (Jan. 1993 through Dec: 1993). Twenty eight of them were males and twenty two were females giving a male: female ratio of 1.2: 1. The age ranged between one and 12 years. Twelve (24%) of the patients had chest pain on presentation. Twenty seven (54%) patients had significant temperature (>38°C). The x-ray findings showed that the right lung was involved in 30 patients, the left in 10 patients and both lungs in 10 patlents. Three patients had pleural effusion that required chest tube insertion. Laboratory profiles showed that the erythrocyte sedimentation rate ranged between 15 and 90mm/h, and their hemoglobin ranged between 4.2 gm and 12 gm/dl. Seven (14%) patients had significantly positive mycoplasma pneumoniae titer. None of the blood cultures was positive. All of our patient received antibiotic, usually either Cefuroxime or Ceftriaxone with Erythromycin in addition to other supportive measures such as blood transfusion, oxygen therapy and hydration therapy.     

Splenectomy in children with sickle cell disease and thalassemia

A number of Saudi children (31) with sickle cell disease and thalassemia underwent splenectomy : 12 for frequent blood transfusions, 15 for chronic hypersplenism (most of whom were also the recipients of periodic blood transfusion) and 4 for splenic abscess. The mean age of splenectomy was 8.8 years (8 months 3–18 years). Eight patients had sickle cell disease, 14 betathalassemia and 9 had sickle cell thalassemia. All patients received prophylaxis against pneumococcal infection. There was one postoperative death most probably due to sepsis. Sixteen of those who required frequent preoperative blood transfusions needed no more transfusions, while in 7 the need for transfusions decreased significantly (p < 0.05). For those with hypersplenism, there was a significant postoperative increase in total hemoglobin (P < 0.001), RBC (P < 0.001) and platelet counts (p < 0.02); and a substantial decrease in reticulocyte counts (p < 0.05). The common post splenectomy complications were chest infection and a brief episode of pyrexia, but without undue morbidity. The study establishes a definite place for splenectomy in a selected population of children with sickle cell disease and thalassemia. Presented at the 9th Congress of the Asian Association of Pediatric Surgeons, April 6–10, 1988, Singapore.