Chest Crisis Research Articles

Pediatric Sickle Cell Disease: A Potential Role for the Complement System

Background: Sickle cell disease (SCD) is one of the most common life-threatening hereditary red blood cell (RBC) disorders, with an estimated 300,000 infants born annually with the disease. In SCD, a mutation in the gene for β-globin results in rigid sickled RBCs that have difficulty navigating the vasculature and increased risk for forming blockages in the micro-vessels within organs, leading to RBC lysis, endothelial cell (EC) damage, ischemia/reperfusion injury, and extremely painful vaso-occlusive crises (VOC). Overtime, this can lead to stroke, serious organ damage, and other complications, resulting in a reduced life expectancy. Emerging research points to the involvement in SCD of complement, an important part of the innate immune system composed of proteins that are activated to help clear invaders and damaged cells from the body. Recent work by others has demonstrated that complement activation occurs in patients with SCD in both acute and chronic phases of the disease, and may be associated with disease severity and VOC (Fig 1A). This study aims to assess the role of complement activity in children with SCD during acute crisis and disease steady state. Methods: Pediatric patients aged 0-18 with SCD (HbSS or HbS/β0) managed at The Hospital for Sick Children (Toronto, Canada) were enrolled in this REB approved study during hospital admission with diagnosed VOC or acute chest crisis (ACS) not caused by infection. Patient serum and plasma was collected during hospital admission (crisis) and during follow-up (steady state, 3 to 12 months following an acute crisis) simultaneously with routine bloodwork. Patients with >3 crisis admissions in the previous 12 months or requiring admission for >7 days were excluded. Pooled normal human serum (NHS) was collected from healthy volunteers for use as a control. Complement activity was measured using the WIESLAB Complement System Screen (Svar Life Science). Immunofluorescence (IF) imaging was used to measure the deposition of C3b and C5b-9 complement proteins on the surface of ECs exposed to patient serum or NHS. Data were analyzed using an unpaired t-test or one-way ANOVA with Tukey's multiple comparisons. Results: Thus far, 58 patients have been enrolled in the study. SCD crisis patients showed significantly decreased hemoglobin compared to steady state (Table 1). Complement activity was assessed for 6 crisis and 5 steady state patients. There was equal classical and alternative pathway activity during disease steady state and crisis, which indicates no in vivo complement protein depletion in patients, with an interesting trend showing elevated MBL pathway activity during crisis compared to steady state (Figure 1B). Complement deposition was assessed via IF in 19 crisis, 16 steady state patients, and 6 replicates of NHS. IF assay data show significantly elevated deposition of C3b on ECs when comparing patient crisis samples and healthy controls, with trends suggesting a potential difference in C5b-9 deposition between NHS and crisis patients, as well as differences in complement deposition between steady state and crisis patients (Fig 1C). Conclusion: Our preliminary data shows complement is active in SCD, resulting in elevated C3b deposition on ECs during SCD crisis. Although not statistically significant, trends suggesting a difference in C5b-9 deposition and differences between steady state and crisis patients are encouraging, as a small change in intravascular complement activity may still have significant physiological consequences. Future work is focused on further quantifying complement activity and understanding its mechanism, assessing the in vitro functional consequences of this on the surface of ECs, and investigating complement blockade as a potential treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Total Body Irradiation Free Haploidentical Stem Cell Transplant with Post-Transplant Cyclophosphamide for Children with Sickle Cell Disease

Introduction- Allogeneic hematopoietic stem cell transplant (HSCT) is a curative option for children with Sickle cell disease (SCD). Children of ethnic minorities lacking a matched sibling donor were unable to access HSCT as most registries lacked matched unrelated donors for them. However, success of haploidentical related donor HSCT with post-transplant cyclophosphamide (PTCy) in SCD has changed that. Now the next need is to avoid total body irradiation (TBI) during conditioning in infants due to its effects on the developing brain and in children with SCD with prior old infarcts to reduce risk of further brain damage. Another need is to avoid severe acute graft vs. host disease (GVHD). Starting cyclosporine as early as day-1 has shown to reduce it. Here we describe outcomes of 3 children with SCD who underwent haploidentical HSCT with PTCy with TBI free conditioning and had early introduction of cyclosporine. Methods- Three children with SCD (Non-identical-twins both females aged 1-year-old and a 14-year-old male) who had no matched related or unrelated donor available underwent haploidentical HSCT after taking informed consent of the parents. Donor for the first twin was her 6/12 matched mother and for the second twin was 7/12 matched older brother and donor for 3rd patient was his 5/10 matched father. Both twins had never been transfused but has had recurrent swollen painful joints while third patient had recurrent bone pain, chest crisis & had received repeated blood transfusions and his MRI had shown multiple old infarcts. The conditioning was with Rituximab 100 mg/m2 IV on day -7, Busulfan 3.6 mg/kg/dose daily IV for 4 days (Day -6 to -3) for the twins and 3.2 mg kg/dose daily for 3rd patient, Fludarabine 40 mg/m2/dose daily IV for 4 days (Day -6 to -3) and Rabbit anti-thymoglobulin (Thymoglobulin) 1.5 mg/kg/dose daily for 3 days (Day -4 to -2). Peripheral blood stem cells-20 million/kg CD34+ cells each for the the twins and 7 million/kg for the 3rd patient was harvested from the respective haploidentical donors and infused to the patients on Day 0. GVHD prophylaxis was with PTCy 50 mg/kg on Day+3 & 4, intravenous cyclosporine from day-1 and MMF from day+5. Results - All three children engrafted (neutrophils on day+19, day+22, day+22 and platelets on day+12, day+15, day+22 respectively). First twin had uneventful course but second twin developed transplant associated microangiopathy on day+28 so cyclosporine was stopped and switched to sirolimus. She recovered fully with methyprednisone and rituximab therapy. Third patient developed atonic seizures, aphasia and severe drowsiness on day+11 needing mechanical ventilation. No new stroke or infective cause was identified. He recovered fully with conservative management and stopping cyclosporine. Chimerism on day+30 and day+100 was fully donor for the twins however 3rd patient developed mixed chimerism on day+22 - 62% donor cells and rejection by day+40- 4% donor cells. Acute GVHD grade I was seen in second twin. No chronic GVHD was observed. All three children are alive at follow up of 244, 231 and 90 days. Both twins are disease free & off immune suppression and 3rd child has had autologous recovery after rejection. Conclusion- Busulfan & Fludarabine based conditioning is a radiotherapy free option for children with SCD undergoing haploidentical HSCT with PTCy. However, in multi-transfused children it may not be sufficient to prevent rejection. Early introduction of cyclosporine is feasible and can possibly reduce acute GVHD. Disclosures No relevant conflicts of interest to declare.

Clinical ‘pearls’ of maternal critical care Part 2

The current review outlines the challenges in managing pregnant women with sickle-cell anemia, who are at risk of becoming critically ill during pregnancy. Sickle obstetric patients pose unique challenges to the anesthetist and intensivist. We discuss the role of prophylactic transfusions for specific indications like acute anemia and twin pregnancies. The management and prevention of vaso-occlusive crises and chest crisis are also outlined. The role of the multidisciplinary team cannot be overstated.Massive obstetric hemorrhage in this population is difficult, and unique considerations such as cell-saver technology and tranexamic acid usage are discussed. Secondary complications such as pulmonary hypertension and stroke are also considered, with a summary of the latest treatment guidelines. This is a challenging cohort of pregnant patients who have a significantly increased morbidity and mortality. This review aims to aid management of these patients on the labor ward for both obstetric anesthetists and intensivists.

Stroke in sickle cell disease

Sickle cell disease (SCD) is the second commonest cause of stroke in the pediatric population. Cerebrovascular complications in SCD may involve large or small vessels and present as large infarctions, intracranial or subarachnoid hemorrhage, moyamoya disease or silent infarcts. Predictors of stroke in SCD include high blood flow velocity on transcranial Doppler, low hemoglobin value, absence of alpha-thalassemia, high white cell count, hypertension, silent brain infarction, and a history of chest crisis. Regular blood transfusions are used for primary and secondary prevention of stroke in SCD. Other management strategies include stem cell transplantation,

Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia

IntroductionCirculating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients.MethodA total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured.ResultsTotal MP AV was lower in crisis (1.26×106 ml−1; 0.56–2.44×106) and steady state (1.35×106 ml−1; 0.71–3.0×106) compared to transfusion (4.33×106 ml−1; 1.6–9.2×106, p<0.01). Protein C levels were significantly lower in crisis (median 0.52 IU ml−1; interquartile range 0.43–0.62) compared with all other groups: HbAA (0.72 IU ml−1; 0.66–0.82, p<0.001); HU (0.67 IU ml−1; 0.58–0.77, p<0.001); steady state (0.63 IU ml−1; 0.54–0.70, p<0.05) and transfusion (0.60 IU ml−1; 0.54–0.70, p<0.05). In addition, levels were significantly reduced in steady state (0.63 IU ml−1; 0.54–0.70) compared with HbAA (0.72 IU ml−1; 0.66–0.80, p<0.01). PS levels were significantly higher in HbAA (0.85 IU ml−1; 0.72–0.97) compared with crisis (0.49 IU ml−1; 0.42–0.64, p<0.001), HU (0.65 IU ml−1; 0.56–0.74, p<0.01) and transfusion (0.59 IU ml−1; 0.47–0.71, p<0.01). There was also a significant difference in crisis patients compared with steady state (0.49 IU ml−1; 0.42–0.64 vs. 0.68 IU ml−1; 0.58–0.79, p<0.05). There was high correlation (R>0.9, p<0.05) between total numbers of AV-positive MP (MP AV) and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05) (platelet activation marker), and also a lower correlation between percentage of MP expressing CD201 (%MP CD201) and %MP CD14 (R=0.627, p<0.001). %MP CD201 was higher in crisis (11.6%) compared with HbAA (3.2%, p<0.05); %MP CD144 was higher in crisis (7.6%) compared with transfusion (2.1%, p<0.05); %CD14 (0.77%) was higher in crisis compared with transfusion (0.0%, p<0.05) and steady state (0.0%, p<0.01); MP CD14 was detectable in a higher number of samples (92%) in crisis compared with the rest (40%); %MP CD235a was higher in crisis (17.9%) compared with transfusion (8.9%), HU (8.7%) and steady state (9.9%, p<0.05); %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L−1 (0.31–0.49) versus steady state: 0.27 nmol L−1 (0.25–0.32; p<0.01) and control: 0.28 nmol L−1 (0.27–0.31; p<0.01). CT-proET-1 levels were reduced in patients on HU therapy: 43.6 pmol L−1 (12.6–49.6) versus control: 55.1 pmol L−1 (45.2–63.9; p<0.05). NO levels were significantly lower in chest crisis (19.3 mmol L−1 plasma; 10.7–19.9) compared with HU (22.2 mmol L−1 plasma; 18.3–28.4; p<0.05), and HbSC (30.6 mmol L−1 plasma; 20.8–39.5; p<0.05) and approach significance when compared with steady state (22.5mmol L−1 plasma; 16.9–28.2; p=0.07).ConclusionProtein C and free PS are reduced in crisis with lower numbers of platelet MP and higher percentage of markers of endothelial damage and of red cell origin. During chest crisis, ADM and ET-1 were elevated suggesting a role for therapy inhibiting ET-1 in chest crisis.

Feritility and Attitudes To Fertility In a Cohort Of Women With Sickle Cell disease In South East London

Introduction Women with Sickle Cell Disease (SCD) have been reported to have delayed menarche, increased rates of miscarriage &amp; still birth. There is little evidence of the impact of SCD severity on fertility, or of patients’ attitudes towards their fertility. Methods Following IRB approval, an anonymised questionnaire was distributed to female patients over the age of 16 attending an SCD clinic. This included questions on menarche, fertility, reproductive history &amp; clinical severity. We also surveyed attitudes to fertility &amp; the role of fertility treatment. Results 101 women gave informed consent &amp; returned the survey of whom 68 (67%) had sickle cell anaemia (HbSS), 31 (31%) had HbSC &amp; 2 (2%) HbSß0 thalassaemia (HbSß0thal), the group mean age was 38yrs (range 17-74). 46 patients had severe disease phenotype (criteria for severity: ≥3 hospital admissions per year / ≥2 episodes of acute chest crisis/ ≥6 crisis at home per year or on Hydroxycarbamide (HU) therapy), 78% (36/46) had HbSS &amp; 49%(2/46) HbSC. 49% (22/46) were on HU, of whom 19 (86%) had HbSS &amp; 3 (14%) HbSC, the mean duration on HU was 4.7 years (range 2 weeks–15 years). 3 patients with HbSS, were on a chronic transfusion program, 1 as secondary stroke prevention &amp; 2 for disease severity. Mean age of menarche was 14 yrs (range 10-19). HbSC patients’ mean age of menarche was 13yrs (range 10-16), HbSS patients mean age of menarche was 14 yrs (range 10-19). 30% (30/101), (24 with HbSS &amp; 6 with HbSC), had never been pregnant. This group had a mean age of 28yrs (range 17-46), 1 never wanted children, 2 had previously been advised not to conceive, 1 was actively trying for a baby, &amp; 1 patient was awaiting in vitro fertilisation therapy (IVF). There was no difference in the severity of sickle disease in this group compared to the group with pregnancies. 70%(71/101) reported a total of 211 pregnancies, resulting in 111 (52%) successful deliveries (SDs) i.e. a live child/children. Further evaluation of 175 (81%) pregnancies revealed 98 (56%) SDs, (5 sets of twins &amp; 1 early neonatal death equating to 102 live births), 45 (26%) miscarriages, 27 (15%) terminations of pregnancy &amp; 5 (3%) still births (pregnancy loss at &gt; 24 weeks gestation). 52% (50/96) &amp; 63% (47/75) of pregnancies in women with HbSS &amp; HbSC resulted in SDs respectively, as did 25%(1/4) of pregnancies in HbSß0thal women. 74% (53/71) had at least 1 miscarriage (mean 1.7, range 1-7) there was no correlation between miscarriage &amp; sickle genotype or age at pregnancy. 46% (20/46) &amp; 63% (36/55) of patients with severe &amp; milder disease phenotype had miscarriages respectively (p = 0.01). The mean age at termination of pregnancy (26yrs) was lower, compared to 30yrs for women who had SDs or miscarriage &amp; stillbirth (31yrs). In total 41% (72/175) pregnancies were unplanned. 96% (26/27) of terminated pregnancies were unplanned, as were 32% (31/98) of SDs &amp; 28% (15/50) of miscarriages. 28% (28/100) of responders were currently using contraception. 12 (16%) of 71 women reporting pregnancies had no children, they had a total of 21 pregnancies (mean 1.75, range 1-7), 8 (67%) had HbSS, 3 (25%) HbSC. 18% (18/101) thought sickle may have affected their fertility, 93% (93/101) reported having children as being important, this included 28 (93%) of 30 women who had reported no pregnancies. 62% (63/101) would consider prenatal diagnoses (PND) if their partner had sickle cell trait, 59% (60/101) would consider pre implantation diagnosis (PIGD) &amp; 24% ( 24/101) would consider termination of an fetus with SCD. Discussion This study confirms that compared to the normal UK population, women with SCD, have a slightly increased rate of miscarriage &amp; a significantly elevated rate of stillbirth 3% vs 0.005%. Menarche is delayed by a year in patients with HbSS &amp; women with HbSC are more likely to have a successful pregnancy. Although 74% of the women had miscarriage &amp; only 56% of pregnancies resulted in a successful delivery, the majority of women were unaware of the effect of SCD on fertility. Most were not currently using any form of contraception, the rate of unplanned pregnancy was lower at 41% than that in the normal UK population of 50%. These women report having a child as being very important to them, &amp; though majority would consider PND &amp; PIGD only a minority (24%) would terminate a foetus diagnosed with SCD. This study is limited by being retrospective &amp; single centred, further multi-centre prospective studies are required to validate these results. Disclosures: Howard: Sangart: Membership on an entity’s Board of Directors or advisory committees.

Salmonella bacteraemia in children with sickle cell disease

<h3>Background</h3> It is well recognised that individuals with sickle cell disease (SCD) are more susceptible to salmonella infection. Children infected with salmonella are prone to developing multisystem infection such as osteomyelitis, liver and splenic abscesses, and overwhelming sepsis sometimes with fatal consequences. <h3>Objectives</h3> Using a case series, we aim to highlight the invasive and virulent nature of salmonella and demonstrate the whole range of potential complications with a strong emphasis on the importance of prevention. We advocate early and aggressive management of salmonella infection, to maximise treatment efficiency and reduce complications. <h3>Methods</h3> A retrospective case notes review of patients who attended a London tertiary sickle cell centre, between 2006 and 2011 was performed in children with reference laboratory confirmed salmonella enteritidis, salmonella paratyphi B, salmonella Thompson or salmonella typhi bacteraemia. We describe their clinical presentation and chronological course of their illness, relevant investigation results, imaging, management and outcome. Important learning points will be highlighted. <h3>Results</h3> 8 children with salmonella bacteraemia suffered severe complications such as stroke, osteomyelitis, chest crisis, liver and splenic abscesses and in two cases overwhelming sepsis resulting in death, emphasising the need for early recognition and therapeutic intervention in all cases. <h3>Conclusions</h3> Salmonella bacteraemia can have catastrophic consequences in patients with sickle cell disease. Presently, aggressive treatment with antibiotics and early recognition of complications are the mainstay of management. Additionally, health promotion strategies to prevent infection play an important role. We conclude more research needs to be carried out on the effectiveness of vaccines to prevent salmonella infection in children with sickle cell disease.

Salmonella pyomyositis complicating sickle cell anemia: a case report

IntroductionPyomyositis is a bacterial infection of skeletal muscle and a rare complication of sickle cell anemia. It may present a difficult problem in diagnosis, leading to delay in appropriate treatment and development of complications including abscess formation and osteomyelitis.Case presentationWe report the case of a 44-year-old Afro-Caribbean woman with homozygous sickle cell disease who presented with chest crisis and later developed pyomyositis of her hip and pelvic muscles. Salmonella agbeni was isolated from blood cultures and magnetic resonance imaging confirmed the diagnosis in this case. It is noteworthy of this case that there were no antecedent signs of gastroenteritis. Drainage was not appropriate and she was treated with intravenous antibiotics for six weeks.ConclusionsFocal Salmonella infections are uncommon in soft tissue. Pyomyositis should be considered in patients with sickle cell anemia that continue to have muscle pain and high fevers, despite initial management of their sickle cell crisis. Radiological imaging, particularly magnetic resonance imaging, is a crucial tool in establishing the diagnosis.

Plasma Adrenomedullin Levels Are Elevated in Pediatric Patients with Severe Sickle Cell Anemia

Nitric Oxide (NO) and endothelin-1 (ET-1) are key modulators of endothelial vessels and actively participate in the pathophysiology of vaso-occlusive events. Sickle cell anemia (SCA) is an important model for the study of blood cells/endothelium interactions. In SCA vaso-occlusive events may be severe and cumulative. Adrenomedullin (ADM) is a strong hypotension-inducer and mediates diuresis, natriuresis and vasodilation. Adrenomedullin levels are raised in chronic cardiovascular conditions. The aim of this study was to investigate the role of adrenomedullin in SCA and its relationship to endothelin-1 and nitric oxide. A cohort of 111 children with HbSS SCA was studied with 18 age-matched controls of sub-Sahara African ethnicity. The patients were in four clinical groups:steady state (n=55, mean age 5.3 years),patients undergoing chest crisis (n=9, mean age 5.3 years),on hydroxyurea (n=30, mean age 7.2 years),on transfusion therapy (n=17, mean age 6.5 years).A third cohort of patients with HbSC genotype (n=13, mean age 6 years) all in steady state was also included. Pro-adrenomedullin and c-terminal endothelin-1 precursor (CT-proET-1) were measured by coated tube assays according to the method by Morgenthaler et al ( Clin Chem. 2005; 51:1823–29) and Papassotiriou et al ( Clin Chem. 2006; 52(6):1144–51), nitric oxide was quantified according to the Griess reaction. Results (median and interquartile range) are shown in table 1. Overall pro-adrenomedullin levels were raised in chest crisis: 0.38 nmol/l (0.31–0.49) vs steady state: 0.27 nmol/l (0.25–0.32; p<0.01) and control: 0.28 nmol/l (0.27–0.31; p <0.01). CT-proET-1 levels were reduced in patients on hydroxyurea therapy: 43.6 pmol/l (12.6–49.6) vs control: 55.1 pmol/l (45.2–63.9; p<0.05). Nitric oxide levels were significantly lower in chest crisis (19.3 mmol/l plasma; 10.7–19.9) compared to hydroxyurea (22.2 mmol/l plasma; 18.3–28.4; p<0.05), and HbSC (30.6 mmol/l plasma; 20.8–39.5; p<0.05) and approach significance when compared to steady state (22.5mmol/l plasma; 16.9–28.2; p=0.07). This study indicates that during chest crisis plasma adrenomedullin levels are elevated compared to normal controls and SCA patients in steady state (see figure 1). Plasma nitric oxide levels are diminished. These observations indicate that markers of ongoing vascular damage are evident in children with SCA with chest crises, and suggest that treatments that prevent onset or progression of pulmonary hypertension, such as bosentan, may also have a role in the prevention of pulmonary hypertension in children with SCA.Table 1. ADM, ET-1, NO and hematological/biochemical values in SCA patients and controls. IR= interquartile range. [Display omitted] [Display omitted]

A Comparison of Echocardiogram Screening for Pulmonary Hypertension in Asymptomatic and Symptomatic Patients with Sickle Cell Disease

Background: Pulmonary hypertension (PHT) is an increasingly recognised complication of sickle cell disease (SCD), even in asymptomatic patients. Studies from the US have shown a prevalence of PHT of between 20–30% and this has been associated with an increased mortality. The prevalence of PHT in the UK sickle cell disease population is unknown.Method: We identified adult patients with a diagnosis of SCD (HbSS, HbSC, HbSB0thalassaemia and HbSB+ thalassaemia) who had screening for PHT using transthoracic echocardiography over a one year period. We compared the echocardiographic findings of symptomatic and asymptomatic patients. Direct measurements of tricuspid regurgitant jet velocity (TRVmax) were recorded, as has been done in previous similar studies with a peak TRV of ≥ 2.5m/s indicating risk of PHT. In order to increase specificity and sensitivity of the echocardiogram recording and as TRVmax is not always measurable other indirect indicators of PHT were also recorded, including ‘time from start of flow to peak velocity’ which is measured by placing the pulsed sample in the centre of the main PA or pulmonary valve annulus; a time of >105ms excluded PHT while a time <80ms made PHT highly likely. Systolic function of the right ventricle was quantified using long-axis measurements: TAPSE (tricuspid annular plane systolic excursion) using a TAPSE <18mmHg as an abnormal threshold and ‘Doppler tissue S velocity’ was measured by placing the Doppler tissue sample in the RV free wall at the tricuspid annulus and recording the peak systolic velocity. A velocity of <10m/s was consistent with a reduced RV ejection fraction or PHT.Results: 32 asymptomatic patients and 40 symptomatic patients had echocardiogram screening for PHT. The asymptomatic group had a mean age (± SD) 36.5 years(± 10.2), 17 patients were men, 20 patients had HbSS, 10 patients had HbSC, 1 patient had HbSB0thalassaemia and 1 patient had HbSB+ thalassaemia. 3/32 (9.4%) of patients had abnormal echocardiograms with a TRV of 2.5, 2.5 and 2.6 m/s respectively. One patient with a TRV = 2.5m/s had a history of chest crisis and was on hydroxyurea. The symptomatic group had a mean age (± SD) 35.8 years (± 11.2), 13 patients were men, 31 patients had HbSS, 8 patients had HbSC, 1 patient had HbSB0thalassaemia. 2 patients who had TRV ≥ 2.5m/s were excluded from analysis as had pulmonary stenosis. 7/38 (18.4%) patients had TRV ≥ 2.5m/s (range 2.5 to 2.7m/s). Of these 7 patients, 6 had HbSS, 1 had HbSC, only one was on hydroxyurea, and only one had a history of chest crisis. In 2 further patients in whom TRV was not measurable, other echocardiographic features were used to identify PHT; 1 patient had a ‘time to peak velocity’ of 58ms and 1 patient had a TAPSE of 17mmHg and a ‘time to peak velocity’ of 80ms. Both patients had HbSS, 1 had a history of chest crisis and none were on hydroxyurea.Conclusion: In the asymptomatic group, 9.4% of patients had abnormal echocardiograms, which were suggestive of PHT. In the symptomatic group, 24% patients had echocardiograms suggestive of PHT with 7 patients having a peak TRV ≥ 2.5m/s and a further 2 patients being identified using other echocardiogram criteria. We conclude that the prevalence of PHT in the asymptomatic group was low but in the symptomatic group, the prevalence of PHT was comparable to figures in the US. In addition, transthoracic doppler echocardiographic screening for PHT should include other criteria apart from TRV.

Management of priapism in a child with sickle cell anemia; successful outcome using epidural analgesia

To describe the successful management of priapism secondary to sickle cell anemia in a child using neuraxial analgesia provided via an epidural catheter. A seven-year-old male presented with chest crisis and priapism which, following hemoglobin electrophoresis led to a new diagnosis of sickle cell anemia. Epidural management was attempted as an alternative to surgery after failure of more conventional medical and surgical methods to treat the priapism. The patient's clinical condition improved with this intervention and together with further conservative therapy resulted in complete resolution of the priapism. Priapism is a well described complication of sickle cell anemia that is painful and difficult to manage. Surgical intervention is the last therapeutic resort and often results in significant long-term morbidity. This case highlights how select cases of priapism can be successfully managed with epidural neuraxial blockade which not only provides superior analgesia for the often painful conservative treatments, but may also per se impart a direct and salutary therapeutic benefit.

Therapy Insight: stroke risk and its management in patients with sickle cell disease

Children with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, 'soft neurological signs', seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or 'silent' infarction. Those with ischemic stroke usually have stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries. Indefinite transfusion prevents recurrence in most patients who have had a stroke, and can prevent first stroke in those with high transcranial Doppler velocities. High white cell count, low hemoglobin and oxyhemoglobin desaturation predict neurological complications. Other risk factors for overt ischemic stroke include hypertension, previous transient ischemic attack, covert infarction and chest crisis. For hemorrhagic stroke, aneurysms are common in adults but not children, who often present with hypertension after transfusion or corticosteroids. Seizures are particularly common in patients with cerebrovascular disease and covert infarction; the latter is also associated with hyposplenism and infrequent pain. Factors associated with cognitive difficulties include thrombocytosis, infarction, large-vessel disease, and perfusion abnormality on neuroimaging. As well as investigating the role of genes and the possibility that hydroxyurea or blood pressure control reduce neurological complications, we should explore the modifiable effects of poor nutrition, chronic infection, hemolysis and oxyhemoglobin desaturation on stroke risk.

Pediatric laparoscopic splenectomy

Lateral laparoscopic splenectomy in adults, first reported in 1991, was begun with children in 1993. The authors reviewed records of 59 patients 2 to 17 years old who underwent laparoscopic splenectomy by the lateral approach between 1994 and 1998 at four medical centers. Patients received prophylactic penicillin or vaccinations preoperatively. Of the 59 patients, 51 required splenectomy for one of the following conditions: idiopathic thrombocytopenic purpura, hereditary spherocytosis, or sickle-cell disease. Splenomegaly was found in 86% of the patients, and ten accessory spleens were resected. No deaths or infection occurred, and only three patients had perioperative complications: acute chest crisis, small diaphragmatic injury, and intraoperative hemorrhage. One operation was converted to a minilaparatomy because of difficulty with specimen extraction. Pediatric laparoscopic splenectomy is safe and effective, resulting in little blood loss, rapid recovery, and a good cosmetic outcome.

SEGMENTAL TESTICULAR INFARCTION DUE TO SICKLE CELL DISEASE

Testicular infarction not associated with torsion is rare and segmental infarction is even more rare. The causes of testicular infarction in adults include trauma, sequela of epididymo-orchitis, polycythemia, hypersensitive angiitis, intimal fibroplasia of the spermatic artery and idiopathic etiology.l.2 In most reported cases the diagnosis of testicular infarction was made several days after the onset of symptoms, and the testis was removed to rule out malignancy. We report a case of segmental infarction of a testis presenting as an acute scrotum in a patient with sickle cell anemia. The clinical and sonographic findings that developed during 18 hours of observation allowed insight into the pathogenesis of large vessel occlusion in patients with sickle cell anemia. CASE REPORT A 27-year-old man with homozygous sickle cell anemia presented to the emergency department with severe pain in the left testicle 6 hours in duration. Previous complications of sickle cell disease included acute chest crisis, splenic infarction, osteomyelitis of the left foot and recurrent hemolytic crises. However, the patient had been free of painful crises for the last 9 years. He was married and the father of l-yearold twins who were born after successful in vitro fertilization. The pain was not accompanied by urinary or gastrointestinal symptoms and there was no history of trauma to the testicles. Physical examination revealed a severely distressed patient with normal vital signs. The left hemiscrotum was slightly swollen, red and tender. It was difficult to differentiate the epididymis from the testis. Urinalysis showed 10 to 20 red blood cells per high power field, hemoglobin was 7.7 gm. (normal 14 to 18) and white blood count was 16,500/mm.3 (normal 4,000 to 10,000). Working diagnosis was testicular torsion and color Doppler ultrasonography was done. Both testes appeared normal in echo texture and arterial blood flow. Analgesics, oxygen supplementation and hydration were administered.