Severe Sickle Cell Research Articles

Hypertransfusion therapy in sickle cell disease in Nigeria.

Introduction. Hypertransfusion refers to chronic blood transfusion therapy aimed at ameliorating disease complications in various haemopathies particularly the haemoglobinopathies. In sickle cell disease, hypertransfusion is aimed at maintaining patient's haemoglobin level at 10 to 11 g/dL using haemoglobin AA blood and its resultant dilutional effect on sickle haemoglobin is sustained by intermittent long-term transfusions. Aim and Objective. This paper highlights hypertransfusion and its privileged position as a secondary measure in prevention and treatment of sickle cell disease, especially in the Nigerian context. Materials and Methods. Relevant literatures were searched on PubMed, Google Scholar and standard texts in haematology and transfusion medicine. Keywords used in the search are hypertransfusion, sickle cell disease, chronic transfusion, and Nigeria. Literatures gathered were reviewed, summarized, and presented in this paper. Result. Immense clinical benefit is associated with hypertransfusion therapy including prevention of stroke and amelioration of severe sickle cell disease especially in transplant ineligible patients. Careful patient selections, appropriate blood component, and prevention of transfusion hazards as well as oversight function of an experienced haematologist are pertinent to a successful hypertransfusion therapy. Conclusion. Improved knowledge of the benefits and practice of hypertransfusion will effectively translate into improved health status even among Nigerian sickle cell disease patients.

Fetal hemoglobin in sickle cell anemia: a glass half full?

Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ∼10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease.

Evaluation of clinical and laboratory correlates of sickle leg ulcers

The exact mechanism for the occurrence of sickle leg ulcers (SLUs) has not been fully explained, although, popular opinion supports a multifactorial etio-pathogenetic process. Leg ulceration in sickle cell is a chronic and debilitating condition which is difficult to treat and may worsen the psychosocial impact of this illness. This study aims to evaluate the laboratory and clinical correlates of SLUs. One hundred sixty-seven patients who had been diagnosed with sickle cell anemia (homozygous S) had their steady-state hemoglobin concentration (Hb), hematocrit, white cell count, platelet count, serum bilirubin, and aspartate transaminase (AST) as well as frequency of crisis per annum evaluated with respect to their relationship to the occurrence of leg ulcers. They were aged 6-53 years (mean age 24.3 years), and prevalence of leg ulcer was found to be 2.75 per 1000 (2.54 per 1000 in females and 2.83 per 1000 in males). The independent sample t-test showed a significant difference in the serum AST levels in those with SLU (p = 0.029), though a positive correlation did not exist. Other predictors of disease severity found to have positive relationship with each other were the AST and total serum bilirubin 0.207 (p = 0.012); Hb and age 0.130 (p = 0.035); Hb and white cell count -0.159 (p = 0.010), white cell count and age -0.113 (p = 0.018). SLUs do not occur in patients with severe disease in sickle cell. The clinical and laboratory indicators of severe sickle cell disease do not correlate positively with the occurrence of SLU. Serum AST may have a relationship with leg ulceration in these patients. Environmental factors most likely play a major part in the etiopathogenesis of leg ulcer and this may require further studies in different sociocultural settings.

The Role of a Low-Dose Ketamine-Midazolam Regimen in the Management of Severe Painful Crisis in Patients With Sickle Cell Disease

ContextAcute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. ObjectivesWe studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. MethodsA retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2–0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5–1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. ResultsNine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). ConclusionLow-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect.

Normalized Transcranial Doppler Velocities, Stroke Prevention and Improved Pulmonary Function after Stem Cell Transplantation in Children with Sickle Cell Anemia

Abnormal transcranial Doppler velocities (TCD) indicate an increased risk of stroke in patients with sickle cell anemia (SCA) and require regular blood transfusions. Hematopoietic stem cell transplantation (HSCT) is under discussion as an alternative to chronic transfusion in these patients. This retrospective analysis includes 9 patients with SCA undergoing HSCT at a single center in Germany. Special focus was given to the neurologic follow-up and to the results of TCD studies. High risk of stroke or previous stroke was an HSCT-indication in 8 of 9 patients, although most patients had more than one indication for HSCT. TCD was normalized in all 5 patients after HSCT in whom this test was available. None of the patients developed a stroke after HSCT. No further strokes occurred even in patients that experienced recurrent strokes during chronic transfusion before HSCT. 2 of the 9 patients received a 10/10 HLA-matched unrelated donor graft, the others matched related grafts.All patients were alive, free of SCA symptoms and transfusion-independent with stable chimerism 3-11 years after HSCT. Pulmonary function tests normalized in 1 patient with severe sickle cell lung disease. HSCT is able to prevent stroke in patients with SCA. Its perspectives and limitations should be discussed early during the treatment of a patient with complicated SCA.

Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and opinions

With rapidly expanding evidence of benefit reported by several groups, allogeneic hematopoietic stem-cell transplantation has become an acceptable treatment option for sickle cell disease. It is currently the only curative therapy available. Hematopoietic stem-cell transplantation was offered primarily as a therapeutic option for severe sickle cell disease in the context of myeloablative matched sibling donor transplants over the last two decades and helped to establish the benefits of transplantation for this disorder. While this approach provided proof of principle, the disadvantages and limitations of transplantation became evident along the way. It has been recognized that transplantation for sickle cell disease does not need to adhere strictly to the principles of transplantation for malignant disorders, such as achievement of full donor cell chimerism. As reviewed here, in recent years the transplant community has set out to explore ways to make stem-cell transplantation more available to patients with the disease, define indications and better timing, and offset toxicities with novel approaches to conditioning and better supportive care.

Safety of Pegfilgrastim (Neulasta) in Patients with Sickle Cell Trait/Anemia

Pegfilgrastim (Neulasta) is a recombinant filgrastim (human granulocyte colony-stimulating factor (G-CSF)) attached to a polyethylene glycol (PEG) molecule and is given as part of chemotherapy regimens that are associated with significant myelosuppression and risk for febrile neutropenia. Prescribing information available on manufacturer's website for the drug warns us about possible severe sickle cell crises related to the medication but does not report the actual incidence or the use in patients with sickle cell trait. Caution is advised when using it in patients with sickle cell disease. Here we present a case of a Caucasian female with known sickle cell trait (SCT) with no prior complications who developed a presumed sickle cell crisis after getting Neulasta, as a part of the chemotherapy regimen used to treat her breast cancer. Based on our literature review, this appears to be the first case report of a patient with SCT developing a sickle cell crisis with the pegylated form of recombinant filgrastim. Given the dearth of literature regarding the use of G-CSF and its related pegylated forms in patients with sickle cell anemia and sickle cell trait, a discussion of potential mechanisms and review of current literature and guidelines is also presented.

Idiosyncratic Side Effects of Hydroxyurea in Patients with Sickle Cell Anemia

Hydroxyurea was approved by the Food and Drug Administration for the treatment of adults with moderate to severe sickle cell anemia and sickle-β0-thalassemia. Its major side effect is myelotoxicity, which is reversible upon discontinuation of the drug. Other side effects that have been described in animal studies but unconfirmed in humans include its teratogenic and carcinogenic potential. Additionally, hydroxyurea has idiosyncratic side effects that occur in some individuals and this may be a genetic or epigenetic phenomenon. We report three idiosyncratic side effects of hydroxyurea in four patients with sickle cell anemia (SS). Desquamating rash, decreased libido and partial complex seizures have not been previously described in patients who are hydroxyurea responders. Although these reactions are rare, they can be serious in some patients.

Severe Sickle Cell Disease Is Characterized by Low ADAMTS13/VWF: Ag Ratio

Abstract 3235Endothelial damage is one of the major mechanisms causing most of the manifestations in sickle cell disease (SCD). We hypothesized that a possible defect in the cleavage of large vWF multimers through the protease ADAMTS13 could add further to the well established chronic activation of the endothelium and consequently to the severity of the disease. For this purpose we measured the activity of the enzyme and looked for any correlations with regard to the clinical phenotype of patients with SCD. We studied 22 steady state patients (9 men/13 women) with a median age of 35(22–74) years. Of them, 3 were in homozygous state(HbSS) and 19 were compound heterozygous for thalassamia β(HbS/β+, HbS/β0). The clinical phenotype was mild in 12 patients, moderate in 3 and 7 were suffering from severe symptoms (history of frequent vaso-occlusive and acute chest crises and need for regular exchange transfusion).We applied FRET (fluorescence resonance energy transfer) technique to measure ADAMTS13 activity (normal values>65%). Factor VIII and vWF: Ag was measured using 1-stage clotting assay and immunoassay respectively (normal values 50–150%). We considered all relevant clinical parameters (spleen size, transfusion frequency, comorbidities, and medications with special regard to iron chelation, hydroxyurea and antiplatelet agents) together with laboratory readings (markers of haemolysis, proportion of haemoglobin fractions using high-performance liquid chromatography HPLC).We used as control group 22 healthy volunteers blood donors with their written consent matched for age, sex, body mass index and ABO blood group. All samples were taken at least 30 days post last transfusion.We found higher levels of both vWF: Ag [189(33–345)] and ADAMTS13 [164(75–310)] in the patients compared to the control group [87(44–152) και 126(55–171) (p<0.001/p<0.025)] respectively. When we analyzed the ratio ADAMTS13/vWF: Ag we found significant difference between the two groups: 1,041(0.3–4.6) vs 1.56(0.5–2.6) (p<0.020). Furthermore, patients with severe disease experienced significantly lower ratio ADAMTS/vWF 0.7(0.5–1.2) compared to both control group (p<0.001) as well as patients with milder clinical phenotype [1.30(0.3–4.6)].Of note, in patients with severe SCD despite the fact that vWF: Ag levels were found considerably higher and in significant difference with the control group [196(130–345) vs 87(44–152)p<0.001], we could not find the same pattern for ADAMTS13 [140(75–210) vs 126(55–171)].The lower ratio found in patients with SCD and in particular in those with severe disease might indicate the need for higher protease levels in comparison to healthy controls. It looks like in this group of patients ADAMTS13, although normal, is not sufficient enough to manage the reasonably high vWF levels that characterize the chronic endothelial activation. This relevant deficiency of the metaloprotease might be caused by either biggest consumption due to large and constant release of its substrate-vWF or by an acquired inhibition of its action as the free intravascular hemoglobin might exhibit an antagonistic role for the binding site of vWF. In conclusion, the low ADAMTS13/vWF: Ag ratio seems to detect patients with severe SCD and would be of interest to prospectively investigate its role both as a prognostic tool as well as a potential therapeutic target. Disclosures:No relevant conflicts of interest to declare.

Hematopoietic stem cell transplantation in SCD

Hematopoietic stem cell transplantation (HSCT) is the one and only curative therapy available for patient with severe sickle cell disease (SCD). Until today, several hundreds of patients have undergone geno-identical HSCT. More than 200 patients were transplanted in France. The first indication was cerebral vasculopathy. Among both malignant and non-malignant diseases treated with HSCT, the success rate obtained in SCD patients appears as the best one. From the year 2000, more than 95% of transplanted patients survived the HSCT procedure and more than 90% are completely cured and experience a very satisfying health condition post-transplantation. However, the current standard procedure includes a myeloablative conditioning regimen for warranting engraftment. Such regime is linked to severe long-term side effects such as hypofertility. Due to the excellent obtained results, we have to think about a possible widening of indications, a decrease of conditioning intensity and toxicity, and about HSCT from alternative stem cell sources, such as mismatch family donor, unrelated volunteer donor or unrelated cord blood.

Adherence to transcranial Doppler screening guidelines among children with sickle cell disease

Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle-β(0) -thalassemia (HbSβ(0) ) aged 2-16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence. A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSβ(0) who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD. Among 338 TCD eligible at-risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD. Publicly insured children with HbSS or HbSβ(0) had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow-up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines.

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: Study protocol for a randomised controlled trial

BackgroundChildren with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain.Methods/designThis study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05.DiscussionThis clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting.Trial registrationCurrent Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Pregnancy outcome in sickle cell disease in the UK: have things changed over three decades?

Sickle cell disease prevalence, albeit low, is increasing in the United Kingdom, from estimates of 5,000 in 1986 to 12,000 in 2010.1 2 Pregnancies in sickle cell disease (SCD) have,...

Relationships between outpatient pain scores and acute care utilization in sickle cell disease

Severe sickle cell pain often but not always leads to utilization of acute care services. We examined the relationship between pain measured during a routine outpatient clinic visit and acute-care utilization events during their first year of an acute-care study. During a routine outpatient clinic visit, adults with SCD completed PAINReportIt, a computerized comprehensive pain assessment tool that is reliable and has published validity and acceptability in adults with SCD. We created a Composite Pain Index (CPI) by converting pain location, intensity, total pain rating index, and pattern scores to a 0-100 scale and summing scores. All acute-care utilization events (Emergency Department, Acute Care Center, inpatient hospitalization) were documented during the subsequent study year for the 137 study participants who had entered the acute-care study phase at the time of this analysis. Their mean age was 34±11 years (65% women; 95% African American). Mean pain intensity at the clinic visit did not differ by utilization group, but least pain (F(2,134)=3.6, p<.03) and worst pain (F(2,134)=4.0, p<.02) in the past 24 hours, and CPI (F(2,134)=6.1, p<.003) differed significantly by utilization group. Patients who had no acute-care utilization events did not differ from other utilization groups on their current pain, but had significantly lower least and worst pain in the previous 24 hours and CPI scores than the other two utilization groups (1-3, ≥4 events). Patients with ≥4 utilization events had higher pain scores on all measures, but these scores were not significantly different than scores reported by patients with 1-3 utilization events. Differences in CPI scores were more profound than least or worst pain intensity. CPI scores should be examined for potential to predict patients at most risk for acute exacerbations of their SCD pain.

Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease: Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

The Sickle Cell Unrelated Donor Transplant Trial (SCURT trial) of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is a phase II study of the toxicity and efficacy of unrelated donor hematopoietic cell transplantation in children with severe sickle cell disease (SCD) using a reduced-intensity conditioning regimen. Here we report the results for the cord blood cohort of this trial. Eight children with severe SCD underwent unrelated donor cord blood transplantation (CBT) following alemtuzumab, fludarabine, and melphalan. Cyclosporine or tacrolimus and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis. Donor/recipient HLA match status was 6 of 6 (n = 1) or 5 of 6 (n = 7), based on low/intermediate-resolution molecular typing at HLA -A, -B, and high-resolution typing at -DRB1. Median recipient age was 13.7 years (range: 7.4-16.2 years), and median weight was 35.0 kg (range: 25.2-90.2 kg). The median pre-cryopreservation total nucleated cell dose was 6.4 × 10(7) /kg (range: 3.1-7.6), and the median postthaw infused CD34 cell dose was 1.5 × 10(5) /kg (range: 0.2-2.3). All patients achieved neutrophil recovery (absolute neutrophil count >500/mm(3)) by day 33 (median: 22 days). Three patients who engrafted had 100% donor cells by day 100, which was sustained, and 5 patients had autologous hematopoietic recovery. Six of 8 patients had a platelet recovery to >50,000/mm(3) by day 100. Two patients developed grade II acute GVHD. Of these, 1 developed extensive chronic GVHD and died of respiratory failure 14 months posttransplantation. With a median follow-up of 1.8 years (range: 1-2.6), 7 patients are alive with a 1-year survival of 100%, and 3 of 8 are alive without graft failure or disease recurrence. Based upon the high incidence of graft rejection after unrelated donor CBT, enrollment onto the cord blood arm of the SCURT trial was suspended. However, because this reduced-intensity regimen has demonstrated a favorable safety profile, this trial remains open to enrollment for unrelated marrow donor transplants. Novel approaches aimed at improving engraftment will be needed before unrelated CBT can be widely adopted for transplanting patients with severe SCD.

Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease: Results of a Phase II Study from the Blood and Marrow Transplant Clinical Trials Network

Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease: Results of a Phase II Study from the Blood and Marrow Transplant Clinical Trials Network

Oocyte cryopreservation in a patient with sickle cell disease prior to hematopoietic stem cell transplantation: first report

To report the first occurrence of successful ovarian stimulation, oocyte retrieval and oocyte cryopreservation for fertility preservation in an adolescent with severe sickle cell disease scheduled to undergo a hematopoietic stem cell transplant Case report. A 19 year old female with severe sickle cell disease presented for fertility preservation counseling prior to hematopoietic stem cell transplantation. She ultimately underwent ovarian stimulation using a minimal stimulation GnRH antagonist protocol resulting in the successful banking of oocytes prior to transplant. The unique hazards associated with ovarian stimulation in patients with sickle cell disease, such as thrombosis and vaso-occlusive events, are discussed and the methods undertaken to minimize these risks are described. Controlled ovarian hyperstimulation and oocyte banking for fertility preservation is feasible in young women with sickle cell disease requiring hematopoietic stem cell transplant and deserves further investigation. Given the elevated risk of thrombosis and predisposition to painful vaso-occlusive events, controlled ovarian hyperstimulation in patients with sickle cell disease is not straightforward and requires a multi-disciplinary team approach to adequately address and minimize the risks in this unique patient population.

To assess the efficacy of hydroxyurea, in children with homozygous sickle cell disease, in the age group of 1 year to 18 years, at tertiary care hospital

Aims: To evaluate the increase in fetal hemoglobin percentage and MCV in children of sickle cell disease treated with hydroxyurea. To observe the safety of hydroxyurea in treated children. To arrive at the therapeutic dose of the drug to produce the beneficial effects.Settings and Design: A single blind randomized controlled trial of 12 months duration was designed to study the effect of hydroxyurea on sickle cell patients which aims to study the clinical and laboratory effects, in tertiary care hospital.Materials and Methods: Sixty children with severe sickle cell disease in the age group of 1-18 years were studied. Outcomes were measured in terms of decrease in number of vaso-occlusive crises, necessity of blood transfusions, laboratory parameters for different organ functions, blood cell counts and toxicity of hydroxyurea.Results: In patients of sickle, cell disease treated with hydroxyurea there was significant reduction in number and severity of vaso- occlusive crises and necessity of blood transfusions. Total hemoglobin, MCV and fetal hemoglobin percentage were raised significantly. Bone marrow suppression as reflected by the decrease in white blood cell and reticulocyte counts occurred but it was not below the defined toxicity levels. Serum bilirubin was decreased significantly. Conclusions: In the present study, we concluded that, hydroxyurea decreases number of vaso-occlusive crises and need for blood transfusions in children with severe sickle cell disease. It increases total, fetal hemoglobin concentration and MCV. It causes bone marrow suppression thereby decreasing white blood cell and reticulocyte count. However, this fall was never below defined toxicity levels. It causes no hematological, hepatic, renal or general toxicities when given on short-term basis. Overall, hydroxyurea has proved to be safe and efficacious in children between the age groups of 1-18 years.

English

Compound heterozygosity for HbS/HbD results in severe hemolytic anemia and a clinical syndrome similar to that of sickle cell disease. Here we report a case of pregnancy with sickle cell disease - D variant. A 25yrs old G2P1L1 residing at Raigad , from tribal community presented for the first time in antenatal OPD at seven months pregnancy with complaints of fever , cough and cold. She had severe anemia, jaundice, splenomegaly and frontal bossing. Initially, she was thought to be a case of severe sickle cell anemia or sickle cell trait. However with the help of alkaline electrophoresis it was confirmed that she is a case of HbS /D disease. Keywords - HbSD variant, sickle cell disease, (Key message: If HbSD disease is confirmed in pregnancy then the possible complications and interventions have to be explained. Counseling through a genetic counselor should be done. It should be kept in mind that patient can have sickle cell crisis and the severity of which is enhanced by HbSD. It is also important to screen the newborn for Hb -SD disease and observe the baby for any splenomegaly or vaso- occlusive crisis or repeated respiratory tract infections. A paediatric hematologist should be consulted regarding patient evaluation and possible disease management.)

Complications of PORT-A-CATH® in patients with sickle cell disease

Red cell exchange/transfusion is frequently used in the management of patients with medical complications related to acute severe sickle cell disease (SCD). However, peripheral venous access is often difficult without central venous catheters (CVCs) in adult patients with moderate or severe SCD. To review our experience with the use of the PORT-A-CATH(®) device in sixteen patients with SCD undergoing exchange or simple transfusions. Among a cohort of 550 patients who frequently visited the inpatient service, sixteen SCD patients required the insertion of a PORT-A-CATH(®) device. These patients included 3 males and 13 females, aged 25-44 years [31.1 ± 2.3; mean ± SD]. A total of 24 PORT-A-CATH(®) devices were implanted in these 16 patients during the study period. Eleven patients had 1 device implanted, three patients had 2 devices, one patient had 3 devices, and one patient had 4 devices implanted. Out of the 24 devices implanted, 17 required removal, due to either infection associated with sepsis and/or thrombosis. The organisms involved were Candida spp. (3), C. Parapsilosis (2), C. albicans (1), C. famata (1), C. lusitanice (1), Staphylococcus spp. (6), and S. aureus (3), as well as the coagulase-negative Staphylococcus (2), alpha hemolytic Streptococcus (1), Diphtheroid bacilli (2), Pseudomonas aeruginosa (2), Ps. Spp. (3), Escherichia coli (3), Klebsiella oxytoca (1), Klebsiella pneumoniae (1), Klebsiella spp. (1), Serratia liquefaciens (1), Serratia fanticola (1), Achromobacter spp. (2) Chromobacterium violaceum (1), Delftia acidovirans (1), Stenotrophomonas maltophile (1), Alcaligenes faecalis (1), and Enterobacter cloacae (1). Two episodes of documented thrombosis were observed. One case presented with right atrial thrombosis/SVC syndrome and the other case presented with left upper arm thrombosis. Two patients died with ports in situ, while five patients had ports in place at the time of this study. The median working life of the ports was 688.5 days (range: 39-3925). The rate of infective complications was 2.63 infections per 1000 catheter days, and the number of infections was significantly correlated with the number of ports [Pearson's r=0.66; p<0.01]. Our results suggest that patients with SCD suffer infective complications associated with the PORT-A-CATH(®), which often necessitate its removal. Although these devices are extremely useful, their optimal beneficial potential is only realized if the patients receive proper care at special centers well-versed in the maintenance of such devices by experienced staff.