Egyptian Pediatric Guidelines for the Management of Children with Isolated Thrombocytopenia Using the Adapted ADAPTE Methodology-A Limited-Resource Country Perspective.

BACKGROUND: Thrombocytopenia is a prevalent presentation in childhood with a broad spectrum of etiologies, associated findings, and clinical outcomes. Establishing the cause of thrombocytopenia and its proper management have obvious clinical repercussions but may be challenging. This article provides an adaptation of the high-quality Clinical Practice Guidelines (CPGs) of pediatric thrombocytopenia management to suit Egypt's health care context. METHODS: The Adapted ADAPTE methodology was used to identify the high-quality CPGs published between 2010 and 2020. An expert panel screened, assessed and reviewed the CPGs and formulated the adapted consensus recommendations based on the best available evidence. DISCUSSION: The final CPG document provides consensus recommendations and implementation tools on the management of isolated thrombocytopenia in children and adolescents in Egypt. There is a scarcity of evidence to support recommendations for various management protocols. In general, complete clinical assessment, full blood count, and expert analysis of the peripheral blood smear are indicated at initial diagnosis to confirm a bleeding disorder, exclude secondary causes of thrombocytopenia and choose the type of work up required. The International Society of Hemostasis and thrombosis-Bleeding assessment tool (ISTH-SCC BAT) could be used for initial screening of bleeding manifestations. The diagnosis of immune thrombocytopenic purpura (ITP) is based principally on the exclusion of other causes of isolated thrombocytopenia. Future research should report the outcome of this adapted guideline and include cost-analysis evaluations.

Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using 'Adapted ADAPTE'.

Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.

Psychosocial and mental profile of children with sickle cell disease and their caregivers.

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.

Tartrate-Resistant Acid Phosphatase 5b in Young Patients With Sickle Cell Disease and Trait Siblings: Relation to Vasculopathy and Bone Mineral Density.

Bone involvement is a frequent cause of acute morbidity in sickle cell disease (SCD). Tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, is produced specifically by activated osteoclasts. We assessed bone mineral density (BMD) in 30 young patients with SCD and 17 asymptomatic patients with sickle cell trait (SCT) compared with 32 healthy controls and determined TRACP 5b levels in relation to vascular complications. Serum ferritin, alkaline phosphatase (ALP), and TRACP 5b were measured. Echocardiography was performed with assessment of BMD using dual energy X-ray absorptiometry (DXA). The BMD was decreased in patients with SCD compared with SCT and controls (P = .005), with no significant difference between the latter 2 groups. Patients with SCD had higher incidence of bone complications than SCT group and controls (P = .03). The SCD group with abnormal DXA scan had higher ferritin and ALP than normal BMD. Serum TRACP 5b was significantly higher in patients with SCD than SCT and controls (P = .003). The TRACP 5b levels were associated with severe vaso-occlusive crisis (P = .022). Patients treated with hydroxyurea and those on chelation therapy had lower TRACP 5b levels than untreated patients. The TRACP 5b level was positively correlated with lactate dehydrogenase, while there was no relation with ferritin, ALP, or BMD. We suggest that bone complications frequently occur in SCD as reflected by low BMD and high ALP and TRACP 5b. Hemolysis and iron overload may be involved in the occurrence of these complications. The lack of correlation between abnormal DXA scan and high TRACP 5b suggests that bone disease in SCD is multifactorial.

Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities.

To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.

Pancreatic functions in adolescents with beta thalassemia major could predict cardiac and hepatic iron loading: relation to T2-star (T2*) magnetic resonance imaging.

The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with ß-thalassaemia major (ß-TM). A total of 50 adolescent patients with ß-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with ß-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=-0.376, p=0.014 and r=-0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.

Glutathione S-transferase gene polymorphism: Relation to cardiac iron overload in Egyptian patients with Beta Thalassemia Major.

OBJECTIVES: Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (ß-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*. METHODS: Hundred patients with ß-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done. RESULTS: Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002). DISCUSSION: Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with ß-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis. CONCLUSION: GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with ß-TM.

Clinical to Molecular Screening Paradigm for ß-Thalassemia Carriers.

ß-Thalassemia (ß-thal) represents a major health problem worldwide and particularly in Egypt. Its prevention, compared to treatment, is cost-effective, possible and practical. In this study we evaluate a proposed paradigm for detection of the ß-thal carrier state. The present study included 1627 children and adolescents of both sexes, presenting as outpatients to clinics of Ain-Shams University Hospitals, Cairo, Egypt, from November 1 2009 to June 30 2010. In the first phase, after performing a complete blood count (CBC), 280 microcytic hypochromic patients were selected. These cases were further analyzed by iron profile and high performance liquid chromatography (HPLC); in the second phase, hybridization detected 22 common ß-globin mutations in 74.0% of the suspected cases. Thus, by HPLC, the Hb A2 level of >3.5% provided 100.0% sensitivity, 70.0% specificity, 75.0% positive predictive value (PPV), 100.0% negative predictive value (NPV) and accuracy of 70.0% to identify ß-thal trait and at a cut-off of 4.0%, it provided 97.4% sensitivity, 72.7% specificity, 92.6% PPV, 88.8% NPV and a diagnostic accuracy of 92%. High performance liquid chromatography is a reliable and cost effective primary screening tool for ß-thal trait at a Hb A2 level of ≥4.0%, while molecular testing is mandatory only for selected cases with borderline Hb A2 values between 3.5 and 4.0%.

13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6-17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study.

BACKGROUND: A large population of older children with sickle cell disease (SCD) is currently vaccinated with only 23-valent pneumococcal polysaccharide vaccine (PPSV23). In immunocompetent adults, PPSV23 vaccination reduces immune responses to subsequent vaccination with a pneumococcal vaccine. The 13-valent pneumococcal conjugate vaccine (PCV13), which addresses this limitation, may offer an advantage to this population at high risk of pneumococcal disease. PROCEDURE: Children with SCD 6-17 years of age previously vaccinated with PPSV23 at least 6 months before study enrollment received two doses of PCV13 6 months apart. Anti-pneumococcal polysaccharide immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured before, 1 month after each administration, and 1 year after the second administration. RESULTS: Following each PCV13 administration, IgG GMCs and OPA GMTs significantly increased, and antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year following dose 2. At 1 year after the second administration, OPA GMTs for all and IgG GMCs for most serotypes remained above pre-vaccination levels. Most adverse events were due to vaso-occlusive crises, a characteristic of the underlying condition of SCD. CONCLUSIONS: Children with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre-vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13.

Alterations of platelet functions in children and adolescents with iron-deficiency anemia and response to therapy.

Several changes in platelets have been reported in patients with iron-deficiency anemia (IDA), so a relationship between iron metabolism and thrombopoiesis should be considered. We aimed to study the alterations of platelet functions in patients with IDA by assessment of platelet aggregation with epinephrine, adenosine diphosphate (ADP) and ristocetin and by measuring platelet function analyzer-100 (PFA-100) closure time together with the effect of iron therapy on the same tests. A follow-up study was conducted in Ain Shams University Children's hospital in the period from June 2011 to June 2012 including 20 patients with confirmed IDA and 20 healthy age- and sex-matched control. Bleeding manifestations were reported. Laboratory analysis included complete blood count, assessment of iron status by measuring serum iron, TIBC and ferritin, assessment of platelet functions by PFA-100 closure time and platelet aggregation with collagen, ADP and ristocetin. Patients with IDA were treated by oral iron therapy 6 mg/kg/day of ferrous sulfate and post-therapeutic re-assessment was done. Mean age of IDA patients was 5.7 ± 4.2 years. Bleeding manifestations were more common in patients group. Mean PFA-100 closure times (with epinephrine) were significantly longer in patients (179.1 ± 86.4 seconds) compared to control group (115 ± 28.5 seconds) (p < 0.05). Platelet aggregation by ADP (38.1 ± 22.2%), epinephrine (19.7 ± 14.2%) and ristocetin (58.8 ± 21.4%) were significantly reduced in patients compared to control (62.7 ± 6.2, 63.3 ± 6.9, 73.8 ± 8.3, respectively; p < 0.001). After treatment platelet aggregation tests induced by ADP (64.78 ± 18.25%), and epinephrine (55.47 ± 24%) were significantly increased in patients with IDA compared to before treatment (39.44 ± 21.85%, 20.33 ± 14.58%; p < 0.001). PFA-100 closure time as well showed significant decreased after treatment (118.4 ± 27.242) compared to before treatment (186.2 ± 90.35; p < 0.05). A negative correlation between platelet aggregation induced by ADP and mean values of serum ferritin before treatment (r = 0.042, p < 0.05) was found. A mutual effect is considered between iron deficiency and platelet functions. Subtle bleeding manifestations can occur in patients with IDA with delay in platelet aggregation and prolongation in PFA-100 closure times which can be reversed by iron therapy.

Health-related quality of life of Egyptian children with immune thrombocytopenia and their parents.

Health-related quality of life has been recognized as an important pediatric outcome measurement. Kid's ITP Tool was used to measure health-related quality of life of 80 Egyptian children with immune thrombocytopenia and their parents in relation to different disease parameters. A positive correlation between scores of child/proxy reports and parent report was found. Patients with newly diagnosed immune thrombocytopenia had significantly lower scores of both child/proxy reports and parent reports than chronic patients. Longer duration of illness was correlated with higher scores of child/proxy reports. Negative correlations were found between severity of bleeding and both scores of child/proxy reports and parent reports. Platelet count was positively correlated with parent report score. Regression analysis revealed that severity of bleeding had the highest significant impact on parent report score. Improving parents' knowledge about the pathogenesis and course of the disease may improve their quality of life.

Morbidities and mortality in transfusion-dependent Beta-thalassemia patients (single-center experience).

BACKGROUND: The improvement of quality and duration of life of transfusion-dependent B thalassemia patients over the last years discloses several complications due to the underling disorder, iron overload and the treatment with iron chelators. Our Aim was to assess the morbidity patterns and mortality rate of transfusion-dependent thalassemia patients, and compare the outcomes in relation to age of onset, type, duration, and compliance to iron chelation therapy and frequency of blood transfusion. PROCEDURE: This retrospective study included 447 transfusion-dependent ß-thalassemia patients who attended the Thalassemia Center, Ain Shams University Children's Hospital over the last 10 years in the period between January 2000 and January 2010. Data were collected from the patients or their caregivers, as well as by reviewing follow up sheets for examinations and investigations done to detect morbidities as well as iron chelation therapies given. Determination of mortality rate and the causes of death were also done. RESULTS: Results revealed that the most common morbidities were endocrinologic (44.7%) followed by cardiovascular (41.3%) and hepatic (40.5%), then renal (4%). The different iron chelation therapy groups showed a comparable prevalence of different morbidities. The mortality rate was 1.5% and infection was the most common cause of death. The 5, 10, 20 years' survival rate among the studied patients was 80%, 50%, 20%, respectively. CONCLUSION: In the past 10 years, the survival and morbidity rates in our center have markedly improved as a result of regular blood transfusion, new iron chelators, and better compliance of the patients.

A longitudinal prospective study of bleeding diathesis in Egyptian pediatric patients: single-center experience.

Keeping an updated registry of bleeding disorders is crucial for planning care and documenting prevalence. We aimed to assess the prevalence of various bleeding disorders including rare inherited coagulation and platelet disorders concerning their clinico-epidemiological, diagnostic data and bleeding manifestations severity. Patients suffering from manifestations of bleeding or coagulation disorders presented to Hematology Clinic during 16 years were included and prospectively followed up. Demographics, clinical characteristics, complete blood count, bleeding, prothrombin and activated partial thromboplastin times, platelet aggregation tests and bone marrow aspiration were recorded. Overall 687 patients with bleeding disorders from total 2949 patients were identified. Inherited coagulation defects were found in 27.2%; hemophilia A (70.6%), hemophilia B (13.9%), factor I deficiency (2.3%), factor V deficiency (1.6%), factor X deficiency (4.2%), factor VII deficiency (2.6%), factor XIII deficiency (1.1%), combined factor deficiency (2.1%) and unclassified coagulation disorders in 1.6% of studied patients. Overall 72.7% had diagnosed with platelet disorders; immune thrombocytopenia was the commonest (74.8%), and inherited conditions represent (25.2%) in the following order: Glanzman's thrombasthenia (11.2%), von Willebrand disease (6.6%), Bernard-Soulier syndrome (1%) and Chediak Higashi in 0.4% and unclassified in 6%. Median age of diagnosis of coagulation and platelet disorders were 33 and 72 months. Presenting symptoms of coagulation disorders were: 25.1% post circumcision bleeding, 22.5% ecchymosis, 20.9% hemoarthrosis and 15% epistaxis. Symptoms of rare coagulation disorders were postcircumcision bleeding (20%), bleeding umbilical stump (20%), epistaxis (12%), hemoarthrosis (8%) and hematomas (4%). Presenting symptoms in rare inherited platelet disorders were purpura, ecchymosis, epistaxis and bleeding gums, respectively. Analysis of the clinico-epidemiological data of patients with bleeding disorders is a useful tool for monitoring and improving their quality of care.

Romiplostim therapy in children with unresponsive chronic immune thrombocytopenia.

Romiplostim, a thrombopoiesis-stimulating peptibody, represents a new therapeutic option in adult refractory chronic immune thrombocytopenia (ITP). This study aimed to assess the short-term efficacy and safety of romiplostim in children with chronic ITP. Eight non-splenectomized patients with chronic ITP refractory to standard lines of medical therapy were recruited from the Pediatric Hematology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt. One patient was initially excluded because of increased bone marrow reticulin (grade 3). Therapy was initiated in seven patients, aged 3.4-15.2 years (median 5.5 years), and the disease duration ranged from 13 months to 7.3 years (median 2.4 years); none were splenectomized. Romiplostim dose was started as 1 µgm/kg/week and the dose escalated by 1 µgm/kg/week according to platelet count. The duration of therapy varied between 1 and 22 weeks (median 12 weeks). Results revealed that four out of the seven patients achieved variable response. Four patients demonstrated rapid increase in platelet count when pulse steroid therapy was added. Most reported adverse events were mild and transient. This case series study reveals variable response rate in children with chronic ITP to romiplostim therapy; addition of steroids especially in emergency bleeding situations could potentiate romiplostim thrombopoietic effect even in patients initially refractory to steroids. Romiplostim safety and efficacy in pediatric ITP needs further long-term studies.

Clinicopathological and radiological study of Egyptian ß-thalassemia intermedia and ß-thalassemia major patients: relation to complications and response to therapy.

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian ß-thalassemia intermedia (ß-TI) patients were compared with 70 ß-thalassemia major (ß-TM) patients. ß-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, ß-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in ß-TM patients compared with ß-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for ß-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between ß-TI and ß-TM. We provide evidence that calls for the use of HU in ß-TI patients.

A trial to assess the efficacy of glutamic acid in prevention of vincristine-induced neurotoxicity in pediatric malignancies: a pilot study.

Vincristine is considered as a backbone of therapy in the induction and consolidation phases of pediatric malignancies. Neurotoxicity is a principal side effect of its use. This study is a randomized single-blinded placebo-controlled clinical trial to evaluate the role of glutamic acid in ameliorating neurotoxicity in pediatric patients with hematologic and solid tumors receiving vincristine during induction course. Fifty-four patients in the glutamic acid group received glutamic acid 1.5 grams daily orally in 3 divided doses during the 4-week induction with vincristine in a dose of 1.5 mg/m² IV weekly. Placebo group (40 patients) received oral placebo 3 times daily in the same way as the glutamic acid group. The onset of neurotoxicity was significantly earlier in placebo group than in glutamic acid group regarding tendon Achilles reflex, Patellar reflex, parasthesia, and increased frequency of constipation. This was statistically significant mostly in third and fourth visits, no severe cases of strength and mental alteration side effects in both groups. Glutamic acid was well tolerated with no gastrointestinal side effects in patients. This study suggests that the coadministration of oral glutamic acid with repetitive intravenous bolus injections of vincristine resulted in a reduction of its neurotoxicity.

Thrombin activatable fibrinolysis inhibitor (TAFI): relationship to hemostatic alteration in patients with beta-thalassemia.

Profound hemostatic changes have been observed among thalassemic patients. Thrombin activatable fibrinolysis inhibitor (TAFI) is a newly discovered protein that potentially attenuates fibrinolysis. The authors aimed to investigate plasma level of TAFI in beta-thalassemia patients in relation to clinical severity and hemostatic alteration. Fifty-one thalassemic patients (mean age 10.79 +/- 5.59 years) (21 splenectomized thalassemia major patients, 18 nonsplenectomized thalassemia major patients, 12 nonsplenectomized thalassemia intermedia) were recruited from Pediatric Hematology Clinic, Ain Shams University; in addition, 32 healthy age- and sex-matched controls (10.31 +/- 5.58 years) were also included. In addition to clinical assessment, laboratory investigations included complete blood count (CBC), hemoglobin electrophoresis, prothrombin time (PT), activated partial thromboplastin time (PTT), liver function tests, viral hepatitis markers, serum ferritin, and plasma TAFI levels. Nine out of 51 patients (17.5%) suffered from bleeding manifestations mainly in the form of epistaxis; none of the studied patients had thromboembolism. Significant reduction in TAFI levels was shown in thalassemic patients compared to controls (P < .0001), in splenectomized compared to nonsplenectomized thalassemia group (P < .0001), and in thalassemia major compared to thalassemia intermedia group (P < .0001). Negative correlation was present between TAFI levels and both liver enzymes and serum ferritin levels (P < .05). Thalassemic patients suffering from bleeding showed lower mean TAFI levels compared to those not suffering from bleeding (P < .001). Marked reduction in TAFI levels was observed in thalassemic patients with splenectomy, altered liver functions, and poor chelation who therefore might be at a higher risk for altered hemostasis.

N-terminal natriuretic peptide and ventilation-perfusion lung scan in sickle cell disease and thalassemia patients with pulmonary hypertension.

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 beta-thalassemia major (beta-TM) and 15 beta-thalassemia intermedia (beta-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 +/- 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, beta-TI and beta-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.

Randomized trial of anti-D immunoglobulin versus low-dose intravenous immunoglobulin in the treatment of childhood chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Chronic idiopathic (immune) thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. Six years ago, low-dose intravenous immunoglobulin (IVIG) treatment of childhood ITP was started at the Pediatric Hematology Unit, Ain Shams University, while intravenous anti-D has been introduced in Egypt in 2001. OBJECTIVES: To assess the efficacy and safety of intravenous anti-D compared to low-dose IVIG in the treatment of children with chronic ITP. PATIENTS AND METHODS: This randomized trial comprised 34 patients with chronic ITP (18 boys and 16 girls) with recurrent bleeding episodes. Median age of the patients was 6.5 years, duration of thrombocytopenia was > 6 months, and platelet count (PC) was < 30 x 10(9)/l (30 K). The patient cohort was divided into two subgroups: group A comprised 18 patients treated with anti-D in a dose of 50 microg/kg i.v. initially, and in 12 of them repeated doses (50 microg/kg) were given every 4 weeks, and group B consisted of 16 children who received IVIG in a dose of 250 mg/kg for 2 consecutive days. Bleeding manifestations, complete blood cell and reticulocyte counts were assessed at baseline and 3, 7, 14 and 28 days after infusion. RESULTS: Clinically, more than 80% of the patients (82.3%) showed good control of bleeding. On day 3, 33.3% of group A versus 37.5% of group B, and on day 7: 66.6% of group A versus 75% of group B patients demonstrated a good response (PC > 50 K and/or doubling of baseline PC). On days 14 and 21, no significant changes in PCs were observed between both groups. However, only 11.1% of group A and 12.5% of group B patients could maintain PC > 100 K on day 28, while 38.8 versus 37.5% of group A and group B, respectively, still had PC > or = double the initial count. The peak response to anti-D was noticed 7 and 14 days following infusion and to IVIG on days 3 and 7. Repeated doses of anti-D could maintain PC > 50 K (or > double the baseline PC) in 75% of patients 1 week after infusion, and in 60% of them by day 28, with good control of bleeding. Splenectomy was postponed and/or avoided in 4 (33.3%) patients on anti-D maintenance therapy who experienced recurrent severe bleeding episodes before starting therapy. The safety of anti-D was judged by the degree of intravascular hemolysis. The mean hemoglobin decrease was 0.8 +/- 0.4 g/dl; in 61.1% of patients the Hb level dropped but none of them experienced a drop of more than 3 g/dl or required transfusion. CONCLUSION: Both single intravenous anti-D and low-dose IVIG effectively increased PC in children with chronic ITP at risk of bleeding or those with previous bleeding episodes. Repeated doses of anti-D could maintain PC above the critical values or double baseline counts in nearly two thirds of the patients showing good control of bleeding and may serve as an alternative to splenectomy in these patients.