A stepwise diagnostic approach for undiagnosed Anemia in children: A model for low-middle income country.

BACKGROUND: Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing. PATIENTS AND METHODS: A one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups: microcytic (n = 19), normocytic (n = 14) and macrocytic (n = 11). An algorithm that included four levels of investigations was devised for each category. RESULTS: After applying a systematic diagnostic approach, 33 patients (75 %) were diagnosed of whom 7 (15 %) had combined diagnoses, while 11 (25 %) patients remained undiagnosed. Based on the first, second, third and fourth levels of investigations, patients were diagnosed, respectively, as follows: of the 11 patients, 7 were microcytic, 3 normocytic and 1 macrocytic; of the 7 patients, 2 were microcytic, 2 normocytic, and 3 macrocytic; of 10 patients, 5 were microcytic, 4 normocytic and 1 macrocytic; finally, of the 16 patients, 8 were microcytic, 6 normocytic and 2 macrocytic. Numbers recorded appear higher than the actual number of the patients because some of them were diagnosed by more than one level of investigation. The diagnoses obtained in the microcytic group showed hemoglobinopathies, iron refractory iron deficiency anemia (IRIDA), membrane defects, sideroblastic anemia, hypo-transferrinemia, a combined diagnosis of sickle cell trait and pyropoikilocytosis. The diagnoses also showed a combined diagnosis of hereditary spherocytosis (HS) and alpha thalassemia minor, and a combined diagnosis of iron deficiency anemia and beta thalassemia minor, while 15 % remained undiagnosed. In the normocytic group, the diagnosis revealed autosomal recessive (AR) HS, vitamin B12 deficiency, pyruvate kinase deficiency (PKD), congenital dyserythropoietic anemia (CDA) type I, Diamond Blackfan anemia and beta thalassemia major. In addition, it showed a combined diagnosis of AR HS and CDA type II, a combined diagnosis of AR HS and PKD, and a combined diagnosis of dehydrated stomatocytosis (DHS) and G6PD carrier, meanwhile 20 % remained undiagnosed. Finally, the macrocytic group was diagnosed by vitamin B12 deficiency, sideroblastic anemia, PKD, a combined diagnosis of PKD and G6PD deficiency carrier, while 45 % remained undiagnosed. CONCLUSION: Conducting a stepwise approach with different levels of investigations may help reach the diagnosis of difficult anemia without having to resort to unnecessary investigations. Combined diagnosis is an important cause of undiagnosed anemia, especially in countries with high frequency of consanguinity. The remaining 25 % of the patients continued to be undiagnosed, requiring more sophisticated investigations.

Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis.

BACKGROUND AND AIM: Patients infected with hepatitis C virus (HCV) often develop chronic liver disease, liver cirrhosis and concurrent thrombocytopenia, which manifests as decreased platelet counts and bleeding complications. Romiplostim, a thrombopoietin mimetic peptibody that stimulates the thrombopoietin receptor, has been used as a treatment for primary immune thrombocytopenia. We monitored the efficacy of preoperative romiplostim over 90 days in 35 male patients with chronic hepatitis C, liver cirrhosis and thrombocytopenia secondary to HCV infection. METHODS: Romiplostim was administered at 2 µg/kg Q1W for a maximum of one month with a target platelet count of 70 × 10(9)/L as a prerequisite for planned surgeries. Bone marrow aspirate was collected at baseline and at the end of the study, along with liver and kidney function assessments. A complete blood count was performed every third day throughout the study period. RESULTS: A rapid response to romiplostim therapy was observed, with 33/35 patients achieving platelet counts ≥ 70 × 10(9)/L and thereby eligible for surgery. An initial mean platelet count of 31 × 10(9)/L increased to a maximum peak range of 73-240 × 10(9)/L, occurring between days 18 and 39. The reticulin bone marrow grade remained negative in all patients. Surgical interventions were associated with no postoperative bleeding or thrombotic complications. CONCLUSIONS: Preoperative romiplostim administration may represent a viable alternative to increase platelet counts to a level acceptable for elective surgical interventions in patients with chronic liver disease and severe thrombocytopenia secondary to HCV infection who are unresponsive to standard therapy. Further studies in larger numbers of patients and over a longer period of time are warranted.

Stem cell transplantation in hematological disorders. A developing country experience-impact of cost considerations.

OBJECTIVE: To describe the experience in setting up a bone marrow transplant program at Ain Shams University, Cairo, Egypt. METHODS: Sixteen patients were transplanted at Ain Shams University Bone Marrow Transplantation unit from March 2005 to January 2008. RESULTS: Sixteen patients were transplanted with a median age of 25 years. Indications for transplantation were chronic myeloid leukemia, acute myeloid leukemia, aplastic anemia, acute lymphoblastic leukemia, and aggressive lymphoma. Seven donors and 6 patients were positive for cytomegalovirus immunoglobulin G (IgG) antibody (Ab) pretransplant. Only one patient was positive for toxoplasma IgG Ab and another had a high titre for toxoplasma IgM Ab pretransplant. Two donors and 2 recipients were positive for hepatitis B antibody markers; however, none were positive for hepatitis B virus DNA by polymerase chain reaction (PCR). None of the patients or donors were positive for hepatitis C virus via PCR pre-transplant. Acute graft versus host disease (GVHD) was seen in 3 patients, while chronic GVHD was seen in 5 patients. Primary cause of death was recurrence in 2 patients and graft failure in one patient. Thirteen are alive and disease free with a median follow-up of 20 months. CONCLUSION: Although our unit is a relatively new unit, these results are comparable to those achieved in the Western world and cost a mean of US$250,000.

Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus.

BACKGROUND AND OBJECTIVES: Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). SUBJECTS AND RESULTS: 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×10(6) to 191×10(6). There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. CONCLUSION: SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis.