Raihan Sajid

Antioxidant status in beta thalassemia major: a single-center study.

BACKGROUND Homozygous β thalassemia may lead to a marked reduction or absence of normal β chain production and accumulation of unpaired alpha-globin chains. A crucial component in the oxidant susceptibility of the thalassemic RBC is the release of heme and iron from the excessive, unpaired α-globin chains. This release can initiate self-amplifying redox reactions, which deplete the cellular reduction potential (e.g., GSH), oxidize additional hemoglobin and accelerate RBC destruction. Furthermore, β-thalassemia patients are under continuous blood transfusion, which, although life-saving, leads to an iron overload with a resultant increase in non-transferrin-bound iron that may cause greater tissue toxicity than iron in other forms. Iron-induced oxidative stress is known to be one of the most important factors determining cell injury in thalassemic patients. Therefore, we designed this study to obtain a comprehensive picture of the iron overload, antioxidant status and cell damage in β thalassemia major patients undergoing regular blood transfusion. MATERIALS AND METHODS A total of 48 diagnosed patients of β thalassemia major and 30 age- and sex-matched healthy subjects were included in the study. Estimation of hemoglobin, hematocrit, glutathione peroxidase (GPX), superoxide dismutase (SOD),vitamin E, serum ferritin, total and direct bilirubin, AST and ALT was carried out. RESULTS The levels of vitamin E, antioxidant enzymes GPX and SOD were significantly lowered in β thalassemic patients as compared with the control group (P<0.001). Serum total and direct bilirubin, AST and ALT were significantly elevated in thalassemic subjects as compared with the control group, indicating liver cell damage. CONCLUSION Thus, our findings indicate that thalassemics are in a state of enhanced oxidative stress and that the administration of selective antioxidants would represent a promising approach toward counteracting oxidative damage and its deleterious effects on the disease status.

Clinical audit of inherited bleeding disorders in a developing country.

OBJECTIVE We did a clinical audit to determine the status of coagulation disorders in a hemophilia care center in Pakistan. SETTING Fatimid foundation blood bank and hematological diseases center, Lahore. STUDY DESIGN This is a retrospective descriptive study. MATERIALS AND METHODS All patients registered at Lahore center were included. Data was collected using a questionnaire including age, gender, diagnosis, hepatitis and human immune deficiency virus (HIV) status, number of episodes of bleeding, most common site of bleeding, severity of disorder and number of transfusions required to treat the episode. RESULTS During the study period, a total of 923 registered patients were reviewed at Lahore center and of these, 408 patients (44.2%) were on regular follow-up. Inherited bleeding disorders identified in these patients included hemophilia A, hemophilia B, vWD, factor VII deficiency, factor V deficiency, factor X deficiency, dysfibrinogenemia, afibrinogenemia, factor XIII deficiency; and platelet function defects. Median age was 17 years with a range of three to 57 years. Median age at diagnosis was one year. There were 329 (80.6%) males and 79 (19.3%) females. The products used in these patients included factor VIII concentrate, fresh frozen plasma, cryoprecipitate, cryosupernatant and platelets. Testing for transmission of viral infections was also done in these patients and one patient (0.2%) was found hepatitis B positive, six patients (1.4%) were hepatitis C positive and two patients (0.49%) were HIV positive. CONCLUSION Hemophilia A, hemophilia B and vWD are the commonly encountered inherited bleeding disorders in our patients followed by other recessively transmitted disorders with a median age of 17 years and male to female ratio of 4: 1. Most of the patients utilized services available at Fatimid foundation with good clinical results. In Pakistan, non-governmental organizations (NGOs) are trying their best for providing optimal treatment to patients with inherited bleeding disorders. There is a need for government participation to improve the availability of current hemophilia care services.

Involvement of bone marrow with intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal large B-cell lymphoma characterized by a selective proliferation of lymphoma cells within the lumina of vessels. We report a case of an 86-year-old man who presented with fever, shortness of breath and altered mental status. The diagnosis of IVLBCL was confirmed on a bone trephine biopsy that revealed positivity of CD20 and PAX5 immunohistochemical staining of lymphoma cells confined within the lumina of vessels. The patient had a rapidly deteriorating clinical course with a fatal outcome even before the specific treatment for the underlying disease was commenced.

Overwhelming bone marrow Leishmaniasis.

doi:10.5152/tjh.2011.97 Visceral Leishmaniasis (kala-azar) is caused by the intracellular parasitic organism Leishmania donovani and is transmitted by the bite of an infected sandfly Phlebotomus argentipes. Clinical manifestations of advanced disease usually include constitutional symptoms, such as prolonged fever, anorexia, weight loss, and marked enlargement of the spleen and liver, with varying degrees of pancytopenia [1]. Pakistan is a tropical country situated in the north-west region of South Asia; all of its neighboring countries are endemic for Leishmaniasis, including China, Afghanistan, Iran, and India [2-4]. Leishmaniasis was first reported from Pakistan in 1960 [5]. Initially, it was limited to the northern mountainous region, but currently it is widespread throughout the country with several endemic foci of varying climatic and geographic conditions [6]. Herein we present a 22-year-old female from Hyderabad, Sindh Province, Pakistan that was referred to our laboratory for bone marrow exanimation due to pyrexia of unknown origin. She had fever with chills and rigors that began 2 months earlier, which did not respond to treatment with antimalarials and multiple antibiotics. At presentation she had massive splenomegaly and marked pallor. Complete blood count showed the following: pancytopenia with hypochromic microcytic anemia; hemoglobin: 7.1 g/dL; hematocrit: 21.8%; MCV: 72.5 fL; MCH: 23.8 pg; MCHC: 29.7%; total white cell count: 1.5×109/L; absolute neutrophil count: 0.4×109/L; platelet count: 48×109/L. Peripheral blood smear did not show a leukoerythroblastic reaction or the presence of abnormal cells. Bone marrow examination showed hypercellular marrow and massive infestation with the amastigote form of Leishmania donovani in the bone marrow macrophages and in some granulocytes. Written informed consent was obtained from the patient. The visceral form of Leishmaniasis can be fatal if not treated in a timely fashion and stibogluconate (sodium antimony gluconate) is the drug of choice. Recently, other agents have become available for the treatment of new and resistant cases of visceral Leishmaniasis, including pentamidine isethionate, amphotericin B, miltefosine, and paramomycin [1]. The presented patient received anti-leishmanial treatment with sodium antimony gluconate 20 mg/ kg/d for 14 d. She began to exhibit improvement within 3 d and was clinically cured after the full course of therapy. She was last followed-up 1 month after completion of the treatment and was asymptomatic and healthy.

Clinicopathologic spectrum of Waldenström's macroglobulinemia: a single center experience.

Waldenströms Macroglobulinemia (WM) is a B cell neoplasm characterized by infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM monoclonal gammopathy. We report a 15-year review of patients diagnosed with WM at our center. A total of 18 patients were diagnosed and treated at our center during the study period. Neurological symptoms were seen in almost 95% while B symptoms were present in almost 80% of patients. More than two-thirds of patients were anemic at the time of presentation and more than 90% showed bone marrow infiltration with lymphoplasmacytoid cells. Anemia, B symptoms, splenomegaly and neurological symptoms were the primary reasons in the majority of patients to initiate treatment. Chlorambucil was the primary treatment in more than half the patients followed by CVP. The median overall survival in all patients was 29 months (range 22-81 months). WM is a rare disorder and novel therapeutic modalities need to be identified to improve survival in these patients.