The Effects of HFE Polymorphisms on Biochemical Parameters of Iron Status in Arab Beta-Thalassemia Patients.

In this study, the potential effect of three HFE gene polymorphisms (C282Y, H63D and S65C) and the SLC40A1 A77D polymorphism on iron balance was investigated in 234 subjects (91 Arab beta-thalassemia major (BTM) patients, 34 beta-thalassemia trait (BTT) individuals and 109 health controls). Genotyping was done using restriction-fragment-length polymorphism and direct-sequencing. Serum-iron, total iron binding capacity, transferrin and ferritin were estimated in all BTT and BTM, and in 65 healthy controls. H63D was the only polymorphism detected in our cohort. Allele frequency was 13% in both BTM and BTT and 10% in controls with no significant difference. Serum iron, ferritin and transferrin saturation were significantly higher in normal males heterozygous for H63D as compared to homozygous wild-type males. Ferritin was significantly higher in BTT males with or without H63D polymorphism when compared to the healthy males with H/H genotype. No such difference was observed between H/H versus H/D BTT subgroups. We conclude that H63D is the only significant hemochromatosis-associated polymorphism in the Arabian Gulf region. The heterozygous state of H63D may significantly alter iron parameters in normal males. In BTT, it appears that the beta-thalassemia allele has an overriding influence on ferritin values, and this generally manifest in males.

Frequencies and phenotypic consequences of association of α- and ß-thalassemia alleles with sickle-cell disease in Bahrain.

INTRODUCTION: Bahrain has high prevalence rates of sickle cell and thalassemia in the population. This study reports the frequencies and phenotypic characteristics of α- and/or ß-thalassemia associated with sickle-cell disease (SCD) in a tertiary care hospital. METHODS: Adult SCD patients (n = 200) were screened for the common α- and ß-thalassemia alleles prevalent in the region using molecular techniques. Results of CBC, hemoglobin analysis, and average annual frequencies of severe pain episodes and numbers of transfused red cell units were documented. RESULTS: Patients were grouped on the basis of molecular studies as sickle-cell anemia (SS, n = 131), SS/α-thalassemia with three normal genes (n = 27), SS/α-thalassemia with two normal genes (n = 11), sickle-ß-thalassemia (Sß, n = 23), and Sß with co-inherited α-thalassemia (n = 8). Identified α-thalassemia determinants were -α3.7 (n = 52), -α4.2 (n = 4), αT-Saudi α (n = 1), and αHph α (n = 1). All ß-thalassemia alleles were ß0 defects. Sickle-thalassemia association resulted in higher hemoglobin, hematocrit, and erythrocyte counts with reduced MCV and reticulocytes. Significant clinical associations were as follows: increased severe pain frequency with α-thalassemia (three-gene group); red cell transfusion with ß-thalassemia alleles and female gender. CONCLUSION: One-third of patients with SCD co-inherited α- and/or ß-thalassemia alleles and these associations explained some of the observed phenotypic variability. A low prevalence of nondeletion α-thalassemia alleles was observed in these patients. The most significant disease amelioration occurred in SCD associated with two α-thalassemia alleles.

Infection-associated haemophagocytosis: the tropical spectrum.

Reactive proliferation and inappropriate activation of mature histiocytes with haemophagocytosis (HP) may occur in association with a wide variety of infections, neoplasms, collagen vascular diseases, and acquired and inherited immunodeficiency states. The association with infections is particularly important because overwhelming HP can obscure the typical clinical features of the primary disease and negatively affects outcome. A high index of suspicion is required for early recognition of associated HP as the cause of cytopenias. Institution of specific therapy is crucial for survival. This study highlights the wide spectrum of tropical diseases that can have associated reactive HP. Thirty cases with documented prominent HP on bone marrow aspiration smears were reviewed. Twenty-one (69%) of the marrows were from patients who had common tropical infections: malaria, typhoid and visceral leishmaniasis and 11 of 15 patients (73%) who were followed up improved on specific infection-directed and supportive measures. The presence of severe HP in bone marrow smears correlated with marked cytopenias. Recognition of HP in this geographical region should stimulate the search for one of these infections as early institution of specific therapy is crucial for patient survival.

Histomorphology of multiple myeloma on bone marrow biopsy.

In a retrospective study, 49 bone marrow biopsies (BMB) of patients with multiple myeloma (MM) were studied for its role in diagnosis and to determine histological parameters of prognostic significance. Sections were analyzed by 2 observers and classified according to: 1. Cytological grading according to differentiation of the neoplastic cells as plasmacytic, pleomorphic and plasmablastic. 2. Volume of infiltration: quantitating the percentage of myeloma cells in the biopsy. 3. Pattern of neoplastic infiltration. The overall marrow cellularity, presence of marrow fibrosis, micro-osteolesions and normal haematopoeisis were also studied. The bone marrow biopsy (BMB) was diagnostic for myeloma in five cases, where the aspirates were hypocellular: four had early myeloma and one had extensive marrow fibrosis. The pattern of infiltration was interstitial in 19 cases (39%), nodular in 19 cases (39%), and diffuse in 11 cases (22%). In majority of the cases (49%), the cell type was plasmacytic (24 cases), plasmablastic in 10 cases and pleomorphic in 15 cases. All cases of poorly differentiated cell type (plasmablastic) had a diffuse or nodular pattern of infiltration, whereas majority of the well-differentiated cell type had an interstitial pattern. The plasma cell burden in biopsy i.e the volume of infiltration was <10% in 8 cases, <50% in 19 cases and >50% in 22 cases and was used for histological staging of MM. Fibrosis was present in 30% of cases. Follow up was available in 11 cases, and cases with poorly differentiated myeloma, diffuse pattern of infiltration and dense fibrosis had survival less than one year. Cases of well differentiated myeloma, interstitial pattern of infiltration and plasma cell load less than 20% with absence of fibrosis had a more than 5-year survival. Different series have quoted that all these histological parameters provide valuable prognostic information, wherever other modalities like beta 2 microglobulin and IL-6 levels, etc are not available. The effects of therapy can also be monitored by sequential biopsies.

The association of antiphospholipid antibodies with ischaemic stroke and myocardial infarction in young and their correlation: a preliminary study.

AIM: The possible etiological role of antiphospholipid antibodies (APA) in thrombotic events on arterial side has become subject of interest. The present study was undertaken to determine the association and possible etiological role of APA in young Indian patients with acute ischaemic stroke and myocardial infarction (MI). MATERIAL AND METHODS: Forty six patients < 40 years of age including 22 with ischaemic stroke (excluding those with rheumatic heart disease and SLE), 24 with an acute MI and 21 age and sex matched healthy controls were enrolled in the study. All the patients and the controls were tested for the presence of lupus anticoagulant (LA) by a lupus sensitive activated partial thromboplastin time (APTT) and kaolin clotting time (KCT) and anti-caridiolipin antibodies (aCL) of IgM and IgG types using an ELISA technique. RESULTS: The screening tests for LA with APTT and KCT were negative in all the patients and the normal controls. In the stroke subgroup 18.18% patients (4/22) and in MI subgroup 4.16% (1/24) patients had raised aCL titers with statistically significant association only for stroke subgroup (p=0.0201) and not for MI subgroup. Significantly higher proportion of aCL positive cases were found in patients without any risk factor for atherosclerosis (4/12), compared to patients with one or more risk factor for atherosclerosis (1/34), p=0.001. CONCLUSION: Younger patients without identifiable risk factors for atheroscerosis presenting with stroke, are more likely to have an underlying antiphospholipid syndrome (APLS) as the etiology, and should be screened for it. No such association however was observed for MI patients.

Pediatric acute leukemia presenting as bilateral renal enlargement. Report of a case with fine needle aspiration cytologic features suggestive of megakaryocytic differentiation.

BACKGROUND: Fine needle aspiration (FNA) cytologic diagnosis of acute myeloid leukemia involving the kidney has rarely been reported, but acute leukemia with cytologic features suggestive of megakaryocytic differentiation has not been described before. CASE: An 8-month-old male presented with an abdominal swelling, bilateral cervical and inguinal lymphadenopathy and enlarged left epididymis. Ultrasonography of the abdomen revealed a space-occupying lesion in the liver and bilateral enlargement of the kidneys. FNA smears from the right kidney and right submandibular lymph node showed numerous blast cells. Since rare blast cells were positive for myeloperoxidase, a cytodiagnosis of involvement by acute myeloid leukemia (AML) was made. However, following the hematologic diagnosis of acute megakaryoblastic leukemia (M7) from peripheral blood and bone marrow smear examination, FNA smears were reviewed. There were cytoplasmic blebs or protrusions in the blast cells and cytologic features suggestive of their differentiation toward micro-megakaryocytes and megakaryocytes. There was also evidence of shedding of platelets, including numerous giant platelets. The reviewed FNA cytodiagnosis was suggestive of AML (M7). CONCLUSION: Extramedullary involvement by acute megakaryoblastic leukemia (M7) can be suspected based on cytomorphologic features in FNA smears.

Haemostatic changes in children with cyanotic and acyanotic congenital heart disease.

This study was undertaken to screen children with congenital heart disease for coagulation abnormalities and to compare the groups of cyanotic and acyanotic children with congenital heart disease with respect to abnormalities of the coagulation system. Following investigations were done in all the patients: complete blood count, erythrocyte sedimentation rate, peripheral smear examination, bleeding time, prothrombin time, activated partial thromboplastin time, assay of fibrinogen, D-dimer, factors VII and VIII and antithrombin III. Red cell indices were determined in 12 control, 12 acyanotic and 20 cyanotic children. Twenty-five patients each, with echocardiographically proven cyanotic and acyanotic congenital heart disease under 12 years of age constituted the study group; as many children of the same age group were included as the control group. The results showed isolated abnormalities of laboratory tests with equal frequency (28%) in acyanotic and cyanotic groups but coexisting abnormalities of more than one test were seen in significantly larger number of cyanotic children (5/25 and 16/25, respectively). A significant association was noted between thrombocytopenia and a high haematocrit in cyanotic patients. It is concluded that laboratory abnormalities of tests of haemostasis are more common in cyanotic congenital heart disease patients. The patterns of laboratory abnormalities suggest a chronic compensated disseminated intravascular coagulation at a subclinical level, reduced synthesis of clotting factors and/or deranged platelet aggregation in different subgroups of patients.

Distinctive AgNOR patterns of myeloid and lymphoid blasts in acute leukemia.

Bone-marrow aspiration smears of 38 cases of acute leukemia (19 acute lymphoblastic leukemia, 19 acute nonlymphocytic leukemia) were stained for argyrophilic nucleolar organiser regions (AgNOR). AgNOR were assessed numerically and morphologically. There were highly significant differences in AgNOR morphology between acute lymphoblastic leukemia and acute nonlymphocytic leukemia ANLL: lymphoblast AgNORs were usually small (<3 microm) "dots/chips," whereas myeloblasts showed larger "blebs," or a combination of the two types (complex structures). AgNOR number was significantly less in acute lymphoblastic leukemia. In acute nonlymphocytic leukemia cases, AgNOR number also showed direct correlation with Ki67 reactivity of leukemic blasts.

Symmetric peripheral gangrene and falciparum malaria--an interesting association.

Symmetric peripheral gangrene (SPG) is a rare syndrome in which disseminated intravascular coagulation (DIC) is the most common underlying condition. We report three cases of SPG in association with Plasmodium falciparum malaria and DIC, an association unreported so far.

Cutaneous T-cell lymphoma diagnosed by fine-needle aspiration: a case report with clinical, cytological, and immunophenotypic features.

A case study of cutaneous T-cell lymphoma in a 40-yr-old Indian male is presented. Prominent clinical features consisted of large skin tumours, lymphadenopathy, and a rapidly progressive course of development. Aspiration smears from tumours, lymph nodes, and bone marrow showed pleomorphic Sezary cells and lymphoid blasts. The neoplastic cells stained positively with anti-HLA DR, CD1, and CD2 antibodies and showed lack of T-cell subset antigens CD4 and CD8. Numerous proliferating cells were identified with 56% of bone marrow cells and 57% of cells in the dermis staining positively with Ki-67 and PC10 antibodies, respectively. This case is reported in view of its uncommon features.