Twice Weekly Vs. Thrice Weekly Low-Dose Prophylactic Factor VIII Therapy in Children with Hemophilia A: An Open Label Randomized Trial.

INTRODUCTION: Low dose factor VIII prophylactic therapy in hemophilia has not been well established till date. This randomized controlled trial compared the efficacy of twice vs. thrice weekly schedule of low dose prophylactic factor VIII in children with hemophilia A as evaluated by the bleeding rate and clinico-radiological evaluation. METHODS: Thirty-three children with severe hemophilia A (≤18 years) were randomized into two groups. Baseline evaluation included detailed history, clinical (HJHS 2.1 score and FISH score) and radiological examination (Pettersson score and ultrasound score). Group 1 received twice weekly factor VIII prophylaxis while group 2 received thrice weekly factor VIII prophylaxis, the dose being 10 U/kg in both groups. All participants were followed up over next 6 months to one year. Data regarding acute bleeding episodes and repeat clinico-radiological assessment at the end of follow up were recorded. RESULTS: We analyzed 14 children in twice weekly prophylaxis group and 16 children in thrice weekly prophylaxis group. Statistically insignificant difference was found between the bleeding rates in both the groups after prophylaxis with the median values of monthly bleeding rate being 0.17 and p-value of 0.79. The differences between the initial and final clinical and radiological scores within each group were found to be statistically significant. There was no significant difference in the clinical and radiological scores in between the groups. CONCLUSION: Twice weekly FVIII therapy is effective, easily administered prophylactic schedule to prevent long-term complications of hemophilia A. Lay summaryHemophilia A is one of the most common congenital coagulation factor deficiencies. Low dose factor VIII prophylaxis is recommended for hemophilia in resource-poor settings to reduce the bleeding episodes and improve the quality of life, although the optimal schedule for the same has not been well established. A randomized controlled trial on 33 children with hemophilia A (≤18 years) was done to compare the efficacy of twice versus thrice weekly schedule of prophylactic factor VIII. Group 1 received twice weekly factor VIII prophylaxis while group 2 received thrice weekly factor VIII prophylaxis, the dose in both groups being 10 U/kg. They were evaluated by the bleeding rate and clinical (HJHS 2.1 score and FISH score) and radiological scores (Pettersson score and ultrasound score). All participants were followed up over next 6 months to one year. Data regarding acute bleeding episodes and repeat clinico-radiological assessment at end of follow up were recorded. When analyzed, statistically insignificant difference was found between the bleeding rates after the two prophylaxis regimes. There was a significant improvement between initial and final clinical and radiological scores in both the groups and no difference was recorded in between the groups. To conclude, twice weekly FVIII therapy is effective, easily administered prophylactic schedule to prevent long-term complications of hemophilia A.

Lead-induced DNA damage and cell apoptosis in human renal proximal tubular epithelial cell: Attenuation via N-acetyl cysteine and tannic acid.

This study investigates the exposure of lead-induced reactive oxygen species (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic intervention using antioxidants in human renal proximal tubular cells (HK-2 cells). Following treatment of HK-2 cells with an increasing concentration of lead nitrate (0-50 µM) for 24 h, the intracellular ROS level increased whereas the GSH level decreased significantly in a dose-dependent manner. Comet assay results revealed that lead nitrate showed the ability to increase the levels of DNA strand breaks in HK-2 cells. Lead exposure also induced apoptosis through caspase-3 activation at 30 µg/mL. Pretreatment with N-acetylcysteine (NAC) and tannic acid showed a significant ameliorating effect on lead-induced ROS, DNA damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the DNA damage and apoptosis via caspase-3 activation. Additionally, supplementation of antioxidants such as NAC and tannic acid may be used as salvage therapy for lead-induced DNA damage and apoptosis in an exposed person.

Inflammatory markers in geriatric anemia: A study from North India.

Background: Inflammation has several effects in the geriatrics with reference to iron deficiency anemia (IDA), anemia of chronic disease (ACD), and unexplained anemia (UA). Whether hyperinflammation is part of their pathogenesis or just incidental is unknown. Data are limited regarding inflammatory patterns in IDA, ACD, and UA in anemic geriatrics and inflammation as a component of UA. There is little known about the overlap of inflammation between ACD and UA. Objective: The study was undertaken to find the proportion of anemic geriatric patients, aged ≥60 years with raised serum levels of inflammatory markers and their study within IDA, ACD, and UA. Materials and Methods: Seventy-five anemic geriatric patients were evaluated for raised serum levels of inflammatory markers: high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) along with serum ferritin (SF). Results: Raised markers were seen in 94.7% of anemic geriatric patients.IL-8 was raised most frequently followed by TNF-α, IL-6, hsCRP, and SF. No distinct inflammatory profile could be elicited between ACD and UA. The hyperinflammatory profile irrespective of the underlying etiology of geriatric anemia suggests that aging per se is pro-inflammatory state. Conclusion: Geriatric anemia can be thought to develop on background of subclinical low-grade inflammation along with superimposed nutritional deficiencies or chronic diseases.

Coagulopathy in the absence of overt DIC in postoperative neurosurgical patients is a strong predictor of poor outcome.

OBJECTIVES: To assess the prevalence of coagulopathy in postoperative neurosurgical patients and correlate it with the outcome. MATERIALS AND METHOD: This longitudinal study was conducted in a tertiary care hospital in the Department of Pathology and Neurosurgery. Ethical approval was taken from the Institutional Ethical Committee - Human Research. Seventy-two (72) participants were recruited within 48 hours of surgery after obtaining consent. Complete clinical and surgical details were recorded. A 6.5 mL venous sample was collected and dispensed in two separate vials. The EDTA sample was run within 2 hours of collection on an automated hematology analyzer to obtain complete blood counts, including platelet count. The citrated sample was run on a fully automated coagulometer to determine PT, APTT, plasma fibrinogen, FVIII assay, and D-dimer levels. Subjects with a DIC-ISTH score of 5 or more were excluded. Coagulopathy was defined as three or more coagulation parameters deranged in a patient. All patients were followed up for the outcome. The outcome was correlated with coagulopathy, and a p-value less than 0.05 was considered statistically significant. RESULTS: The study found that the number of hemostatic parameters deranged correlated with outcome (P < 0.001). The proportion of patients with coagulopathy was 32/72 (44.4%), while those without coagulopathy were 40/72 (55.6%). Of patients with coagulopathy, 87.5% (28/32) had an adverse outcome, while 12.5% (4/32) had a favorable outcome. The difference was found to be statistically significant (P < 0.001). CONCLUSIONS: Coagulopathy, defined as the derangement of three or more parameters, is a predictor of poor outcomes in postoperative neurosurgical patients. This timely recognition of coagulopathy can help triage patients requiring appropriate blood products, significantly reducing morbidity and mortality associated with postoperative neurosurgical patients.

Correlation of T-regulatory Cells and Iron Status in ß-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent ß-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficient evidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in ß-thalassemia major patients. Methods In this study, 20 ß-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70% cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

Serum Vascular Endothelial Gowth Factor Correlates with Hasford Score in Chronic Myeloid Leukemia.

Introduction and Aim Increased angiogenesis in BM is one of the characteristics of chronic myeloid leukemia (CML) implicated in its progression. Vascular endothelial growth factor (VEGF) one of the most potent regulator of angiogenesis is increased in CML. The prognostic impact of serum VEGF in CML is largely unknown with sparse literature from India. So the present study aimed to measure serum VEGF levels in different phases of CML and to assess its prognostic significance using Hasford score. Methods Forty Ph + patients of CML were enrolled in the study. Complete clinical history and physical examination was done. Hemogram was done by Beckman Coulter LH 500. Peripheral smear (Wright's stain) was done by microscopy. Serum VEGF (plain vial) using ELISA was calculated. Statistical analysis was performed using SPSS software version 20. Results The mean serum VEGF levels were significantly higher in patients than in controls (p < 0.0001). The patients in accelerated/blast phase demonstrated significantly higher levels of serum VEGF (mean 151 pg/mL) than those in the chronic phase (mean 90.87 pg/mL) (p = 0.02). Serum VEGF levels showed a significant positive correlation with the overall Hasford prognostic score (p = 0.023). Conclusion Serum VEGF levels can serve as an independent prognostic marker in CML patients irrespective of phase of CML. Also, S. VEGF levels can be used to monitor patients on imatinib therapy and identify those who might benefit from antiangiogenesis therapy. However, larger studies are needed with a larger number of patients in different phases of CML to validate our findings and thus pave the way for future research.

Effect of Helicobacter pylori eradication therapy in iron deficiency anaemia of pregnancy - a pilot study.

BACKGROUND & OBJECTIVES: Despite routine iron supplementation and promotion of diet modification, iron deficiency anaemia (IDA) remains widely prevalent in our antenatal population. Recent studies in pediatric population have highlighted the role of Helicobacter pylori infection in IDA. This study was undertaken to study the effect of eradication therapy in H. pylori infected pregnant women with IDA. METHODS: Randomized placebo-controlled double blind clinical trial was done on 40 antenatal women between 14-30 wk gestation, with mild to moderate IDA and having H. pylori infection, as detected by stool antigen test. These women were randomly divided into group I (n=20): H. pylori treatment group (amoxicillin, clarithromycin, omeprazole for 2 wk) and group II (n=20): placebo group. Both groups received therapeutic doses of iron and folic acid. Outcome measures were improvement in haematological parameters and serum iron profile after 6 wk of oral iron therapy. RESULTS: The prevalence of iron deficiency in pregnant women with mild to moderate anaemia was 39.8 per cent (95% CI 35.7, 44.3); and 62.5 per cent (95% CI 52, 73) of these pregnant women with IDA were infected with H. pylori. After 6 wk of therapeutic oral iron and folic acid supplementation, the rise in haemoglobin, packed cell volume, serum iron and percentage transferrin saturation was significantly (P<0.05) higher in the group given H. pylori eradication therapy as compared to the placebo group. INTERPRETATION & CONCLUSIONS: Our results showed a high occurrence of H. pylori infection in pregnant women with IDA. Eradication therapy resulted in significantly better response to oral iron supplementation among H. pylori infected pregnant women with IDA.

Peripheral Blood and Bone Marrow Findings in Chronic Alcoholics with Special Reference to Acquired Sideroblastic Anemia.

Anemia associated with alcoholism has numerous causes, most common being megaloblastic anemia and acquired sideroblastic anemia (SA). The bone marrow aspirate (BMA) and bone marrow iron (BMIr) findings and their correlation with peripheral blood smear (PBS) have not been extensively described in literature. We aim to study the spectrum of hematological abnormalities in chronic alcoholics. Complete blood count (CBC), PBS, BMA and BMIr of 71 chronic alcoholics were studied retrospectively over a period of 3 years. The slides were reviewed by 2 pathologists. The clinical history, CBC, PBS, BMA and BMIr findings were recorded. Out of 71 patients, 68 (95.77%) had anaemia. Red cell morphology varied from normocytic-normochromic, microcytic-hypochromic, macrocytic, to dimorphic anaemia. Principal findings seen on BMA were erythroid hyperplasia and megaloblastic maturation. BMIr was available in 41 patients; iron stores were decreased in 2 (4.88%), normal in 14 (34.15%), increased in 25 (60.97%). Seven (17.07%) cases showed presence of ring sideroblasts. Chronic alcoholics show a variety of abnormalities in BMA, which closely mimic many haematological disorders. A history of alcoholism should always be taken in these circumstances. SA should be ruled out in all chronic alcoholics with anaemia not responding to vitamin B12/folic acid, even with macrocytic picture on PBS.

Serial Serum Lactic Acid in Pregnancy-Associated Sepsis for Maternal Outcome.

OBJECTIVE: To correlate serial monitoring of lactic acid in pregnancy-associated sepsis (PAS) subjects with maternal prognosis. METHODS: All pregnant, post-abortal (2 weeks) and postpartum women with suspected sepsis fulfilling any 2 of the Quick Sequential Organ Failure Assessment criteria were considered as cases. Lactic acid was measured at 0, 24 and 48 h of admission, and lactate clearance was calculated. RESULTS: The mean value of lactic acid was significantly higher in the Intensive Care Unit (ICU) group than the Non-ICU group at 0, 24, and 48 h with values being (6.00 ± 2.46 mmol/l vs 3.25 ± 1.92 mmol/l), (4.44 ± 2.24 mmol/l vs 2.91 ± 1.77 mmol/l) and (5.65 ± 2.91 mmol/l vs 2.99 ± 1.93 mmol/l), respectively. Lactic acid in the survivor group was significantly lower as compared to the mortality group (3.79 ± 0.32 mmol/l vs 7.3 ± 0.56 mmol/l). A cut-off of 3.8 mmol/l with area under the curve of 0.814 has a sensitivity of 84% and specificity of 68% for predicting ICU admission. The mean lactate clearance was 46% in cases who survived and 22.5% in cases who had mortality. When lactate clearance was 60%, no mortality was seen, whereas when there was 100% rise in lactic acid, they all had mortality. CONCLUSION: The mean lactic acid at 0, 24 and 48 hours was significantly higher in the ICU group as compared to the Non-ICU group. Serum lactic acid at zero hours of the presentation was significantly higher in ICU cases. Lactate clearance (fall) helps to prognosticate as fall of ≥ 60% lactic acid level is associated with 100% survival, whereas a rise of 100% in serum lactic acid is associated with 100% mortality.

Markers of Fibrinolysis in Indian Patients with Isolated Head Trauma.

CONTEXT: Head injury causes disseminated intravascular coagulation as the most severe complication which is associated with high mortality. Elevated levels of markers of fibrinolysis such as D-dimer and fibrinopeptide A (FPA) have been correlated with poor outcome in these patients. AIM: The study aimed to correlate the levels of plasma fibrinogen, D-dimer, and FPA with outcome in patients with isolated head trauma. SETTINGS AND DESIGN: This cross-sectional descriptive study was conducted in the Departments of Pathology and Neurosurgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, on 100 patients admitted within 12 h of isolated head trauma. SUBJECTS AND METHODS: Plasma fibrinogen, D-dimer, and FPA were measured in 100 patients admitted within 12 h of isolated head trauma. While plasma fibrinogen and D-dimer were estimated in all patients, FPA was measured in 45 patients. STATISTICAL ANALYSIS: SPSS (20.2) software was used for mean, standard deviation, and median values of the quantitative parameters, and for all qualitative parameters, their frequencies were obtained. P < 0.05 was considered significant. RESULTS: Elevated D-dimer (>250 ng/ml) and FPA (>3 ng/ml) were observed in 64% and 91.1% patients, respectively. Both D-dimer and FPA were elevated in 66.6% of patients. Disseminated intravascular coagulation (DIC) score, calculated using standard criteria, was ≥5 in 28% of patients indicating overt DIC. Hypofibrinogenemia was observed in 48% of patients. D-dimer, FPA, and DIC score was significantly (P < 0.001) higher and plasma fibrinogen significantly (P < 0.001) lower in nonsurvivors as compared to survivors. Elevated D-dimer and FPA and low fibrinogen levels were seen in patients irrespective of severity of injury. CONCLUSIONS: Elevated D-dimer and FPA were frequently observed in patients with isolated head trauma. As these markers rise soon after injury and indicate poor outcome, their measurement will help identify patients who will benefit with additional therapy, thus reducing morbidity and mortality.