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.

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.

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.

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.

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.

Safety and effectiveness of intravenous iron sucrose versus standard oral iron therapy in pregnant women with moderate-to-severe anaemia in India: a multicentre, open-label, phase 3, randomised, controlled trial.

BACKGROUND: Intravenous iron sucrose is a promising therapy for increasing haemoglobin concentration; however, its effect on clinical outcomes in pregnancy is not yet established. We aimed to assess the safety and clinical effectiveness of intravenous iron sucrose (intervention) versus standard oral iron (control) therapy in the treatment of women with moderate-to-severe iron deficiency anaemia in pregnancy. METHODS: We did a multicentre, open-label, phase 3, randomised, controlled trial at four government medical colleges in India. Pregnant women, aged 18 years or older, at 20-28 weeks of gestation with a haemoglobin concentration of 5-8 g/dL, or at 29-32 weeks of gestation with a haemoglobin concentration of 5-9 g/dL, were randomly assigned (1:1) to receive intravenous iron sucrose (dose was calculated using a formula based on bodyweight and haemoglobin deficit) or standard oral iron therapy (100 mg elemental iron twice daily). Logistic regression was used to compare the primary maternal composite outcome consisting of potentially life-threatening conditions during peripartum and postpartum periods (postpartum haemorrhage, the need for blood transfusion during and after delivery, puerperal sepsis, shock, prolonged hospital stay [>3 days following vaginal delivery and >7 days after lower segment caesarean section], and intensive care unit admission or referral to higher centres) adjusted for site and severity of anaemia. The primary outcome was analysed in a modified intention-to-treat population, which excluded participants who refused to participate after randomisation, those who were lost to follow-up, and those whose outcome data were missing. Safety was assessed in both modified intention-to-treat and as-treated populations. The data safety monitoring board recommended stopping the trial after the first interim analysis because of futility (conditional power 1·14% under the null effects, 3·0% under the continued effects, and 44·83% under hypothesised effects). This trial is registered with the Clinical Trial Registry of India, CTRI/2012/05/002626. FINDINGS: Between Jan 31, 2014, and July 31, 2017, 2018 women were enrolled, and 999 were randomly assigned to the intravenous iron sucrose group and 1019 to the standard therapy group. The primary maternal composite outcome was reported in 89 (9%) of 958 patients in the intravenous iron sucrose group and in 95 (10%) of 976 patients in the standard therapy group (adjusted odds ratio 0·95, 95% CI 0·70-1·29). 16 (2%) of 958 women in the intravenous iron sucrose group and 13 (1%) of 976 women in the standard therapy group had serious maternal adverse events. Serious fetal and neonatal adverse events were reported by 39 (4%) of 961 women in the intravenous iron sucrose group and 45 (5%) of 982 women in the standard therapy group. At 6 weeks post-randomisation, minor side-effects were reported by 117 (16%) of 737 women in the intravenous iron sucrose group versus 155 (21%) of 721 women in the standard therapy group. None of the serious adverse events was found to be related to the trial procedures or the interventions as per the causality assessment made by the trial investigators, ethics committees, and regulatory body. INTERPRETATION: The study was stopped due to futility. There is insufficient evidence to show the effectiveness of intravenous iron sucrose in reducing clinical outcomes compared with standard oral iron therapy in pregnant women with moderate-to-severe anaemia. FUNDING: WHO, India.

Sepsis in Obstetrics Score (SOS) utility and validation for triaging patients with obstetric sepsis in the emergency department: Evidence from a low income health care setting.

BACKGROUND: Illness severity scores commonly used in critical care settings are not considered appropriate in obstetric practice as they do not account for pregnancy physiology. A new illness severity score called the 'Sepsis in Obstetrics Score' (SOS) was introduced by Albright et al. for triaging patients with sepsis in pregnancy in an emergency department setting. OBJECTIVES: We aimed to determine whether this score could predict the need for critical care support using the presence of organ failure as the identification criteria. Severity and culture positivity in pregnancy-associated sepsis was also assessed. MATERIALS AND METHODS: All pregnant, postabortal and postpartum women with suspected sepsis were enrolled (as per systemic inflammatory response syndrome criteria) were enrolled. Severe pregnancy-associated sepsis was defined as dysfunction of one or more organs due to sepsis. The severity of pregnancy-associated sepsis was graded according to the number of organ failures. A SOS cut off of 6 was taken for statistical analysis. RESULTS: Out of 100 women with pregnancy-associated sepsis, 'severe sepsis' was present in 58%. When the SOS test performance was compared with the severity of pregnancy-associated sepsis, it had sensitivity of 68.9% and specificity of 80.9%, positive predictive value of 83% and negative predictive value 65% to predict severe sepsis. The area under curve for the SOS detecting severe pregnancy-associated sepsis was 0.810. SOS predicted organ failure in pregnancy-associated sepsis and this was statistically significant for all organs involved. Culture positivity did not correlate with the SOS in our study. CONCLUSIONS: Sepsis in Obstetrics Score correlated well with organ failure in pregnancy-associated sepsis. It had a high positive predictive value (83%) for severe sepsis.

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.

Correlation of expression of aberrant immunophenotypic markers in T-ALL with its morphology: A pilot study.

INTRODUCTION: Aberrant expression of immunophenotypic markers is commonly found in patients of acute leukemia. T-ALL also shows aberrant markers such as CD13, CD33, CD117, CD10, and CD79a. Morphologically, T-ALL has been categorized into L1, L2, and L3 subtypes. Till now, no study has been done to correlate these markers with morphological features of T-ALL. This study aimed to correlate the expression of aberrant immunophenotypic markers with morphology in T-ALL. MATERIALS AND METHODS: All the cases of T-ALL diagnosed by flow cytometry over a period of 2½ year were taken out from the records of Hematology Section of Department of Pathology of University College of Medical Science and Guru Teg Bahadur Hospital and Max Hospital, Saket. Their peripheral blood smear was screened to correlate the morphology of blasts with the expression of aberrant markers. RESULTS: A total of 40 cases of T-ALL were identified during 2½ year period of our study. Morphological correlation was available for 23 cases. Aberrant expression of CD10 was present in 6 (35.3%) cases, CD79a in 9 (47.36%) cases, CD117 in 5 (42.28%) cases and myeloid antigen CD33 in 5 (38.46%) cases. CD117 and CD33-positive cases showed L2 morphology with the presence of convolutions, while cases with expression of CD79a had L1 morphology with absent-slight convolutions. CD10-positive cases had L1/L2 morphology with absent occasionally present convolutions. CONCLUSIONS: There seems to be an association of aberrant markers with L1 and L2 morphology. However, this needs to be tested for statistical significance on a larger sample size.

Serum ferritin <70 µg/L predicts functional iron deficiency in patients with chronic kidney disease.

Anemia is a common complication of chronic kidney disease (CKD) which is treated by erythropoiesis-stimulating agents. However, most of the patients do not respond adequately due to the development of functional iron deficiency (FID). The study was conducted to explore the value of inflammatory markers, high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) along with serum ferritin (SF) in the diagnosis of FID. Seventy-seven clinically diagnosed patients of CKD (Stage 3, 4, and 5) of either sex, age >18 years with hemoglobin <11 g/dL were included in the study. Complete hemogram with peripheral smear, serum iron, total iron binding capacity, transferrin saturation, SF, transferrin receptors (sTfR), hsCRP, IL-6, and erythrocyte sedimentation rate were estimated and statistically analyzed. sTfR/log ferritin (taken as gold standard) detected 31/77 patients as having iron-deficient erythropoiesis. Nineteen patients were detected as having FID. SF at a cut-off <70 µg/L showed the best sensitivity (83.87%) and specificity (73.91%) in detecting FID in these patients and identified 14/19 cases of FID. The 5 FID cases who were missed had raised hsCRP. The presence of raised hsCRP reduced the sensitivity to 79.16%. SF <70 µg/L emerged as the most sensitive and specific in the identification of iron-deficient erythropoiesis. SF >12 µg/L - SF <70 µg/L was able to identify 14/19 cases of FID. Furthermore, hsCRP further stratified the subgroup of CKD patients in which FID could be detected with higher sensitivity and specificity.

Hemostatic Abnormalities in Multiple Myeloma Patients

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases.

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.

Plasma Fibrinogen and D-dimer in Children With Sepsis: A Single-Center Experience.

BACKGROUND & OBJECTIVE: In sepsis, enhanced fibrin formation, impaired fibrin degradation, and intravascular fibrin deposition lead to a prothrombotic state. The current study aimed at measuring various coagulation parameters to predict an early marker for disseminated intravascular coagulation(DIC). METHODS: The current prospective study was conducted from January 2012 to April 2013 on 50 children aged 1-10 years with clinically suspected sepsis referred to the Department of Pediatrics of a tertiary care center in New Delhi, India. Patients were evaluated in accordance with criteria for acute infection (ie, symptoms less than seven days) confirmed in all patients in the laboratory. Patients receiving antibiotics 24-48 hours preceding admission were excluded from the study. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen, and D-dimer were measured at the time of admission in 50 patients and 50 controls. RESULTS & CONCLUSION: D-dimer was positive in 36 (72%) patients and negative in all controls. The difference was statistically significant (P<0.01). Plasma fibrinogen was significantly (P<0.01) higher in patients compared with the controls. It was decreased in 6% and increased in 8% of the patients, and normal in all controls.PT and APTT were significantly (P<0.01) higher in patients compared with the controls.Though none of the current study patients developed overt disseminated intravascular coagulation, the high positivity for D-dimer suggested that it should be measured in children with sepsis for early identification of DIC. This can aid better management as additional coagulation based therapy such as recombinant anti-thrombin and thrombomodulin may help to improve prognosis.

Morphological Changes in Bone Marrow Post Imatinib Therapy in Chronic Phase CML: A Follow up Study on Sequential Bone Marrow Aspirates and Biopsies.

INTRODUCTION: Imatinib mesylate is used extensively for first line treatment of Chronic Myeloid Leukemia (CML). However, not many studies have documented morphological changes in bone marrow biopsies produced during Imatinib therapy with reference to myelofibrosis. AIM: To document the morphological changes produced in the bone marrow during Imatinib therapy. MATERIALS AND METHODS: This longitudinal study followed up 75 Philadelphia Chromosome Positive Chronic Myeloid Leukemia with chronic phase(Ph+ CML- CP) patients sequentially, receiving 400-600mg Imatinib over a period of 12 or more months. Haematologic parameters were measured at admission, 2 weeks, 1 month, 3 months, 6 months and 12 or more months. Morphologic changes in bone marrow aspirate and biopsy were evaluated at admission, 6 months and ≥12 months of treatment in accordance with National Comprehensive Cancer Network(NCCN) guidelines. RESULTS: Complete Haematologic Response (CHR) was seen in 47.1%, 80%, 85.4%, 90.4% at ≥1 month, 3 months, 6 months and 12 months respectively after therapy. It was noted that patients not showing CHR by 3 months were less likely to show CHR at 6 months and beyond. Bone marrow aspirates and biopsies showed reduction in cellularity and myeloid precursors with regeneration of erythroid precursors in 70-83% at ≥12 months. A significant decrease in myelofibrosis (p-value< 0.04) was noted as early as 6 months. Mild to moderate hypoplasia was noted in 31.8% of biopsies within 6 months. Pseudo gaucher cells and benign lymphoid nodules were also seen. CONCLUSION: Sequential analysis showed that Imatinib reduced the grade of myelofibrosis significantly (p-value< 0.04). It also prevented development of myelofibrosis in patients who did not have it at presentation. Hence Imatinib is effective when used early in the course of CML-CP.