Haematology audit of 801 COVID-19 patients' basics and beyond- Prospective observational study.

Background and Objective: COVID-19 has become a major health concern since 2020. Its clinical presentation varies from asymptomatic cases to cases with respiratory failure needing ICU management. It has created a huge burden on limited health care resources. We need better understanding of the pathogenesis and interplay between virus and other factors which decide outcome. We seek biomarkers to predict severe illness to offer better triaging of patients to provide hospital-based care to the patients at risk of severe illness. Material and Methods: We took 801 consecutive RT-PCR-positive COVID cases coming to our center. Their hematological work-up, such as complete blood count, peripheral smear, reticulocyte count, and G6PD activity, was tested. The pattern of hematological abnormalities was assessed across disease severity groups to identify predictors of severe illness from basic investigation. Also, the interplay between iron deficiency and possible hemoglobinopathy trait and COVID was explored. Results Discussion and Conclusion: We found old age, male gender, diabetes, neutrophilia, lymphopenia, monocytopenia, and eosinopenia at presentation to be associated with moderate to severe illness and may help in triaging with other inflammatory and radiological parameters. We found thrombocytosis rather than thrombocytopenia as a predictor of severe illness. Our preliminary findings suggest the need to explore the protective role of hemoglobinopathy traits and iron deficiency against severe COVID illness.

Evaluation of utility of immunohistochemistry markers as a tool for objective diagnosis of low-grade myelodysplastic syndrome in routine reporting: Prospective observational study.

Purpose: Diagnosis of myelodysplastic syndrome (MDS) primarily relies on the detection of morphological dysplasia in bone marrow. It is subjective and many studies have reported lack of interobserver agreement in reporting. Biopsy is preferred specimen for megakaryocyte assessment. We studied 43 bone marrow biopsies from 40 suspected MDS patient having persistent undiagnosed cytopenia. Utility of immunohistochemistry (IHC) with CD61 and p53 in detecting low-grade MDS was analyzed over routine morphology. Method and Results: Total number of megakaryocytes and number of dysplastic megakaryocytes seen on CD61 IHC was significantly higher than that on H and E stain (P value < 0.05) Out of total 43 biopsies, 13 [30.2%] cases showed dysplastic megakaryocytes that were confirmed by interobserver agreement after IHC. From 30 cases with no significant dysplasia on morphology, 21/43 [48.8%] cases showed >10% dysplastic megakaryocytes on CD61 (P value 0.0001). Nine cases showed no significant dysmegakaryopoiesis with either H and E or CD61 IHC. Fourteen cases could meet higher cut off (30%) of dysmegakaryopoiesis with CD 61 IHC. Out of total 34 cases showing significant dysplasia 7 cases (20.6%) showed positivity for p53 on IHC, which is little less than that reported in low-grade MDS. Conclusion: CD61 IHC is helpful in making correct diagnosis of MDS in cases with minimal dysplasia and should be performed before excluding possibility of MDS on morphology in a patient with undiagnosed cytopenia. IHC is cost effective tool for MDS diagnosis in developing world where access to extensive flow cytometery and molecular testing is limited.

Study of Bone Marrow Lymphocyte Subset in Acute Myeloid Leukemia.

Introduction Acute myeloid leukemia (AML) is a heterogenous disorder consisting of clonal expansion of myeloblasts. Tumor immunity plays an important part in the pathobiology of AML. Understanding the components of tumor immunity is important for understanding tumor pathogenesis and the principles of immunotherapy. Methods We studied 41 patients with AML, for total lymphocyte, CD4 positive helper T cells, CD8 positive cytotoxic T cells, and CD16/56 positive natural killer (NK) cells proportion. Quantification was done on bone marrow aspirate sample by flowcytometry. Whenever available, post induction bone marrow was also analyzed for the lymphocyte subset. Results No significant difference was noted in the percentage of blasts among the three risk categories: favorable, intermediate, and adverse. However, there was significant difference in the total lymphocyte among the risk stratification groups, being highest in the favorable group and lowest in the adverse group. CD8 positive cytotoxic T cells were significantly less in Acute Promyelocytic Leukemia (APML) cases ( p = 0.001). Total lymphocytes were, however, more numerous in APML ( p = 0.005). NK cell proportion was not significantly different between APML and non-APML patients. On completion of induction chemotherapy, bone marrow samples for 12 patients could be processed for lymphocyte subset. On comparing the baseline against the post induction bone marrow, it was observed that there was significant increment in the proportion of CD4 positive T lymphocytes ( p = 0.046). Conclusion There is a difference in lymphocyte subset amongst patients with AML. Larger studies including functional aspects are needed to better define the role of lymphocytes in disease pathogenesis.

The Development of Ecchymosis after Administration of Convalescent Serum in a Patient with COVID-19 Associated with Thrombocytosis.

COVID-19 can have an unpredictable and severe course, leading to many hypotheses regarding its pathophysiology and clinical manifestations. Haematological manifestations are a significant predictor of disease severity. The most common observation is lymphopenia with an increased neutrophil:lymphocyte ratio. Platelets have been implicated in thrombogenic events, but the most frequently reported abnormality is mild thrombocytopenia. Here we present an interesting case of a patient with moderate COVID-19 who presented with cutaneous ecchymoses and thrombocytosis, and discuss this paradox. LEARNING POINTS: Bleeding manifestations such as ecchymoses can occur as an idiosyncratic reaction to the administration of convalescent plasma therapy in COVID-19.Thrombocytosis can occur in COVID-19 and could be a contributory factor to disease vasculopathy.

Inherited and acquired thrombophilia in women of Indian ethnicity with recurrent pregnancy loss: An observational study from North India.

OBJECTIVES: The spectrum of thrombophilia in women with recurrent pregnancy loss (RPL) is different in Indian ethnicity as reported by few studies. We aimed to study the prevalence of thrombophilia in RPL patients referred to hematology department of a tertiary centre. MATERIAL AND METHODS: This is an observational study of 112 RPL patients with no apparent cause after extensive workup for non-hematological causes. The investigations performed were routine coagulogram, APLA workup, plasma homocysteine, MTHFRC677T polymorphisms, Protein C, free Protein S, Anti-thrombin III levels, test for Activated Protein C resistance (APC-R) ,Factor V Leiden and Prothrombin gene G20210A mutation. RESULTS: Of 112 patients, at least one thrombophilia was identified in 70.5% and combined thrombophilia in 12.5% patients. Hyperhomocysteinemia (30.4%) and APLA (25.9%) were the commonest thrombophilia whereas anticoagulant defects were seen in 12.5% of the population. Protein C deficiency (5.35%) was the commonest anticoagulant defect followed by APCR (3.6%). Mutational analysis revealed MTHFRC677T polymorphism in 20.5% whereas Factor V Leiden heterozygous in 1.8% patients. None of the patients had homozygous Factor V Leiden or Prothrombin gene G20210A mutation. Hyperhomocysteinemia, MTHFRC677T and Protein C deficiency were more associated with early pregnancy losses whereas Protein S deficiency, Factor V Leiden and APLA caused both early and late losses. Patients with greater number of losses were positive for homozygous MTHFRC677T, factor V Leiden and APLA. CONCLUSION: The approach to investigating Indian women with RPL should be based on the prevalence of thrombophilia which is unique to Indian ethnicity.

A case of splenomegaly with RK-39 positivity: A diagnostic pitfall.

Long-standing moderate to marked splenomegaly suggests several differential diagnoses, both haematological and infectious, particularly leishmaniasis and malaria in endemic areas. Non-infectious causes may be missed in these regions, especially if pitfalls of serological testing are not considered. Careful patient evaluation is necessary to arrive at the correct diagnosis. We report a case of a young male whose hereditary spherocytosis was initially missed because of RK-39 positivity, splenomegaly and the fact that he hailed from an endemic region.

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients.

BACKGROUND: Tumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS. PATIENTS AND METHODS: We planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration. RESULTS: Fifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose. CONCLUSION: Single-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.

Approach to the Diagnosis of Amyloidosis.

Amyloidosis is heterogeneous group of disorder characterized by extracellular deposition of misfolded insoluble proteinaceous material with cross beta pleated sheet structure leading to organ dysfunction. This disease is rare and indeed heterogeneous, as it may be hereditary (familial amyloidosis), secondary to spectrum of inflammatory conditions (AA amyloidosis) or member of plasma cell neoplasm family (AL amyloidosis). AL amyloidosis is the most common type of amyloid, however, is rarely accompanied by multiple myeloma or other lymphoproliferative disorder. This disparity in its origin and presentation needs to be addressed by exhaustive battery of investigation tools, to arrive at right diagnosis with correct typing. This is of utmost importance in guiding the treating physicians to choose appropriate therapeutic options. This review deals with diagnostic approach to amyloidosis and its various subtypes.