Fanconi anemia (FA) is a rare congenital disease associated with chromosomal instability, bone marrow failure, congenital anomalies, and predisposition to malignancies. It results primarily from mutations in genes of the Fanconi anemia/breast cancer-associated (FA/BRCA) DNA repair pathway. This pathway repairs defect in interstrand crosslink (ICL). FA shows an autosomal recessive inheritance in most cases, though other variants also exist. Clinically, FA manifests as pancytopenia, growth retardation, and skeletal malformations. These patients carry a significantly increased risk of development of acute myeloid leukemia and squamous cell carcinomas. Here we review the mechanisms involved in pathophysiology of FA. Understand the epidemiology and inheritance patterns of Fanconi anemia. Describe the clinical manifestations including hematological and non-hematological features in brief. Explain the molecular mechanisms underlying defective DNA repair in FA. Appreciate the implications of genotype–phenotype correlations and cancer predisposition.
Sickle cell anaemia (SCA) is a major public health challenge in Chhattisgarh, India, where approximately 10
Anti thymocyte globulin (ATG) is a polyclonal antibody primarily derived from rabbit, horse, or porcine sources, used to prevent or treat T-cell-mediated rejection, graft-versus-host disease (GVHD), and aplastic anaemia (AA). It has demonstrated efficacy in reducing both acute and chronic GVHD and improving graft survival in hematopoietic stem cell transplantation (HSCT) and solid organ transplant settings without affecting overall survival. Mechanistically, ATG depletes T-cells, modulates myeloid cells via PDL1 induction, and induces immune regulation. Rabbit ATG (rATG) is commonly used in organ transplants and HSCT. Horse or equine ATG (eATG) has proven efficacy in haematological disorders, particularly AA. Indigenous eATG (Thymogam) is widely used as part of immunosuppressive therapy (IST) in AA. Porcine ATG (pATG) is emerging as a therapeutic alternative in AA. Therapeutic drug monitoring (TDM) has potential to improve dosing precision and immune reconstitution. Future directions focus on optimizing dosing, personalization and expanding indications. Manufacturing of ATG is complex process and requires multilevel monitoring and quality control to ensure efficacy and safety of the products for human use. This article aims to summarise the developmental evolution, composition, mechanism of action, overview of clinical uses of ATG, dosing, administration, and monitoring strategies, including the role of TDM and a brief description of the manufacturing process and various quality aspects of ATGs for clinical use.
Aplastic anemia (AA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and hypo cellular marrow. While hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy remain the definitive treatment options for severe immune-mediated AA, most patients require immediate supportive care to stabilize clinical status, prevent complications, and bridge to definitive therapy. Key supportive strategies include phenotype-matched restrictive transfusion support, management of thrombocytopenia-related bleeding, leukoreduction and selective irradiation of blood components, iron chelation in transfusion-dependent patients, comprehensive infection prevention and timely antimicrobial therapy, vaccination planning, and psychosocial support. The role of androgens continues in selected patients, particularly in non-severe disease or resource-limited settings. Evidence-based supportive care is crucial to improving survival, reducing morbidity, and maintaining quality of life, especially in the Indian context where resource constraints influence therapeutic decisions. To understand the principles and rationale of supportive care in aplastic anemia. To review evidence-based strategies for transfusion support, infection prevention, and iron chelation. To recognize the role and limitations of vaccination, psychosocial support, and androgen therapy. To apply practical, context-specific supportive care approaches relevant to resource-constrained settings such as India.
Hemophilia A is an X-linked recessive bleeding disorder caused by deficient or dysfunctional Factor VIII (FVIII), with a global prevalence of approximately 1 in 5,000 males, including populations in Eastern India. The disorder disrupts normal hemostasis, resulting in spontaneous or trauma-induced bleeding. The incidence of FVIII inhibitors varies across regions of India. This bleeding tendency is attributed to either quantitative or qualitative defects in FVIII. Prior studies in India have emphasized the relevance of certain intronic polymorphisms—namely IVS7-SNP, Bcl-I (in intron 18), and Hind-III (in intron 19)—for carrier detection using linkage analysis. In a cohort of 345 unrelated Indian males with Hemophilia A, Amplification Refractory Mutation System (ARMS) primers were employed to evaluate allele frequencies of these polymorphisms. To assess the frequency of intronic polymorphisms IVS7-SNP (G/A), Bcl-I (T/A), and Hind-III (C/T) in the FVIII gene using PCR-Amplification Refractory Mutation System (PCR-ARMS) among Hemophilia A patients from Eastern India and evaluate their association with disease incidence, inhibitor development, and molecular variations. This study involved 345 male children from 205 unrelated families with Hemophilia A. Hematological assessments (CBC, PT, APTT, correction studies, and FVIII assays) were conducted. Genomic DNA was extracted and genotyped for the three polymorphisms using ARMS-PCR. Joint swelling (83.8
Hemoglobin E (HbE) is a prevalent hemoglobinopathy whose hematological profile can be significantly influenced by the co-inheritance of α-thalassemia trait (ATT) and iron deficiency anaemia (IDA). Understanding these interactions is crucial for the proper screening of anaemia in endemic regions.: To evaluate the independent effects of the ATT and IDA on red cell indices and HbA2 in HbAE and HbEE.Methods: A total of 319 subjects were analyzed. Multiplex GAP-PCR to detect seven common alpha deletions. A subset of 234 subjects with complete iron profile was subgrouped by alpha-mutation status (wild type vs. alpha-trait) and IDA status analysed separately. Univariate and multivariate model was used and Benjamini–Hochberg correction was applied to control type I error. Frequency of α-thalassemia in HbE syndrome was 19.8
Aplastic anaemia (AA) is a rare but potentially curable bone marrow failure disorder. With the advances in immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) the survival rates have reached 60–80
Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph + ALL) was historically associated with poor survival. The introduction of tyrosine kinase inhibitors (TKIs) has improved survival to 70–80
High-yield single donor platelet apheresis collections are on the rise to provide therapeutic doses, to maintain platelet inventory due to the shrinking donor pool, to reduce donor exposure, prevent complications and to mitigate costs. However, high-yield collections can affect donor haematological parameters, raising concerns regarding donor safety. This study was therefore done to assess the changes in haematological parameters among donors following double-dose plateletpheresis(DDP) and to see the agreement in the post-donation platelet count and Haematocrit(Hct) between the apheresis machine and post-donation sample analysed with standard automated haematology analyser. The study was conducted among 178 platelet apheresis donors who underwent DDP procedures using 3 different cell separators (Amicus, SpectraOptia,Trima). Pre and post donation haematological parameters, namely Haemoglobin (Hb), Hct, Platelet count, White Blood cell (WBC) count, Platelet Distribution Width (PDW) and Mean Platelet Volume (MPV), were analysed. Post-procedure Hct and platelet count were compared with those shown by the apheresis machine. There was a significant increase in Hb, Hct and WBC and decrease in platelet count following DDP. None of the donors had a platelet count less than 1lakh/µL. There was no agreement observed between post-donation Hct and platelet value shown by the apheresis machine with that from post-sample analysed by automated haematology analyser. DDP procedure is a safe and cost-effective procedure. Post donation counts shown by the apheresis machine, being a non-invasive way of ensuring donor safety, should be taken with caution. Recent guidelines on pre-donation platelet counts for double-dose collections should hence be followed strictly to ensure donor safety.
To explore the dynamic expression characteristics of serum cytokines in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and screen out independent predictive biomarkers for acute graft-versus-host disease (aGVHD), so as to provide the markers for early clinical prediction and targeted intervention against aGVHD. A prospective self-paired design and case series analysis were adopted to enroll 43 patients with hematological diseases who underwent allo-HSCT in our hospital from March 2023 to March 2025. Serum samples were collected before transplantation, on the 21st day after transplantation (early stage of hematopoietic reconstitution) and at the time of aGVHD occurrence. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of 11 cytokines including soluble growth stimulation expressed gene 2 protein (sST2) and interleukin-10 (IL-10). The differences in cytokine expression between aGVHD group and non-aGVHD group were compared, and univariate and multivariate Logistic regression analyses were used to screen independent predictive factors for aGVHD. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the biomarkers, and the dynamic changes of cytokines during aGVHD occurrence were analyzed. Among the 43 patients, 23 developed aGVHD (aGVHD group) and 20 did not (control group) within 100 days after transplantation, with no significant difference in baseline clinical characteristics between the two groups (P > 0.05). In the aGVHD group, the levels of sST2, Elafin, IFN-γ, sTNFR1, IL-10 and IL-17a on the 21st day after transplantation were significantly different from those before transplantation (all P < 0.05), while only IL-10 level in the control group had a significant change (P = 0.036). The increase amplitudes of sST2, IFN-γ, sTNFR1 and IL-10 in the aGVHD group were significantly higher than those in the control group (P < 0.05). Multivariate Logistic regression analysis showed that the change amplitude of sST2 (OR = 1.53, 95
Relapsed or refractory aplastic anemia (AA) remains a challenging clinical scenario despite significant advances in first-line therapy. AA is an immune-mediated bone marrow failure characterized by pancytopenia and hypocellular marrow. In adult patients, first-line immunosuppressive therapy (IST) with horse antithymocyte globulin (ATG) plus cyclosporine A (CsA) achieves hematologic response rates of 60–80
The activated partial thromboplastin time (aPTT) is widely used to monitor unfractionated heparin (UFH), but as a clot-based assay it is affected by variables that can dissociate it from the true anticoagulant effect. Chromogenic anti-factor Xa (anti-Xa) assays measure drug activity more directly. We retrospectively reviewed haematology consultations and laboratory records at a tertiary care hospital between July 2024 and June 2026. Four cases were purposively selected to illustrate mechanistically distinct causes of aPTT unreliability in which anti-Xa changed management. Discordance was defined as paired results falling into opposite therapeutic categories. The four cases were: postoperative pseudo-heparin resistance from acute-phase factor VIII elevation (anti-Xa 1.2 IU/mL with a prolonged but persistently subtherapeutic aPTT); residual apixaban activity in chronic kidney disease, estimated with an LMWH-calibrated assay; UFH monitoring during venovenous extracorporeal membrane oxygenation, where the aPTT varied from 35 to 112 s; and paediatric UFH monitoring, where an anti-Xa of 0.85 IU/mL accompanied a subtherapeutic aPTT. Anti-Xa results prompted dose reduction in two cases, a dose increase in a third, and determined surgical timing in the fourth. These cases illustrate the potential value of anti-Xa testing when the aPTT conflicts with the clinical picture. They are hypothesis-generating and do not establish superiority over aPTT monitoring.
Bone marrow aspirate and trephine biopsy examinations are indispensable components of the diagnostic workup for a wide spectrum of hematological and non-hematological disorders. An ideal bone marrow report should provide a comprehensive and integrated evaluation of all available specimens, including aspirate smears, imprint (touch) preparations, cytochemistry, and trephine biopsy sections. It should also indicate the need for further appropriate ancillary investigations such as immunophenotypic, cytogenetic, and molecular studies when indicated. These findings should be interpreted in conjunction with the clinical history and other relevant laboratory data to ensure an accurate, meaningful, and clinically relevant diagnosis, facilitate therapeutic decision-making, and support optimal patient management. This document provides practical recommendations for developing a standardized synoptic reporting format for bone marrow biopsy. The proposed framework is intended to be practical, reproducible, and readily implementable, thereby promoting uniformity, consistency, and quality in bone marrow reporting across India.
