Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 µg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

Absolute Neutrophil Count in Cases of Pancytopenia.

Pancytopenia is a common cause of hematological consultation. Common underlying causes include vitamin deficiency (vitamin B12, folic acid), drugs (hydroxyurea, phenytoin, methotrexate), and bone marrow failure syndrome. Aplastic anemia is one of the rarest hematological diseases and presents as pancytopenia. However, it is the most sinister one and is a hematological emergency that needs urgent medical attention. Absolute neutrophil count (ANC) is a measure of disease severity and is expected to be low in patients with pancytopenia of any cause. Aim & Objective: We aimed to analyze the absolute neutrophil count (ANC) level in patients presenting with pancytopenia. Material & Method: This prospective, observational study was conducted at a tertiary care hospital in northern India. We included patients with pancytopenia diagnosed at our center or reported to our center for therapy. ANC was measured before starting therapy. Observation: One hundred twenty-seven patients were included in this study. After evaluation, megaloblastic anemia was the commonest underlying cause in 42 (33%) patients followed by myelodysplastic syndrome in 31 (24.4%) patients. Twenty-three (18.1%) patients having pancytopenia were diagnosed with aplastic anemia. Other causes included leukemia, paroxysmal nocturnal hemoglobinuria and drugs. The median age was 37 years (range 18-75 years), and 67 (52.75%) were male. The mean hemoglobin was 5.5 g/dL (95% CI ±1.9). The median WBC was 2570/cmm (300-3130) and the median platelet was 36000/cmm (2000-92000). The median ANC in patients with aplastic anemia was 594/cmm (range 25- 3850). When compared, the ANC level was significantly lower in aplastic anemia than other causes of pancytopenia (p<0.001). Conclusion: On univariate and multivariate analysis ANC was significantly lower at baseline in patients of aplastic anemia. A longer follow-up of the patients will be required to assess the value of ANC in predicting response to therapy.

Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population.

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95 ± 17.16 pg/ml, controls: 70.55 ± 15.87 pg/ml, p < 0.001). G allele of 603A>G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p = 0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p = 0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738-2.651) and 4.41 fold (95% CI 1.404-13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.

Reversal of Glanzmann thrombasthenia platelet phenotype after imatinib treatment in a pediatric chronic myeloid leukemia patient.

Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm characterized by proliferation of Philadelphia positive clonal pluripotent hematopoietic cells. Bleeding is a rare presentation of CML that can occur due to platelet dysfunction. Both pre-treatment and post-treatment platelet function abnormalities in CML have been described in the literature. We describe a rare case of childhood CML who presented with mucocutateous bleeding manifestations. On laboratory workup, a Glanzmann Thrombasthenia (GT) like platelet phenotype was demonstrated along with confirmation of diagnosis of CML in chronic phase. The acquired nature of platelet function defect was confirmed by demonstrating recovery of platelet antigens glycoprotein IIb/IIIa after achieving complete hematological response with Imatinib. Due to presenting complaint of bleeding diathesis and absence of hepatosplenomegaly, the case was undiagnosed for CML until the patient reported to us. Careful evaluation of complete blood counts, peripheral blood picture and detailed laboratory workup was the window to proper diagnosis and treatment in this case.

Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India.

Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited. Significantly higher mean FVIII levels were observed in patients as compared to controls [patients: 132.3 ± 30.7 IU/ml, controls: 117.5 ± 17.7 IU/ml, p = 0.025]. A significant negative correlation was also observed between FVIII and APC ratio (Pearson correlation = 0.368, p = <0.001). Mean FV levels in patients [107.1 ± 13.1 IU/ml] and controls [102 ± 11.9 IU/ml] were not statistically significant (p = 0.119). Anti ß2 glycoprotein I (Anti-ß2-GPI, IgG) showed significant association with APCR phenotype (p = 0.050), unlike other factors such as protein C, protein S, lupus anticoagulant and anticardiolipin antibodies. The strong association of FVIII and anti-ß2 GPI (IgG) antibodies with APCR phenotype is suggestive of incorporation of these factors in APCR positive DVT patients in the absence of FV Leiden mutation in India. However more studies in large sample size are required for setting up the proper investigation protocol in these patients.

Chronic myeloid leukemia with a rare fusion transcript, e19a2 BCR-ABL1: A report of three cases from India.

The µ-bcr breakpoint connects exon 19 of BCR with ABL giving rise to the e19a2 transcript corresponding to the p230 fusion protein (micro-BCR breakpoint) which is rarely seen in chronic myeloid leukemia (CML) patients. Here we report three patients with p230 fusion protein presenting with different clinical presentations and diagnosed as CML-CP. These patients received Imatinib (tyrosine kinase inhibitor-TKI) and are still in remission.

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) masquerading as acute leukemia.

ABSTRACT: Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic drug reaction characterized by fever, rash, and lymphadenopathy associated with atypical lymphocytosis and eosinophilia. Visceral organ involvement is also seen and hence it often mimics hematolymphoid malignancies. A 19-year-old girl presented with generalized pruritic rash, fever, lymphadenopathy, and lymphocytosis. Subsequently, she developed respiratory distress with a fall in SpO2. Flow cytometry, bone marrow studies, and infectious workup were normal. Skin biopsy and clinical assessment criteria established the diagnosis of DRESS secondary to minocycline intake. Discontinuation of the offending drug is most important to abet the hypersensitivity reaction. Visceral organ involvement requires the use of steroids and immunosuppressive agents. Our patient responded well to treatment and is presently symptom-free and on follow-up for the last 6 months.

Rare complications of heart transplant: Autopsy findings.

BACKGROUND: Heart transplantation has evolved as the only treatment option for patients with refractory heart failure. CASE PRESENTATION: We here, report two unusual complications that developed following cardiac transplant to which the recipients succumbed. Post mortem conducted revealed the cause of death as severe antibody mediated rejection in one case and ruptured mycotic aneurysm of ascending aorta in the second recipient. CONCLUSION: Hence, autopsy remains the key procedure that can help establish the cause of death after cardiac transplant. It is also imperative for clinicians to have awareness and high index of suspicion for early detection of the ongoing complications and intervene either surgically or medically to prevent catastrophic events.

To Evaluate Platelet Indices, Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio as Prognostic and Risk Factors in Patients with Coronary Artery Disease.

To evaluate platelet indices, platelet to lymphocyte ratio and neutrophil to lymphocyte ratio as prognostic and risk factors in patients with coronary artery disease Introduction: cardiovascular diseases have 12 million deaths annually which is one of the commonest causes of death globally. Platelet parameters like Mean platelet volume (MPV), platelet distribution width (PDW) and WBC parameters like Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio(PLR) have recently been emerging as a new prognostic marker in number of coronary artery disease (CAD) with limited studies to explore their utility. AIMS AND OBJECTIVES: this study aimed to evaluate MPV, P-LCR, PDW, PLR, NLR and GRACE risk score in CAD patients. MATERIAL AND METHODS: this descriptive cross-sectional study was done in 330 cases of CAD and 200 healthy controls were studied.MPV, platelet-large cell ratio (P-LCR), PLR, NLR and PDW of patients were analyzed. RESULTS: In our study, 245 were males and 85 were females. Mean PDW, MPV, Mean PLCR, Mean NLR was significantly higher in CAD cases as compared to controls (p value < 0.05). Mean PLR was not significantly different in CAD cases and controls. MPV was more associated risk predictor of CAD (8.98 times) followed by NLR (2.79 times), PDW (1.53 times) and PLCR (1.02 times). DISCUSSION AND CONCLUSION: platelet indices, NLR and PLR are simple cost effective parameters and in future these might be useful adjuvant tests in conjunction with conventional biochemical cardiac markers in early prediction of risk of CAD in patients admitted to hospital and can guide clinicians in assessing the prognosis on short and long term follow up of these patients in terms of morbidity and mortality.

Medicinal plants traditionally used in health care practices by inhabitants of Paddar region of Jammu and Kashmir, India.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study is the first quantitative assessment of ethno-medicinal plants of Paddar region of Jammu and Kashmir. AIM OF THE STUDY: The study aimed to document the relative importance of medicinal plants used in human ailments by the villagers in the Paddar region of Jammu and Kashmir, India. MATERIAL AND METHODS: Data were collected from 132 informants (72 male and 60 female) through semi structured interviews and group discussions. Use report (UR) and Informant consensus factor (ICF) were employed to quantitatively examine the data. RESULTS: The inhabitants of Paddar reported the use of 98 plants species of 55 families to treat 63 ailments. Rosaceae (10 spp.) was the most frequently used family in the study area. Herbs were dominantly (66 spp., 50%) utilized in herbal preparation and leaves the mostly used plant parts (25%). The highest informant consensus factor (ICF = 0.96) was obtained for parasitic problems. Important new uses for species stated by informants to treat human diseases were; Viburnum grandiflorum Wall. ex DC., Sium latijugum C.B.Clarke, Corylus jacquemontii Decne., Capsella bursa-pastoris (L.) Medik., Cannabis sativa L., Taraxacum campylodes G.E.Haglund, Euphorbia helioscopia L., Juglans regia L., Cotoneaster acuminatus Lindl., Ficus palmata Forssk., Plantago lanceolata L., and Eleusine coracana (L.) Gaertn. CONCLUSIONS: The current study contributes towards the preservation of indigenous plants' based knowledge. Although the therapeutic value of most of the preferred medicinal plants has already been validated, some medicinal plants lack proper scientific validation. We recommend further phytochemical investigations and pharmacological validations of Viburnum grandiflorum, C. jacquemontii, F. palmata, Viola pilosa, Cotoneaster acuminatus, Eleucine coracana, Sium latijugum, Aquilegia pubiflora, Euphorbia helioscopia, Plantago lanceolata and Pinus gerardiana.

Medicinal plants traditionally used in the health care practices by the indigenous communities of the Trans-Himalayan region of Ladakh, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Ladakh, "the land of high-rising passes," is a cold arid desert located in the India's northernmost part of the Trans-Himalayan region. Traditional knowledge of medicinal plants in this fragile ecosystem is an important part of the primary healthcare system, particularly in remote areas where modern medical facilities are not fully operational. There is a need to update the traditional information on medicinal plants from time to time to understand any addition of plants or uses to assist in developing new drugs through pharmacological and phytochemical studies. AIM OF THE STUDY: The study was conducted to document the traditional knowledge and current therapeutic practices of the indigenous communities of Ladakh. Besides, the study strives to evaluate previous studies from Ladakh to identify plants that have not been previously reported for medicinal use. MATERIAL AND METHODS: Ethnomedicinal information was collected from 350 local informants through open and semi-structured questionnaires and field surveys in 35 villages of 8 regions of Ladakh. The primary data were analyzed for use reports (UR) and the informant consensus factor (ICF). The reported diseases were classified according to the International Classification of Primary Care-2 (ICPC-2). New reported medicinal plants and unreported medicinal uses in this study were identified and compared to 36 prior studies conducted in Ladakh. RESULTS: In the study, 176 medicinal plants belonging to 45 families and 131 genera were reported to treat 116 diseases of 16 (ICPC-2) groups with a total of 4841 use reports. Based on the highest use reports (UR), the most utilized species were Thymus linearis Benth. (134), followed by Aconitum heterophyllum Wall. (127) The highest informant consensus factor (ICF) was reported for Pregnancy, Childbearing, and Family Planning (ICF = 1) followed by respiratory (ICF = 0.91), and digestive (ICF = 0.90) disorders. Based on the comparative literature review, a total of 518 plant species (502 previously reported plus 16 newly cited) are being used in the Ladakh region. A total of 133 use reports for 16 newly cited plants using 30 diseases were recorded. The highest degree of overlapping of medicinal plants and uses for medicines was recorded in regions with comparable ethnicity, and shorter geographical distances. Based on the IUCN Red List, recorded medicinal plants include 7 critically endangered, 9 endangered, and 13 vulnerable species. CONCLUSION: Ladakh's indigenous populations use a diverse range of medicinal plants to treat a variety of illnesses. The introduction of species and medicinal uses not previously cited in the primary health care system demonstrates that shared knowledge of traditional medicine among Ladakhi is still rich. The medicinal value of preferred medicinal plants has already been validated, but some medicinal plants lack scientific validation. We recommend further scientific studies on Aconitum violaceum Jacquem. ex Stapf,Anaphalis nepalensis var. monocephala (DC.) Hand.-Mazz., Allardia nivea Hook. f. & Thomson ex C.B. Clarke, Atriplex hortensis L., Eriophyton tibeticum (Vatke) Ryding, Iris lactea Pall. and Rheum webbianum Royle.

Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea.

Paediatric primary myelofibrosis (PMF) is exceedingly rare and distinct compared with adult PMF. It is characterised by peripheral blood cytopenias, leucoerythroblastosis, reticulin fibrosis, extramedullary haematopoiesis and hepatosplenomegaly. In the absence of laid down diagnostic criteria, the diagnosis is largely of exclusion. Though early haematological stem cell transplant (HSCT) remains the treatment of choice, spontaneous remission or remission with steroids and/or cytoreductive agents is described in around 20% of cases of paediatric PMF. Moreover, HSCT in paediatric PMF is associated with high mortality (30%-45%). Therefore, it may be prudent to consider a trial of steroids and/or cytoreductive agents in all transfusion-dependent paediatric PMF while considering HSCT and ongoing bone marrow donor search. We describe one such infant with PMF who had complete remission of clinical and haematological parameters with a combination therapy of steroids and hydroxyurea.

Hematogones: The Supreme Mimicker and a Cytomorphological Confounder in Acute Lymphoblastic Leukemia.

Objective B-lymphocyte progenitors, namely the hematogones (HGs), may pose problems in morphological assessment of bone marrow, not only during the diagnostic workup but also while evaluating bone marrow for remission status following chemotherapy. Here, we describe a series of 12 cases of acute lymphoblastic leukemia (ALL) that included both B-ALL and T-ALL cases, which were evaluated for remission status and revealed blast-like mononuclear cells in bone marrow in the range of 6 to 26%, which on immunophenotypic analysis turned out to be HGs. Materials and Methods This is a case series of 12 ALL cases who were undergoing treatment at the Army Hospital (Referral and Research), New Delhi. All these cases were under workup for post-induction status (day 28) and to check for suspected ALL relapse. Bone marrow aspirate (BMA), biopsy, and immunophenotyping were performed. Multicolored flow cytometry was performed using CD10, CD20, CD22, CD34, CD19, and CD38 antibodies panel. Results BMA assessment of 12 cases revealed a maximum of 26% blastoid cells and a minimum of up to 6%, raising the suspicion of hematological relapse. However, on clinical assessment, these patients were well preserved, with preserved peripheral counts. Hence, marrow aspirates were subjected to flow cytometry using the CD markers panel, as discussed above, which revealed HGs. These cases were followed by minimal residual disease (MRD) analysis that revealed MRD-negative status, further confirming our findings. Conclusion This case series highlights the importance of morphology and bone marrow immunophenotyping in unveiling the diagnostic dilemma in post-induction ALL patients.

A Comprehensive Review on Phytochemistry and Pharmacology of Rosa Species (Rosaceae).

The Rosa L. genus is a significant plant family in the Rosaceae group, consisting of around 200 species, primarily shrubs. In India, it has 37 species, most located in the Western Himalayan region of Jammu and Kashmir and Himachal Pradesh. Roses are highly regarded for their beauty and growth and are popular worldwide for their nutritional, therapeutic, ornamental, and cosmetic value. The rose hips are utilized in creating various food and drink items, such as jams, jellies, teas, and alcoholic beverages. The Rosa species has various pharmacological activities, including anti-inflammatory, antidiabetic, hepatoprotective, antimicrobial, anti-proliferative/anticancer, anti-arthritic, neurological, and anti-obesity activity. This review aims to provide an in- -depth overview of the phytochemistry and pharmacology of the Rosa species in India, focusing on Rosa indica L., which has significant potential for future chemical and biological research.

Prevalence and Impact of HMOX1 Polymorphism (rs2071746: A > T) in Indian Sickle Cell Disease Patients.

Introduction Fetal hemoglobin (HbF) levels play significant role in lowering down the morbidity and mortality in sickle cell disease (SCD) patients. Coinheritance of heme oxygenase-1 (HMOX1) rs2071746:A > T polymorphism may contribute to variable HbF levels in Indian SCD patients. Objective This study was aimed to evaluate the role of HMOX1 polymorphism and its impact on HbF level in Indian SCD patients. Materials and Methods One-hundred twenty confirmed cases of SCD and 50 healthy controls were recruited. Their mean age was 11.5 ± 8.6 years (range: 3-23 years). Quantification of Hb, HbA2, HbF, and HbS was done by capillary zone electrophoresis. Allele-specific polymerase chain reaction was used to genotype HMOX1 (rs2071746:A > T) gene polymorphism. Results Out of the 120 cases of SCD, 65 were hemoglobin sickle-shaped (HbSS) and 55 were sickle-beta thalassemia (Sß). Out of 65 HbSS patients, 29 (44.6%) were heterozygous (AT), 20 (30.76%) were homozygous (TT), and 16 (24.61%) were found wild-type (AA) genotype. Out of 55 Sß, 22 (40%) were heterozygous, 18 (32%) were homozygous and 15 (28%) were wild-type. Patients carrying HMOX1 (rs2071746:A > T), AT, and TT genotypes had less anemia, painful crisis, splenomegaly, hepatomegaly, jaundice, and blood transfusion. HbF level was found higher in TT genotype (in HbSS the HbF levels was 25.1 ± 4.4; in sickle-beta thalassemia the HbF levels was 36.1 ± 4.7) than wild-type(AA) and was statistically significant ( p -value <0.001). Conclusion The TT genotype of the rs2071746:A > T polymorphism was associated with increased levels of Hb F ( p < 0.001). It can serve as a HbF modifier in Indian sickle cell diseases patients.

Development and analysis of de novo transcriptome assemblies of multiple genotypes of Cymbopogon spp. reveal candidate genes involved in the biosynthesis of aromatic monoterpenes.

Despite the high economic value of the monoterpene-rich essential oils from different genotypes of Cymbopogon, the knowledge about the genes and metabolic route(s) involved in the biosynthesis of aromatic monoterpenes in this genus is limited. In the present study, a comprehensive transcriptome analysis of four genotypes of Cymbopogon, displaying diverse quantitative and qualitative profiles of volatile monoterpenes in their essential oils has been carried out. The comparative analysis of the deduced protein sequences corresponding to the transcriptomes of the four genotypes revealed 4609 genotype-specific orthogroups, which might contribute in defining genotype-specific phenotypes. The transcriptome data mining led to the identification of unigenes involved in the isoprenogenesis. The homology searches, combined with the phylogenetic and expression analyses provided information about candidate genes concerning the biosynthesis of monoterpene aldehyde, monoterpene alcohol, and monoterpene esters. In addition, the present study suggests a potential role of geranial reductase like enzyme in the biosynthesis of monoterpene aldehyde in Cymbopogon spp. The detailed analysis of the candidate pathway genes suggested that multiple enzymatic routes might be involved in the biosynthesis of aromatic monoterpenes in the genus Cymbopogon. The present study provides deeper insights into the biosynthesis of monoterpenes, which will be useful for the genetic improvement of these aromatic grasses.

Correlation of Thrombosis and Clinicohematological Parameters with JAK2V617F Mutation in Philadelphia-Negative CMPNs: A Study from India.

Objective Philadelphia-negative chronic myeloproliferative neoplasms (CMPNs), which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by the presence of JAK2V617F (exon 14) mutation, and this occurs in 90 to 95% cases of PV and 50 to 60% cases of ET and PMF. Still, this is a matter of debate regarding the correlation of this mutation with thrombosis and clinicohematological parameters in CMPNs. So, we conducted this study to ascertain the association of JAK2V617F mutation with thrombotic complications and clinicohematological parameters of these patients. Materials and Methods This prospective and retrospective study was conducted during 2018 to 2019 at the Department of Laboratory Sciences and Molecular Medicine of a tertiary care hospital, and 160 CMPN patients were enrolled. Complete hemogram was done and DNA was extracted, followed by real-time qualitative polymerase chain reaction to check for JAK2V617F mutation. This mutation was then correlated with complications, mainly thrombosis, hematological parameters, and clinical parameters such as age and splenomegaly. Results Among 160 CMPN patients, 60 were females and 100 were males, with male to female ratio of 1:0.6, and age range of 27 to 85 years. Total 91 (56.9%) patients were JAK2V617F positive and the remaining 69 (43.1%) were negative for this mutation. We observed statistically significant correlation of leukocyte count, splenomegaly, and thrombosis in JAK2V617F-mutated patients as compared to unmutated patients. Conclusion This study emphasizes the importance of JAK2V617F mutation in CMPNs and stresses on its association with clinical, hematological phenotype, and thrombotic complications, which may open new horizons in prognostication and management protocol.

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.

Safety and efficacy of azathioprine in immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine. METHOD: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects. RESULT: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/µL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment. CONCLUSION: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Safety and efficacy of splenectomy in immune thrombocytopenia.

BACKGROUND: Immune Thrombocytopenia (ITP) is characterized by low platelet counts. Splenectomy has been in practice for the treatment of ITP since the early 20th century. We aimed to analyze the data of ITP patients from our hospital who underwent splenectomy and further present the long-term outcome and safety profile in these patients. METHOD: This study was a single-center, registry based study conducted at a tertiary care hospital in Northern India. Patients aged 18 years or more, who underwent splenectomy after at least one line of therapy, were included in the study. The primary outcome was the overall response rate (ORR) at one month after splenectomy. Secondary outcomes were sustained response, relapse-free survival, factors affecting the ORR, and adverse events after splenectomy. RESULTS: Forty-five patients of ITP were included in the study. Thirty-six patients underwent splenectomy in the first half (2001-2010), of the study period. The median age of the patients was 38 (19-56) years. The median duration from diagnosis to splenectomy was 1.76 (0.47-2.58) years. The median number of therapy received before splenectomy was 3 (1-6). The overall response rate (ORR) post-splenectomy at day 30 was 89.2% with 61.8% complete response (CR). The ORR was 88.5% at 1-year, with 48.8% CR. The relapse-free survival (RFS) at 5-years was 57.38% (95% Confidence Interval 40.59-71.02%), There was no effect of duration of disease, age, gender, and prior therapy received, on the ORR at one-month. At one year, the platelet response was significantly better in patients who had a CR at one-month than patients who had a partial response at one month. The relapse-free survival was better in patients who achieved CR after 1-month of splenectomy. During the median follow-up of 5.02 (1 month-20 years) years, there were five cases of overwhelming post-splenectomy infection (OPSI). There was no recorded incidence of perioperative mortality, deep vein thrombosis, or mesenteric thrombosis. DISCUSSION: Despite the variation in outcome from different studies, splenectomy gives the best possible long-term treatment-free remission amongst all the available second-line agents. It is also, one of the most financially affordable therapies. Despite advantages, the number of ITP patients undergoing splenectomy has been on the decline and largely attributable to the newer and more effective second-line therapies. There is no pre-surgery variable predicting the ORR after splenectomy. CONCLUSION: Splenectomy in ITP offers a long-term sustained response at an economical cost.