Positive direct antiglobulin tests in cancer patients on immune checkpoint inhibitors: A case series from India.

Tumour cells activate immune checkpoints such as programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) signalling pathways to inhibit T lymphocyte activation and thus escape from immune surveillance. Immune checkpoint inhibitors (ICPis) reactivate T lymphocytes to recognize cancer cells by blocking CTLA-4 or PD-1. Autoimmune haemolytic anaemia is a rare, but often severe, complication of ICPis. Therefore, we performed a retrospective clinical case review, including serologic, haematology, and biochemistry laboratory results, of three patients who developed autoantibodies to erythrocytes following treatment with pembrolizumab, an anti-PD-1 inhibitor. Serologic testing of blood samples from these patients showed their red cells were positive for direct antiglobulin test (DAT + for IgG in two cases and IgG with C3d in one case). Antibody detection test was negative. No patient had clinical and laboratory features of haemolysis. There were no additional immune-related adverse events. IgG antibodies coating red cells were neither IgG1 nor IgG3 in class and elution was found negative in all. In conclusion, immunohaematology laboratories should be aware of the possibility of erythroid autoantibodies and their nature in cancer patients receiving ICPis. The result of a positive DAT should be interpreted carefully in these patients to exclude other possible causes of anaemia.

Evaluation of Vascular Health of E-Beta Thalassemia Patients: Effect of Iron Overload.

Hb E-ß thalassemia is the most common form of hemoglobinopathy in Southeast Asia and eastern India. Iron overload resulting from blood transfusion and increased intestinal iron absorption promotes the formation of reactive oxygen species (ROS), leading to oxidative stress, organ dysfunction, and tissue damage. Of these, cardiovascular complications are the leading cause of mortality. Impaired endothelial function is a biomarker of vascular health in patients with cardiovascular risks. Therefore, assessment of endothelial function is a useful prognostic tool. In the present study, 60 E- ß thalassemia patients and 60 healthy, age, sex matched control subjects were taken. The mean hemoglobin and ferritin of thalassemic patients were 7.43gm/dl and 1032 mcg/dl respectively. The vascular health was compared by measuring flow-mediated vasodialation (FMD), arterial elastic parameters, and carotid intima-medial thickness (CIMT). There was lower FMD (7.49%) and higher CIMT (0.46mm) in thalassemic group than control (10.52 % and 0.36mm respectively) (p value< 0.05). Also arterial stiffness is elevated and arterial distensibility is lower in thalassemic patients than control. Among the thalassemic patients FMD or CIMT did not correlate with serum ferritin value. So, the E- ß thalassemia patients had poor vascular health and are at a higher risk of developing atherosclerosis and cardio-vascular complication than normal population. The vascular dysfunction does not correlate with serum ferritin value, so regular monitoring with Doppler study is required for early diagnosis of subclinical atherosclerosis in this group of patients. However the effects of chelation therapy, Hydroxyurea, or other targeted therapies needs to be validated by further study.

The Impact of Thromboelastography on Blood Transfusion Policy in Adult Cardiac Surgery-A Retrospective Observational Study from Eastern India.

This study was conducted to determine the impact of thromboelastography (TEG) on blood transfusion policy regarding utilization and preparation of cryoprecipitate in adult cardiac surgery. The differences in total transfusion requirement, length of postoperative ICU stay and 24 h mortality were also studied after introduction of TEG in transfusion protocol. It was a retrospective, single-center, observational study conducted in adult patients underwent cardiac surgery from April 2008 to March 2016. Two thousand patients underwent surgery when TEG was used compared with 1000 control patients before availability of TEG. Significantly more patients in the TEG group versus the control group received cryoprecipitate (41 vs. 7%; p < 0.05), while fewer received a transfusion (60 vs. 87.5%; p < 0.05). Significant increase in cryoprecipitate preparation was observed after introduction of TEG. Patients underwent surgery in TEG group showed substantial reduction in administration of PRBC (2.1 vs. 3.5 U; p < 0.05); FFP (2.4 vs. 3.8 U; p < 0.05) and platelets (1.1 vs. 2.7 U; p < 0.05) compared to control group without compromising the length of ICU stay or postoperative mortality. A TEG-guided approach in adult patients undergoing cardiac surgery may increase the use of cryoprecipitate, while decreasing the overall requirement of blood transfusion.

Pancreatitis in Acute Promyelocytic Leukemia: Drug-induced or Differentiation Syndrome?

Acute promyelocytic leukemia (APL) constitutes about 15% of all acute myeloid leukemia patients and can now be treated even without any chemotherapy, with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Acute pancreatitis (AP) is a rare adverse event in APL, which is primarily reported to be secondary to hypertriglyceridemia. Here, we have reported AP developed in a patient of APL, during induction with ATRA and ATO, but it was not associated with hypertriglyceridemia. Rather, it was associated with respiratory distress and weight gain, coincidental leukocytosis, bilateral pleural effusion, and edematous pancreatitis without any necrosis. Hence, AP in this case is diagnosed to be a manifestation of differentiation syndrome, and it responded to steroid.

POEMS Syndrome with Biclonal Gammopathy: A Rare Association.

Polyneuropathy, Organomegaly, Endocrinopathy, M protein and Skin changes (POEMS) syndrome is rare plasma cell dyscrasia with multisystem involvement. The name comes from the five characteristic features: Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes. The presence of biclonal M band is a rare manifestation. Here, we are describing the cases of a 60-year-old lady, presented with bilateral pedal oedema and pericardial effusion and peripheral neuropathy. She also had hepatosplenomegaly, hyperpigmented rash and hypothyroidism and hyperparathyroidism. The serum protein electrophoresis and the immunofixation electrophoresis revealed two distinct monoclonal bands, immunoglobulin IgG kappa and IgA lambda. There was a mild increase in plasma cells and sclerotic bone lesion in pelvis. The POEMS syndrome is generally associated with lambda light chain restriction. The presence of biclonal gammopathy involving kappa and lambda is a rare manifestation. The pathogenic or prognostic role of different paraprotein is not known. Further studies are required to delineate such effect.

Disseminated Histoplasmosis in Immunocompetent Individuals- not a so Rare Entity, in India.

INTRODUCTION: Histoplasmosis is a rare fungal disease caused by dimorphic fungi Histoplasma capsulatum. The causative fungus persists in soil, infects through inhalation and manifests in three main types-acute primary, chronic cavitary and progressive disseminated histoplasmosis. Disseminated Histoplasmosis (DH) is defined as a clinical condition where the fungus is present in more than one location. Among the forms of histoplasmosis, DH is the rarest and mostly found in an immuno-compromised individual. Here we are presenting our experiences of the series of cases of DH in immuno-competent individuals who have been diagnosed in our institute in last 5 years. MATERIALS AND METHODS: This is a single centre retrospective observational study, conducted in Institute of Haematology and Transfusion Medicine, which is a referral centre for Eastern India, from May 2009 to April 2014. Only cases with DH in otherwise healthy immuno-competent individuals were included in the study. The histoplasmosis was confirmed either by presence of Histoplasma in biopsy specimen from an extrapulmonary organ or by positive growth in fungal culture. RESULT: Total seven patients met the inclusion criteria. Five out of 7 patients were male. The mean age was 35 years. Five of the 7 patients presented with fever for a long duration. Six patients complained of significant weight loss before diagnosis. On examination, one patient had skin nodules, five patients had hepato-splenomegaly, and two patients had lymphadenopathy. The laboratory investigations revealed anaemia in six out of 7 patients, and pancytopenia in 3 patients. Two patients had features of the hemophagocytic syndrome in the bone marrow. All patients were treated with conventional amphotericin B deoxycholate and azole antifungal. One patient with adrenal involvement died in hospital. The patient with skin nodule had recurrent relapses. The other patients had resolution of symptoms and were clinically cured. CONCLUSION: DH is not an uncommon aetiology of fever of prolonged duration even in immuno-competent individual and should be kept as a differential diagnosis. Targeted investigation through early bone marrow biopsy and fungal culture may help in the diagnosis of DH. Imaging study to exclude adrenal involvement prevents case fatality. Cytopenia may be due to a secondary hemophagocytic syndrome, which improves with anti-fungal therapy. Treatment with either amphotericin B or itraconazole gives excellent outcome though therapy may have to be given for a prolonged period in case of relapses.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE); a rare association with phyllodes tumour of breast.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare entity mainly found in elderly males. It is characterized by pitting edema mainly of dorsum of both hands giving a "boxing glove hand" appearance; rarely involving feet also, acute in onset, negative rheumatoid factor and a good response to low dose corticosteroid therapy. Clinically it almost resembles a case of polymyalgia rheumatica, late onset rheumatoid arthritis or other seronegative spondyloarthropathy.Though there are multiple underlying factors causing this rare entity but it has very close associations with many malignancies.So far its association with solid tumours and hematological malignancies has been reported. Phyllodes tumour of breast shows wide spectrum of activity from a benign condition to a locally aggressive and sometimes metastatic tumour.One fourth of the cases recur after definitive treatment.Our case represent an unusual association with recurrent phyllodes tumour of breast with RS3PE.

Nephropathy in association with annular psoriasis.

Occurrence of glomerular diseases in psoriasis is rare, although the number of reports is increasing in recent years. Different types of glomerular involvement have been reported but mesangioproliferative glomerulonephritis with IgA deposits, AA amyloidosis and membranous nephropathy are relatively common in association with psoriasis. The term 'psoriatic nephropathy' has been introduced recently. We contribute a case to the ongoing discussin regarding psoriatic nephropathy. Our patient had mesangio-proliferative glomerulonephritis (with IgG and C3 deposition) in association with annular psoriasis (rare variety of chronic plaque psoriasis). Presence of messangio-proliferative glomerulonephritis with IgG deposition is rare in association with psoriasis. The patient responded well to weekly methotrexate (15 mg) injection. Methotrexate has not been tried previously in psoriatic nephropathy or reported to be effective in it.

Hypokalemic periodic paralysis due to proximal renal tubular acidosis in a case with membranoproliferative glomerulonephritis.

Proximal renal tubular acidosis (pRTA) is a rare disorder. Hypokalemia may be associated with it; occasionally leading to features like hypokalemic periodic paralysis. Though pRTA is a tubulointerstitial kidney disease, glomerulonephritis may occasionally lead to pRTA by tubular damage through leaking proteins, cytokines or by inflammatory infiltrates. In our reported case a 27 year old male had recurrent episodes of hypokalemic quadriparesis. Investigations revealed features of pRTA including hypokalemia and non-anion-gap hyperchloremic metabolic acidosis. His urine pH dropped to 5 with NH4Cl loading test. Kidney biopsy showed membranoproliferative glomerulonephritis with tubulointerstitial damage. Hypokalemic periodic paralysis and pRTA are uncommon associations of membranoproliferative glomerulonephritis.