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Metabolites Oct 2023Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However,...
Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However, thiopurine S-methyl transferase (TPMT) plays a role in early toxicity in all thiopurines. We aimed to describe the hazards and opportunities of tioguanine use in inflammatory bowel disease (IBD) patients with aberrant TPMT metabolism and propose preventative measures to safely prescribe tioguanine in these patients. In this retrospective cohort study, all determined genotypes (2016-2021) were evaluated for aberrant metabolism (i.e., intermediate and poor TPMT metabolisers). Subsequently, all IBD patients on tioguanine with aberrant genotypes were evaluated for tioguanine dosages, adverse drug events, lab abnormalities, treatment duration and effectiveness. genotypes were determined in 485 patients, of whom, 50 (10.3%) and 4 patients (0.8%) were intermediate and poor metabolisers, respectively. Of these patients, 12 intermediate and 4 poor TPMT metabolisers had been prescribed tioguanine in varying doses. In one poor TPMT metaboliser, tioguanine 10 mg/day induced delayed pancytopenia. In general, reduced tioguanine dosages of 5 mg/day for intermediate TPMT metabolisers, and 10 mg two-weekly for poor TPMT metabolisers, resulted in a safe, long-term treatment strategy. Diminished or absent TPMT enzyme activity was related with a pharmacokinetic shift of tioguanine metabolism which is associated with relatively late-occurring myelotoxicity in patients on standard tioguanine dose. However, in strongly reduced dose regimens with strict therapeutic drug and safety monitoring, tioguanine treatment remained a safe and effective option in IBD patients with dysfunctional TPMT.
PubMed: 37887379
DOI: 10.3390/metabo13101054 -
Oxford Medical Case Reports Mar 2024We treated a 78-year-old Japanese man with gastric diffuse large B cell lymphoma. The patient received three courses of chemotherapy and involved-field local radiation...
We treated a 78-year-old Japanese man with gastric diffuse large B cell lymphoma. The patient received three courses of chemotherapy and involved-field local radiation therapy to the stomach. Three years after chemotherapy, the patient become sick with anorexia and pancytopenia. He was cachexic, however, levels of vitamin B12, folate, zinc, and copper were normal. His bone marrow revealed focal eosinophilic deposit characterized by mixture of vivid atrophic fatty cells, which was pathologically diagnosed as gelatinous bone marrow. The patient's gelatinous marrow was characterized by CD68-stained vivid atrophic fatty tissue. We found that this finding is a possible alternative marker for gelatinous marrow.
PubMed: 38532751
DOI: 10.1093/omcr/omae013 -
European Journal of Case Reports in... 2023Intravesical bacillus Calmette-Guérin (BCG) is used for urothelial carcinoma. Systemic side effects are rare and commonly include organ involvement but rarely include...
UNLABELLED
Intravesical bacillus Calmette-Guérin (BCG) is used for urothelial carcinoma. Systemic side effects are rare and commonly include organ involvement but rarely include bone marrow. We describe a patient who had received intravesical BCG and presented shortly afterwards with constitutional symptoms. Initial work-up revealed pancytopenia and immune haemolysis. He was presumptively diagnosed with systemic BCG infection and secondary warm autoimmune haemolytic anaemia. Isoniazid, rifampin and ethambutol was started. The bone marrow biopsy revealed granulomas. Within 6 weeks of treatment, the patient's clinic and laboratory results were dramatically improved. A high level of suspicion is crucial for diagnosis and treatment.
LEARNING POINTS
Systemic bacillus Calmette-Guérin (BCG) infection following intravesical BCG instillation is a rare but serious consequence. A high level of suspicion and scrutiny of history is of paramount importance for diagnosis.Autoimmune haemolytic anaemia secondary to systemic BCG infection is even rarer.Autoimmune haemolytic anaemia resolution was in parallel with improvement in systemic BCG infection.
PubMed: 37680784
DOI: 10.12890/2023_004009 -
Internal and Emergency Medicine Apr 2024Cytopenia is a common finding in patients admitted to internal medicine wards and the clinical workup may be long and time-consuming. In this single-center observational... (Observational Study)
Observational Study
Cytopenia is a common finding in patients admitted to internal medicine wards and the clinical workup may be long and time-consuming. In this single-center observational study, we analyzed a series of 151 inpatients who received hematologist referral due to cytopenia observed during hospital admission. Patients were mainly elderly (median 71 years, 15-96) and 87% had at least one comorbidity. Anemia was the most common cytopenia (91%), followed by thrombocytopenia (51%), and neutropenia (22%); 73 (48%) patients had a bicytopenia and 5 (3%) pancytopenia. Cytopenias were mainly severe, 66% of cases required RBC transfusions, and 21% platelet pools. During a median hospital stay of 15 days (1-166), 53 subjects (35%) received a hematologic discharge diagnosis, whilst the two-thirds had secondary cytopenia mainly due to associated comorbidities. Only about 34% of 2,728 diagnostic tests performed (including laboratory, imaging, and histology) clearly informed the discharge diagnosis in this heterogenous setting. Specifically, bone-marrow evaluation indicated in 46 (30%) patients, was diagnostic in 32 (69.6%). Eleven percent of patients died due to progression of the oncohematologic disease (29%), sepsis (24%), and solid tumor progression (24%). In conclusion, cytopenias in the internal medicine setting are mainly severe, more frequently secondary to associated comorbidities (2/3 of patients) and deserve proper workup before second/third-level tests (immune-hematological assays and CT scan or PET and bone-marrow evaluation, respectively).
Topics: Humans; Aged; Female; Male; Aged, 80 and over; Internal Medicine; Middle Aged; Thrombocytopenia; Pancytopenia; Adult; Anemia; Adolescent; Neutropenia; Cytopenia
PubMed: 38270774
DOI: 10.1007/s11739-023-03517-z -
IDCases 2023Strongyloidiasis is an opportunistic infection caused by the nematode helminth and transmitted mostly via soil. The disease is usually asymptomatic, limited, and...
Strongyloidiasis is an opportunistic infection caused by the nematode helminth and transmitted mostly via soil. The disease is usually asymptomatic, limited, and long-standing. Herein, we report a case of strongyloidiasis in a patient who seemed to be immunocompetent despite his malnourished appearance. He was presented with pancytopenia and aplastic anaemia and well responded to albendazole therapy with complete resolution of symptoms within three months. We recommend, prior to beginning of immunosuppressive regimens, it may be prudent to examine all patients presenting with abdominal discomfort along with pancytopenia for a possible worm infestation. Bone marrow suppression induced by worm infestation is an extremely rare but potentially comorbid condition that can lead to pancytopenia and severe aplastic anaemia.
PubMed: 37663134
DOI: 10.1016/j.idcr.2023.e01883 -
International Journal of Surgery Case... Oct 2023Sheehan's syndrome (SS) is a rare cause of hypopituitarism resulting from postpartum haemorrhage and pituitary necrosis. It remains an underdiagnosed condition,...
INTRODUCTION
Sheehan's syndrome (SS) is a rare cause of hypopituitarism resulting from postpartum haemorrhage and pituitary necrosis. It remains an underdiagnosed condition, especially in developing countries due to poor obstetric care and home deliveries. This case report highlights the significance of recognizing atypical presentations of SS, such as pancytopenia, to aid in early diagnosis and management.
CASE PRESENTATION
A 40-year-old female presented with acute abdomen symptoms and was initially diagnosed with acalculous cholecystitis. However, a detailed history revealed a history of postpartum haemorrhage 18 years prior, leading to a provisional diagnosis of SS. Further investigations confirmed panhypopituitarism, including hypothyroidism, hypocortisolism, and hypogonadism. Notably, the patient also exhibited pancytopenia, a rarely reported haematological manifestation of SS.
DISCUSSION
SS often presents with nonspecific symptoms, leading to delayed or missed diagnoses. In this case, the patient's initial presentation of acute abdomen symptoms was attributed to secondary adrenal insufficiency due to panhypopituitarism. The presence of pancytopenia, along with hyponatremia, further complicated the clinical picture. Hormone replacement therapy led to a remarkable improvement in the patient's condition, emphasizing the importance of early diagnosis and intervention.
CONCLUSION
SS is a common cause of panhypopituitarism in developing countries, but its atypical presentations, such as pancytopenia, are rare and often overlooked. This case highlights the need for increased awareness among clinicians to consider SS in patients with unexplained haematological abnormalities, particularly in regions with high rates of postpartum haemorrhage. Early recognition and appropriate hormone replacement therapy can significantly improve patients' outcomes and prevent long-term complications associated with this underdiagnosed syndrome.
PubMed: 37738831
DOI: 10.1016/j.ijscr.2023.108831 -
Clinical Case Reports Jan 2024In this case report we describe a patient with Grave's disease (GD) who was first diagnosed with pancytopenia and did not have any typical symptoms of GD. His...
KEY CLINICAL MESSAGE
In this case report we describe a patient with Grave's disease (GD) who was first diagnosed with pancytopenia and did not have any typical symptoms of GD. His hematologic abnormalities were alleviated after treatment with an anti-thyroid drug. Hence, in patients with pancytopenia, GD should also be considered.
ABSTRACT
A variety of hematologic abnormalities can be seen in Graves' disease (GD), however; here, we describe a patient with GD and a very rare complication; pancytopenia. His hematologic abnormalities and clinical status were alleviated after treatment with an anti-thyroid drug. Hence, in patients with pancytopenia and normal bone marrow examination, GD should also be considered.
PubMed: 38188850
DOI: 10.1002/ccr3.8312 -
Cureus Apr 2024Platelet count and its associated indices like mean platelet volume (MPV) and platelet distribution width (PDW) are cost-effective biomarkers that are easily accessible...
BACKGROUND
Platelet count and its associated indices like mean platelet volume (MPV) and platelet distribution width (PDW) are cost-effective biomarkers that are easily accessible and have a potent role in the diagnosis and management of thrombocytopenia. Since anaemia and thrombocytopenia often go together in pregnancy, it is advisable to utilise these indices for feto-maternal benefit.
MATERIAL AND METHODS
The study was conducted in the Department of Obstetrics and Gynaecology at a tertiary care centre in New Delhi from July 2022 to December 2023 wherein pregnant women of age 18-40 years, period of gestation >28 weeks with thrombocytopenia or abnormal platelet indices were enrolled. Women with pancytopenia, bone marrow suppression or past or current SARS-CoV-2 positive status were excluded.
RESULTS
A total of 150 women were enrolled in the study. The mean age of study population was 25.33 ± 2.90 (range 19-34) years. Subjects were divided into three groups - Group A (mild thrombocytopenia) 24.6%, Group B (moderate thrombocytopenia) 64.6% and Group C (severe thrombocytopenia) 10.6% based on thrombocytopenia severity. Analysing the risk factors, Group C was found to have a significantly higher number of patients with anaemia (p=<0.001), fever (p=0.031), abnormal liquor volumes (p=0.004) and need for blood and platelet transfusion (p=0.077). On correlation of thrombocytopenia with abnormal platelet indices, it was observed that manual platelet count (MPC) and MPV were indirectly correlated (p=0.027). PDW was found to be directly associated with severe thrombocytopenia and indirectly associated with moderate thrombocytopenia. Conclusion: Thrombocytopenia in pregnancy is directly correlated to factors like maternal fever and anaemia, fetal growth restriction, abnormal liquor, blood products and platelet transfusions. It was also concluded that platelet indices like PDW and MPV play an important role in predicting the feto-maternal outcome and hence timely interventions can be done to improve the same.
PubMed: 38803765
DOI: 10.7759/cureus.59156 -
BMC Nephrology Nov 2023Glomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops...
BACKGROUND
Glomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS.
CASE PRESENTATION
A 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68 foam cells (histiocytes) intermingled with many CD3 T-cells (predominantly CD8 cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8 cells (CD8, HLA-DR cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient's extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar.
CONCLUSION
To our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8 T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.
Topics: Male; Humans; Adult; Macrophage Activation Syndrome; Kidney Transplantation; CD8-Positive T-Lymphocytes; Kidney; Kidney Diseases; Lipidoses; Proteinuria; Triglycerides
PubMed: 37936128
DOI: 10.1186/s12882-023-03380-2 -
The Journal of International Medical... Dec 2023Gaucher disease is a rare, autosomal recessive disorder caused by inborn errors of metabolism. Globally, more than 27 million people are born each year, and...
Gaucher disease is a rare, autosomal recessive disorder caused by inborn errors of metabolism. Globally, more than 27 million people are born each year, and approximately 19,000 neonates are born with lysosomal storage disease. We report a rare case of Gaucher disease in an adult female patient of non-consanguineous parents in a subtropical area of Jiangxi Province, China. This area has a high prevalence of schistosomiasis. The diagnosis of this case posed a great challenge because of the possible differential diagnoses of pancytopenia with hepatomegaly and giant splenomegaly. The key component of the patient's diagnosis was her medical history in which it was documented that her brother had died of hepatocellular carcinoma of unknown origin. We diagnosed the patient through a combination of a pathological biopsy and imaging plus the patient's medical history.
Topics: Humans; Male; Adult; Infant, Newborn; Female; Gaucher Disease; Rare Diseases; Splenomegaly; Diagnosis, Differential; Liver Neoplasms
PubMed: 38150565
DOI: 10.1177/03000605231220887