scholarly journals The Utility of Thiopurine Methyltransferase Enzyme Testing in Inflammatory Bowel Disease

2013 ◽  
Vol 27 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Laura Chisick ◽  
Curtis Oleschuk ◽  
Charles N Bernstein

OBJECTIVE: To assess the levels of red blood cell thiopurine methyltransferase (TPMT) in subjects with inflammatory bowel disease (IBD) and to determine how these levels impacted thiopurine dosing and leukopenia over the first six months of therapy.METHODS: A retrospective chart review was performed on all adult IBD patients (n=423, 88.2% Caucasian) who had TPMT levels measured by 11 participating gastroenterologists in Manitoba between 2008 and 2010. In addition to descriptive data, white blood cell count, dose and reason for discontinuation were analyzed for the first six months of therapy. Patients receiving ≥2.0 mg/kg of azathioprine (AZA) or ≥1.0 mg/kg of 6-mercapatopurine were considered to be ‘substantially’ dosed.RESULTS: Of the 423 patients, 8.3% had intermediate levels and 93.4% had normal levels of TPMT. Only one subject had a low level. A total of 216 patients had sufficient data to be included for full analysis. Patients with intermediate TPMT levels were generally started at lower doses of thiopurine than patients with normal TPMT levels (mean [± SD] 1.0±0.6 mg/kg versus 1.8±0.5 mg/kg). Of the subjects with normal TPMT levels, only 37.8% were dosed with ≥2.0 mg/kg of AZA. Each month, approximately 5% of subjects were leukopenic. These subjects received a mean overall AZA dose of 1.9±0.3 mg/kg and had a mean white blood cell count of 3.8±0.4×109/L.CONCLUSIONS: Normal TPMT levels did not prevent the development of leukopenia, although life-threatening leukopenia was rare. Physicians are not using TPMT levels to substantially dose thiopurines at the outset, which may limit the speed at which adequate doses are reached to facilitate remission.

2017 ◽  
Vol 39 (4) ◽  
pp. 399-405 ◽  
Author(s):  
Berrie Meijer ◽  
Abraham J. Wilhelm ◽  
Chris J. J. Mulder ◽  
Gerd Bouma ◽  
Adriaan A. van Bodegraven ◽  
...  

2021 ◽  
Vol 11 (3) ◽  
pp. 195
Author(s):  
Yitang Sun ◽  
Jingqi Zhou ◽  
Kaixiong Ye

Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60–0.95), 0.70 (95% CI: 0.54–0.92), and 0.85 (95% CI: 0.73–0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy.


2021 ◽  
pp. 247553032110007
Author(s):  
Eric Munger ◽  
Amit K. Dey ◽  
Justin Rodante ◽  
Martin P. Playford ◽  
Alexander V. Sorokin ◽  
...  

Background: Psoriasis is associated with accelerated non-calcified coronary plaque burden (NCB) by coronary computed tomography angiography (CCTA). Machine learning (ML) algorithms have been shown to effectively identify cardiometabolic variables with NCB in cross-sectional analysis. Objective: To use ML methods to characterize important predictors of change in NCB by CCTA in psoriasis over 1-year of observation. Methods: The analysis included 182 consecutive patients with 80 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative, a prospective, observational cohort study at baseline and 1-year using the random forest regression algorithm. NCB was assessed at baseline and 1-year from CCTA. Results: Using ML, we identified variables of high importance in the context of predicting changes in NCB. For the cohort that worsened NCB (n = 102), top baseline variables were cholesterol (total and HDL), white blood cell count, psoriasis area severity index score, and diastolic blood pressure. Top predictors of 1-year change were change in visceral adiposity, white blood cell count, total cholesterol, c-reactive protein, and absolute lymphocyte count. For the cohort that improved NCB (n = 80), the top baseline variables were HDL cholesterol related including apolipoprotein A1, basophil count, and psoriasis area severity index score, and top predictors of 1-year change were change in apoA, apoB, and systolic blood pressure. Conclusion: ML methods ranked predictors of progression and regression of NCB in psoriasis over 1 year providing strong evidence to focus on treating LDL, blood pressure, and obesity; as well as the importance of controlling cutaneous disease in psoriasis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tao Xiang ◽  
Ming Cheng

Abstract Background Enoxaparin is an anticoagulant that falls in the class of medications called low molecular weight heparins (LMWHs), and is used to prevent or treat patients with deep vein thrombosis (DVT) and pulmonary embolism. Enoxaparin is the most widely used LMWH for DVT prophylaxis following knee or hip replacement surgery. Common side effects of enoxaparin include bleeding, petechiae at the injection site, and thrombocytopenia. However, reactive thrombocytosis is a rarely reported adverse reaction. We managed a patient who developed enoxaparin-associated thrombocytosis, which was completely resolved after treatment cessation. Case presentation A 78-year-old female was hospitalized for post-hip replacement rehabilitation. Low molecular weight heparin 40 mg/day was administered subcutaneously to prevent deep venous thrombosis (DVT). At admission, her platelet count was normal (228 × 109/L) and her white blood cell count was slightly elevated (12.91 × 109/L). Seven days after admission, the patient developed thrombocytosis, which peaked on the 14th day (836 × 109/L), while her white blood cell count had returned to normal (8.86 × 109/L). Her therapeutic regimen was reviewed, and enoxaparin was identified as a potentially reversible cause of reactive thrombocytosis. Switching from enoxaparin to rivaroxaban lead to a gradual decrease in the patient’s platelet count, which eventually returned to normal levels 16 days after enoxaparin was discontinued. No complications secondary to thrombocytosis was observed, and no conclusion was reached on the use of small doses of aspirin for antithrombotic therapy under these circumstances. Conclusion Enoxaparin-induced reactive thrombocytosis should be suspected in patients with thrombocytosis following enoxaparin administration as an anticoagulant to prevent certain complications.


Author(s):  
Dustin E Bosch ◽  
Patrick C Mathias ◽  
Niklas Krumm ◽  
Andrew Bryan ◽  
Ferric C Fang ◽  
...  

Abstract Background An elevated white blood cell count (>15 thousand/μL) is an established prognostic marker in patients with Clostridium difficile infection (CDI). Small observational studies have suggested that a markedly elevated WBC should prompt consideration of CDI. However, there is limited evidence correlating WBC elevation with the results of C. difficile nucleic acid testing (NAAT). Methods Retrospective review of laboratory testing, outcomes, and treatment of 16,568 consecutive patients presenting to 4 hospitals over four years with NAAT and WBC testing on the same day. Results No significant relationship between C. difficile NAAT results and concurrent WBC in the inpatient setting was observed. Although an elevated WBC did predict NAAT results in the outpatient and emergency department populations (p<0.001), accuracy was poor, with receiver-operator areas under the curve of 0.59 and 0.56. An elevated WBC (>15 thousand/μL) in CDI was associated with a longer median hospital length of stay (15.5 vs. 11.0 days, p<0.01), consistent with leukocytosis as a prognostic marker in CDI. NAAT-positive inpatients with elevated WBC were more likely to be treated with metronidazole and/or vancomycin (relative ratio 1.2, 95% confidence interval 1.1–1.3) and die in the hospital (relative ratio 2.9, 95% CI 2.0–4.3). Conclusions Although WBC is an important prognostic indicator in patients with CDI, an isolated WBC elevation has low sensitivity and specificity as a predictor of fecal C. difficile NAAT positivity in the inpatient setting. A high or rising WBC in isolation is not a sufficient indication for CDI testing.


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