Noppacharn Uaprasert

Elevated serum transferrin receptor levels in common types of thalassemia heterozygotes in Southeast Asia: A correlation with genotypes and red cell indices

BACKGROUND Serum transferrin receptor (sTfR) measurement is a helpful test for diagnosis of iron deficiency. Increased values are detectable in thalassemia syndromes due to increased erythropoiesis. However, sTfR has never been studied in hemoglobin E (HbE) carriers and their interactions with alpha-thalassemia heterozygotes that are common in Southeast Asia. METHODS We determined sTfR concentrations using a particle enhanced immunoturbidimetric assay in 113 early pregnancies without iron deficiency. RESULTS Patients were genotypically classified into 6 groups: 23 normal (mean sTfR+/-SD mg/l, 0.94+/-0.22), 14 alpha(+)-thalassemia heterozygotes (1.06+/-0.45), 21 alpha(0)-thalassemia heterozygotes (1.31+/-0.35), 30 HbE heterozygotes (1.11+/-0.26), 13 HbE heterozygotes with alpha(+)-thalassemia heterozygotes (1.09+/-0.32), and 12 HbE heterozygotes with alpha(0)-thalassemia heterozygotes (1.16+/-0.27). sTfR concentrations in all thalassemic groups were higher than controls, and significantly correlated with high red cell count, low MCV and MCH (p<0.001). When alpha(0)- or alpha(+)-thalassemia combined with HbE, sTfR concentrations were declined compared with alpha(0)-thalassemia or hemoglobin E, respectively, suggesting more balances in alpha- and beta-globin chain production. CONCLUSIONS Mildly increased erythropoiesis represented by increased sTfR concentrations in alpha-thalassemia and HbE heterozygotes and illustrated alpha- and beta-thalassemic gene interaction. These findings warrant further investigations on sTfR in diagnosis of iron deficiency in thalassemia carriers.

Risk factors for symptomatic venous thromboembolism in Thai hospitalised medical patients

Thromboprophylaxis for venous thromboembolism (VTE) failed to reduce overall mortality in hospitalised medical patients. As a VTE prediction model for Asians is still lacking, this study aimed to identify very high risk patients who would be the main target for prevention. In 2009, medical patients admitted to King Chulalongkorn Memorial hospital, a tertiary care centre, were prospectively evaluated for risk factors. The high-risk cohort was monitored for symptomatic VTE until six weeks after discharge. No heparin prophylaxis was given. Of 1,290 high-risk patients, 27 (2.1%, 95% confidence interval [CI] 1.3-2.9) developed proven VTE, 25.9% of which were diagnosed after discharge. Cases with VTE stayed longer in the hospital (median 18 vs. 11 days, p < 0.001). The significant risk factors in a multivariate analysis were autoimmune disease, solid tumours, family history of VTE, varicose vein and oestrogen with the relative risks of 11.8, 4.7, 120.3, 40.1 and 17.1 (p < 0.001, 0.001, 0.001, 0.002 and 0.038), respectively. Either autoimmune disease or solid tumours were found in 63% of VTE with the relative risk of 4.5 (95% CI 2.1-9.7, p < 0.001). In contrast, previously reported VTE scores in western patients could not stratify the VTE risks, but all the scores predicted higher mortality. In conclusion, VTE is common in Asian hospitalised medical patients. Patients with autoimmune disease and those with solid tumours are highly susceptible to VTE. A prophylactic strategy in these groups is required.

Diagnostic utility of isoelectric focusing and high performance liquid chromatography in neonatal cord blood screening for thalassemia and non-sickling hemoglobinopathies

BACKGROUND Thalassemia syndromes are highly prevalent in Southeast Asia. In Thailand, high performance liquid chromatography (HPLC) is the most common technique routinely performed in diagnosis of thalassemia and hemoglobinopathies, while isoelectric focusing (IEF) is rarely employed. We compared the diagnostic utility of IEF and HPLC in neonatal screening for thalassemia and non-sickling hemoglobinopathies. METHODS Two-hundred and forty-one cord blood samples were analyzed using IEF and HPLC, β-thalassemia short program. The results were correlated with red cell indices and molecular analyses. Hemoglobin (Hb) Barts was quantified only on IEF. RESULTS Of 241 newborns, IEF and HPLC yielded 85.4% and 76.4% sensitivity to identify α-thalassemia syndrome, respectively. HbBarts≥2% yielded 100% sensitivity to identify 2 α-globin gene deletions and/or mutations, while MCV≤95fl and MCH≤30pg yielded 100% sensitivity to identify 2 α-globin gene deletions. DNA analysis revealed HbE mutation in all 61 subjects with HbA2>1% on both IEF and HPLC. CONCLUSION IEF is an effective method in neonatal screening for thalassemia and non-sickling hemoglobinopathies. The HbBarts level, MCV and MCH are helpful for identifying α-thalassemia. The presence of HbA2 higher than 1% in cord blood indicates HbE carriers in Southeast Asian newborns.

Invasive pulmonary infection caused by Chrysosporium articulatum: the first case report

Chrysosporium species, saprobic soil fungi, comprise more than 60 species. There is some confusion regarding the taxonomy and nomenclature between Chrysosporium and Emmonsia since the causative agents of adiaspiromycosis, the development of big thick‐walled spores (adiaspores) in humans or animals, were previously thought to be Chrysosporium. Chrysosporium articulatum has never been reported to cause invasive infection in humans. We report herein the first case of invasive pulmonary infection caused by Chrysosporium articulatum in a 16‐year‐old man with acute T‐cell lymphoblastic leukaemia. He was successfully treated with voriconazole.

Comparison of diagnostic performance of the heparin-induced thrombocytopenia expert probability and the 4Ts score in screening for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a serious immunological complication of heparin administration. Diagnosis of HIT is challenging, especially in critically ill patients. The clinical scoring model for predicting HIT is helpful for guiding clinical decision. We analysed data of patients who underwent the heparin-induced platelet aggregation (HPA) test from 2006 to 2010 and compared diagnostic performance of the novel model HIT expert probability (‘HEP’), which has been validated in a population mainly comprising surgical patients first, by the previously published model ‘4Ts’ score. Clinical courses of the patients were also reviewed to ensure that HPA test results were accurate. There were 47 suspected HIT patients. The majority was from medical (70.2%) and/or critical care (61.7%) units. Ten (21.3%) yielded positive HPA. Among positive HPA patients, eight were medical patients. The HEP score ranged from −3 to 13, whereas the 4Ts score ranged from 3 to 7 in positive HPA patients. Both HEP and 4Ts scores were significantly higher in positive HPA than in negative HPA patients (5.35 vs. 1.81, P = 0.010 and 4.85 vs. 3.32, P = 0.001, respectively). The HEP score did not display better diagnostic performance than the 4Ts score, with receiver operating characteristic (ROC) area under curve of 0.72 and 0.79 (P = 0.31), respectively. The HEP score did not show better diagnostic performance than the 4Ts score for predicting HIT in our population. A large prospective validation in different sets of patients is warranted.

Hematological characteristics and effective screening for compound heterozygosity for Hb constant spring and deletional α+‐thalassemia

Hemoglobin Constant Spring (HbCS) is an unstable α-globin variant causing α-thalassemia phenotypes. The prevalence of compound heterozygosity for HbCS and deletional α + -thalassemia (HbCS/α + -thal) and its characteristics compared with HbCS heterozygosity have not been reported. We performed molecular analysis to detect α + -thal alleles in 75 HbCS heterozygotes and correlated with hematological characteristics. There were 34 HbCS heterozygotes (45.3%) carrying α + -thal. Hematological parameters of HbCS/α + -thal demonstrated lower Hb, MCV, MCH, and MCHC than HbCS heterozygotes, but higher HbCS levels. MCH was the most helpful variable in differentiating these two groups with ROC area under curve (AUC) of 0.927. MCH > 27 pg was able to exclude the presence of α + -thal, while MCH 27 pg was able to exclude the coinheritance with α + -thal, while MCH < 25.5 pg was an effective cut-off for predicting α + -thal with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 95.2%, 70.8%, 58.8%, and 97.1%, respectively. Therefore, this could be a cost-effective screening criterion to identify deletional α + -thal in HbCS heterozygotes avoiding expensive molecular testing.

Two cases of acquired haemophilia A associated with chronic myelomonocytic leukaemia.

Acquired haemophilia A (AHA) is an uncommon, but potentially fatal, bleeding diathesis caused by autoantibodies against circulating coagulation factor VIII (FVIII). The incidence is approximately 0.15 cases per 100 000 person-years. The underlying causes of AHA can be identified in approximately half of the patients, of which malignancies account for 10–20%. Heretofore, there has been only one case report of AHA concomitant with chronic myelomonocytic leukaemia (CMMoL), which previously was a subtype of the myelodysplastic syndrome. In this article, we report two more cases of AHA with CMMoL in our hospital and review possible causal relations between these two rare blood disorders.

Monocyte count associated with subsequent symptomatic venous thromboembolism (VTE) in hospitalized patients with solid tumors.

BACKGROUND Solid tumor is the strongest risk factor for VTE in Thai medical in-patients. This study aimed to identify the markers predicting symptomatic VTE in this group. METHODS Solid tumor patients admitted to the medical wards from June 2007 to December 2009 were monitored for VTE symptoms, excluding patients with VTE on admission. Anticoagulant prophylaxis was not given. Cases were all symptomatic VTE within 6 weeks after discharge. The controls were active solid tumor in-patients admitted in 2009 and did not develop VTE. The cases and controls were compared for the risk factors of VTE and complete blood count (CBC) on admission. RESULTS There were 28 radiology-confirmed VTE cases during the 2.5-year study period. There were 280 solid tumor patients without VTE as the controls. There was no difference in age (58.4 vs. 61.6 years), sex (53.6% vs. 64.3% male), presence of leg paralysis, acute infection and obesity between cases and controls, respectively. The cases showed higher absolute monocyte counts compared with the controls (0.76 vs. 0.56×10(9)/L, p 0.013), but there were no differences in other CBC parameters. In a multivariate analysis, cancer of unknown primary (Odds ratio [OR] 13.7, 95% confidence interval [CI] 2.74-68.7, p 0.001), biliary cancer (OR 6.6, 95% CI 1.80-24.3, p 0.004) and a monocyte count over 0.5×10(9)/L (OR 5.0, 95% CI 1.62-15.5, p 0.005) significantly associated with VTE. CONCLUSION Metastatic diseases with obscured primary sites, biliary carcinomas and higher monocyte counts on admission are related to subsequent VTE in hospitalized cancer patients.

Iron deficiency anemia interfering the diagnosis of compound heterozygosity for Hb constant spring and Hb Paksé: The first case report

Diagnosis of thalassemia or hemoglobinopathy concomitant with iron deficiency anemia (IDA) is challenging.