The diagnosis of iron deficiency in hospital patients can be difficult in the presence of inflammation. A raised serum transferrin receptor (sTfR) level is useful as a marker of iron deficiency as it is unaffected by inflammation. However, diseases that cause an increase in erythropoietic activity can also result in a raised sTfR level. In South-East Asia, the prevalence of thalassaemia trait is high. As thalassaemia trait is associated with ineffective erythropoiesis and therefore an increase in the sTfR level, we studied the influence of thalassaemia trait on the diagnosis of iron deficiency in hospital patients. Among 431 patients with different combinations of iron deficiency, alpha- and beta-thalassaemia trait, we found that the sTfR level is an excellent diagnostic test for iron deficiency only in patients without thalassaemia trait. alpha-Thalassaemia trait worsened its diagnostic accuracy and beta-thalassaemia trait rendered it a non-diagnostic test. We conclude that in populations with a high prevalence of thalassaemia trait, the sTfR level is not useful in diagnosing iron deficiency unless the patient's thalassaemia status is known.

Aplastic anaemia is a rare clinical syndrome associated with diminished or absent precursors in the bone marrow. Acquired aplastic anaemia secondary to human immunodeficiency virus (HIV) is very rare. We present a 71-year-old woman with severe aplastic anaemia secondary to HIV infection, which was after extensive exclusion of other causes. She achieved undetectable viral load after 5 months of combination antiretroviral therapy but remains profoundly pancytopenic, complicated by recurrent infectious and bleeding complications. HIV infection should be considered in patients with pancytopenia.

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Background: Slightly less than half of the patients with essential thrombocytosis (ET) and primary myelofibrosis (PMF) do not have specific gene mutations. Recent discovery of CALR mutation in JAK2V617F-negative ET and PMF patients have accounted for 20-25% of ET and PMF patients, and therefore redefining diagnostic approach to ET or PMF. Here we reported the incidence of CALR mutation and clinical features of clinically diagnosed Jak2V617F-negative ET and PMF in Singapore. Method: We retrospectively identified 140 cases of Jak2V617F-negative ET and PMF from two healthcare institutions in Singapore since 2006. Sanger sequencing was performed for the targeted detection of CALR exon 9 mutations. Clinicopathologic correlation was carried out by assessing relevant clinical data and the CALR mutation status, and compared with JAK2-positive cases (25 cases of ET and 9 cases of PMF). Results: The Jak2V617-negative ET/PMF patients were ethnic Chinese (76.2%), Malay (13.9%) and others (9.9%). CALR mutations were detected in 32.8% (40/122) of Jak2V617-negative ET and 55.6% (10/18) Jak2V617-negative PMF patients. Higher platelet count was observed in CALR-positive ET patients with median platelet count of 1056.5 x 109/L and 637.5 x 109/L for CALR-positive and -negative patients respectively (p<0.001). CALR-positive ET also required higher doses of hydroxyurea to maintain platelet count below 600 x 109/L (p=0.038). There was no difference in thrombotic events, presence of splenomegaly, presenting WBC count or hemoglobin (Hb) level between CALR-positive and -negative ET. However, when compared to Jak2-positive ET, Jak2-negative ET had a significantly lower incidence of thrombotic events (Jak2-negative ET, 8.2%; Jak2-positive ET, 50.0%, p<0.001), and lower Hb level (p<0.001). The incidence of thrombotic events in CALR-positive ET and PMF were 10.3% and 10.0% respectively. There was also no significant difference in presenting WBC count, platelet count, Hb level, presence of splenomegaly, or thrombotic event between CALR-positive vs -negative PMF. Lactic acid dehydrogenase (LDH) level at diagnosis however, was significantly higher in CALR-positive ET/PMF when compared to CALR-negative group (p=0.011). There was also significantly higher incidence of elevated peripheral blasts of >1% in CALR-positive ET/PMF (12% in CALR-positive and 3.3% in CALR-negative group, p=0.045). Blast transformation occurred in 6% of patients with CALR-positive PMF while only 1.1% in CALR-negative PMF. Besides the two commonly reported mutations (CALR52del, 30.8%; CALR5ins, 33.3%) in our screening of the CALR exon 9 in Jak2V617F-negative ET and PMF patients, 7 other novel mutations (c.1098_1137delinsTTTCTT, c.1102_1104delAAG, c.1122_1155delinsGGGCCAGGCACTTGTCG, c.1129_1153delinsCTTTGCGTTTCTTTT, c.1132_1155delinsTGTCG, c.1139delA, c.1141delG) were also found individually. All mutant CALR proteins possess an altered C-terminus with a longer peptide stretch caused by a disrupted reading frame due to these frameshift mutations. Conclusion: CALR mutation is common in Jak2V617F-negative PMF and ET in this multiracial Singaporean cohort, and has similar frequency when compared with Western report. It was associated with higher platelet count in ET, higher level of LDH and possibly a higher risk of blast transformation in PMF. 7 novel CALR mutations were identified and more subtypes of CALRmutation variants are expected to be uncovered in the near future. Disclosures No relevant conflicts of interest to declare.