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RET-Y and RBC-Y in the diagnosis of iron deficiency associated with anaemia of inflammation

Jayaranee S, Sthaneshwar P

Int J Lab Hematol, 2010 Oct;32(5):512-8.
PMID: 20109166 DOI: 10.1111/j.1751-553X.2009.01215.x

We evaluated the usefulness of RET-Y and RBC-Y in distinguishing functional iron deficiency from iron-deficiency anaemia (IDA) in patients with anaemia of inflammation (AI). Sixty healthy blood donors constituted the control group. We studied RET-Y and RBC-Y in 115 patients with hypochromic/microcytic anaemia. Of these 42 patients had uncomplicated IDA and 73 had AI. The AI patients were further subdivided into AI with IDA and AI with functional IDA based on soluble transferrin receptor (sTfR) levels. The mean RBC-Y and RET-Y values in iron-deficient patients were 122.4 and 119.8, respectively, which were significantly lower than the control (P < 0.001). The mean level of RET-Y in patients with AI associated with IDA was 149.3 and this level in AI patients with functional iron deficiency was 147.4. RET-Y levels in both subgroups of AI patients were significantly lower than control but no significant difference was observed between the two subgroups. Similar findings were observed for RBC-Y. Receiver operating characteristic analysis also showed lower specificity for RBC-Y and RET-Y compared with that of sTfR and its log ferritin ratio (F-index). RET-Y and RBC-Y are useful in the diagnosis of simple IDA but have limited utility in the diagnosis of IDA with AI.
Fulltext Soluble transferrin receptor, ferritin and soluble transferrin receptor--Ferritin index in assessment of anaemia in rheumatoid arthritis

Pavai S, Jayaranee S, Sargunan S

Med J Malaysia, 2007 Oct;62(4):303-7.
PMID: 18551934

Anaemia of chronic disease (ACD) is a frequent complication of rheumatoid arthritis (RA). A diagnostic difficulty in RA is the distinction between iron deficiency anaemia (IDA) and ACD. The aim of our study was to evaluate the usefulness of serum soluble transferrin receptor (sTfR) and sTfR/log ferritin (TfR-F) index to diagnose iron deficiency in RA patients with anaemia. Routine laboratory indices of anaemia and sTfR were measured in 20 healthy persons to form the control group, 30 patients with iron deficiency anaemia and 28 RA patients with anaemia. Serum sTfR levels were significantly elevated above the cut-off value in patients with IDA and those in the iron depleted RA subgroup (ferritin < 60 microg/L) compared with those in the control and iron repleted RA subgroup (ferritin > 60 microg/L). The same was observed for TfR-F index. However, five patients in the iron repleted RA sub group had an elevated sTfR level, of which two had increased TfR-F index. Serum sTfR correlated well with the markers of anaemia and not with ESR. Ferritin had no correlation with markers of anaemia but correlated well with ESR. Measurement of sTfR and TfR-F index are good indicators of iron deficiency in RA patients with anaemia. To be cost effective, sTfR can be estimated in RA patients with anaemia when the ferritin level is more than 60 microg/L.
Chediak-Higashi syndrome: a case report

Jayaranee S, Menaka N

Malays J Pathol, 2004 Jun;26(1):53-7.
PMID: 16190108

A 5-month-old Chinese male infant was referred to the University Hospital, Kuala Lumpur for persistent fever, generalised rash and abdominal distension. Clinically he was suspected to have haemophagocytic lymphohistiocytosis. Haematological findings including the presence of several abnormal giant granules in neutrophils and single large azurophilic granules in many lymphocytes and monocytes in the peripheral blood established the diagnosis of Chediak-Higashi syndrome. The patient responded to allogeneic bone marrow transplant. This paper discusses the characteristic features, clinical course and management of this rare disorder. We suggest that peripheral blood film examination for the abnormal giant granules in granulocytes is an essential investigation in all young children with frequent recurrent infections or who are suspected to have virus-associated haemophagocytic syndrome or familial haemophagocytic lymphohistiocytosis.
Fulltext Serum soluble transferrin receptor in hypochromic microcytic anaemia

Jayaranee S, Sthaneshwar P

Singapore Med J, 2006 Feb;47(2):138-42.
PMID: 16435056

The objective of this study was to assess the clinical significance of soluble transferrin receptor (sTfR) in hypochromic microcytic anaemia.
Practice and performance of lupus anticoagulant tests: A single centre experience

Tay Za K, Jayaranee S, Shanmugam H

Malays J Pathol, 2020 Apr;42(1):51-57.
PMID: 32342930

INTRODUCTION: Lupus anticoagulant (LA) is a well-known risk factor for thrombosis. Correct diagnosis of LA is essential in patient management with anticoagulation. The objectives of this study were to document the clinical and laboratory characteristics of patients tested for LA and to evaluate existing LA testing methods in our laboratory with the aim of improving the performance of LA test interpretation and reporting.
METHODS: Tests for LA include dilute Russell's viper venom time (dRVVT) and Kaolin clotting time (KCT). Patients with LA ratio (dRVVT screen ratio/dRVVT confirm ratio) of ≥1.2 were considered as LA positive irrespective of KCT results. KCT was considered positive if there was a prolongation in KCT screening test which was not corrected on mixing with normal plasma.
RESULTS: Of 577 patients' results, 295 were normal, 178 were KCT positive with negative dRVVT and 104 were LA positive. Incidences of thrombosis, connective tissue disease (CTD) and bad obstetric events were noted in 13%, 16% and 44% of normal patients, 9%, 22% and 49% of KCT+ patients and 23%, 37% and 17% of LA+ patients respectively. On further evaluation of dRVVT screen ratios, 431 had a ratio of <1.1, 59 had a ratio between 1.1 and 1.2 and 87 had a ratio of >1.2. Positive LA results were found in 3%, 29% and 87% of patients with dRVVT screen ratios of <1.1, 1.1 - 1.2 and >1.2 respectively.
CONCLUSION: LA+ patients had higher incidences of thrombosis and CTD as compared to normal and KCT only positive patients. There was no significant difference in clinical characteristics between normal and KCT+ patients which suggests the presence of a high rate of false-positive KCT results. Since confirmatory testing for KCT is not widely used, the option of using another LA screening test method should be considered. In regard to dRVVT testing, confirmatory test should only be performed in patients with prolonged dRVVT screening result which was not corrected upon mixing with normal plasma as required by the International Society of Thrombosis and Haemostasis guidelines on LA testing. This practice will not only result in significant cost reduction but also avoid diagnostic confusion.
RBC-Y/MCV as a discriminant function for differentiating carriers of thalassaemia and HbE from iron deficiency

Nadarajan VS, Sthaneshwar P, Jayaranee S

Int J Lab Hematol, 2010 Apr;32(2):215-21.
PMID: 19566741 DOI: 10.1111/j.1751-553X.2009.01174.x

Individuals with alpha-thalassaemia (ATT), beta-thalassaemia (BTT) and HbE trait (HET) are often initially identified based on haematological parameters. However, the values of these parameters usually overlap with iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD). We evaluated the use of RBC-Y in 156 normal individuals and 332 patients; ATT (n = 37), BTT (n = 61), HET (n = 25), HbH disease (n = 5), ACD (n = 67), IDA (n = 83) and ACD with IDA (n = 54). Diagnostic efficiency was analysed by receiver operating characteristics (ROC). MCH was better compared with RBC-Y in discriminating normal from abnormal with sensitivity and specificity of 94% at a cut-off of 26 pg. The Green and King (G&K) index performed the best in discriminating carriers from IDA and ACD with area under the ROC curve (AUC(ROC)) of 0.81. However, if ACD was excluded, RBC-Y/MCV was a good discriminator for carriers from IDA with AUC(ROC) = 0.845. In general screening of populations with ATT, BTT and HET, we propose that hypochromic individuals be first identified by MCH <26 pg and carriers distinguished within these hypochromic individuals from IDA by using RBC-Y/MCV. However, if the prevalence of ACD were high within the screening population, G&K index would be a more suitable discriminator.
Serum prohepcidin concentrations in rheumatoid arthritis

Jayaranee S, Sthaneshwar P, Sokkalingam S

Pathology, 2009 Feb;41(2):178-82.
PMID: 18972320 DOI: 10.1080/00313020802436840

AIM: Hepcidin, a recently identified peptide, acts as a central regulator of iron metabolism. It is regarded as a factor regulating the uptake of dietary iron and its mobilisation from macrophages and hepatic stores. It is considered as a mediator of anaemia of inflammation. The aim of this study was to assess whether serum prohepcidin concentration is able to distinguish iron deficiency from anaemia of inflammation in patients with rheumatoid arthritis (RA).
METHOD: Blood samples were obtained from 20 healthy blood donors, 30 RA patients who presented with anaemia and 30 patients who had pure iron deficiency anaemia (IDA). The samples were analysed for full blood count, iron, ferritin, transferrin, soluble transferrin receptor and prohepcidin.
RESULTS: The mean prohepcidin level in the control subjects was 256 microg/L. The prohepcidin level was significantly lower in IDA patients (100 microg/L; p < 0.0001) but not significantly different from that of control in RA patients (250 microg/L; p > 0.05). Higher serum soluble transferrin receptor (sTfR) levels were observed in IDA (p < 0.0001) but not in RA compared with that of control (p > 0.05). RA patients were divided into iron depleted and iron repleted subgroups based on the ferritin level. Prohepcidin in the iron depleted group was significantly lower than the iron repleted group and the control (p < 0.0001) and higher levels were observed in the iron repleted group (p < 0.01). sTfR levels in the iron depleted group were significantly higher than the control and the iron repleted patients (p < 0.001). In the iron repleted group, sTfR level was not statistically different from that of control (p > 0.05).
CONCLUSION: Serum prohepcidin is clearly reduced in uncomplicated iron deficiency anaemia. The reduced prohepcidin levels in the iron depleted RA patients suggests that there may be conflicting signals regulating hepcidin production in RA patients. In RA patients who have reduced hepcidin in the iron depleted group (ferritin <60 microg/L) where sTfR levels are increased suggests that these patients are iron deficient. Further studies with a larger cohort of patients are required to substantiate this point.
Fulltext Immune haemolysis after renal transplantation secondary to ABO minor-mismatch between donor and recipient

Jayaranee S, Ramesh P, Nadesan V

Singapore Med J, 2002 Aug;43(8):421-2.
PMID: 12507029

Immune haemolysis following renal transplantation has been reported and known causes include infection, medication and metabolic disturbances (1,2). Autoimmune haemolysis after renal transplantation secondary to ABO minor mismatch is an uncommon but important cause that should be considered in the differential diagnosis of post-transplantation haemolysis. A case of haemolytic anaemia caused by graft versus host antibody formation is presented. We suggest that direct Coomb's test should be done as a routine in all cases of ABO mismatch renal transplantation and red cells compatible with both donor and recipient or group "O" packed cells should be transfused if transfusion is indicated.
An analysis of blood utilization for elective surgery in a tertiary medical centre in Malaysia

Jayaranee S, Prathiba R, Vasanthi N, Lopez CG

Malays J Pathol, 2002 Jun;24(1):59-66.
PMID: 16329557

The purpose of this study is to determine the efficiency of blood utilization for elective surgery at the University of Malaya Medical Centre (UMMC). A similar study conducted six years earlier in the same unit resulted in the introduction and implementation in December 1997 of the local Maximum Surgical Blood Order Schedule (MSBOS) and the Group Screen and Hold (GSH) procedure instead of a full crossmatch. This paper compares the findings of the current study with that conducted earlier.
Fulltext Acquired Factor VIII Inhibitors: Three Cases

Kyaw TZ, Jayaranee S, Bee PC, Chin EF

Turk J Haematol, 2013 Mar;30(1):76-80.
PMID: 24385759 DOI: 10.4274/tjh.2012.0009

Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients' ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time) to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed.
Modification to reporting of qualitative fluorescent spot test results improves detection of glucose-6-phosphate dehydrogenase (G6PD)-deficient heterozygote female newborns

Nadarajan V, Shanmugam H, Sthaneshwar P, Jayaranee S, Sultan KS, Ang C, et al.

Int J Lab Hematol, 2011 Oct;33(5):463-70.
PMID: 21501392 DOI: 10.1111/j.1751-553X.2011.01309.x

INTRODUCTION:
The glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test (FST) is a useful screening test for G6PD deficiency, but is unable to detect heterozygote G6PD-deficient females. We sought to identify whether reporting intermediate fluorescence in addition to absent and bright fluorescence on FST would improve identification of mildly deficient female heterozygotes.

METHODS:
A total of 1266 cord blood samples (705 male, 561 female) were screened for G6PD deficiency using FST (in-house method) and a quantitative enzyme assay. Fluorescence intensity of the FST was graded as either absent, intermediate or normal. Samples identified as showing absent or intermediate fluorescence on FST were analysed for the presence of G6PD mutations using TaqMan@SNP genotyping assays and direct nucleotide sequencing.

RESULTS:
Of the 1266 samples, 87 samples were found to be intermediate or deficient by FST (49 deficient, 38 intermediate). Of the 49 deficient samples, 48 had G6PD enzyme activity of ≤ 9.5 U/g Hb and one sample had normal enzyme activity. All 38 intermediate samples were from females. Of these, 21 had G6PD activity of between 20% and 60%, and 17 samples showed normal G6PD activity. Twenty-seven of the 38 samples were available for mutation analysis of which 13 had normal G6PD activity. Eleven of the 13 samples with normal G6PD activity had identifiable G6PD mutations.

CONCLUSION:
Glucose-6-phosphate dehydrogenase heterozygote females cannot be identified by FST if fluorescence is reported as absent or present. Distinguishing samples with intermediate fluorescence from absent and bright fluorescence improves detection of heterozygote females with mild G6PD deficiency. Mutational studies confirmed that 85% of intermediate samples with normal enzyme activity had identifiable G6PD mutations.
An audit of fresh frozen plasma usage in a tertiary referral centre in a developing country

Prathiba R, Jayaranee S, Ramesh JC, Lopez CG, Vasanthi N

Malays J Pathol, 2001 Jun;23(1):41-6.
PMID: 16329547

This paper evaluates the practice of fresh frozen plasma (FFP) transfusion at the University Hospital, Kuala Lumpur, and analyses its usage by the various clinical departments. The aim of this study is to identify where it is inappropriately used and the clinical indications in which such misuse is common. A retrospective analysis of the blood bank request forms and work sheets during a 6-month period between January 1998 and June 1998 formed the basis of this study. Overall, 40% of 2665 units transfused were considered appropriate. However, out of the 931 episodes of FFP transfusions only 31% were for appropriate indications. The average FFP requirement when used for appropriate indication was about 4 units per episode, whereas for inappropriate indication it was 2.5 units per episode. Inappropriate use in terms of the number of units was highest by the surgical services (68%) and Orthopaedics (64%), while the Department of Paediatrics had the lowest incidence of inappropriate use (40%). When Paediatrics was used as the benchmark, the incidence of inappropriate use by other departments was significantly higher (p < 0.01). As for FFP usage in common clinical indications, there was a high incidence of inappropriate use in burns (82%), perioperative period (73%), cardiac surgery (68%), massive bleeding (62%) and trauma (60%). The findings in this study, specifically the use of FFP for volume support in trauma, massive bleeding and burns, routine requests without identified indication in cardiac bypass surgery, and prophylactic use in the perioperative period can be the basis for recommendations to minimize the inappropriate use of FFP in the future.
Fulltext Anti-lymphocyte globulin therapy in aplastic anaemia--a university hospital experience

Leong KW, Teh A, Bosco JJ, Jayaranee S, Sadat U

Med J Malaysia, 1995 Jun;50(2):158-61.
PMID: 7565186

Antilymphocyte globulin (ALG) was given every other day for 5 doses with platelet transfusions immediately following ALG administration in 6 patients with aplastic anaemia. Four patients responded and 3 durable remissions were achieved. One patient relapsed and further treatment with anti-thymocyte globulin and cyclosporin also failed. One patient died of Flavobacterium septicaemia 6 days after completion of ALG. Our data suggests that using an alternate day regimen, a response rate similar to a daily regimen can be obtained.
Fulltext Acquired haemophilia--a therapeutic challenge

Teh A, Leong KW, Bosco JJ, Koong PL, Jayaranee S

Med J Malaysia, 1995 Jun;50(2):166-70.
PMID: 7565188

Acquired haemophilia is a rare clinical condition arising from the spontaneous development of inhibitors to factor VIII. We describe two cases encountered in the University Hospital over the past five years. We also review the literature and discuss the therapeutic difficulties faced in dealing with patients with high levels of inhibitors. In one of these patients we also describe, for the first time in this region, a novel method in managing the acute bleeding episode in acquired haemophilia using recombinant factor VIIa.

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