A national common massive transfusion protocol (MTP) is a feasible and advantageous option for centralized blood services and hospitals.

BACKGROUND: A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals. METHODS: Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients. RESULTS: There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation. CONCLUSION: This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.

Ministry of health clinical practice guidelines: clinical blood transfusion.

The Health Sciences Authority (HSA) and the Ministry of Health (MOH) publish clinical practice guidelines on Clinical Blood Transfusion to provide doctors and patients in Singapore with evidence-based guidance for blood transfusion. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the HSA-MOH clinical practice guidelines on Clinical Blood Transfusion, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=25700). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Rapid reversal of coagulopathy in warfarin-related intracranial haemorrhages with prothrombin complex concentrates.

We report our initial experience using Profilnine SD, a 3-Factor prothrombin complex concentrate (PCC) in combination with fresh frozen plasma and vitamin K in seven patients admitted to our neurointensive care unit with oral anticoagulation therapy-related intracranial haemorrhage over a six-month period, to achieve rapid normalisation of the international normalised ratio (INR) and allow surgical evacuation when indicated. Four patients presented with subdural haematomas while three had intracerebral haematomas. Six of seven patients had admission INR in the appropriate therapeutic range for oral anticoagulation therapy. The median dose of PCC administered was 28.5 IU/kg body weight (interquartile range 21.3 to 38.5 IU/kg). All four patients with subdural haematoma underwent surgical evacuation once INR was less than 1.5. Median time from computed tomography diagnosis to surgery was 275 minutes (range 102 to 420 minutes). The median time to INR normalisation post-PCC administration was shorter, at 85 minutes (range 50 to 420 minutes) for the four patients who survived, versus 10 hours (range 9 to 44 hours) in the three patients who died. Two of the three patients who died had haematoma increase, worsening midline shift and subfalcine herniation, leading to withdrawal of therapy. Prothrombin complex concentrates should be considered for use in the urgent reversal of INR in oral anticoagulation therapy-related intracranial haemorrhage, potentially halting haematoma expansion and expediting urgent neurosurgical intervention, although data from randomised controlled trials is still lacking. The literature supporting the use of PCC is reviewed and a protocolised emergent treatment algorithm is proposed, which may help achieve earlier consistent normalisation of the INR.

Accuracy of serum transferrin receptor levels in the diagnosis of iron deficiency among hospital patients in a population with a high prevalence of thalassaemia trait.

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.

Accuracy of various iron parameters in the prediction of iron deficiency in an acute care hospital.

INTRODUCTION: Iron parameters like serum ferritin and iron saturation are routinely used in diagnosing iron deficiency. However, these tests are influenced by many factors. We aimed to review the accuracy of iron parameters among inpatients in an acute care hospital. MATERIALS AND METHODS: From October 1997 to April 2002, bone marrow aspirate samples from patients on whom concurrent iron studies had been done were analysed. Accuracy of the various iron parameters was analysed using receiver operating characteristic curves. RESULTS: Among 92 bone marrow aspirate samples, 58, 86 and 83 had a concurrent serum ferritin, serum iron and percentage iron saturation done respectively. Serum ferritin is the best marker for predicting the presence of iron deficiency. This is followed by percentage iron saturation and lastly by serum iron. At the most optimal, a serum ferritin of <60 ng/mL has a positive likelihood ratio of 24.35, sensitivity of 69.6%, specificity of 97.1% and positive predictive value of 94.1%. An iron saturation of <7% has a positive likelihood ratio of 21.62, sensitivity of 44.1%, specificity of 98.0% and positive predictive value of 93.8%. Seven out of 50 samples, which had concurrent measurements of iron saturation and serum ferritin, were discordant in indicating the presence of iron deficiency. In 6 cases, the iron saturation was the spurious result. CONCLUSION: A serum ferritin of <60 ng/mL or a percentage iron saturation of <7% is highly predictive of iron deficiency among inpatients in an acute care hospital.

Causes of isolated prolonged activated partial thromboplastin time in an acute care general hospital.

INTRODUCTION: To determine the causes of isolated prolonged activated partial thromboplastin time (APTT) in an acute care general hospital setting so as to rationalise fresh frozen plasma usage. METHODS: A prospective study of consecutive patients with isolated prolonged APTT presenting to our hospital between February 2002 and January 2004 was performed. All patients had normal prothrombin time and thrombin time. For all patients, an initial 50:50 correction with plasma was done and a standard panel of tests was performed. These included detection of lupus anticoagulant using two different sensitive tests; measurement of coagulant factors VIII (FVIII), IX, XI and XII, which are involved in the intrinsic arm of haemostasis; von Willebrand factor antigen (vWF:Ag) levels and for those with FVIII levels less than 10 percent, an inhibitor assay using the Nijmegen modification of the Bethesda method. RESULTS: 177 patients were included in the study. The cohort was typical of an acute care general hospital patient population in Singapore in terms of age, sex and racial distribution. The most common cause of an isolated prolonged APTT in our study was the presence of lupus anticoagulant (53.1 percent of cases). In 31.6 percent of cases, obvious cause could be detected after our panel of tests. These patients mostly had mildly prolonged APTT that could be both correctable and non-correctable by normal plasma. Prolonged APTT due to factor deficiency was relatively rare with those that may potentially cause haemorrhagic problems only accounting for 4.5 percent of cases. CONCLUSION: Our study suggests that most of the causes of isolated prolonged APTT do not lead to haemorrhagic complications. In fact, in a majority, it may signify an underlying thrombophilic condition. As a result, prolongation of APTT should be fully investigated and correction with fresh frozen plasma should be used only when appropriate.

Haematological parameters in severe acute respiratory syndrome.

Clinical presentation of severe acute respiratory syndrome (SARS) is non-specific and isolation of all suspected patients is difficult because of the limited availability of isolation facilities. We studied changes in haematological parameters in SARS patients using median values analysed according to the day of symptom onset. White cell (WCC), absolute neutrophil, absolute lymphocyte (ALC) and platelet counts followed a v-shaped trend with the nadir at day 6 or 7 after symptom onset except for ALC in the ICU group that had not reached the nadir by day 12. None of our patients had a platelet count < 80 x 10(9)/l and WCC < 2 x 10(9)/l in the first 5 days of symptoms and these parameters may allow early stratification of febrile patients into likely and unlikely SARS cases to allow effective utilization of isolation facilities. On multivariate analysis, age is the only independent predictor for ICU admission.

CD4 lymphocyte enumeration in patients with human immunodeficiency virus infection using three-colour and four-colour dual-platform flow cytometry: an inter-laboratory comparative evaluation.

INTRODUCTION: This study aims to evaluate the correlation and agreement between 2 methodologies of CD4 lymphocyte enumeration. MATERIALS AND METHODS: Fifty-two blood samples from patients with human immunodeficiency virus (HIV) infection were sent for CD4 lymphocyte enumeration at 2 major hospitals using dual-platform flow cytometry where the absolute lymphocyte counts were determined on separate haematology analyzers. CD4 cell enumeration was accomplished using 3-colour flow cytometry on the FACSCalibur cytometer (Becton Dickinson) in Hospital A and 4-colour flow cytometry on the Coulter Epic XL cytometer (Beckman Coulter) in Hospital B. The percentages and absolute counts of CD4 lymphocytes obtained were analysed using both linear regression and Bland-Altman plots. RESULTS: On linear regression plots, the total white cell counts, absolute lymphocyte counts, CD4 lymphocyte percentages and absolute CD4 counts from the 2 hospitals correlated well with correlation coefficients, r > 0.95. On the Bland-Altman plots, there was a mean difference of 0.13 x 10(9)/L and 0.06 x 10(9)/L in the total white cell and absolute lymphocyte counts from the 2 hospitals respectively. The CD4 lymphocyte percentages revealed a mean difference of only 0.05% (95% limits of agreement, -3.6 to 3.7%) but there was a mean difference of 14/uL in the absolute CD4 lymphocyte counts (95% limits of agreement, -113 to 142/uL). CONCLUSIONS: The CD4 lymphocyte percentages obtained using the 3-colour and 4-colour flow cytometry correlated and agreed well. However, the absolute CD4 lymphocyte counts obtained using the dual-platform technique in both the hospitals did not agree well. Hence, absolute CD4 lymphocyte counts from the 2 hospitals cannot be used interchangeably in clinical practice due to poor inter-laboratory comparability.

Morbidity after a bite from a 'non-venomous' pet snake.

We report the first recorded case of morbidity from the bite of a red-neck keelback snake (Rhabdophis subminiatus) from South East Asia. This is a species of the Colubrid family which originated from South East Asia. Severe envenomation from this snake was reported as poisonous in the West as far back as 1978 but it is still being classified as non-venomous. This classification led our patient to keep this 'harmless' snake as a pet. We recommend that this snake be reclassified as 'venomous' or at least warnings be issued to the public not to keep it as a pet.

Identification and characterization of two missense mutations causing factor XIIIA deficiency.

In this study, two amino acid substitutions, Arg260His and Val414Phe, have been identified in the factor XIIIA subunits of factor XIII deficient patients of Syrian and Indian descent, respectively. To confirm the deleterious effects of these substitutions, both variant sequences have been engineered into cDNA clones and the mutant enzymes expressed in yeast. Determination of the transglutaminase activity and immuno detection of the mutant enzymes together with mRNA hybridization revealed that the mutations dramatically reduce both the catalytic activity and the level of enzyme expressed in yeast. The mutations Arg260His and Val414Phe occur within the 'core' domain of the enzyme. Computer modelling of the mutant enzymes reveals that the substitution of the Arg260 by His results in the loss of a conserved electrostatic interaction whereas the effect of the Val414Phe substitution is a consequence of the large increase in side-chain volume. Although both mutations do not effect the active site directly, they are predicted to reduce the stability of the enzyme. The effects of these two amino acid substitutions on enzyme expression and three-dimensional structure strongly confirm that residues which are located outside of the active site can have a significant effect on protein stability and function.

Cardiovascular risk factors in relation to cigarette smoking: a population-based survey among Asians in Singapore.

To investigate how cigarette smoking increases the risk of cardiovascular disease, risk factors were compared between 166 cigarette smokers and 312 non-smokers, in a random sample of males (Chinese, Malays and Asian Indians) aged 30-69 years from the general population of Singapore. There was adjusted for age and ethnic group. The prevalence of hypertension was lower in cigarette smokers (15.2%) than non-smokers (21.9%), with the difference reduced by adjustment for body mass index (BMI). Smokers had: lower mean serum HDL-cholesterol (0.76 versus 0.81 mmol/l) and higher mean serum fasting triglyceride (1.92 versus 1.71 mmol/l), which will increase atherosclerosis; higher mean plasma fibrinogen (2.75 versus 2.67 g/l) and plasminogen activator inhibitor 1 [PAI-1] (24.9 versus 22.2 ng/ml), which will increase thrombosis; and lower mean plasma vitamin C (4.4 versus 6.4 mg/l) and serum selenium (118 versus 123 microg/l), which may increase atherosclerosis. Adjustment for BMI slightly increased the differences for HDL-cholesterol, fasting triglyceride, fibrinogen and PAI-1, indicating that less generalised obesity among smokers reduces their increased cardiovascular disease risk. Smoking was not found to be related to: diabetes mellitus; serum total cholesterol, LDL-cholesterol, apolipoproteins A1 and B and lipoprotein(a); plasma factor VIIc and prothrombin fragment 1 + 2; and plasma vitamins A and E and serum ferritin. There was no evidence of increased insulin resistance in smokers, as measured by mean fasting serum insulin.

Structuring a safer donor-replacement program.

BACKGROUND: Replacement donors are more likely than volunteer donors to have positive or abnormal tests for transfusion-transmissible disease. In an effort to increase the donor pool, workers sought to identify a safer replacement-donor subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS: In a retrospective review and cohort study, the replacement-donor effect was separated from the new-donor effect. The relative effect the replacement donor has on the risk of transfusion-transmissible diseases, donor retention, and frequency of returning donations was then quantified by comparison against the effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times the risk and 0.72 times the donor retention rate and made 0.81 times as many returning donations as the repeat volunteer donor. The figures for the new-donor effect were similar. The two risks were additive, making a new replacement donor particularly hazardous. If replacement donations only from repeat replacement donors were considered, the donor risk and the number of donations per returning donor were made comparable to those for the general (combined) volunteer donor. CONCLUSION: The negative effect of the replacement donor is similar in magnitude to that of the new volunteer donor. A replacement-donation program targeting repeat replacement donors has an acceptable risk profile and may be a valuable adjunct to the collection of blood from general volunteer donors.

Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore.

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.

A comparison between intravenous iron polymaltose complex (Ferrum Hausmann) and oral ferrous fumarate in the treatment of iron deficiency anaemia in pregnancy.

Anaemia is the most common medical disorder in pregnancy with iron deficiency anaemia accounting for the majority of cases. Over 90% of the iron deficiency anaemia is due to red cell iron deficiency associated with depleted iron stores and deficient intake. The two main modalities of treating iron deficiency anaemia are oral or parenteral iron. Ferrous Hausmann (iron dextrin) is the latest iron preparation which can be used for intravenous parenteral administration as a total dose infusion. This study compares the efficacy of Ferrum Hausmann with oral ferrous fumarate therapy in the treatment of iron deficiency anaemia in pregnancy. Our study shows that treatment with intravenous Ferrum Hausmann (iron dextrin) resulted in a significantly better level and rate of increase of haemoglobin (p<0.001). Serum ferritin, which is the best indicator of iron stores, was significantly higher (p<0.001) in the intravenous group. Other indices of iron status such as serum iron, serum transferrin and zinc protoporphyrin also showed a significant improvement in the intravenous group compared to those given oral iron. The results suggest that intravenous iron as a total dose infusion is able to replenish iron stores more efficiently, completely and at a faster rate than oral iron therapy, thus providing the fuel for stimulation of full erythopoiesis compared to oral iron. There were also no reports of any adverse reactions with intravenous iron dextrin, whereas there were a considerable proportion of women on oral iron therapy who reported side effects. In conclusion, intravenous iron therapy with Ferrous Hausmann (iron dextrin) is a suitable, effective and safe alternative to oral iron therapy in the treatment of iron deficiency anaemia in pregnancy.

Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore.

STUDY OBJECTIVE: To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is at least partly explained by central obesity, insulin resistance, and syndrome X (including possible components). DESIGN: Cross sectional study of the general population. SETTING: Singapore. PARTICIPANTS: Random sample of 961 men and women (Indians, Malays, and Chinese) aged 30 to 69 years. MAIN RESULTS: Fasting serum insulin concentration was correlated directly and strongly with body mass index (BMI), waist-hip ratio (WHR), and abdominal diameter. The fasting insulin concentration was correlated inversely with HDL cholesterol and directly with the fasting triglyceride concentration, blood pressures, plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA), but it was not correlated with LDL cholesterol, apolipoproteins B and A1, lipoprotein(a), (Lp(a)), fibrinogen, factor VIIc, or prothrombin fragment (F)1 + 2. This indicates that the former but not the latter are part of syndrome X. While Malays had the highest BMI, Indians had a higher WHR (men 0.93 and women 0.84) than Malays (men 0.91 and women 0.82) and Chinese (men 0.91 and women 0.82). In addition, Indians had higher fasting insulin values and more glucose intolerance than Malays and Chinese. Indians had lower HDL cholesterol, and higher PAI-1, tPA, and Lp(a), but not higher LDL cholesterol, fasting triglyceride, blood pressures, fibrinogen, factor VIIc, or prothrombin F1 + 2. CONCLUSIONS: Indians are more prone than Malays or Chinese to central obesity with insulin resistance and glucose intolerance and there are no apparent environmental reasons for this in Singapore. As a consequence, Indians develop some but not all of the features of syndrome X. They also have higher Lp(a) values. All this puts Indians at increased risk of atherosclerosis and thrombosis and must be at least part of the explanation for their higher rates of CHD.

Splenic lymphoma with villus lymphocytes--an uncommon cause for lymphocytosis.

We describe the clinical and laboratory features of four patients who presented with mild to moderate lymphocytosis but with no peripheral lymphadenopathy. These patients in the past, would have been classified as chronic lymphocytic leukaemia (CLL). However, it is now realised that chronic lymphoproliferative disorders are very heterogeneous and the clinical and laboratory features of our patients would support a diagnosis of splenic lymphoma with villus lymphocytes (SLVL) with characteristic morphological features. SLVL usually runs a benign clinical course but symptoms related a benign clinical course but symptoms related to splenomegaly or hypersplenism may be a problem. Splenectomy is considered the treatment of choice in these patients. Two of our patients had splenectomy and the other two patients are on regular follow-up without any specific treatment. It is therefore important to recognise this uncommon condition and also to differentiate it from CLL.