Screening and treating pre-operative anaemia and suboptimal iron stores in elective colorectal surgery: a cost effectiveness analysis.

Our study investigated whether pre-operative screening and treatment for anaemia and suboptimal iron stores in a patient blood management clinic is cost effective. We used outcome data from a retrospective cohort study comparing colorectal surgery patients admitted pre- and post-implementation of a pre-operative screening programme. We applied propensity score weighting techniques with multivariable regression models to adjust for differences in baseline characteristics between groups. Episode-level hospitalisation costs were sourced from the health service clinical costing data system; the economic evaluation was conducted from a Western Australia Health System perspective. The primary outcome measure was the incremental cost per unit of red cell transfusion avoided. We compared 441 patients screened in the pre-operative anaemia programme with 239 patients not screened; of the patients screened, 180 (40.8%) received intravenous iron for anaemia and suboptimal iron stores. The estimated mean cost of screening and treating pre-operative anaemia was AU$332 (£183; US$231; €204) per screened patient. In the propensity score weighted analysis, screened patients were transfused 52% less red cell units when compared with those not screened (rate ratio = 0.48, 95%CI 0.36-0.63, p < 0.001). The mean difference in total screening, treatment and hospitalisation cost between groups was AU$3776 lower in the group screened (£2080; US$2629; €2325) (95%CI AU$1604-5947, p < 0.001). Screening elective patients pre-operatively for anaemia and suboptimal iron stores reduced the number of red cell units transfused. It also resulted in lower total costs than not screening patients, thus demonstrating cost effectiveness.

Associations of nadir haemoglobin level and red blood cell transfusion with mortality and length of stay in surgical specialties: a retrospective cohort study.

Few studies have investigated if, and how, red cell transfusion and anaemia interact. We analysed 60,955 admissions to three metropolitan hospitals in Western Australia between 2008 and 2017 to determine whether the relationship between red cell transfusion and outcomes in surgical patients differed by lowest (nadir) level of haemoglobin. At levels above 100 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratios (ORs) (95%CI) being 8.80 (4.43-17.45) p < 0.001 and 3.68 (1.93-7.02) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.83 (1.28-2.61) p = 0.001, respectively. Likewise, between 90 g.l-1 and 99 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratio (95%CI) being 3.76 (2.23-6.34) p < 0.001 and 1.96 (1.23-3.12) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.34 (1.05-1.70) p = 0.017, respectively. Length of stay was longer with transfusion at nadir haemoglobin levels above 100 g.l-1 and in the following ranges: 90-99 g.l-1 , 80-89 g.l-1 , 70-79 g.l-1 and 60-69 g.l-1 , the adjusted rate ratio (95%CI) being 1.38 (1.25-1.53) p < 0.001, 1.18 (1.10-1.27) p < 0.001, 1.17 (1.13-1.22) p < 0.001, 1.07 (1.02-1.12) p = 0.003 and 1.24 (1.13-1.36) p < 0.001, respectively. Mortality was higher with red cell transfusion at haemoglobin levels greater than 90 g.l-1 , whereas at all levels below 90 g.l-1 mortality was not significantly higher or lower. Length of stay was longer with transfusion at nadir haemoglobin levels of 60 g.l-1 or above. Our results suggest that nadir haemoglobin modified the relationship between red cell transfusion and outcomes and adds to the evidence recommending caution before transfusing red cells.

Acute myeloid leukaemia in Western Australia 1991-2005: a retrospective population-based study of 898 patients regarding epidemiology, cytogenetics, treatment and outcome.

BACKGROUND: Patient characteristics and cytogenetics of acute myeloid leukaemia (AML) in clinical trials do not reflect that of the general population. There has not been a large population-based study that has examined cytogenetic features and outcomes of AML in Australia. AIM: Investigation of epidemiological, prognostic, treatment and outcome data in adults diagnosed with AML in Western Australia between 1991 and 2005. METHODS: Patients were identified utilising the Western Australia Cancer Registry, cytogenetic databases and hospital inpatient discharge diagnoses. Data were retrospectively collected from patients presenting to tertiary hospitals on patient characteristics, karyotype, induction therapy, remission, transplantation and survival. RESULTS: A total of 987 patients with AML was identified, of which 91% (898) attended a tertiary hospital. Median age was 67 years and 45% of cases represented secondary AML. Cytogenetic analysis was available in 81% of patients. Frequent karyotypes were normal (38.8%), complex (13.8%) and -7/add(7q)/del(7q) (12.1%). Aggressive therapy was initiated in 62.6%. Less than 15% were enrolled in clinical trials. Overall 16.5% received a stem cell transplant. Median overall survival for all patients was 5.6 months. In patients treated aggressively, complete remission was achieved in 56.9% and median overall survival was 12.2 months. Age, secondary disease and karyotype were significantly predictive of remission and overall survival. CONCLUSION: Age distribution, remission and survival rates were comparable with published population-based studies. High median age was reflected in the rate of secondary AML and trial eligibility. These findings highlight the need for prospective data collection.

Effectiveness of a patient blood management data system in monitoring blood use in Western Australia.

The aim of this paper is to describe a linked patient blood management (PBM) data system and to demonstrate its usefulness by presenting the blood usage data obtained. Our existing datasets already collected much of the required information in relation to PBM. However, these datasets were not linked. A patient identifier was used to link the Patient Administration System with the Laboratory Information System. Data linkage was achieved by linking the Laboratory Information System with the Patient Administration System records where blood transfusion or laboratory result date/time fell between admission and discharge date/time. The two datasets were then consolidated into the PBM data system. Blood usage data obtained from the system showed that between August 2008 and July 2009 there were 59,627 patient completed separations in the pilot hospital. Of the total transfused units, 62% were red blood cells (RBC), followed by fresh frozen plasma (22%), cryoprecipitate (9%) and platelets (8%). Around 50% of RBC transfusions were administered to patients >70 years of age. General medicine represented 21% of RBC usage, followed by haematology (19%), orthopaedics (17%) and general surgery (16%). Patients with 100 g/l pre-transfusion haemoglobin received 9% of RBC transfusions and patients with 71-100 g/l pre-transfusion haemoglobin received 73% of RBC transfusions. The post-transfusion haemoglobin in RBC transfusions exceeded 100 g/l in 33% of patients. Databases were successfully linked to produce a powerful tool to monitor blood utilisation and transfusion practices within a pilot PBM program. This will facilitate effective targeting of PBM strategies and ongoing monitoring of their impact.

When should iron chelation therapy be considered in patients with myelodysplasia and other bone marrow failure syndromes with iron overload?

Despite the absence of a robust evidence base, there is growing consensus that effective treatment of iron overload leads to decreased morbidity and premature mortality in patients with good prognosis myelodysplastic syndromes (MDSs). Furthermore, new treatment modalities, including disease-modifying therapies (lenalidamide and azacytidine) and reduced intensity conditioning therapies for allogeneic blood stem cell transplants, are offering the prospect of longer survival for patients with traditionally less favourable prognosis MDS, who might also benefit from iron chelation. This article proposes assessment of patients with MDS and related bone marrow failure syndromes to determine suitability for iron chelation. Iron chelation therapy options and monitoring are discussed.

From blood transfusion to patient blood management: a new paradigm for patient care and cost assessment of blood transfusion practice.

The ageing population in developed countries, including Australia, is putting increasing demands on blood transfusion services. With a falling donor pool there is likely to be a shortage of blood and blood products in the next 20 to 30 years unless there are significant changes in medical practice. The National Health and Medical Research Council/Australasian Society of Blood Transfusion Clinical Practice Guidelines on the Use of Blood Components from 2001 are being redeveloped by the National Health and Medical Research Council/Australian and New Zealand Society of Blood Transfusion as evidence-based patient-focused Patient Blood Management guidelines with the aim of improving patient outcomes by reducing inappropriate blood and blood product use and targeting therapies for improving the management of anaemia and coagulopathies.

Fluoroquinolone-induced immune thrombocytopenia: a report and review.

Fluoroquinolones are an emerging but underrecognized cause of drug-induced thrombocytopenia. Due to their broad spectrum they are often used in empirical treatment of febrile neutropenic, thrombocytopenic patients following myelosuppressive chemotherapy. They are associated with a range of immunohaematopathology. A 76-year-old male developed severe thrombocytopenia following treatment with ciprofloxacin on two occasions for community-acquired pneumonia. The temporal association, response to dechallenge, dramatic response to rechallenge and exclusion of other causes combined with detection of platelet-reactive antibodies of the immunoglobulin G class against glycoprotein IIb/IIIa following ciprofloxacin rechallenge makes causality probable. We present a brief review of immunohaematopathology associated with fluoroquinolones and draw attention to the structural similarity between quinolones and quinine to explore potential mechanisms for the phenomenon. Fluoroquinolones can induce drug-dependent, platelet-reactive antibodies causing complement-mediated destruction of platelets. The underlying mechanism to explain this is unclear; however, we hypothesize that the chemical similarities shared with quinine may be contributory. When using these agents clinicians should be aware of the possibility of drug-induced thrombocytopenia or thrombotic thrombocytopenic purpura.

Repeat treatment with iodine-131-rituximab is safe and effective in patients with relapsed indolent B-cell non-Hodgkin's lymphoma who had previously responded to iodine-131-rituximab.

BACKGROUND: Small series suggest retreatment of indolent lymphomas with murine anti-CD20 radioimmunotherapy is effective. The longer half-life of iodine-131 ((131)I)-rituximab may result in increased bone marrow exposure, with greater toxicity on repeat administration. We examined the effects of a second (131)I-rituximab in patients with indolent lymphoma following relapse. PATIENTS AND METHODS: We analyzed two institutional databases from January 2000 to July 2007 for retreatment with (131)I-rituximab. The severity of cytopenia, development of myelodysplasia (MDS), acute myeloid leukemia (AML) and hypothyroidism was noted. We compared response duration and toxicity of the treatments. RESULTS: Fourteen of 16 patients responded with nine complete responses (CRs), with a median duration of 10.5 months in responders. Six of 13 reresponders had the same or a longer response and six more remain in complete response. The median event-free survival was not significantly different for the two treatments. There was no significant difference in the severity of myelosuppression. Four patients developed hypothyroidism with three requiring thyroxine. One patient developed AML, with no other cases of MDS. The actuarial progression-free survival rate at 12 months was 36%. CONCLUSIONS: Repeat (131)I-rituximab induces high response rates, some of which result in durable remissions in patients who had previously responded.

Acquired Factor VIII autoantibody: four cases demonstrating the heterogenous nature of this condition and problems involved in diagnosis and treatment.

The development of an autoantibody to human Factor VIII is rare and presents many problems for diagnosis and treatment. We have seen several cases at our institution recently with widely heterogenous clinical and laboratory presentations. A wide range of treatment modalities were used in these cases with no gold standard of treatment or widely accepted guidelines existing. This has prompted us to examine all cases of this condition presenting at Fremantle Hospital over the last decade. We describe four cases which demonstrate the heterogeneity of this condition and its treatment and review the recent literature on the subject.

Detection of hairy cell leukaemia in blood and bone marrow using multidimensional flow cytometry with CD45-PECy5 and SS gating.

CD45 and right angle light scatter (SS) gating are used commonly in clinical flow cytometry to differentiate cells of various lineages (Stelzer et al., 1993). We have used CD45-PECy5 (Clone J33) since 1998 and have noticed that malignant lymphoid cells such as hairy cells can form distinct populations. Previous studies indicate that hairy cells reside where normal monocytes are usually found in CD45/SS scatter plots (Wells et al., 1998). We studied six patients with hairy cell leukaemia (HCL) and found that hairy cells have a higher CD45 mean cell fluorescence than normal lymphocytes and monocytes. Two of the six patients presented with mild unexplained cytopenias, without the usual clinical, morphological and cytochemical findings. In both cases, CD45/SS gating of bone marrow cells showed a small population with strong expression of CD45. The presence of hairy cells was confirmed using a panel of monoclonal antibodies. In one patient with HCL variant, CD45 expression was indistinguishable from that of normal lymphocytes. We conclude that CD45-PECy5 (Clone J33) is useful for screening peripheral blood and bone marrow and for the detection of HCL without obvious morphological involvement.

Thermolabile methyltetrahydrofolate reductase associated with unusual venous and arterial thromboses.

We report a patient with unusual venous and arterial thromboses in association with the common thermolabile methyltetrahydrofolate (MTHFR) variant. The patient responded directly to folate supplementation. To our knowledge, this is the first report describing hyperhomocysteinemia in association with this type of thrombosis.

Cross-reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand.

BACKGROUND: Inhibitory antibodies which neutralise factor VIII develop in 10-20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity. AIMS: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22. METHODS: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A. RESULTS: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients, 1-19% in six, 20-39% in 11 and 40-80% in five. In six of nine patients with acquired haemophilia cross-reactivity was < or = 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor. CONCLUSIONS: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor VIIa or prothrombin complex concentrates.

Assessment of the therapeutic potential of cytokines, cytotoxic drugs and effector cell populations for the treatment of multiple myeloma using the 5T33 murine myeloma model.

The therapeutic potential of six cytokines, eight cytotoxic drugs and two effector cell populations for the treatment of multiple myeloma was assessed in vitro using the 5T33 murine myeloma model. The efficacy of combination IFN-alpha and melphalan therapy was also evaluated in vitro and in vivo. Of the cytokines tested in vitro using the MTT assay, only IFN-alpha demonstrated significant inhibition of myeloma cell growth at non-toxic concentrations (ED50 = 1508.3 +/- 181.3 U/mL and 2617.9 +/- 334.0 U/mL for murine IFN-alpha [mIFN-alpha] and human IFN-alpha hybrid B/D [hIFN-alpha B/D], respectively). The ED50 for the eight cytotoxic drugs tested ranged from 2.3 x 10(-9) to 4.3 x 10(-13) mol/L and all were within the therapeutic range for humans. Combination hIFN-alpha B/D and melphalan were found to be additive in their inhibitory effects on myeloma cell growth in vitro and this finding was confirmed in vivo in C57BL/KaLwRij mice bearing disseminated 5T33 myeloma. Control animals demonstrated a median survival duration of 25.3 days whereas hIFN-alpha B/D or melphalan treatment alone increased survival to 30.5 and 33.3 days, respectively (P < 0.001). Combination IFN-alpha/melphalan therapy increased median survival duration to 38.5 days (P < 0.001) which was also significantly greater than that obtained with single agent therapy (P < 0.01). The murine myeloma cells were found to be resistant to NK cell lysis but susceptible to lysis by LAK cells (49.3 +/- 6.3% lysis at an effector to target ratio of 100:1).(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of reversible platelet aggregates in the blood of smokers and ex-smokers with peripheral vascular disease.

OBJECTIVE: To demonstrate that smoking increases platelet aggregation in vivo, that smoking cessation reverses platelet aggregation and that this explains, in part, why smoking perpetuates the development of peripheral vascular disease. DESIGN: Prospective case-control study involving three groups of patients: smokers with peripheral vascular disease, ex-smokers with peripheral vascular disease and smokers with peripheral vascular disease who quit smoking during the study. SETTING/PARTICIPANTS: Fourteen smokers and seven ex-smokers, new patients with confirmed peripheral vascular disease, attending the vascular clinic at Fremantle Hospital between February and November, 1988. INTERVENTIONS: Blood samples taken weekly from all subjects for five weeks. Week 1 was taken as the baseline before smoking cessation in the six smokers who were assigned to stop smoking during the study. MAIN OUTCOME CRITERIA: Platelet aggregate ratio, an indicator of in-vivo platelet aggregability where an increase in platelet aggregate ratio suggests a decrease in platelet function. RESULTS: Only three of six smokers stopped smoking for the duration of the study. Median platelet aggregate ratios were: smokers = 0.85 (range, 0.79-0.92) v. non-smokers = 0.93 (range, 0.91-1.00). The difference was statistically significant P less than 0.0002. The difference in platelet aggregate ratios between smokers and quitters was not statistically significant. CONCLUSIONS: This study demonstrated an increase in platelet aggregability in smokers compared to ex-smokers but there was no clear evidence that platelet function was fully reversed after only four weeks cessation of smoking. The data suggested that platelet function of the ex-smokers had fully reversed to normal over a longer period. This could explain the decreased incidence of complications of peripheral vascular disease in ex-smokers. The small number of patients able to quit smoking impeded this study.

Functional analysis of a clonal expansion of Leu 11 positive NK active lymphoid cells.

A female patient with an unusual lymphoproliferative disease associated with marked neutropenia has been observed for 36 months. The expanded cell population consists of large lymphocytes, many of which contain large azurophilic granules with acid phosphatase activity. These cells were T3, T8, T11 and Leu 11 positive but lacked the M1, T10, IL-2 receptor and HLA.DR antigens. The majority of these cells (60-70%) were also Leu 7 (HNK-1) positive. Strong natural killer (NK) activity was found in both the Leu 7 positive and negative cell populations. This cytotoxic activity was inhibited by monoclonal antibodies known to inhibit NK activity but was unaffected by antibodies which block T cell and T/NK cell cytotoxicity. Further functional analysis indicated that these cells suppressed normal T cell responses to mitogens, MLC responses and PWM induced B cell immunoglobulin synthesis. No effect on bone marrow progenitor cell growth was demonstrated. Antibody dependent cellular cytotoxic (ADCC) activity was barely detectable despite the presence of the Leu 11 antigen. Southern blot DNA analysis demonstrated clonal rearrangement of the T cell receptor beta gene thereby confirming that this variant of T gamma lymphoproliferative disease was a neoplastic condition.

Expression of antigens of the platelet glycoprotein IIb/IIIa complex on human hematopoietic stem cells.

Several cell surface and cytoplasmic markers specific for the megakaryocyte-platelet lineage have been described. However, as yet, none of these has been shown to be expressed on cells earlier than the committed megakaryocyte progenitor, CFU-Meg. The present study was aimed at determining whether platelet lineage antigens could be detected on human pluripotential stem cells. Rabbit antiserum against human platelets (APS) was extensively absorbed with erythrocytes and either platelets, neutrophils, monocytes, or cells of the monocytic cell line U937. The anti-stem cell antibodies in each absorbed antiserum were determined using a complement-dependent cytotoxic assay for the pluripotential stem cell CFU-mix. Platelets alone removed anti-stem cell antibodies from APS. Absorption of APS with platelets from a patient with Glanzmann's thrombasthenia failed to remove the anti-stem cell activity, providing evidence for involvement of the platelet glycoprotein IIb/IIIa complex. Antiserum against purified glycoprotein IIb and against glycoprotein IIIa also recognized stem cells, resulting in reduced formation of mixed colonies. Absorption of these antisera with normal platelets removed the anti-stem cell activity, indicating that both IIb and IIIa are represented on stem cells. Hence, cell surface antigens specific for the stem cell-megakaryocyte-platelet pathway are expressed on the platelet glycoprotein IIb/IIIa complex.