Improving the outcomes of anticoagulation in rural Australia: an evaluation of pharmacist-assisted monitoring of warfarin therapy.

OBJECTIVE: The aim of this project was to assess whether rural pharmacist involvement in the management of patients receiving warfarin has the potential to lead to safer and more effective anticoagulation, and is valued and welcomed by patients and their general practitioners (GPs). METHODS: A convenience sample of rural pharmacists was trained in the use of the CoaguChek S International Normalized Ratio (INR) monitor and then conducted pharmacy-based testing for approximately 3 months. Two types of testing were performed in the pharmacy: (i) comparison testing was defined as pharmacy-based tests taken within 4 h of conventional laboratory testing or (ii) additional testing, which was a pharmacy-based test with no direct comparison laboratory test taken. Pharmacists, GPs and patients completed anonymous satisfaction surveys after the completion of the pharmacy-based testing. RESULTS: Pharmacists from 16 rural pharmacies were trained to use the CoaguChek S monitor. During the trial period, 518 INR tests were performed in the pharmacies on 137 different patients. A total of 120 tests were evaluated against results from laboratory testing. The pharmacy-based INR values were significantly correlated with the laboratory INR values (mean of 2.32+/-0.77 and 2.32+/-0.59 respectively; r=0.88, P<0.0001). A total of 398 additional pharmacy-based tests were conducted in the pharmacy and 8.5% of the additional tests resulted in a subsequent dosage change. The monitoring was well received by pharmacists, GPs and patients. CONCLUSIONS: The results of the trial were very positive. The CoaguChek S monitor in pharmacy-based testing performed accurately compared with conventional laboratory testing. Further research needs to be conducted on the impact of community pharmacy-conducted INR monitoring on patient care and outcomes.

Improving the outcomes of anticoagulation: an evaluation of home follow-up of warfarin initiation.

OBJECTIVES: A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy. This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community. DESIGN: Open-label randomized controlled trial. SETTING: Home-based follow-up of patients discharged from acute care hospital in southern Tasmania, Australia. SUBJECTS: A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner (GP) care were enrolled in the study. Sixty were randomized to home monitoring (HM) and 68 received usual care (UC). INTERVENTIONS: HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio (INR) testing on alternate days on 4 occasions, with the initial visit two days after discharge. The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control. RESULTS: At discharge, 42% of the HM group and 45% of the UC group had a therapeutic INR. At day 8, 67% of the HM patients had a therapeutic INR, compared with 42% of UC patients (P < 0.002). In addition, 26% of UC patients had a high INR, compared with only 4% of HM patients. Bleeding events were assessed 3 months after discharge and occurred in 15% of HM patients, compared with 36% of the UC group (P < 0.01). CONCLUSIONS: This programme improved the initiation of warfarin therapy and resulted in a significant decrease in haemorrhagic complications in the first 3 months of therapy.

Accuracy, reproducibility and clinical utility of the CoaguChek S portable international normalized ratio monitor in an outpatient anticoagulation clinic.

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.

Association between high interleukin-6 levels and adverse outcome after autologous haemopoietic stem cell transplantation.

We studied interleukin-6 (IL-6) levels on the day of transplantation in 31 patients undergoing autologous haemopoietic stem cell transplantation (SCT) (either peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation (BMT)) for neoplastic diseases to determine if there was a relationship between IL-6 level and rate of haemopoietic recovery, length of stay in hospital, and survival. There was no apparent delay in post-transplant recovery associated with elevated IL-6 levels. However, increased values of IL-6 tended to be associated with an increased length of stay in hospital (P = 0.083). There was a highly significant adverse association between higher IL-6 levels and survival following transplantation (P = 0.0001). This association remained significant (P = 0.013) in the uniform subgroup of patients with malignant lymphoma with chemosensitive disease who had undergone BMT (that is, excluding patients who had undergone PBSCT) (n = 13). Knowledge of IL-6 levels on the day of transplant has the potential to provide valuable prognostic information in patients undergoing autologous haemopoietic SCT.

Educational campaign to improve the prevention of postoperative venous thromboembolism.

BACKGROUND: Recent studies have revealed considerable scope for improvement in preventing postoperative venous thromboembolism. This project comprised a baseline assessment of the use of preventive measures within the Royal Hobart Hospital, followed by the implementation and evaluation of an educational program directed at hospital staff. AIM: To determine whether the Royal Hobart Hospital's guidelines for the prophylaxis of postoperative venous thromboembolism were being utilized effectively and, if necessary, attempt to improve use of the guidelines through an educational programme. METHODS: Data were collected retrospectively from the medical records of 250 surgical patients undergoing a procedure during February 1997. Patients were classified as being at a low, medium or high risk of venous thromboembolism using two sets of criteria. The percentage of patients receiving the appropriate prophylaxis was determined. An educational programme to promote the hospital's guidelines for the prophylaxis of postoperative venous thromboembolism was then implemented. Included were presentations to staff, posters placed throughout the hospital and the wide distribution of the results and a glossy card showing the hospital's guidelines. Follow-up data were subsequently collected from another 250 surgical patients. RESULTS: Only 59% of patients received appropriate prophylaxis according to the hospital's approved guidelines, with little change when those patients with possible contraindications to thromboprophylaxis were excluded. When those patients at a high risk of venous thromboembolism were examined, only 25% were prescribed the recommended preventive measures. There was no difference between elective versus emergency surgery and the use of appropriate prophylaxis. Following the implementation of the educational programme, data collection from another 250 surgical patients revealed a significant increase (P < 0.05 by chi-square test) in the level of appropriate thromboprophylaxis to 70% of patients, with 77% of the high-risk patients being prescribed the recommended preventive measures. CONCLUSIONS: A pharmacy-based educational intervention significantly improved adherence to the hospital's guidelines for the prophylaxis of postoperative venous thromboembolism.

Circulating CD34+ cells: an adverse prognostic factor in the myelodysplastic syndromes.

As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU-GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients (P less than 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P less than 0.03). The Bournemouth score was also significantly associated with transformation to AML (P less than 0.0001) and poor survival (P less than 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU-GM colony growth.

Zidovudine (AZT) therapy in children with HIV infection: the Australian experience.

Fifteen children (11 males and four females), on oral Zidovudine (AZT) for symptomatic HIV infection were studied retrospectively. Twelve acquired HIV via blood products, two from vertical transmission (maternal intravenous needle sharing) and one through breast feeding. Their mean age at the start of therapy was 8.6 years (s.d. 4.4 years, range 1.8-15.3 years). The main indications for therapy were failure to thrive (FTT) in 10, recurrent respiratory tract infections (RRTI) in eight, and developmental delay (DD) in one, with overlapping indications being Pneumocystis carinii pneumonia (PCP) in one and pulmonary lymphoid hyperplasia (PLH) in two. The mean commencement dose was 24 mg/kg per day orally in 3-6 divided doses (range 16-35 mg/kg per day). The duration of therapy was 2 weeks-2 1/2 years. Significant improvement in growth was observed by 2 months; at 6 months, growth was sustained in these otherwise ill children, with only two falling below pretreatment weight. Decrease in the frequency of RRTI based on subjective reports of the attending clinicians was observed in seven of the eight evaluable children still on therapy. Improvement in PCP and PLH occurred in two children and modest improvement was subjectively reported in PLH in one while still early in the course of therapy. Overall, AZT was well tolerated. Dose modifications were for neutropenia in three (of which only two were drug related), rapidly falling neutrophil count in one, anaemia in two (with concurrent history of chronic gastrointestinal tract blood loss in one), severe GIT irritation in one and transient sedation in one. Seven opportunistic infections were reported (three in the same patient) of which two occurred following cessation of therapy, one after only 2 weeks of therapy, and one had not been on primary prophylactic therapy. Three deaths occurred, one associated with opportunistic infections and two while off therapy (one respiratory failure, one PCP).

Haematology of the Australian eastern quoll, Dasyurus viverrinus--II. Red cell enzymes and metabolic intermediates.

1. The activity of 21 red cell enzymes and three red cell metabolic intermediates were measured in adult Dasyurus viverrinus and compared with published data on other marsupials. 2. Phosphofructokinase (PFK), glyceraldehyde dehydrogenase (GAPD) and phosphoglycerate kinase (PGK) were elevated in comparison to other marsupials. 3. Enolase (ENO) and 2,3-diphosphoglycerate (2,3 DPG) were lower than in other marsupials.

Alcohol-associated haemolysis in Zieve's syndrome: a clinical and laboratory study of five cases.

In 1958 Zieve described a syndrome of jaundice, hyperlipidaemia, and transient haemolytic anaemia associated with alcohol abuse. The clinical and laboratory features of five cases are reviewed. All patients presented with acute abdominal pain and fever. Four had a history of a recent alcohol binge. Hyperlipidaemia was present in two patients; this subsided before the onset of haemolysis. The red cells showed features of an acquired pyruvate kinase deficiency: an increased autohaemolysis with only partial correction with glucose, low red cell ATP, and instability of pyruvate kinase when haemolysate was heated to 55 degrees C. These changes were not observed in a control group of chronic alcoholics without haemolysis.

Warfarin dosage requirements: prospective clinical trial of a method for prediction from the response to a single dose.

We have previously described a model for predicting individual daily maintenance dosage (MD) requirements of warfarin 24 h after the administration of a single dose. This model relies on measurement of the initial anticoagulant response as the 24 h percentage fall in plasma clotting factor VII activity. It permits prediction of the individual MD given the size of the initial dose, a baseline and desired maintenance value of the prothrombin ratio, and a baseline and 24 h plasma level of factor VII activity. We now present the results of a prospective clinical trial of the method. Data from 65 patients were suitable for analysis. The mean daily MD of warfarin was 4.0 mg (range 1-10 mg). There was a moderately strong linear relationship between predicted and actual MDs of warfarin (r = 0.66, P less than 0.001). Actual vs predicted MDs in individual patients were not significantly different. The mean difference was 0.39 mg. The results of this prospective trial suggest that our model predicts warfarin MD requirements with reasonable accuracy. Nevertheless, the accuracy of the model is not sufficient to replace careful clinical and haematological monitoring of each patient commencing warfarin therapy.

Hemoglobin Hobart or alpha 20(Bl)His----Arg: a new alpha chain hemoglobin variant.

A new alpha chain hemoglobin variant, Hb Hobart, alpha 20(Bl)His----Arg, was detected in a 60-year-old female of British nationality. The proposita had a history of severe rheumatoid arthritis and had been treated for many years for a refractory microcytic anemia and/or iron deficiency. A hemoglobin electrophoresis screen indicated the presence of a hemoglobin variant, with electrophoretic characteristics similar to a Hb Lepore. However, the level of the variant (17.9%) and the presence of a minor variant Hb A2 band (0.4%) suggested that further investigation was indicated. The variant hemoglobin was purified by column chromatography and the alpha chain subjected to aminoethylation and tryptic digestion. Peptide mapping and amino acid analysis indicated that the histidine residue 20 had been substituted by an arginine residue. The substitution in Hb Hobart is at the first residue in the B Helix of the alpha chain of hemoglobin. As this is an externally placed amino acid in the hemoglobin molecule, a substitution at this position of the hemoglobin molecule would not be expected to cause any functional problems. A family study has shown that at least three other relatives are heterozygous for Hb Hobart. These family members have normal hematological findings.

Functional and phenotypic analysis of a T cell prolymphocytic leukemia.

Peripheral blood mononuclear cells obtained from a patient with prolymphocytic leukemia expressed the surface membrane markers characteristic of resting mature T helper lymphocytes. These cells responded to the T cell mitogens PHA and Con A in a blast transformation assay but not the anti-T cell monoclonal antibody Leu 4 and the B cell mitogen, PWM. The concentration of PHA or Con A eliciting maximum blast transformation was less than that required by normal mononuclear cells. The leukemic cells recognised and responded to allogeneic pooled mononuclear cells in a mixed lymphocyte culture. In addition, although they did not express Ia antigens, they served as effective stimulators in the mixed lymphocyte reaction. Consistent with the helper phenotype, the leukemic cells did not produce suppressor factors, but provided help for normal B-enriched lymphocytes to respond to PWM as assessed by both blast transformation and IgG production. T lymphocyte colonies developed when the leukemic cells were treated with PHA during a 20 h liquid culture prior to being seeded into semisolid agar medium containing either PHA or an IL2-containing lymphokine. There was no growth when untreated cells were seeded directly into IL2-containing agar. Analysis of colony formation indicated that, as with normal resting T lymphocytes, proliferation occurred in two distinct steps; activation in response to PHA and replication in response to IL2-like growth factors. These findings demonstrate that in this case the helper T prolymphocytes have the functional capabilities of normal mature T lymphocytes as predicted from their helper phenotype.

Bone marrow transplantation using fractioned total body irradiation: Absence of pulmonary toxicity despite cytomegalovirus viraemia.

Bone marrow transplantation was performed on a 22-year-old male with acute myeloid leukaemia in early relapse. The donor was his HLA-identical, but ABO-incompatible, brother. Total body irradiation (TBI) was given in six daily doses of 2GY rather than as the usual single dose of 10GY. After transplantation, cytomegalovirus viraemia occurred, but the patient did not develop pneumonia despite the reported high association of these events. Four hundred days after transplantation, the patient was fit and active with no haematological abnormalities. The use of fractionated TBI may be associated with a lower incidence of respiratory complications than standard single-dose TBI.

Stereological studies on chronic lymphocytic leukaemia and hairy cell leukaemia.

Using stereological techniques at the ultrastructural level, 7 quantitative parameters for 7 patients with hairy cell leukaemia, 27 patients with chronic lymphocytic leukaemia, and 8 normal individuals. These quantitative data show clear differences between normal lymphocytes, CLL cells and the abnormal cells of HCL. They also show that it may be possible to subdivide CLL into distinct groups on quantitative criteria.