Biomedical subjects
Publications and source records attributed to S J Machin.
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We report a feasibility study of patient self-testing telemedicine for anticoagulant management using TOPCARE (Telematic Homecare Platform in Cooperative Health Care Provider Networks, developed by the European Commission for a user-friendly information society). TOPCARE comprises a Home Telematic Box (TOPCARE BOX), a central database held on a remote server and secure computer terminals in the anticoagulant clinic. The TOPCARE BOX transmits encrypted International Normalized Ratio (INR) results from the CoaguChek S monitor (Roche Diagnostics) via the patient's telephone line to the database, which is accessed by health-care professionals via the Internet. The database displays the patient's anticoagulant record, highlighting out of range results, overdue tests and quality control results. The database can also send information back to the TOPCARE box, although currently only the next test date can be transmitted. 23 patients, on long-term oral anticoagulation were recruited from the hospital anticoagulant clinic. After completing a nurse-led training course, patients tested their INR weekly on a CoaguChek S and transmitted their results via the TOPCARE BOX. The nurse specialist accessed the patient's results, electronically entered the date of the next test. Changes in warfarin dose were telephoned. Four patients dropped out early in the study and 19 patients received TOPCARE BOXs of which nine were fully functional. Unintentional software misconfiguration meant that remaining 10 TOPCARE BOXs were nonfunctional (these were later reconfigured but not reintroduced into the study). Patients successfully transmitted 222 results over a 5-month period using the TOPCARE system. Early server problems were resolved, but intermittent problems with database access persisted and five results were not received by the server. Although concerns were raised regarding technical problems, feedback from patients and staff was favourable and the system thought to be user-friendly. In conclusion, this pilot study showed that telemedicine is a feasible option for anticoagulant management, but that the technology requires thorough testing prior to installation.
summary. The decision to prophylactically transfuse platelets is dependent on the platelet count, careful regular clinical assessment and agreed local protocol. The ability to predict when platelet recovery will occur should allow a more reasoned approach to platelet transfusion. An increase in reticulated platelets demonstrates impending platelet recovery. A new rapid automated method to assess reticulated platelets, the immature platelet fraction (IPF), is described, and its clinical utility assessed. The IPF is identified by flow cytometry with the use of a nucleic acid specific dye in the reticulocyte channel on the Sysmex XE-2100. Fifty healthy adult volunteers were used to establish the normal range. Patients where platelet marrow production or destruction might be abnormal were studied, and some patients followed serially during treatment. Thirty patients receiving cytotoxic chemotherapy were tested, and 13 of these patients followed serially. Fifteen patients post-autologous or allogeneic transplant were followed daily for platelet count and IPF percentage to monitor platelet recovery. The method demonstrates good reproducibility and stability. The recovery phase of thrombocytopenia in most chemotherapy and transplant patients was preceded by a rise in IPF percentage several days prior to platelet recovery. In particular, patients undergoing autologous transplantation (n = 8) using peripherally collected stem cells have a characteristic IPF percentage motif, with a rise one or two days prior to engraftment. The automated IPF is a useful parameter in the clinical evaluation of the thrombocytopenic patient and has the potential to allow optimal transfusion of platelet concentrates.
Although haematology analysers provide reliable full blood counts, they are known to be inaccurate at enumerating platelets in severe thrombocytopenia. If the thresholds for platelet transfusion, currently set at 10 x 10(9)/l, are to be further reduced, it is vital that the limitations of current analysers are fully understood. The aim of this large multicentre study was to determine the accuracy of haematology analysers in current routine practice for platelet counts below 20 x 10(9)/l. Platelet counts estimated by analysers using optical, impedance and immunological methods were compared with the International Reference Method for platelet counting. The results demonstrated variation in platelet counting between different analysers and even the same type of analyser at different sites. Optical methods for platelet counting on the XE 2100, Advia 120, Cell-Dyn 4000 and H3* were not superior to impedance methods on the XE 2100, LH750 and Pentra analysers. All analysers except one overestimated the platelet count, which would result in under transfusion of platelets. This study highlights the inaccuracies of haematology analysers in platelet counting in severe thrombocytopenia. It re-emphasizes the need for external quality control to improve analyser calibration for samples with low platelet counts, and suggests that the optimal thresholds for prophylactic platelet transfusions should be re-evaluated.
There is a limited evidence base for self-testing and -management for oral anticoagulation management. Available data suggest that these are credible models for a significant minority of patients if underpinned by structured training and follow-up. The guidelines presented are necessarily consensual and outline procedures for patient selection, training, product procurement, product maintenance, quality assurance procedures, dosage adjustment and clinical supervision. The cost-effectiveness of these models remains to be elucidated within the UK. Further data on both health economic and clinical outcomes are required from UK based studies before widespread implementation of self-testing and management can be recommended on a wider scale.
OBJECTIVE: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. METHODS: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte-platelet complexes in patients with acute (0-21 days, n = 19) and convalescent (79-365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (> or =70%) carotid stenosis. Most patients were treated with aspirin (37.5-300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. RESULTS: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil-platelet (p = 0.004), monocyte-platelet (p = 0.046), and lymphocyte-platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil-platelet and monocyte-platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte-platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. CONCLUSION: Increased platelet count and leucocyte-platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis.
Thrombotic thrombocytopaenic purpura (TTP) results from deficiency of von Willebrand factor-cleaving protease (vWF-cp) activity. Eight HIV-infected patients presented with TTP, representing 12.5% of all TTP treated at this centre. In four patients presentation with TTP revealed underlying HIV infection, the other four patients were previously known to be HIV infected, with plasma exchange and highly active antiretroviral therapy (HAART) all recovered. Normalization of vWF-cp activity was associated with recovery. Relapse occurred in two patients who discontinued HAART against medical advice, suggesting that HIV has a causal role in this condition. Given the clear benefit from HAART in addition to plasma exchange, these data suggest that all patients presenting with TTP should undergo HIV testing.
In the half century since the first use of automated analyzers, manual techniques, especially microscopic examination of a stained blood film, have complemented analyzer results to provide a comprehensive hematology report on a patient's blood sample. Over the years, as the capabilities and performance of automated analyzers have improved, the respective roles of the automated analyzer and the complementary procedures have changed. Manual action (most commonly smear review) following automated analyzer results is usually triggered by determining whether the results trigger one of a series of criteria for review of results. There is little uniformity among different laboratories on criteria for action. Recognizing the long-standing need for generally accepted guidelines ("rules") which could be applied to criteria for review of CBC and differential results from automated hematology analyzers, Dr. Berend Houwen invited 20 experts to a meeting in the Spring of 2002 to discuss the issues and determine the most appropriate criteria. At this meeting, 83 rules were developed by consensus agreement. These rules were then tested in 15 laboratories on a total of 13,298 blood samples. After a detailed analysis of the data, the rules were refined and consolidated to produce 41 rules that are presented here. They include rules for first-time samples as well as delta rules for repeat samples within 72 hours from a patient. It is hoped that these rules will be useful to a large number of hematology laboratories worldwide. To facilitate validating these rules in individual laboratories before implementation in routine operation for patient samples, a suggested protocol is attached to this paper.
Replacement of normal levels of von Willebrand factor-cleaving protease (VWF:CP, ADAMTS13) activity from infused plasma is important in plasma exchange (PEX) for the treatment of thrombotic thrombocytopenic purpura (TTP) patients. We have studied the VWF:CP activity, VWF multimer distribution, VWF:Ag, protein S (PS) activity and free PS antigen levels in fresh frozen plasma (FFP), cryosupernatant (CSP) and virally inactivated components treated with methylene blue/light (MB) or solvent detergent (SD) processes. VWF:CP activity was normal in all components tested and was retained following overnight storage at room temperature. CSP and SD plasma contained reduced levels of the highest molecular weight VWF multimers. Protein S activity was reduced below the normal range in SD plasma, but within the normal range for the other components tested. Virally inactivated SD- and MB-treated plasma may be an effective alternative to FFP and CSP in PEX for TTP. Reduced PS activity in SD plasma may predispose to venous thromboembolism, especially if infused in large volumes.
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The importance of testing for anticardiolipin antibodies (aCL) in the diagnosis of antiphospholipid syndrome (APS) in patients with thrombosis has recently been challenged (ISTH SSC meeting, Boston 2002). We have analyzed the antiphospholipid serology of 123 patients with persistent antiphospholipid antibodies (aPL) attending our hematology department. The cohort was tested for anti-beta(2)-glycoprotein I (beta(2)-GPI) antibodies and aCL of IgG and IgM class and for lupus anticoagulant (LA). Ninety-six of these patients fulfilled Sapporo clinical criteria for APS and 70 of these patients had venous and/or arterial thrombosis. Patients with LA plus anti-beta(2)-GPI antibodies had significantly higher levels of IgG aCL and anti-beta(2)-GPI antibodies than those exhibiting positivity for only LA or anti-beta(2)-GPI antibodies (P < 0.05). Patients with aCL IgG levels over 60 GPLU were found in all cases to be positive for LA and anti-beta(2)-GPI antibodies; 25.2% (31/123) of all patients and 26.04% (25/96) of patients fulfilling Sapporo clinical criteria for APS were positive for aCL only. The mean IgG aCL level in the Sapporo clinical criteria positive patients who had aCL only was 11.5 GPLU (normal < 5 GPLU). These data indicate that omission of aCL testing from the clinical investigation of APS could lead to a failure to diagnose the syndrome in a proportion of patients.
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The spun packed cell volume (PCV, hematocrit) is a key measurement on which are based hematology instrument calibration, reference range determination, and assignment of values to calibrators/controls. In 2001, the International Council for Standardization in Haematology (ICSH) recommended a Reference PCV method, which is fully traceable to the ICSH reference hemoglobin method. Because of its complexity, however, this method is impractical for occasional use in routine laboratories and is therefore intended primarily for use by manufacturers of capillary microhematocrit tubes, liquid calibrators, and multichannel analyzers. In response to the need for a simpler method--accessible to all routine laboratories--the ICSH offers this "Surrogate Reference" PCV procedure. It is traceable to the original ICSH Reference PCV method and is based on spun PCVs obtained using borosilicate capillary tubes with an already-known relationship to this reference procedure. This ICSH "Surrogate Reference" PCV method is substantially simpler, thus putting it within the reach of most routine hematology laboratories.
Medical practitioners are searching for ways to improve the quality and outcome of care while decreasing cost. One technological advance that may facilitate this is point-of-care testing. The pocH-100i hematology analyzer (Sysmex Corporation, Kobe, Japan) is a compact device designed specifically for point-of-care testing environments. The analyzer provides a full blood count and a 3-part differential leukocyte count. A distinct advantage is that neutrophils are reported separately, which is useful for monitoring oncology patients. The device was evaluated in accordance with International Council for Standardization in Haematology (ICSH) guidelines for precision, linearity, carryover, and effects of sample aging. The pocH-100i analyzer was compared with the Sysmex KX-21N device. The results for all parameters tested were almost identical. When samples including blast cells, immature granulocytes, and nucleated red blood cells were excluded, the pocH-100i automated differential compared well with a 400-cell manual differential. Results for neutrophils (r2 = 0.996), lymphocytes (r2 = 0.999), and the "mixed" population of cells (r2 = 0.611) indicated the pocH-100i analyzer would be highly suitable for low-volume laboratories and near-patient services.
A comparative evaluation of four commercial coagulation test kits for screening the protein C pathway kits was performed at two centres. The tests were Acticlot V-OUT (V-OUT), the PCA test (PCA), the GradiThrom PCP test (PCP) and ProC Global (ProC). Reference ranges were established in 40 normal subjects and, with the exception of V-OUT and ProC, significant differences were observed between males and females. Consequently, sex-specific normal cut-off values (fifth percentile) were used that led to greatly improved sensitivity when compared with the manufacturers' recommended cut-off values. Plasma from patients with factor V Leiden (n = 23), congenital protein S deficiency (n = 19), congenital protein C deficiency (n = 11), lupus anticoagulant (n = 17) and thrombophilia with no demonstrable protein C pathway defect (n = 20) were tested. All kits showed 100% sensitivity to factor V Leiden, but sensitivity was variable for protein C deficiency (27-73%), and poor for protein S deficiency (29-35%). The lupus anticoagulant affected all kits to some degree, with 29-35% giving values below the fifth percentile of normal, whereas all kits gave 1/20 unexpected abnormal results in the thrombophilia group, with the same sample accounting for the abnormal results in three of the four kits. Overall sensitivity and specificity, respectively, for defects in the protein C pathway were: V-OUT, 60 and 91%; PCA, 70 and 86%; PCP 75 and 94%; and ProC, 66 and 88%. We conclude that all four kits lack the sensitivity and specificity required for routine laboratory screening for defects in the protein C pathway and cannot replace assays for the individual proteins of this system.
A significant proportion of patients with Essential Thrombocythaemia (ET) have thrombotic complications which have an important impact upon the quality, and duration of their life. We performed a retrospective cross sectional study of the prevalence of antiphospholipid antibodies (APA) in 68 ET patients. Compared to 200 "elderly" controls (>50 years) there was a significant increase in anticardiolipin IgM (p < 0.0001) and anti beta2 glycoprotein I (anti-beta2GPI) IgM (p < 0.0001) antibodies in ET. Thrombosis occurred in 10/20 with APA and 12/48 without, p = 0.04, relative risk 2.0 (95% confidence intervals 1.03-3.86): these patients did not differ in terms of other clinical features. The prevalence of thrombosis in patients with dual APA (6/7) was significant when compared to those with single APA (p = 0.02) and the remaining patients (p < 0.0002). Also anti-beta2GP1 IgM antibodies either alone, or in combination with another APA, were associated with thrombosis (p = 0.02). These results suggest that the prevalence of APA in ET and their influence upon thrombotic risk merit investigation in a larger study.
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