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Biomedical subjects

Paul Harrison

Publications and source records attributed to Paul Harrison.

At least 19 recordsLinked to original sources
PubMed2006

Methods for counting platelets in severe thrombocytopenia.

Accurate platelet counts in severe thrombocytopenia are critical in clinical practice to facilitate decisions at prophylactic platelet-transfusion thresholds. Until recent years, the accuracy of platelet counts has been limited by the reliance of hematology analyzers on calibration material values derived from the manual platelet counting method. The calibration of hematology analyzers in thrombocytopenia and the reduction of variation between instruments have been hindered by a lack of adequate quality control materials, making the accuracy of automated methodologies in routine practice difficult to assess. This situation could now be vastly improved by the use of the International Reference Method (IRM) to assign calibration materials and by further knowledge of the accuracy and limitations of the particular types of automated platelet count available to the clinician. These changes will improve clinical confidence in the accuracy of a platelet count and thus inform clinical decisions at the current level of prophylactic platelet transfusions.

Automation↗
PubMed2005

Screening for aspirin responsiveness after transient ischemic attack and stroke: comparison of 2 point-of-care platelet function tests with optical aggregometry.

BACKGROUND AND PURPOSE: Recent studies suggest that patients who do not respond to aspirin (ASA) therapy may be at increased risk of ischemic vascular events. The availability of simple to use point-of-care (POC) platelet function tests now potentially allows aspirin nonresponsiveness to be identified in routine clinical practice. However, there are very few data on whether the different tests produce consistent results. We therefore compared 2 POC tests (PFA-100 device and the Ultegra-RPFA [RPFA]) with conventional light transmission aggregometry (LTA). METHODS: Platelet function was assessed by all 3 tests in 100 patients receiving low-dose ASA therapy after transient ischemic attack (TIA) or ischemic stroke. RESULTS: The incidence of ASA nonresponsiveness was 17% by the RPFA and 22% by the PFA-100, compared with only 5% by LTA (ie, as defined with both arachidonic acid and ADP). Agreement between the RPFA and the PFA-100 and arachidonic acid induced LTA was poor (kappa=0.16, 95% CI, -0.08 to 0.39, P=0.11; and kappa=0.09 -0.12 to 0.30, P=0.32, respectively). Agreement between the 2 POC tests was also poor (kappa=0.14, -0.08 to 0.36, P=0.15). Only 2% of patients were aspirin nonresponders by all 3 tests. CONCLUSIONS: The prevalence of apparent ASA nonresponsiveness was higher with both the POC tests than with LTA. However, agreement between the tests was poor and very few patients were ASA nonresponsive by all 3 tests. Aspirin nonresponsiveness is therefore highly test-specific and large prospective studies will be required to determine the prognostic value of each of the separate tests.

Adult↗
PubMed2005

Platelet function analysis.

Since the last guidelines for BCSH platelet function testing were written in the late 1980s, many new tests have become available. Previously most platelet function tests were traditionally utilized to aid in the diagnosis and management of patients with platelet and haemostatic disorders. Most traditional tests were also largely restricted to the specialized laboratory or centre. However, nowadays there is also much renewed interest in monitoring the efficacy of anti-platelet therapy and measuring platelet hyper-function. A number of dedicated platelet function instruments have now become available that are much simpler to use and are beginning to be utilized as point of care instruments. These can now provide measurement of platelet function within whole blood without the requirement of sample processing. Some are also beginning to be incorporated into routine clinical use and can be utilized as not only as general screening tests of platelet function but to monitor anti-platelet therapy and to potentially assess both risk of bleeding and/or thrombosis. Modern flow cytometric-based platelet function analysis now also provides a wide variety of specific tests that can assess different aspects of platelet biology that are useful for diagnostic purposes. This review will highlight some of these of new tests/instruments and discuss their potential utility both within the haemostasis laboratory but also as potential point of care instruments.

Blood Platelet Disorders↗
PubMed2005

Platelet activation can occur by shear stress alone in the PFA-100 platelet analyser.

The PFA-100 platelet function analyser simulates high-shear platelet function; however, the relative importance of the high shear rates alone has not been examined in this system. Normal blood was analysed by the PFA-100 using modified cartridges that contained a blank membrane lacking the usual platelet agonists (collagen/epinephrine or collagen/ADP) thus isolating the effects of shear stress alone. We found evidence of platelet activation with significant increases in platelet-leucocyte aggregates. There was no significant change in surface CD62P nor PAC-1 expression. A degree of platelet activation occurs in the PFA-100 due to shear stress alone.

Blood Platelets↗
PubMed2005

Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA.

Vascular events commonly recur in stroke patients on aspirin, and may reflect incomplete inhibition of platelet function with aspirin therapy. The platelet function analyser (PFA-100) activates platelets by aspirating a blood sample at a moderately high shear rate through a capillary to a biologically active membrane with a central aperture. The membrane is coated with collagen, and either ADP (C-ADP) or epinephrine (C-EPI). The time taken for activated platelets to adhere, aggregate, and occlude the aperture is called the closure time. Previous studies have shown that aspirin prolongs the C-EPI closure time, without prolongation of the C-ADP closure time, in the majority of control subjects. We hypothesised that the PFA-100 would provide a sensitive assay for the detection of early and convalescent phase cerebrovascular disease (CVD) patients who had incomplete inhibition of platelet function with aspirin. We investigated potential cyclooxygenase-dependent and -independent mechanisms that might influence the responsiveness to aspirin using the PFA-100. Patients were studied during the early (< or = 4 weeks, n=57) and convalescent phases ((< or = 3 months, n=46) after ischaemic stroke or TIA. To investigate potential mechanisms that could contribute to aspirin responsiveness on the PFA-100, we measured von Willebrand factor antigen levels, and carried out platelet aggregometry experiments in platelet-rich plasma in response to sodium arachidonate (1 mM) and ADP (5 microM). Sixty percent of patients in the early phase and 43% of patients in the convalescent phase did not have prolonged C-EPI closure times on 75-300 mg of aspirin daily, and were defined as aspirin non-responders. Median C-ADP closure times were significantly shorter in aspirin non-responders than aspirin-responders in both the early and convalescent phases after symptom onset (P=0.008), suggesting platelet hyper-reactivity to collagen or ADP in the aspirin non-responder subgroup. There was a significant inverse relationship between plasma von Willebrand factor antigen levels and C-EPI closure times in both early and convalescent phase CVD patients (P=0.008). Mean von Willebrand factor antigen levels were significantly higher in aspirin non-responders than aspirin responsive patients in the early (P=0.001), but not convalescent phase (P=0.2) after stroke and TIA. None of the patients studied were defined as being aspirin-resistant using sodium arachidonate- or ADP-induced platelet aggregometry. A large proportion of ischaemic CVD patients have incomplete inhibition of platelet function with low to medium dose aspirin using the PFA-100. The results suggest that cyclooxygenase-independent mechanisms, including elevated von Willebrand factor antigen levels, play an important role in mediating aspirin non-responsiveness on the PFA-100.

Adenosine Diphosphate↗
PubMed2005

Platelet hyper-function in acute coronary syndromes.

Previous studies have demonstrated shortened bleeding times in patients with acute coronary syndromes, especially in myocardial infarction (MI). In this study we have investigated platelet hyper-function using the PFA-100 with collagen/adenosine diphosphate and collagen/epinephrine cartridges in 78 patients presenting with acute chest pain. Patients were classified into MI, unstable angina (UA) and non-specific chest pain. All patients received 300 mg aspirin (ASA) more than 2 h before blood samples were collected. Twenty healthy normal subjects were also tested before and 2 h after 300 mg ASA (n = 10). The collagen/adenosine diphosphate closure time was significantly shorter in MI patients (median, 71 s; P = 0.0237) but not in UA patients (median, 81 s; P > 0.05) compared with normal subjects (median, 92.5 s). The collagen/epinephrine closure times were significantly longer in UA patients (median, 233 s) than in untreated controls (median, 125 s; P < 0.0001), as expected, but there was no difference in MI patients (median, 149.24 s; P > 0.05), suggesting that the MI patients were not all responding to ASA. Analysis of a subset of the apparent ASA non-responders (n = 5) by platelet aggregation demonstrated that this was not related to failure of ASA to block cyclo-oxygenase activity. Von Willebrand factor levels were significantly elevated in both UA and MI patients compared with normal subjects (mean, 175.5 and 248.9 versus 89.1 s; P < 0.0001 and P < 0.0001, respectively) and were also significantly higher in the MI group compared with the UA group (P < 0.05). There is evidence for platelet hyper-function and elevated von Willebrand factor levels in the MI group that could explain their decreased responsiveness to ASA on the collagen/epinephrine cartridge.

Administration, Oral↗
PubMed2005

The role of PFA-100 testing in the investigation and management of haemostatic defects in children and adults.

The PFA-100 provides a simple global measure of high shear-dependent platelet function, and as such is not diagnostic or specific to any disorder. Prolonged closure times must be interpreted in conjunction with a full blood count, von Willebrand factor (VWF) screen and other platelet tests. The PFA-100 may also give false negative results with relatively common platelet defects. If clinical suspicion is high, further detailed platelet function testing and VWF screening are required to exclude abnormal platelet function, even if the PFA-100 is normal. In more recent studies the PFA-100 has been used for preoperative identification and management of surgical patients with haemostatic defects and for assessing the clinical effectiveness of platelet transfusion therapy. This review highlights the up to date, evidence-based, advantages and disadvantages of the PFA-100 test in the investigation and management of haemostatic disorders in both children and adults.

Adult↗
PubMed2005

Does funding for HIV and sexually transmitted disease prevention matter? Evidence from panel data.

Since the onset of the AIDS epidemic, the Centers for Disease Control and Prevention (CDC) has allocated several billion dollars for the prevention of HIV and other sexually transmitted diseases (STDs) in the United States. Using state-level data from 1981 to 1998, the authors found that greater amounts of prevention funding in a given year are associated with reductions in reported gonorrhea incidence rates in subsequent years. The authors conclude that funding for STD and HIV prevention, on the whole, appears to have a discernable impact on the incidence of STDs.

Centers for Disease Control and Prevention, U.S.↗
PubMed2004

Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P </= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P </= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

Acute Disease↗
PubMed2004

Circulating reticulated platelets in the early and late phases after ischaemic stroke and transient ischaemic attack.

The percentage of reticulated platelets (% RP) could be a useful marker of increased platelet production and/or turnover in patients with increased platelet activation, but few flow cytometric studies have measured the % RP in patients with ischaemic cerebrovascular disease (CVD). Whole blood flow cytometry using thiazole orange was performed to compare the % RP in patients in the early (1-27 d, n = 79) and late phases (79-725 d, n = 70) after ischaemic stroke or transient ischaemic attack (TIA) with controls without CVD (n = 27). The impact of aspirin dose escalation (75-300 mg/d) on the % RP was investigated in 10 patients in the late phase after stroke/TIA. The platelet count and mean platelet volume (MPV) were similar in CVD patients and controls. Compared with controls, the unadjusted % RP was not significantly higher in early or late phase CVD patients (P < or = 0.3). However, having adjusted for age, the % RP was higher in early (P = 0.047) and late phase CVD patients (P = 0.01). There was a positive correlation between % RP and MPV in EDTA- and citrate-anticoagulated blood in both early and late phase CVD patients (P< or = 0.01). The % RP was not significantly influenced by aspirin dose. These data do not convincingly support an excessive stimulus to platelet production in the early or late phases after ischaemic stroke/TIA, but are consistent with the hypothesis that reticulated platelets are larger than more mature 'non-reticulated' platelets in ischaemic CVD.

Aged↗
PubMed2004

High incidence of defective high-shear platelet function among platelet donors.

BACKGROUND: Because single-donor plateletpheresis concentrates now account for a large percentage of PLT concentrates, the PLT quality of individual donations is increasingly important. There has been little previous work on PLT function in blood donors. STUDY DESIGN AND METHODS: The aim of this study was to investigate the prevalence of defective PLT function among 100 healthy UK PLT donors on 3 consecutive donation days. Citrated blood samples were taken before plateletpheresis. High-shear PLT function testing was performed by a PLT function analyzer (PFA-100, Dade Behring), within both collagen-ADP (CADP) and collagen-epinephrine (CEPI) cartridges. RESULTS: Sixteen percent of PLT donors (mainly over the 3 donating days) had prolonged CEPI closure times (CTs) only, indicative of an aspirin-like pattern; 9 percent had a severe defect with prolonged CEPI CTs between 200 and 300 seconds, and 4 percent had maximal CEPI CTs of greater than 300 seconds. The majority of prolonged CEPI CTs appeared transient in nature. CONCLUSION: PLT dysfunction as detected by the PFA-100 is surprisingly common within a voluntary PLT donor population. The majority of CEPI defects appeared transient in nature and are indicative of surreptitious intake of cyclooxygenase inhibitors (e.g., aspirin). Identification of defective PLT function within donors would provide a simple means to eradicate defective PLTs from being clinically utilized.

Adult↗