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David Connor

Publications and source records attributed to David Connor.

3 recordsLinked to original sources

Increased procoagulant phospholipid activity in blood from patients with suspected acute coronary syndromes: a pilot study.

Increased platelet activation is well documented in patients with acute coronary syndromes and can be detected by various methods, including flow cytometry and enzyme-linked immunosorbent assay. However, such techniques require several steps and cannot provide quick results. Platelet activation ultimately results in procoagulant phospholipid exposure and we have previously described a simple activated factor X-activated clotting time (XACT) test that is insensitive to resting platelets but that is significantly shortened by activated platelets, microparticles and procoagulant phospholipids. Our aim was to determine whether the XACT test could be used to distinguish patients with chest pain due to cardiac ischaemia from those having chest pain due to non-cardiac causes. We thus carried out XACT tests on ethylenediamine tetraacetic acid whole blood and plasma samples obtained from 46 patients presenting to the emergency department with chest pain and from 30 controls. Sixteen cases (30%) were subsequently diagnosed as acute coronary syndromes. Blood samples from these patients displayed overall significantly shortened XACT results relative to both healthy controls (P<0.001) and chest pain not due to cardiac ischaemia (P<0.004). This discrimination was much better with whole blood samples than when platelet-poor plasmas were tested (P=0.153), suggesting that free microparticles were not the only factors responsible. Thus, the detection of increased procoagulant phospholipid activity in whole blood by shortened XACT results may be a simple and rapid diagnostic marker of some cardiac ischaemic events.

Acute Disease↗

A new activated factor X-based clotting method with improved specificity for procoagulant phospholipid.

An improved activated factor X-based clotting method was used to investigate activity of procoagulant phospholipid (PPL) in blood samples collected into various anticoagulants and in plasmas with a range of abnormalities. The dilute activated factor X-activated clotting time (XACT) was carried out on a mixture of specimen with phospholipid-free porcine plasma. PPL from the test sample is then rate-limiting, controlling the clotting time so that the XACT is shortened from a maximum of approximately 120 s with citrated platelet-free plasma to approximately 30 s with freeze-thawed platelet-rich plasma. XACT results were only shortened slightly by fresh normal platelet-rich plasma, but were shortened significantly by platelets that had been activated by freeze-thawing. This improved method for PPL was not prolonged by deficiencies of known clotting factors and therapeutic levels of heparin, and it was surprisingly resistant to most lupus anticoagulants. However, it was extremely sensitive to PPL, detecting down to 50 ng/ml synthetic phospholipid added to phospholipid-free plasma. Excellent correlation was achieved between XACT shortening and microparticle count assessed by annexin V-binding and flow cytometry in normal plasma spiked with platelet microparticles. In citrated blood specimens, XACT shortened with time in a temperature-dependent manner. XACT results on blood samples anticoagulated with ethylenediamine tetra-acetate were more stable, and these would be preferable for assessing PPL expression ex vivo. XACT was significantly shorter in whole blood samples than in normal platelet-rich or platelet-poor plasmas, suggesting that PPL was normally expressed more by cells or aggregates larger than platelets or microparticles.

Annexins↗