Biomedical subjects

R J Luddington

Publications and source records attributed to R J Luddington.

8 recordsLinked to original sources

PubMed2005

Thrombelastography/thromboelastometry.

The term thrombelastograph (TEG) was used to describe the trace produced from the measurement of the viscoelastic changes associated with fibrin polymerization. Recently the term rotational thromboelastometry has been applied to the output of the ROTEM instrument. Since its first description in 1948, the TEG/ROTEM has been successfully used in the near patient assessment of haemostasis. The greatest use has been the application of TEG-guided transfusion of blood components in hepatic and more widely in cardiac surgery. Recent years have seen a renewed interest in the technology with applications for both pharmaceutical monitoring and patient screening being described. The present review gives a broad overview of the developments and applications related to thrombelastography/thromboelastometry.

Female↗

PubMed1992

Streptokinase resistance: when might streptokinase administration be ineffective?

OBJECTIVE: (a) To develop an assay for streptokinase resistance. (b) To determine the prevalence of streptokinase resistance in patients presenting with acute myocardial infarction for the first time. (c) To determine the prevalence of streptokinase resistance in patients after exposure to streptokinase or streptococcal infection. DESIGN: Open, prospective. PATIENTS: 30 healthy volunteers. 40 patients admitted to the coronary care unit at Addenbrooke's Hospital with suspected acute myocardial infarction, 12 patients 12 months after streptokinase treatment, eight patients 24 months after streptokinase treatment, and sera from 12 patients with raised anti-streptolysin O (ASO) titres. METHODS: Three assays were used; a dilution neutralisation assay, an enzyme linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) anti-streptokinase antibodies, and an in vitro fibrin plate lysis assay. All measurements were performed on venous blood samples. RESULTS: Neutralisation and IgG antibody titres were positively correlated. Mean (SEM) antistreptokinase concentrations in the 30 controls were 87 (10) U/ml (neutralisation assay) and 28 (6.3) U/ml (ELISA). Corresponding concentrations in patients before streptokinase were 68 (6.1) U/ml and 18 (4.5) U/ml with a mean fibrin plate assay 117 (7.1)% that of controls. Resistance to streptokinase was detectable in one patient after 72 hours and in all patients by day 10. By day 10 concentrations were 4388 (919) U/ml, 773 (109) U/ml, and 17 (5.4)%. At both 12 and 24 months resistance was present in 75% of patients. Similarly 66% of high ASO titre sera showed resistance. The fibrin plate lysis assay detected significantly reduced streptokinase dependent fibrinolysis in vitro in the absence of raised total concentrations of antistreptokinase antibodies. CONCLUSIONS: The prevalence of streptokinase resistance in patients presenting with their first myocardial infarction is low. Resistance develops early after treatment and is still present in 75% of patients after 24 months. Retreatment with streptokinase is likely to be suboptimal even after 24 months. The fibrin plate lysis assay detects resistance in patients with normal concentrations of streptokinase antibodies. Streptococcal infection is associated with a high incidence of streptokinase resistance.

Antibodies↗

PubMed1991

Changes in endothelial-related coagulation proteins in response to venous occlusion.

One hundred patients with a history of thrombophilia were divided into two groups based on fibrinolytic response to venous occlusion. Good responders with a euglobulin clot lysis time less than or equal to 105 min showed significant release of tPA, PAI and vWF. Of the poor responders with an ECLT greater than 105 min, 24% showed a subnormal increase in tPA, and a significant proportion of these also showed a reduced or absent rise in vWF. We have shown poor fibrinolytic response was related to either raised levels of PAI, poor release of both tPA and vWF, or poor release of tPA or vWF alone suggesting different mechanisms of fibrinolytic impairment. Protein S levels were not significantly changed in either group following occlusion.

Adult↗

PubMed1991

The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease.

210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a dysfunctional antithrombin variant. The variants have all been characterized by DNA analysis and in three the mutations have been confirmed by peptide sequencing (antithrombin Basel (41 Pro to Leu). Hamilton (382 Ala to Thr). Cambridge I (384 Ala to Pro) and Cambridge II (384 Ala to Ser). The incidence of antithrombin deficiency in patients with a history of venous thrombosis has previously been quoted at between 2% and 3%: there is no published data available on the incidence of antithrombin variants. In our series 5% of patients who presented before the age of 40 years had antithrombin deficiency, and 2% of the total number of patients investigated had a dysfunctional variant. Our figures indicate that a significant number of cases of antithrombin deficiency are due to dysfunctional variants and that the true incidence of antithrombin deficiency in patients with a history of venous thrombosis is in the order of 5%.

Adult↗

PubMed1991

Evaluation of the Ciba Corning Biotrack 512 coagulation monitor for the control of oral anticoagulation.

The Ciba Corning Biotrack 512 coagulation monitor requires a minimal degree of technical expertise to operate, and is already in use for near-patient testing. This study evaluated the monitor for possible use in decentralised control of oral anticoagulant treatment. The monitor compared well with Manchester Reagent, suggesting that it could be used in areas where this thromboplastin is used for centralised control. The inability of the monitor to allow for locally determined geometric mean normal prothrombin times in the calculation of the International Normalised Ratio (INR), and possibly the high International Sensitivity Index (ISI) of the thromboplastin used with the monitor, resulted in poor comparability with some other thromboplastins, particularly Thrombotest. These problems need to be addressed if the monitor is to be used for decentralised anticoagulant control.

Administration, Oral↗

PubMed1989

Coagulation changes following hepatic revascularization during liver transplantation.

The coagulation changes during liver transplantation have been studied in 14 selected patients. Blood usage in all cases was limited to 8.5 liters, and the preoperative coagulation results were only minimally deranged. Bleeding during the operative procedure was easily managed in all cases. Nonetheless, even in this selected group of "low risk" patients, we have demonstrated that during the anhepatic phase and particularly following hepatic revascularization there is activation of both coagulation and fibrinolysis. These findings imply that if bleeding occurs following revascularization, in addition to the use of replacement blood products, treatment should be directed at reducing the consumptive coagulopathy and inhibiting fibrinolysis. We suggest as a first step antithrombin supplementation to maintain activity above 70%, and an antifibrinolytic agent, such as aprotonin, should be considered as adjuncts to therapy at revascularization.

Age Factors↗

PubMed1989

An enzyme-linked immunosorbent assay for measurement of protein S.

Protein S is an important component of the haemostatic balance mechanism, and deficiency of this protein predisposes to thrombotic risk. We describe an inexpensive and reliable enzyme-linked immunosorbent assay for measurement of protein S, which is suitable for use in routine hospital laboratories.

Blood Proteins↗

PubMed1988

Protein C deficiency and portal thrombosis in liver transplantation in children.

Changes in plasma protein C and antithrombin concentrations after liver transplantation were monitored in fourteen children and a control group of fourteen adults. In the children, there was a persistent deficiency in the plasma concentration of protein C and a less pronounced deficiency in antithrombin during the early postoperative period, causing a hypercoaguable state. A concomitant rise in plasminogen activator inhibitor further increased the risk of thrombosis by inhibiting fibrinolysis. These changes coincided with the peak incidence of portal vessel thrombosis (4-10 days). Replacement of plasma antithrombin, together with heparin, did not prevent portal thrombosis in two of the children. It is concluded that successful prevention will require protein C replacement together with antithrombin supplements up to, but not exceeding, normal plasma activity.

Adult↗