Young Adult Myocardial Infarction and Ischemic Stroke: the role of paradoxical embolism and thrombophilia (The YAMIS Study).

Objectives: We aimed to investigate the frequency of venous-to-arterial circulation shunts (v-aCS), usually caused by patent foramen ovale (PFO), and thrombophilia in young adults suffering myocardial infarction (MI) and ischemic stroke (IS) and matched healthy control subjects.

Background: The cause of MI and IS in young adults is often uncertain, and paradoxical embolism might be more frequent than previously thought.

Methods: Young adults (ages 16 to 39 years) surviving MI (n = 101) and IS (n = 101) between 1993 and 1998 were matched by age and gender to 202 control subjects from the same general practitioner practices.

Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF).

Unlabelled: Hepatic veno-occlusive disease (VOD) is a common and potentially fatal complication of high dose chemotherapy with allogeneic/autologous stem cell transplant (SCT). The diagnosis and treatment of hepatic VOD is controversial. Clinical features are non-specific and may be mimicked by a number of other conditions causing hyperbilirubinaemia post-transplantation.

The importance of locally derived reference ranges and standardized calculation of dilute Russell's viper venom time results in screening for lupus anticoagulant.

Three commercial dilute Russell's viper venom time (DRVVT) kits were evaluated at four UK centres experienced at performing lupus anticoagulant (LA) tests. Each centre established a normal reference range for the DRVVT ratio calculated against local pooled normal plasma from 20 healthy normal subjects. Plasma from LA-positive patients and LA-negative thrombophilia patients was also tested.

Calculation vs calibration curve for INR determination. Results of an interlaboratory proficiency scheme.

We surveyed 271 laboratories participating in a quality assessment program to ascertain whether the use of a calibration curve for determining the international normalized ratio (INR) would improve interlaboratory accuracy and precision. Lyophilized warfarinized samples with INR values assigned through manual calibration against internationally assigned rabbit reference thromboplasts were assayed for prothrombin time. Calibration analysis on the results was performed by linear regression.

Why do outpatients fail to keep their clinic appointments? Results from a survey and recommended remedial actions.

We undertook a survey of 2555 outpatients (both new and review) to look at the reasons for high non-attendance (DNA) rates. Completed questionnaires (n = 983, 38.5% response) indicated the main reasons: forgetting or not receiving the appointment because of illness, and less often because of feeling better; transport problems; and short notice.

The determination of INR in stored whole blood.

Aims: To examine the reliability of international normalised ratio (INR) determination on samples stored as whole blood for up to two days at room temperature.

Methods: The INR of 40 patients receiving oral anticoagulants was determined on fresh blood and on samples stored for 24 and 48 hours, using five locally calibrated prothrombin time systems. These incorporated Manchester reagent, Recombiplastin, IL PT Fibrinogen HS Plus, Manchester combined capillary prothrombin time reagent, and a freeze dried in-house reference rabbit brain thromboplastin, RBT 1010.

Local INR correction: justification for a simplified approach.

Aims: Errors in reporting International Normalised Ratios (INR) may be corrected by assignment of a System International Sensitivity Index (System ISI). This 57 centre study tests the validity of several procedures for INR correction.

Methods: Prothrombin times of eight lyophilised coumarin calibrants, a lyophilised normal pool calibrant, and eight frozen coumarin plasmas were determined at each centre.

Heat stability of two candidate international reference preparations for recombinant human tissue factor.

Adequate heat stability of international reference preparations (IRP) for thromboplastin (tissue factor) is an essential requirement. Accelerated degradation testing was performed by three laboratories on two candidate IRP for recombinant human tissue factor. Heat treatment of these candidates resulted in slight shortening of the PT, contrasting with heat-induced prolongation of the PT observed with a conventional human brain derived IRP.

System ISI calibration: a universally applicable scheme is possible only when coumarin plasma calibrants are used.

Coagulometer-induced errors in International Normalized Ratios (INR) may be corrected by assigning an International Sensitivity Index (ISI) specific for the local combination of coagulometer and thromboplastin reagent (System ISI). In the present study, 57 laboratories determined the INR of eight frozen coumarin plasmas. There was considerable variation in INR reported at the different centres, with coefficients of variation (CV) ranging from 11.

Calculation of System International Sensitivity Index: how many calibrant plasmas are required?

Aims: To determine the minimum number of calibrant plasmas required to assign an accurate System International Sensitivity Index (ISI).

Methods: Eighteen lyophilised adsorbed and eight frozen coumarin plasmas were despatched to 57 participating laboratories. Each centre determined the prothrombin time of all of the plasmas using their routine system of coagulometer and thromboplastin reagent and provided their system mean normal prothrombin time (MNPT).

Soluble P selectin in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease and its risk factors.

Circulating levels of the adhesion molecule P-selectin (CD62P) are increased in the plasma of patients with atherosclerosis, but its relationship to the anatomical location of symptomatic disease or extent of symptomatic disease is unknown. The influence of the risk factors for atherosclerosis on soluble P-selectin is also unclear. To clarify these questions we analysed plasma samples from 170 patients with symptomatic peripheral vascular disease and 119 asymptomatic controls who were, as a group, age- and sex-matched.

Treating paracetamol overdose by charcoal haemoperfusion and long-hours high-flux dialysis.

After serious paracetamol overdose, charcoal haemoperfusion was used to remove paracetamol from the circulation, aiming to reduce the severity of subsequent hepatic damage. Daily long-hours high-flux dialysis was given to patients with grade III-IV hepatic encephalopathy, and also to those at risk of developing encephalopathy. We reviewed patients treated in this manner who had not received N-acetylcysteine within the first 15 h after overdose.

Haematology and coagulation indices in paired samples of arterial and venous blood from patients with arterial disease.

To investigate whether there are differences in haematology and coagulation indices in arterial and venous plasma, and whether those changes related to damage to the endothelium in atherosclerosis, we obtained blood samples from 22 subjects undergoing diagnostic angiography. There were no differences in any of the 15 routine haematological indices measured. There were no differences in prothrombin time, activated partial thromboplastin time, fibrinogen, tissue plasminogen activator, D-dimer, leucocyte elastase, soluble P-selectin or von Willebrand factor.

An easier alternative to orthogonal regression for calculation of International Sensitivity Indexes.

Aims: To evaluate an easier alternative method to orthogonal regression analysis for calculating International Sensitivity Indexes (ISI).

Methods: ISI for 18 reagents were estimated from reference and test reagent prothrombin times using plasma from 60 stabilised patients undergoing anticoagulation therapy and 20 normal subjects. ISI were also derived for 12 systems (instrument/reagent combination) using lyophilised plasma calibrants.

Activated partial thromboplastin time for automated techniques: a comparison of two commonly used reagents.

In a comparison between two widely used activated partial thromboplastin time reagents (Instrumentation Laboratories, Manchester low-opacity), using one popular instrument (Automated Coagulation Laboratory, model 300R), a wide range of defects and 40 normals were tested. There was generally good agreement between methods, although for samples from patients on high heparin dosages the agreement was poor. The manufacturer's recommendation for the therapeutic range for heparin for the Instrumentation Laboratory reagent was lower than the range in current general use.

The correction of coagulometer effects on international normalized ratios: a multicentre evaluation.

One hundred and twenty-nine centres in the U.K. participated in a study to test the reliability of the three methods of correction for coagulometer effects on international normalized ratios (INR).

Clotting factors after emergency contraception.

Unlabelled: Women with a previous history of thromboembolic disease have often been denied oral emergency contraception because of a theoretical concern about increasing their risk of thrombosis.

Methods: Eleven healthy volunteers with regular periods were recruited to the study. A thrombophilia screen was done at the first visit and they each had four measurements of Factor VII and antithrombin III taken at mid-cycle for two cycles.

Effect of the choice of WHO International Reference Preparation for thromboplastin on International Normalised Ratios.

Aims: To compare the International Normalised Ratio (INR) obtained directly with the two types of WHO plain International Reference Preparation for thromboplastin in patients treated with coumarin.

Methods: Prothrombin times were performed in parallel at four centres using WHO human plain IRP (BCT/253) and rabbit plain IRP (RBT/79). Sixty patients and 20 normal controls were tested at each centre.

Safety of anticoagulation in the elderly: reasons for discontinuing therapy.

We have conducted a retrospective study on the reasons for discontinuing anticoagulants in 50 patients over the age of 75 years compared with 198 adults under 75 years to determine the safety of therapy in the elderly. Venous thromboembolism and arterial embolization were the most common indications for therapy in the elderly and the median duration of therapy in all patients was 7 months (9 days-22 years). There were no deaths attributable to anticoagulants.

Assessment of value of calibrated lyophilised plasmas to determine International Sensitivity Index for coagulometers.

An attempt was made to correct for the effects of coagulometers on the International Sensitivity Index (ISI) in a series of collaborative studies. Modified ISI were derived from the prothrombin time results with coagulometer systems using a range of calibrated plasmas. Two alternative approaches to correction of the ISI were evaluated.