Measurement of cross linked fibrin derivatives in plasma: an immunoassay using monoclonal antibodies.

Abstract

SUMMARY Fibrinogen degradation, fibrin polymerisation, and the insertion of cross links into fibrin by fibrin stabilising factor lead to the appearance of new antigenic determinants. Antibodies against these antigenic sites may react specifically with the derivatives but not with the parent molecules. We have utilised a monoclonal antibody, which interacts with the cross linked fragment D dimer and related high molecular weight fibrin derivatives, to develop an enzyme immunoassay which measures cross linked fibrin derivatives in plasma and serum using D dimer as standard. Mean concentration in plasma from normal subjects was 75 ng/ml with an upper limit of about 144 ng/ml. Concentrations in patients with pulmonary embolism, deep venous thrombosis, arterial thromboembolism, and disseminated intravascular coagulation were raised in all cases. Confirmation of the specific increase of cross linked fibrin derivatives in patients with disseminated intravascular coagulation was obtained by parallel monitoring of their fibrin degradation products in serum using affinity chromatography and sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. In many patients the plasma concentrations greatly exceeded the serum values of cross linked fibrin degradation products, suggesting that the procedure can measure fibrin derivatives in plasma which are absent from serum.

Role of the Peripheral Intravenous Catheter in False‐positive D‐dimer Testing

“…However, the D-dimer levels of our study group agree reasonably well with the 75 ng/mL mean concentration documented by Whitaker et al in a study of 25 healthy blood donors (age unknown). 10 The present data also indicate that the increase in D-dimer concentration induced by peripheral IV insertion is relatively trivial compared with other non-thromboembolic etiologies. For example, Goldhaber et al reported the Ddimer concentration to be 2208 Ϯ 2236 ng/mL in 128 hospitalized patients with suspected pulmonary embolism but with normal pulmonary angiograms.…”

Diagnostic approach to pulmonary embolism and lessons from a busy acute assessment unit in the UK

“…D-dimer, a proteolytic derivative of degraded fibrin, can be detected in venous thromboembolism (VTE) as well as many other conditions, including inflammatory disorders, trauma, infections and neoplasia [13,14]. Although a positive D-dimer test has no significant diagnostic value, a negative D-dimer test has a high negative predictive value and makes the diagnosis of PE unlikely.…”

D-dimer: Simple Test, Tough Problems

“…[4][5][6] The clinical conditions associated with elevated levels of D-dimer are numerous. Some of these include thrombosis (arterial or venous), pulmonary embolism, venous thrombosis, disseminated intravascular coagulation, myocardial infarction, stroke, postoperative state, liver disease, malignancy, and pregnancy.…”