Summary
Characteristic changes induced by dextran during the conversion of fibrinogen to fibrin
have previously been shown to be associated with profound alterations in morphology
of fibrin. However, whether dextran is incorporated into the fibrin molecule and whether
morphological changes are associated with alterations in mechanical behaviour of formed
fibrin was unclear. The investigations described show that the fibrin made in the
presence of dextran has a shortened syneresis time, a lowered modulus of elasticity,
an increased elongation and diminished ultimate strength at break. The molecular composition
of fibrin clots remains unaltered despite the altered mechanical properties and morphological
changes. Furthermore, dextran is not incorporated into the fibrin structure in any
appreciable quantity. It is suggested that these several effects of dextran on clot
morphology, tensile behaviour and kinetics of fibrin formation arise from increased
forces of attraction between fibrin molecules such that fibrin chains are held together
by weak secondary cross-links rather than by stronger primary cross-links which are
hidden within the thicker fibrin chain bundles.
Recently Muzaffar et al. (1972 a, c) showed that the addition of small amounts of
dextran in vitro to purified fibrinogen solution as well as platelet – poor plasma induces characteristic
alterations in the kinetics of fibrin formation on account of accelerated polymerization
of fibrin monomer. Further, fibrin made under such conditions was found to differ
morphologically from control fibrin (Muzaffar et al. 1972 b) and to show an increased
coarseness of individual fibrin fibre on electron microscopy together with an associated
looseness of fibrin mesh. The degree of abnormality in fibrin morphology was found
to be determined by the final dextran concentration. More significantly, dextran was
demonstrated to induce similar changes in the kinetics of fibrin formation as well
as in fibrin morphology of clots made from plasma after the infusion of clinical dextran
fractions in pharmacological dosage in man. However, it is not clear whether dextran-induced
structural alterations in fibrin are indicative ofbasic differences in its molecular
composition nor whether these changes are associated with alterations in the mechanical
strength of fibrin. Clearly these are fundamental questions with respect to the pharmacological
effects of dextran in relationship to its clinically well documented antithrombotic
activity (Lambie et al. 1970). We have investigated both these questions and report
here our principal findings.
