Polyurethanes (PUs) represent a heterogenous family of artificial P materials that can be synthesized ranging from soft rubbery materials to rigid rough polymers. They are described as &dquo;biomedical grade&dquo; if they are &dquo;systemic pharmacologically inert substances designed for implantation within living systems&dquo; [1]. The most common PUs used as biomaterials are polyetherurethanes (PEU) which consist of chains of aromatic or aliphatic &dquo;hard&dquo; segments connected by flexible polyether &dquo;soft&dquo; segments (Figure 1). The hard and soft segments of PUs separate into phases and the bulk material consists of domains of hard segments suspended in soft segment matrix, which give the PUs their unique combination of flexibility and strength. PUs exhibit several properties that make them particularly attractive for biomedical applications [2] (Table 1).

An in vitro method has been developed for human non-anticoagulated blood to evaluate the enhancing effect of hemostatic agents on both plasmatic and cellular activation of the coagulation cascade. The coagulation time and the sequential generation of fibrinopeptide A (FpA) have been used as parameters. The kinetics of generation of FpA has been modelized and mathematically analyzed using the latence time, the slope of the linear part of the curve, and the time necessary to reach half maximal amplitude of FpA in the tube. A maximal amplitude of FpA in the tube. A very precise evaluation of the hemostatic activity of five different molecules, four being collagenous in nature, is given.

The interactions of two gadolinium complexes (Gd-DOTA meglumine and Gd-DTPA meglumine) with hemostatic function have been analyzed using: (1) coagulation reactions (extrinsic and intrinsic pathways and fibrinoformation) and (2) platelet function investigations (aggregation, release of Ca++ and ATP after stimulation with collagen 2.5 micrograms/mL). The data obtained with Gd-DTPA meglumine (Mgl) exhibited a significant increase of the intrinsic coagulation pathway and a delay in fibrinoformation, although there is no alteration of the effect of thrombin on fibrinogen (fibrinopeptid A determinations). Platelet aggregation and release are moderately modified. In contrast, Gd-DOTA Mgl exerts no effect on the coagulation system and only minor effects on platelet functions. It is suggested that at least one mechanism involves the complexation of ionized calcium because Gd-DTPA Mgl and Gd-DOTA Mgl complex, respectively, 45% and 23% of ionized calcium in plasma. However, other mechanisms such as an alteration of fibrin polymerization are not unlikely.

Bulk heparinized catheters (1 mm internal diameter) containing 10 % heparin ionically bound, were tested in four human volunteers. Catheters containing 0 % and 10 % heparin were compared in each individual using ultrasound microflow velocimetry, permeability test, sequential determinations of activated partial thromboplastin time, heparin levels and generation of Fibrinopeptide A, ß thromboglobulin and Platelet factor 4. Although the release of heparin expressed by its anti-IIa activity is of similar range in the four individuals the release of anti-Xa activity is variable and generally of greater magnitude, suggesting a privileged migration of low molecular weight components of heparin. These antiproteasic activities of heparin are sufficient to inhibit fibrin formation and blood coagulation despite their relative inability to prevent platelet activation.

The anticoagulant activity of seven intravascular radiocontrast molecules (RCM) was evaluated in different in vitro systems using citrated human plasma. Each RCM was tested in a concentration range of 5 to 50 mM. The thrombin time and the reptilase time showed a dose-dependent lengthening of fibrinoformation, the recording of fibrinoformation exhibited a significant delay of fibrin monomer generation and polymerization although the amplitude of the fibrinoformation was not decreased. The interfering effect with fibrin clot formation impairs also global coagulation tests and monospecific coagulation tests using fibrinoformation as the final step of the assay, but a possible interaction between RCM and some specific coagulation factors cannot be excluded. RCM potentiated the anti-thrombin action of heparin but the inhibition or delay of fibrinoformation is not related to an antithrombinic effect of contrast media. The thrombin amidolytic activity is not modified by RCM but the generation of FpA is delayed and decreased. The ultrastructure of the fibrin clot is not altered at the end of the polymerization.

Healing in skin wounds was compared in rabbit fetuses between the 21st and 27th gestational days and in adults. The plasma levels of the fibrin-stabilizing factor (FSF) were measured. Healing of the wound was characterized by histology and scanning electron microscopy. In the fetuses the healing wounds lacked normal epithelium, an inflammatory reaction, granulation tissue, and fibroblasts. At these gestational stages the plasma levels of FSF were about 10–15% of that of male adults. No FSF was found in the amniotic fluid. The similarities of wound healing in fetuses and in patients congenitally deficient in FSF suggest that the peculiarities of fetal cicatrization may be due to the low levels of FSF in fetal life.

Experimentally induced hypothermia (20 degrees C) for 60 minutes in dogs provokes a significant decrease in the platelet count, which reverses during subsequent rewarming, and the constant release of a heparin-like factor, which reacts as a specific inhibitor of factor Xa. This phenomenon is also rapidly reversible, and heparin values are not significantly different from control levels after 90 minutes of rewarming. The mean maximal concentration of heparin-like material is 0.54 U/ml, or about double control levels. Its half-life is approximately 90 minutes. The level of circulating antithrombin III was not modified during hypothermia and rewarming.