Experimental Aspects of Topical Haemostatic Agents

Abstract: Control of haemorrhage is vital in all operative settings. As complement to traditional surgical haemostatic techniques, a heterogeneous collection of absorbable substances with haemostatic capacity have been developed; topical haemostatic agents. The widespread variety of the products and the study-populations (clinical or experimental) make interpretation of previously performed studies difficult. The general aim of this thesis was to evaluate the haemostatic efficacy of four principally different basic substances in two separate experimental bleeding models. Two coagulation factors; bovine thrombin (bT) and recombinant FVIIa (rFVIIa) and two passive substances; gelatine and microporous polysaccharide hemospheres (MPH) were evaluated, separately and combined, in a randomized fashion. Heparinized rats were used in all studies. In Paper I a new arterial high flow bleeding model was used and in Paper II-IV a renal bleeding model. The animals were additionally platelet inhibited in Paper III. Neither pure coagulation factors nor MPH was better than gauze (negative control). Gelatine was effective in heparinized rats, when platelet inhibition was added complementary bT was required for rapid and durable haemostasis. Topical rFVIIa proved a weak haemostatic effect compared to the effect when administered IV (positive control). Degradable starch microspheres (DSM) are similar to MPH. In Paper IV chemical modifications of DSM were performed, evaluated in vitro (thrombin generation and platelet adhesion tests), and in vivo. DSM modified to activate platelets demonstrated best haemostatic effect. In conclusion; for sufficient haemostatic effect, a topical agent is required to: adhere rapidly to the bleeding source, activate platelets and also stimulate the coagulation.