Blood Coagulation and Vascular Integrity :

T HE MECHANISMS responsible for the maintenance of hemostasis on the level of terminal blood vessels are only partially understood. Although platelets have a major role in preventing or arresting hemorrhages from small vessels, clinical and experimental evidence suggests that other factors may also be involved. The role of blood coagulation products or components requires further elucidation, although attention has recently been focused on the deposition of fibrin on the endothelial surface as a means of increasing vascular resistance.’ The occurrence of spontaneous hemorrhages in the course of anticoagulant therapy is of interest in this respect. The spontaneous onset of hematuria, epistaxis or other types of bleeding in patients receiving heparin or Dicumarol is similar to that in patients with hemorrhagic tendencies due to vascular impairment. Previous studies in animals have suggested a decreased vascular resistance following administration of the above anticoagulants.2’3 The bioassays employed, however, have not permitted a more extensive consideration of these effects. Studies by Drinker4 on the mechanisms regulating lymph formation and composition have demonstrated that macromolecules as well as particulate material, including red blood cells, may appear in the lymph without morphologic change of the small blood vessels. Red blood cells are present in the lymph in small numbers under physiologic conditions. Studies of lymph composition have recently indicated that increased red cell diapedesis occurs in thrombocytopenic x-irradiated animals as a result of generalized endothelial damage.5 This phenomenon has been utilized in a sensitive bioassay for the quantitative evaluation of thrombocytopenic bleeding in animals.#{176} The lymph duct cannulation technic and determination of red blood cell diapedesis in rats were employed in the present investigation for the assessment of vascular changes following administration of heparin.