Immunoenzymehistochemical detection of fibrin microthrombi during disseminated intravascular coagulation in rats

Summary In tissue of rats with disseminated intravascular coagulation, fibrin microthrombi can be sensitively detected by immunohistochemical methods, using antisera against rat fibrinogen or fibrin monomer. An indirect immunoperoxidase procedure on paraplast-embedded sections yields best results with regard to the morphology of the thrombi and their localization in the tissue.Only fibrillar immunoreactive material, oriented lengthwise in the vessels, should be regarded as microthrombi formed in vivo.     

The syndrome of pneumococcemia,disseminated intravascular coagulation and asplenia.

A 58-year-old man who survived an episode of fulminant pneumococcal septicemia with disseminated intravascular coagulation had undergone splenectomy 23 years previously. In the literature there are 25 reported cases of fulminant septicemia and disseminated intravascular coagulation associated with asplenia in adults (excluding cases in which corticosteroid or immunosuppressive therapy was given). The pneumococcus was responsible for all of these cases as well. The mortality in this series was more than 90%, and death occurred within 24 hours of presentation at hospital in almost 70% of the fatal cases and was associated with high-density bacteremia and adrenal hemorrhage. Gram-staining of the buffy coat of the peripheral blood or the exudate from purpuric skin lesions was carried out in only 6 of the 26 cases but yielded positive results in all but 1. It is concluded that a diagnosis of septicemia in asplenic adults can be established within a short time of presentation on the basis of statistical probability and the results of Gram-staining of the peripheral blood and exudate from the skin lesions. Prevention appears to be the cornerstone of management because of the variable interval from splenectomy to the onset of the syndrome and the high mortality.     

Prevention of intravascular blood coagulation in rats by DIP-alpha-thrombin administration

The possibility of prevention of intravascular blood coagulation in rats by DIP-alpha-thrombin devoid of proteolytic activity and capable of stimulating the reaction of anticoagulation system was studied. The injection of lethal thromboplastin dose was shown to produce a sharp increase in soluble fibrin blood content, total disappearance of fibrinolytic activity and intravascular blood coagulation. The animals died of thrombosis in 90% of cases. It was established that the injection of lethal thromboplastin dose 5 min after DIP-alpha-thrombin injection caused a 13% lethality from thrombosis. No reliable changes in fibrinolytic activity and soluble fibrin content were observed. A significant increase in thrombin and recalcification time was recorded. It is suggested that DIP-alpha-thrombin prevents intravascular blood coagulation induced by lethal thromboplastin dose due to mobilization of the reserve capacities of neuro-humoral anticoagulation system.     

Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans

We used cardiopulmonary bypass (CPB) as a model of activation of the contact system and investigated the involvement of the plasma and tissue kallikrein-kinin systems (KKS) in this process. Circulating levels of bradykinin and kallidin and their metabolites, plasma and tissue kallikrein, low and high molecular weight kininogen, and kallistatin were measured before, during, and 1, 4, and 10 h after CPB in subjects undergoing cardiac surgery. Bradykinin peptide levels increased 10- to 20-fold during the first 10 min, returned toward basal levels by 70 min of CPB, and remained 1.2- to 2.5-fold elevated after CPB. Kallidin peptide levels showed little change during CPB, but they were elevated 1.7- to 5.2-fold after CPB. There were reductions of 80 and 60% in plasma and tissue kallikrein levels, respectively, during the first minute of CPB. Kininogen and kallistatin levels were unchanged. Angiotensin-converting enzyme inhibition did not amplify the increase in bradykinin levels during CPB. Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB.     

Effect of thymalin on the function of the blood kallikrein-kinin system in thymectomized rats

The effects of thymus ablation and injection of thymalin on the blood plasma kallikrein-kinin system were studied. Thymus ablation was followed by activation of kinin formation, evidenced by an elevation of the total kallikrein activity and drop of the kininogen level. Injection of thymalin into thymectomized animals makes the characteristics under study return to normal.     

Activation of blood coagulation and fibrinolysis in Graves' disease.

We studied blood coagulation and fibrinolysis activities in hyperthyroidism before and after methimazole or 131I. Fibrinopeptide A and B beta 15-42, in vivo indicators of thrombin and plasmin activity, were measured by RIA, while fibrinogen by the Clauss method. We studied 50 patients, affected by toxic diffuse goiter. We evaluated 21 of them before and after treatment. Fibrinogen, fibrinopeptide A, and B beta 15-42 were higher in patients than in controls (p less than 0.0001). There was no difference in fibrinopeptide A nor in B beta 15-42 before or after treatment. In euthyroidism fibrinogen returned to normal values. Inflammation of the thyroid gland secondary to autoimmunity may activate blood coagulation by release of tissue factor. High fibrinogen before treatment may be explained as an aspecific response. Since it persists in euthyroidism, autoimmunity could account for high fibrinopeptide A and B beta 15-42 aftertreatment.     

Parasympathetic component of the regulation of the kallikrein-kinin system in experimental pneumonia

Experimental vagus-bacterium pneumonia was modeled on 53 rabbits. Influence of nervous vagus on kallikrein-kinin system (KKS) was studied on 23 rats. It is obvious that disturbance of parasympathetic regulation may be an additional factor of KKS activation. Lowering of kinase II under experimental pneumonia was discovered both in the blood and in the lung. Activation of kinase II in the blood was after vagotomy. So parasympathetic regulation of kinase activity is of no significance in experimental pneumonia, and lowering of kinase activity is connected with bacterial factors.     

Appearance of microthrombi in vessels of central nervous system in the course of disseminated intravascular coagulation syndrome in acute leukemias

In 35 cases out of 37 (88%) microthrombi have been found in CNS. They appeared much more frequently than it could be expected on the basis of the clinical picture of DIC syndrome or changes in the coagulation system. Microthrombi occurred prevalently in white substance of the frontal and occipital lobes as well as in thalamus. In 15 cases the microthrombi were the only evidence of DIC syndrome, besides clinically "mute" one. It should be emphasized that almost in half of the cases we encountered numerous disseminated microthrombi in many regions of CNS. Unequal distribution of microthrombi in CNS points out the significance of the local factor in the pathogenesis of DIC syndrome.