Effect of Recombinant Human Soluble Thrombomodulin on Coagulation-Related Variables in Patients With Sepsis-Induced Disseminated Intravascular Coagulation: A Retrospective Observational Study

To evaluate associations among coagulation-related variables, resolution of disseminated intravascular coagulation (DIC) and mortality, we retrospectively investigated 123 patients with sepsis-induced DIC treated with recombinant human soluble thrombomodulin (rTM). Changes in coagulation-related variables before and after treatment with rTM were examined. Further, associations between coagulation-related variables and DIC resolution were evaluated. The platelet count, prothrombin international normalized ratio (PT-INR), and fibrin/fibrinogen degradation products (FDP) significantly ( p < .001) improved after rTM administration in survivors (n = 98), but not in nonsurvivors (n = 25). However, the DIC score significantly ( p < .001) reduced in survivors and in nonsurvivors. Among coagulation-related variables examined before rTM, only PT-INR was significantly ( p = .0395) lower in survivors than in nonsurvivors, and PT-INR before rTM was significantly ( p = .0029) lower in patients attaining than not attaining DIC resolution (n = 87 and 36, respectively). The 28-day mortality was significantly lower in patients attaining than not attaining DIC resolution (11.5% vs 41.7%, p = .0001). In conclusion, the initiation of rTM administration before marked PT-INR elevation may be important to induce DIC resolution and thus to decrease mortality in patients with sepsis-induced DIC. Conversely, the treatment with rTM in patients with marked PT-INR elevation may be not so effective in achieving such goals.

Non-plasmin fibrinolysis with immobilized subtilisins

Введение. В современной клинической медицине технология фармакологического тромболизиса в подавляющем большинстве случаев реализуется посредством применения активаторов плазминогена. Плазминовый фибринолиз ограничен ввиду ингибирования плазмина продуктами деградации фибрина. Фибринолиз субтилизинами может рассматриваться как альтернативная технология фармакологического тромболизиса. Цель исследования: изучить особенности фибринолитического действия иммобилизированных субтилизинов in vitro. Материалы и методы. В соответствии с задачами исследования было проведено 5 серий экспериментов: со специфичным к плазмину хромогенным субстратом с очищенным препаратом фибринмономера с оценкой наличия прямой фибринолитической активности с оценкой торможения полимеризации (самосборки) фибринмономера со сравнением тромболитической активности препарата иммобилизированных субтилизинов по отношению к аналогичной активности плазмина и трипсина in vitro. Результаты. Проведенные исследования продемонстрировали высокую фибринолитическую активность иммобилизированных субтилизинов. Показано, что действие последних на фибрин реализуется напрямую и с четким дозозависимым эффектом. Заключение. Фибринолитическая активность субтилизинов представляет собой феномен экзогенного неплазминового фибринолиза. Introduction. Pharmacological thrombolysis is traditionally using plasminogen activators. Followed fibrinolysis can become limited in some time due to plasmin depletion and its inhibition by fibrin/fibrinogen degradation products. We assumed the subtilisin can perform alternative mode of fibrinolysis. Aim: to study features of fibrinolytic activity of immobilized subtilisins in vitro. Materials and methods. Subtilisin fibrinolytic activity, and fibrinmonomer selfassembling deceleration, and comparing thrombolytic activities immobilized subtilisins, plasmin and trypsin each to other were examined with five in vitro experiments using plasminspecific chromogenic substrates and purified fibrinmonomer. Results. Immobilized subtilisins have shown high direct fibrinolytic activity which seems having dosedependent manner. Conclusion. Exogenous immobilized subtilisins are plasmin/plasminogen bypassing agents. Their proteolytic action at fibrin might be considered as a phenomenon of nonplasmin fibrinolysis.

The significance of the levels of fibrin/fibrinogen degradation products for predicting trauma severity

Background: On initial treatment in the emergency room, trauma patients should be assessed using simple clinical indicators that can be measured quickly. Objectives: The purpose of this study is to investigate the relationship between the injury severity score and blood test parameters measured on emergency room arrival in trauma patients. Methods: Trauma patients transferred to Gunma University Hospital between May 2013 and April 2014 were evaluated in this prospective, observational study. Blood samples were collected immediately on their arrival at our emergency room and their hematocrit, platelet, international normalized ratio of prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products, and D-dimer were measured. We evaluated the correlations between the injury severity score and those biomarkers, and examined whether the correlation varied according to the injury severity score value. We also evaluated the correlations between the biomarkers and the abbreviated injury scale values of six regions. Results: We analyzed 371 patients. Fibrin/fibrinogen degradation products and D-dimer showed the greatest coefficients of correlation with injury severity score (0.556 and 0.543, respectively). The area under the curve of the receiver operating characteristic was larger in patients with injury severity score ⩾ 9 than in those with injury severity score ⩾ 4; however, patients with injury severity score ⩾ 9 or ⩾16 showed no significant differences. The area under the curve of fibrin/fibrinogen degradation products was larger than that of D-dimer at all injury severity score values. The chest abbreviated injury scale had the strongest relationship with fibrin/fibrinogen degradation products. Conclusion: Fibrin/fibrinogen degradation products and D-dimer were positively correlated with injury severity score, and the relationships varied according to trauma severity. Chest trauma contributed most strongly to fibrin/fibrinogen degradation product elevation.