Mechanisms and management of the coagulopathy of trauma and sepsis: trauma-induced coagulopathy, sepsis-induced coagulopathy, and disseminated intravascular coagulation

Abstract

Disseminated intravascular coagulation can occur due to different causes but commonly following sepsis. Trauma-induced coagulopathy (TIC) occurs on hospital arrival in approximately 25% of seriously injured patients who initially presents with impaired hemostasis and a bleeding phenotype that can later progress to a prothrombotic phase. Following traumatic injury, ineffective hemostasis is driven by massive blood loss, tissue damage, and hyperfibrinolysis. This initial impaired hemostasis continues until surgical or other management strategies not only to stop the causes of hemorrhage but also progresses to a prothrombotic and hypofibrinolytic state, also termed fibrinolytic shutdown. Prothrombotic progression is also promoted by inflammatory mediator release, endothelial injury, and platelet dysregulation, which is commonly seen in sepsis with increased mortality. Unlike TIC, the early phase of sepsis is frequently complicated by multiorgan dysfunction described as sepsis-induced coagulopathy (SIC) that lacks a hemorrhagic phase. The phenotypes of SIC and TIC are different, especially in their initial presentations; however, patients who survive TIC may also develop subsequent infections and potentially sepsis and SIC. Although the pathophysiology of SIC and TIC are different, endothelial injury, dysregulated fibrinolysis, and coagulation abnormalities are common. Management includes treatment of the underlying cause, tissue injury vs infection is critical, and supportive therapies, such as hemostatic resuscitation and circulatory support are essential, and adjunct therapies are recommended in guidelines. Based on clinical studies and certain guidelines, additional therapies include tranexamic acid in the limited timing of initial traumatic injury and anticoagulants, such as antithrombin and recombinant thrombomodulin in disseminated intravascular coagulation.

Keywords: anticoagulant; coagulopathy; disseminated intravascular coagulation; endothelial cell; fibrinolysis.

Figure 1.. Bleeding and thrombus in the microcirculation in a sepsis model of rat

Rat mesenteric microcirculation was observed under the intravital microscope after lipopolysaccharide injection. At three hours, micro bleedings are observed (left panel, white arrowheads). In the right panel, round stiff leukocytes adhered to the unsmooth and swelled endothelial cells and formed microthrombi (white arrows). The leukocytes transmigrated to the extravascular space (black arrows). The extravasation of the red blood cells was also seen in this panel (white arrowhead). Along with these changes, the blood flow gradually decreased.

Figure 2.. Clinical course of the case

A 42-year-old man was suffered multiple trauma by a car accident. The respiratory failure and hemorrhagic shock were recognized at presentation. Respiratory support and fluid resuscitation were initiated followed by blood transfusion. The patient was diagnosed trauma-induced coagulopathy (TIC) due to impaired hemostasis. Pelvic fixation and pelvic packing were performed successfully after transfusion and anti-fibrinolytic therapy. On six postoperative day, high fever and shivering suddenly presented and the patient fell into shock on the next day. Sepsis-induced coagulopathy (SIC) score was six, and anticoagulant therapy was initiated along with antibiotic therapy. SIC was resolved on day 10, and the patient was moved to a general ward. DIC, disseminated intravascular coagulation; TXA, tranexamic acid; MODS, multiple organ dysfunction syndrome

Figure 3.. Time courses of trauma-induced coagulopathy and sepsis-induced coagulopathy

Tissue damage-induced activated coagulation, massive blood loss, tissue malcirculation, and hemodilution are the important factors of impaired hemostasis seen in early trauma-induced coagulopathy (TIC). In contrast, such a phase is rarely seen in sepsis-induced coagulopathy (SIC). Inflammatory and procoagulant reactions play critical roles in the development of widespread microthrombosis. Hemorrhagic early TIC turns to thrombotic late TIC and progresses to overt disseminated intravascular coagulation (DIC).

Figure 4.. Treatment for disseminated intravascular coagulation

The treatment for disseminated intravascular coagulation (DIC) is different depending on the phases. For early trauma-induced coagulopathy (TIC), the use of tranexamic acid is considered if the time is within 3 hours after the accident, and the blood transfusion is performed by following the massive fusion protocol. For late TIC and sepsis-induced coagulopathy, thrombus prophylaxis is recommended. Anticoagulant therapy for SIC is recommended in Japanese guidelines. For the consumptive coagulopathy in overt DIC, supplemental therapy is performed. PT-INR, prothrombin time-international normalized ratio; FFP, fresh frozen plasma