The two therapeutic strategies of surgical intervention and medical management in a patient with enhanced-fibrinolytic type of disseminated intravascular coagulation after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure

Disseminated intravascular coagulation (DIC) is systemic coagulant disorder caused by underlying diseases, such as severe infection, malignant tumor, liver failure, and vascular disorders. This syndrome is characterized by bleeding tendency with consumption of platelets and coagulation factors, and by multiple organ failure with microvascular thrombosis [1, 2]. DIC is classified into three types by the degree of fibrinolytic activation: suppressed-fibrinolytic type, balanced-fibrinolytic type, and enhanced-fibrinolytic type. Enhanced-fibrinolytic type DIC, which is associated with marked fibrinolytic activation, have been reported in acute promyelocytic leukemia (APL) and aortic disorders such as aortic aneurysm and dissection [3]. Especially, DIC associated with aortic disorders progress chronically in no symptom, but some invasions can induce a decompensated state with hemorrhagic complication [4]. The optimal treatment for DIC associated with aortic disorders is surgical intervention, however it is not often suitable due to the patient’s medical condition such as advanced age or severe comorbidities [2, 5]. Several case reports showed that medical treatments, such as anticoagulant agents, antifibrinolytic agents, and a combination of both, were effective for inoperable patients with DIC associated with aortic disorders [4, 6‐13]. We describe a case in which two strategies of surgical intervention and medical treatment were effective for the enhanced-fibrinolytic type DIC after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure.

Enhanced-fibrinolytic type DIC is characterized by marked fibrinolysis activation corresponding to coagulant activation. This type of DIC has been reported in APL and aortic disorders such as aneurysm and dissection. The mechanism of DIC differs depending on the underlying disease. In APL, abnormally high levels of expression of annexin II on APL cells induces marked fibrinolytic activation [14]. On the other hand, DIC associated with aortic disorders is caused by excessive consumption of coagulation factors due to endothelial disruption with atheromatous plaque or dissection of the aorta [4, 11]. DIC associated with aortic disorders decompensates when triggered by trauma or an invasive procedure such as tooth extraction triggers, resulting in hemorrhagic complications that are difficult to control. In this case, we assumed that chronic DIC was caused by excessive consumption of coagulation factors due to hematoma leakage from prosthetic vascular grafts and some incident triggered the hematoma around the CRT-D as hemorrhagic complications [4].

The optimal treatment for DIC is the treatment for the underlying disease. Hence, surgical intervention is the optimal treatment for DIC associated with aortic disorders. However, it is often difficult due to the patient’s medical condition such as advanced age or severe comorbidities [2, 5]. Several anticoagulant agents have been reported to be effective for DIC, such as heparin [6], synthetic protease inhibitors [7, 8], recombinant soluble thrombomodulin [9], and direct oral anticoagulants [4, 10]. Antifibrinolytic agents such as tranexamic acid are generally not recommended for the DIC due to the increased risk of thromboembolic complications, but it could be a reasonable option in combination with anticoagulant agents for DIC with marked activation of fibrinolysis [2, 11‐13, 15]. In the first admission of this case, we performed the third sternotomy as the treatment for the underlying disease because the hematoma around the CRT-D was not controlled despite the administration of recombinant soluble thrombomodulin. However, the hematoma might improve spontaneously because D-dimer had been decreased in association with administration of the agent, if we continued the administration without invasive procedures on the hematoma. On the contrary, multiple invasive procedures on the hematoma might lead to a worsening of the DIC. The recurrence of DIC leading to the second admission may also have been triggered by the invasive procedure of the CRT-D replacement. In the second admission, we could control the hematoma by the combination of synthetic protease inhibitor and tranexamic acid. We chose gabexate mesilate of synthetic protease inhibitor concerned about hyperkalemia of the side effect of nafamostat mesilate because she had severe renal dysfunction, although there were no reports of gabexate mesilate for DIC associated with aortic disorders to the best of our knowledge. Because gabexate mesilate had less antifibrinolytic activity than nafamostat mesilate, we determined to add tranexamic acid [16]. Subsequently, in contrast to the first admission, we could observe a reduction of the hematoma without invasive procedures after decreasing the coagulation markers of D-dimer and FDP with the medical therapy. In addition, by continuing a synthetic protease inhibitor and tranexamic acid as oral agents after discharge, we were able to suppress the hemorrhagic complication in the long term. We did not switch to an AF-adapted DOAC because she had severe renal dysfunction. We believed that the long-term use of these agents was reasonable because of recurrent hemorrhagic events.

In summary, we experienced two different strategies for enhanced-fibrinolytic type DIC with the hemorrhagic complication in one case. This case showed the importance of a successful combination of surgical and medical therapy for hemorrhagic complications due to enhanced-fibrinolytic type DIC.