Therapeutic Strategies for Disseminated Intravascular Coagulation Associated with Aortic Aneurysm

Abstract

Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both coagulation and fibrinolysis are markedly activated. Typical cases show decreased platelet counts and fibrinogen levels, increased concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer, and increased FDP/D-dimer ratios. Thrombin-antithrombin complex or prothrombin fragment 1 + 2, as markers of coagulation activation, and plasmin-α2 plasmin inhibitor complex, a marker of fibrinolytic activation, are all markedly increased. Prolongation of prothrombin time (PT) is not so obvious, and the activated partial thromboplastin time (APTT) is rather shortened in some cases. As a result, DIC can be neither diagnosed nor excluded based on PT and APTT alone. Many of the factors involved in coagulation and fibrinolysis activation are serine proteases. Treatment of enhanced-fibrinolytic-type DIC requires consideration of how to control the function of these serine proteases. The cornerstone of DIC treatment is treatment of the underlying pathology. However, in some cases surgery is either not possible or exacerbates the DIC associated with aortic aneurysm. In such cases, pharmacotherapy becomes even more important. Unfractionated heparin, other heparins, synthetic protease inhibitors, recombinant thrombomodulin, and direct oral anticoagulants (DOACs) are agents that inhibit serine proteases, and all are effective against DIC. Inhibition of activated coagulation factors by anticoagulants is key to the treatment of DIC. Among them, DOACs can be taken orally and is useful for outpatient treatment. Combination therapy of heparin and nafamostat allows fine-adjustment of anticoagulant and antifibrinolytic effects. While warfarin is an anticoagulant, this agent is ineffective in the treatment of DIC because it inhibits the production of coagulation factors as substrates without inhibiting activated coagulation factors. In addition, monotherapy using tranexamic acid in cases of enhanced-fibrinolytic-type DIC may induce fatal thrombosis. If tranexamic acid is needed for DIC, combination with anticoagulant therapy is of critical importance.

A case of abdominal aortic aneurysm presenting as symptomatic disseminated intravascular coagulation treated with endovascular aneurysm repair and postoperative administration of Nafamostat mesylate

“…Treatment for DIC consists of treating the underlying disease. However, treatment strategies for AAAs presenting with DIC are unclear, as there is still no high-level evidence [ 3 ].…”

Distinguishing immune-mediated thrombotic thrombocytopenic purpura from septic disseminated intravascular coagulation using plasma levels of haptoglobin and factor XIII activity

“…Therefore, differentiating between iTTP and septic DIC using these markers alone may be unreliable. Although these markers may be highly useful for classifying DIC types [ 8 , 29 , 30 ], they were found to be insufficient for differentiating iTTP from septic DIC.…”

“…This study has several limitations. First, we did not include enhanced fibrinolytic-type DIC [ 8 ], which is often seen in acute promyelocytic leukemia [ 8 , 40 ], aortic aneurysm [ 8 , 29 , 30 ], or vascular malformations [ 30 , 41 ]. The trends of plasma haptoglobin and FXIII in enhanced fibrinolytic–type DIC may differ from the results in septic DIC.…”

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination

“…Nafamostat has inhibitory effects on serine proteases, inhibiting coagulation factors such as factors VIIa, IXa, Xa, and IIa (thrombin), all of which are serine proteases [ 128 ]. These factors are also inhibited by heparin, but heparin is antithrombin-dependent, whereas nafamostat can inhibit these factors in a heparin-independent manner.…”

“…In chronic DIC (e.g., cases with aortic aneurysms and vascular malformations), the invasiveness of vaccination may cause severe bleeding and should be discussed with the attending physician [ 128 ].…”