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.
Highlights
In 1967, Fine et al first reported that aortic aneurysm can be complicated by disseminated intravascular coagulation (DIC) [1]
Various factors are thought to be involved in the development of DIC, including coagulation activation associated with blood turbulence within the aortic aneurysm and fibrinolytic activation in the aortic aneurysm wall
We have experienced a case of DIC with enhanced fibrinolysis associated with vascular malformations in which combination therapy with direct oral anticoagulants (DOACs) and tranexamic acid resulted in dramatic improvement of DIC, and the patient continued treatment on an outpatient basis for more than 3 years [32]
Summary
The coagulation cascade underlies the production of fibrin clots via two quite different pathways, comprising extrinsic and intrinsic coagulation activation (Figure 1). Resulting from these, thrombin and activated factors VII, IX, and X play roles as serine proteases. Resulting from these, thrombin and activated factors IX, X, XI and XII play roles as serine proteases. The fibrin produced by the above mechanism polymerizes to form a fibrin clot This fibrin clot is converted to a stabilized form by activated factor XIII (activated by thrombin). In cases of DIC associated with aortic aneurysm, the main mechanism of coagulation activation may be intrinsic coagulation activation following exposure to subendothelial collagen or foreign bodies such as stents, but this issue remains to be investigated in detail. Whether suppression of multiple serine proteases present in the coagulation cascade or targeting and suppression of specific coagulation factors represents the best option for the treatment of DIC is an issue still to be properly investigated
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