Division of Vascular and Endovascular Surgery, Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan Takahiro Toyofuku
Received Date: April 07, 2013; Accepted Date: June 10, 2013; Published Date: June 12, 2013
Citation: Igari K, Kudo T, Toyofuku T, Jibiki M, Inoue Y (2013) A Case of Disseminated Intravascular Coagulation Caused by a Ruptured Abdominal Aortic Aneurysm for which Recombinant Human Soluble Thrombomodulin was Effective. J Vasc Med Surg 1:109. doi: 10.4172/2329-6925.1000109
Copyright: © 2013 Igari K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Recombinant human soluble thrombomodulin (rhTM) is a new anticoagulant agent that exerts anticoagulatory and anti-inflammatory effects and is effective in the treatment of disseminated intravascular coagulation (DIC). We herein report the case of a 67-year-old male with DIC that developed following the surgical repair of a ruptured abdominal aortic aneurysm (AAA). After the initial operation, DIC occurred and became prolonged. rhTM was then administered, and the DIC state was relieved. In this case, rhTM might be effective for the treatment of DIC after the repair of ruptured AAA.
Recombinant human soluble thrombomodulin; Disseminated intravascular coagulation; Ruptured abdominal aortic aneurysm
Disseminated intravascular coagulation (DIC) is a clinical entity characterized by the systemic activation of coagulation pathways that can result in organ failure via the generation of fibrin clots and may lead to clinical bleeding due to the consumption of platelets and coagulation factors. In patients with DIC, the disease progresses rapidly and the outcome is poor, with a 30–40% mortality rate due to the presence of severe underlying diseases such as infections, sepsis, malignancy, collagen disease, trauma and hematological disease [1,2]. Therefore, anticoagulant therapies are expected to benefit the treatment of DIC.
Recombinant human soluble thrombomodulin (rhTM) (Recomodurin®, Asahi Kasei Pharma Corp., Tokyo, Japan) is a new anticoagulant agent that exerts anticoagulatory and anti-inflammatory effects via the activated protein C (APC) pathway . Thrombomodulin (TM) is a transmembrane protein on the endothelial cell surface that plays an important role in the regulation of intravascular coagulation . rhTM binds to thrombin to inactivate coagulation, and the thrombin-rhTM complex activates protein C to produce APC, which, in the presence of protein S, inactivates factors VIIIa and Va, thereby inhibiting further thrombin formation. Therefore, rhTM has been recently identified as efficacy on the treatment of DIC .
We herein present a case of disseminated intravascular coagulation caused by a ruptured abdominal aortic aneurysm (AAA) that was successfully treated with rhTM.
A 67-year-old male presented with sudden lower back pain and was admitted to another hospital. Computed tomography showed an infrarenal AAA measuring 66 mm with a massive hematoma located primarily in the right side of the retroperitoneal space. The patient was then transferred to our hospital. On physical examination, the patient’s blood pressure was 80/38 mmHg, and he had lower abdominal tenderness. Blood tests revealed a hemoglobin level of 14.0 g/dL and a serum creatinine (Cre) level of 0.75 mg/dL; however, the patient’s vital signs were unstable. He was then intubated and sustained with 4 units of red cell concentrate and 2,000 ml of Ringer’s solution. Furthermore, the left brachial artery was not palpable; then we cut down and a 22-Fr occlusion balloon was placed in the descending thoracic artery. After that, the patient’s blood pressure became elevated to 148/84 mmHg, and emergency surgery was performed.
The surgical repair of the ruptured aneurysm was performed through a midline incision. Immediately, proximal aortic control was achieved at the level of the infrarenal aorta, which was clamped. The aneurysmal wall was found to be ruptured between the posterior region and the right side. Aneurysmectomy and bifurcated graft replacement with a 16 × 8 mm knitted Dacron graft was performed. The operation lasted 171 minutes, and the intraoperative blood loss measured 3,889 ml, and the intraoperative urine loss measured 90 ml. A blood transfusion of 14 units of red cell concentrates, 18 units of fresh frozen plasma and 20 units of platelet concentrates was required, therefore, to avoid abdominal compartment syndrome, we decided the open management of abdomen, which was closed at 14 postoperative day (POD). After the operation, the laboratory data revealed a low platelet count (10.9 × 104/µL) and abnormal coagulation factors (fibrinogen: 153 mg/dL; fibrin/fibrinogen degradation products (FDP): 81.4 µg/ mL; D-Dimer: 51.8 µg/mL; prothrombin time (PT): 16.4 seconds; activated partial thromboplastin time: 47.7 seconds; PT – international normalized ratio: 1.53). DIC was diagnosed on the basis of the Japanese Ministry Health and Welfare (JMHW) scoring tool (Table 1) . The DIC state was caused by a massive hemorrhage due to ruptured AAA, which we treated conservatively. On the third POD, the DIC score was 7 (Figure 1), and rhTM (12,800 U/day) was administered intravenously. Additionally, the patient’s renal function worsened after the first operation, which occurred due to hemorrhage shock. On the third POD, the Cre level was 5.6 mg/dL (Figure 2). Therefore, continuous hemodiafiltration (CHDF) was also introduced. The FDP and D-Dimer levels and the DIC score improved the day after the initial administration. Then, the DIC score was 5 and the DIC state was relieved. We discontinued the administration of rhTM on the 15th POD. The DIC score was 5 or 6; however, the FDP and D-Dimer levels gradually increased. We suspected the abnormal coagulation factors to represent a pre-DIC state, and rhTM (12,800 U/day) was readministered intravenously on the 21st POD. The antithrombin-III (AT-III) level was low (51.1%), and AT (3,000 U/day) was administered on the 24th POD for five days. The FDP and D-Dimer levels and the DIC score improved the day after the readministration of rhTM, and the DIC score was 4 on the 29th POD, then, rhTM was administered until the 48th POD. The patient’s renal function did not improve (Cre: 4.4 mg/dL), and hemodialysis (HD) was required three times a week. The Cre level gradually improved, and his urine volume gradually increased. Then, HD was ended on the 88th POD. After that, the Cre level was under 2 mg/dL, with urine volume over 1,000 ml/day, and the patient did not require further HD. He was discharged on the 101st POD. Six months after discharge, he has remained well with a Cre level of 1.4 mg/dL.
|Platelet counts (x 103μ/L)||> 80 but < 120||> 50 but < 80||< 50|
|FDP (μg/mL)||> 10 but < 20||> 20 but < 40||> 40|
|Fbg (mg/dL)||> 100 but < 150||< 100|
|PT ratio||> 1.25 but < 1.67||> 1.67|
Table 1: The Japanese Ministry Health and Welfare disseminated intravascular coagulation diagnostic criteria.
Figure 2: Changes in the serum creatinine levels before and after treatment with CHDF and HD and the administration of rhTM. Serum creatinine levels had gradually improved, which might be concerned with the administration of rhTM. (CHDF; continuous hemodiafiltration, HD; hemodialysis, rhTM; recombinant human soluble thrombomodulin.).
The novel biological agent rhTM was approved and is being used clinically for DIC treatment in Japan. The effects of rhTM on DIC were previously examined in a multicenter, randomized clinical trial in Japan , and resolution of DIC was significantly better in the group treated with rhTM than in the group treated with unfractionated heparin. Therefore, the indications for rhTM administration to treat coagulation abnormalities have gradually expanded. Sugawara et al.  reported that 10 patients with severe postpartum hemorrhage with DIC were treated with rhTM, and rhTM reduced the coagulation abnormalities, including the D-Dimer levels. Therefore, rhTM may be effective adjunctive therapy in the management of DIC related to hemorrhage. In this case, we were able to successfully manage the patient’s DIC state caused by a massive hemorrhage from a ruptured AAA using rhTM.
Furthermore, acute renal failure (ARF) occurred after the operation in this case. ARF is said to complicate between 20% and 46% of all ruptured AAA repairs . Ischemic/reperfusion (IR)-induced renal injury is an important cause of ARF. Ischemic injury leads to the release of many cytokines that downregulate the expression of thrombomodulin (TM), hence causing a state of relative TM deficiency that leaves the microvasculature in a procoagulant state. Salomaa et al.  demonstrated that a high plasma level of soluble TM may protect endothelial cells from injury. Some articles [10,11] have reported that treatment with rhTM markedly reduces IR-induced renal dysfunction and that rhTM might be effective for the treatment of ARF. Even though rhTM might be effective for treating ARF; however the time could mainly improve ARF in this case. In conclusion, we believe that rhTM was effective for the treatment of DIC in this case limitation.