There are several well-recognized causes of retroperitoneal hematoma, including ruptured aortic aneurysm, traumatic vascular injury, retroperitoneal neoplasms, and coagulopathy [1]. However, idiopathic or spontaneous retroperitoneal hematoma is rare, and there are only a few documented reports implicating heparin, warfarin, low-molecular-weight heparin, or antiplatelet agents as a potential cause [3]. As a lesson from our cases, we consider administration of an anticoagulant drug and hemodialysis to be risk factors for SRB. There are no reports of nafamostat mesilate as a risk factor for SRB, to our knowledge, and we believe this is the first report.
Nafamostat mesilate is a serine protease inhibitor used clinically as an anti-inflammatory. It inhibits protein degrading enzymes such as thrombin, active form coagulation factors (XIIa, Xa, and VIIa), kallikrein, plasmin, and complements such as C1r, C1s, C3, and C5 convertases. It is also effective in inhibiting elements in the alternate pathway such as factors B and D. Similarly, it can counter the activation of key molecules in the coagulation cascade such as thrombin and plasmin and is thus used as an anticoagulant. The inhibitory action of thrombin develops without the need for antithrombin III. The half-life of nafamostat mesilate is short, 2–3 hours [7]. Use of nafamostat mesilate for anticoagulation is safe compared with that of heparin, and therefore, it is used in critical patients or those with a bleeding tendency.
We recognized hemorrhage in our patients on the basis of progressive anemia, tachycardia with low blood pressure, and abdominal distension. Abdominal ultrasonography was not useful for identifying retroperitoneal hemorrhage because none of our patients showed the presence of any intraabdominal fluid. However, enhanced CT was useful for the accurate diagnosis of SRB. Bleeding was slow in our patients, and thus it was hard to recognize SRB in the early phase. Trans-catheter embolization is reported to be useful in achieving hemostasis in SRB [8]. Multiple sites of bleeding were present in our patients, and bleeding occurred in peripheral arteries in three of the patients. SPONGEL® was used as the embolic material, and complete hemostasis was achieved in all patients with no incidents of re-bleeding or complications.
The mechanism of SRB was not clear. A previous report suggested that forceful muscular strain might be a mechanism of SRB [9]. In our patients and in previous reports, sites of bleeding were mostly intramuscular, occurring in the posterior region of the iliopsoas or gluteal muscles [9]. The sites of bleeding were the lumbar arteries in the majority of our patients. We considered one possible mechanism of blood vessel rupture in our patients to be the long time in which they had lain in the supine position, which resulted in compression of the posterior side of the involved muscle. Another possible mechanism might have been muscle strain of the iliopsoas muscle occurring during routine patient care of which neither the nursing staff nor the patients were aware. The patients with iliopsoas hematoma were in the supine position for an average of 11 days (range, 10–13 days), and changing of patient position was limited because they were being treated with continuous hemodiafiltration. Multiple sites of bleeding were present in all but one of our patients. Although our results may suggest that achievement of hemostasis in SRB with transcatheter arterial embolization was more useful than that by surgical treatment, this report included a very small number of cases from a single center. Thus, there is a need to collect more cases from additional centers. Further, we could not definitively determine that the cause of SRB was directly related to nafamostat mesilate. However, we suggest that nafamostat mesilate may be one risk factor for SRB.
