Case Presentation
A 76-year-old male patient was admitted to our institution to investigate his left lower back pain and systemic subcutaneous bleeding. On hospital day 1 (HD1), coagulation workup showed no abnormal findings but revealed a prolonged activated partial thromboplastin time (APTT) of more than 300 seconds and a low hemoglobin level of 7.6 g/dL. Computed tomography (CT) showed a low-density lesion, suggestive of left psoas hematoma, and no gallbladder stones (Figure 1a). The APTT level could not be corrected by mixing with normal plasma, which was indicative of the presence of coagulation factor inhibitors. Therefore, intravenous prednisolone 1 mg/kg/day and recombinant activated factor VII (rFVIIa) 90 mcg/kg every 3 h were administered to eliminate coagulation factor inhibitors and to prevent life-threatening bleeding, respectively.
Thereafter, laboratory tests revealed low factor VIII activity (<1%) and a high factor VIII inhibitor level of 143 BU/mL. His bleeding predisposition was attributed to AHA. On the night of HD1, the patient developed a high-grade fever and was prescribed intravenous CTRX 2.0 g every 12 h, considering psoas abscess or cellulitis.
After the bypassing agent therapy was administered, his left low back pain and systemic subcutaneous bleeding were improved. Therefore, we finished administering rFVIIa to the patient on HD5. CT on HD6 demonstrated that the low-density lesion, suggestive of left psoas hematoma, had improved, while a high-density lesion in the gallbladder had emerged (Figure 1b). The patient showed no clinical symptoms of acute calculous cholecystitis, and there were no remarkable changes in his laboratory findings. The patient was diagnosed with CTRX-associated pseudolithiasis, and CTRX was discontinued since his high-grade fever had improved.
Extensive subcutaneous bleeding of the right back occurred on HD10, and rFVIIa was promptly resumed. Since the APTT and low factor VIII activity were not improved and the factor VIII inhibitor level remained high, intravenous methylprednisolone 1 g/kg/day was administered from HD14 to HD16. However, despite the further immunotherapy, his bleeding symptoms and abnormal coagulation-related laboratory data due to AHA were not improved. Furthermore, CT demonstrated that hematoma of the left psoas and the right back had expanded, and the high-density area in the gallbladder remained.
Thus, rFVIIa was switched to activated prothrombin complex concentrates (APCC) 100 IU/kg every 12 h on HD16. Thereafter, the systemic subcutaneous bleeding improved, and the dose of APCC was reduced to 100 IU/kg every 12 h on HD21. On the same day, however, the patient developed a high-grade fever, so piperacillin and tazobactam were administered. On HD22, the patient complained of abdominal pain in the right upper quadrant. Enhanced CT with intravenous contrast demonstrated not only a high-density area, indicative of CTRX-associated pseudolithiasis but also pericholecystic stranding, a thickened gallbladder wall, and extravasation of contrast into the gallbladder, indicative of hemorrhagic cholecystitis (Figure 1c, d). Several hours later, the patient suddenly died after rapid progression of abdominal bloating.
At the autopsy, the gallbladder was severely swollen and ruptured with hemorrhaging and contained a large amount of hematoma. Intra-abdominal blood clots were connected to the gallbladder, and the primary source of hemorrhaging was thought to be the gallbladder (Figure 2a, b). Histology of the gallbladder demonstrated hemorrhagic and necrotic changes with focal neutrophilic cell infiltration and fresh thrombi (Figure 2c).