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).