A 78-year-old man was admitted with a chief complaint of black stool. Ten days prior to his recent hospitalization, the patient was admitted to a nearby hospital with the same complaint. Esophagogastroduodenoscopy (EGD) was performed, and hemostatic procedures were done three times because of exudative hemorrhage and a Dieulafoy’s lesion in the lesser curvature of the antrum and upper body of the stomach (). Melena was observed during digital rectal examination at the time of admission, and fresh red-colored blood was noted in gastric lavage via a nasogastric tube. The patient has been taking medications for hypertension, heart failure, and asthma, excluding anticoagulants or antiplatelet medications. He was a non-smoker and non-alcoholic.\nAt the time of visit, no symptoms other than the main complaint was noted during a systems review. Upon physical examination, he had an acute ill-looking appearance, and the conjunctiva and skin were slightly pale. There was no scleral jaundice and liver or spleen enlargement. His blood pressure was 110/70 mm Hg, pulse rate was 98 times/min, respiratory rate was 20 times/min, and body temperature was 38.6℃. Chest X-ray revealed no abnormalities, and the electrocardiogram showed sinus tachycardia.\nLaboratory tests were conducted. Peripheral blood tests evaluated the leukocyte (19,570/mm3) and platelet count (205,000/mm3) and hemoglobin level (5.8 g/dL). Biochemical tests included measurement of aspartate aminotransferase (17 mg/dL), alanine aminotransferase (46 mg/dL), total protein (4.1 g/dL), albumin (2.2 g/dL), total bilirubin (1.0 mg/dL), serum sodium (135 mEq), and serum potassium (3.7 mEq/L) levels. Blood urea nitrogen (41 mg/dL), creatine (1.24 mg/dL), C-reactive protein (11.89 mg/dL) levels were all elevated. The prothrombin time (PT) was 15.4 seconds, and the activated partial thromboplastin time (aPTT) was 49.8 seconds, both of which were prolonged.\nSince disseminated intravascular coagulation (DIC) due to repeated bleeding was suspected, the patient underwent an EGD based on the findings of melena and hemoglobin decline. Vascular formation was observed in the lesser curvature of the mid-body of the stomach, and argon plasma hemostasis was done (). On day 3 of admission, the hemoglobin level decreased, and follow-up EGD was performed. Argon plasma hemostasis revealed oozing bleeding in the upper body of the stomach (). The patient complained of back pain, and a bruise was observed on the right flank (). Computed tomography revealed a hematoma approximately 7 cm in size in the right psoas muscle (). On day 4 of admission, 650 cc of melena was noted. Hence, EGD was performed. Results showed the presence of a gastric ulcer directly below the esophagogastric junction. An epinephrine solution was injected around the ulcer. On day 5, the patient complained of 200 cc of melena, and the hemoglobin level declined. Surgery was performed on the seventh day to achieve surgical hemostasis. At the time of surgery, there was no source of bleeding except on the area just below the esophageal junction. On the day following surgery, exudative hemorrhage from the surgical wound and 350 cc of black stool were observed. Hemoglobin level was reduced to 6.0 g/dL, PT was prolonged to 14.9 seconds, and aPTT was prolonged to 55.4 seconds. PT was corrected in the plasma mixing test; however, the aPTT was not corrected. In the additional test, antibody against blood coagulation FVIII (2.52 BU) was observed. Based on this test, the patient was diagnosed with AHA and bleeding. Then, he was transferred to the Hematology Department, and recombinant activated FVIII was administered. Consequently, the bleeding seemed to stop. Nonetheless, he refused recombinant activated FVIII because of the cost burden, and he died of shock on the 16th day of admission despite continued supportive care.
The second patient was a 68-year-old man with a history of cerebral infarction who had developed dementia (ECOG performance status, 3-4), in addition to arteriosclerosis obliterans, diabetes mellitus (DM), and hypertension. He had been taking a small amount (5 mg) of PSL for nephrotic syndrome. He was admitted to the local hospital having developed a non-traumatic subcutaneous hemorrhage in his right forearm. An abdominal computed tomography scan revealed hepatocellular carcinoma (file size 5.5 cm in diameter) (Figure ). The anemia had progressed and his Hb levels had reduced from 12.7 to 8.1 g/dL, and 1 unit of packed RBC had been transfused. The APTT was prolonged to between 70 and 80 s, and he was transferred to our hospital.\nOn admission, the patient had anemia lasting, with an Hb of 7.8 g/dL and a prolonged APTT of 94.0 s. FVIII activity was reduced to 3.1%, the inhibitor titer had increased to 57.1 BU/mL, and he was diagnosed with AHA. Although his liver function tests were normal, he tested positive for hepatitis C virus antibodies, and the values of alpha-fetoprotein and protein induced by vitamin K absence-II were significantly higher at 1862 ng/mL and 210 mAU/mL, respectively. His anemia had worsened (Hb level, 6.8 g/dL), and 1 unit of packed RBC was transfused. Bypassing agents were not used as the bleeding was not considered to be severe at that time. In addition to continuing PSL administration (5 mg/d), rituximab (RTX 375 mg/m2) was administered 5 times every week in order to eradicate the inhibitors without eliciting side effects. As a result, the inhibitor titer was reduced to 3.5 BU/mL after 3 wk and hemostasis was achieved. The patient was transferred back to his previous hospital to continue treatment for HCC. At this hospital, eradication of the inhibitors was confirmed approximately 1 mo after RTX treatment had terminated. Although transcatheter arterial chemoembolization was performed for HCC, the treatment was not effective, and the HCC continued to progress aggressively. The patient died at the hospice 7 mo after the HCC diagnosis.