A 74-year-old Caucasian female with myasthenia gravis admitted with melena and a hemoglobin of 5.8 g/dl. Her history was significant for small bowel perforation requiring bowel resection and anastomosis two years before the current presentation followed by multiple admissions for anemia treated with blood transfusions and iron supplementations. She did not have any personal or family history of malignancies or bleeding disorders. She was diagnosed with myasthenia gravis a year before the current presentation and was started on pyridostigmine and high dose steroids initially. The steroids were tapered down to prednisone 5 mg daily, six months before the current presentation. She reported non-compliance with her medications for myasthenia gravis. One month before the current presentation, she had an episode of life-threatening acute gastrointestinal bleeding; however, endoscopy did not reveal a clear bleeding source, and the cause was attributed to erosive esophagitis. During the current admission for melena, both endoscopy and colonoscopy failed to show active bleeding. Tagged red blood cell scan, CT angiogram (CTA), capsule endoscopy showed oozing from the bowel anastomotic area. Surgical exploration was deferred given her multiple comorbidities. Later embolization of the bleeding vessel at the site of anastomosis was done by interventional radiology. One week after the procedure, she started to have melena and CTA demonstrated active extravasation again from the anastomotic area. Coagulation studies were performed in the setting of repeated bleeding and showed isolated activated partial thromboplastin time (APTT) prolongation which was not corrected by mixing study. Her FVIII activity was markedly reduced to <1% and factor IX activity was normal. Prothrombin time, fibrinogen, von Willebrand factor, lupus anticoagulant, malignancy workup, and hepatitis panel were normal. Bethesda titer showed elevated inhibitor levels at 91 Units. Steroids and rituximab were administered, and she was discharged with a plan of weekly rituximab for four weeks. She was readmitted two days after the discharge with spontaneous chest wall hematoma. CTA showed a large left pectoral hematoma measuring 14 x 13 x 5 cm with active extravasation (Figure ). Factor Eight Inhibitor Bypassing Agent (FEIBA), recombinant factor VIIa, and steroids were given to control active bleeding. Clinically patient had stability of bleeding. However, during her subsequent hospital course, she acutely became unresponsive and resuscitative efforts proved to be unsuccessful, and the patient passed away. Intracranial hemorrhage was considered as a possible cause for her sudden death; however, an autopsy was not performed according to her family’s wishes.
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.