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.
A male, 52-year-old patient visited the Instituto Nacional de Cancerología (INC) in Bogotá, Colombia, because of the development of a mass in the back region. There had been progressive growth and multiple drainage attempts due to a suspected abscess at various referral sites without relief. He was given non-oncological surgical resection in another institution, and his pathology report was compatible with high-grade sarcoma with positive margins. Additionally, he referred to bilateral vision loss that had been evolving for one month. The initial clinical exam revealed a patient with normal vital signs who was disoriented with regard to space and time though awake and had poor communication with the examiner. He presented a hyperpigmented tumor measuring 10 x 8 cm in the back region, along with a scarred postsurgical lesion without inflammatory signs. The biopsy was reviewed by the INC Pathology Department, which indicated a high-grade sarcoma compatible with myxofibrosarcoma.\nHe was examined by the Ophthalmology Department, which considered bilateral retinal detachment probable. An abdominal computed tomography (CT) scan was performed, which showed a diffuse density alteration of the subcutaneous cellular tissue, without evidence of lesions, probably due to edema. A chest computed tomography (CT) scan with contrast showed an undefined heterogeneous mass dependent on the soft tissues in the posterior thorax wall, with infiltration signs in the muscular plane and the density alteration of the subcutaneous cellular tissue and skin (See Figure ). He was examined by clinical oncology, surgical oncology, and radiation oncology services, which indicated he was not a candidate for chemotherapy, surgical treatment, or radiotherapy because of the significant extension of the tumor into the upper and lower back, the inadequate response of these tumors to chemotherapy, and the patient’s poor Zubrod performance score.\nDuring inpatient care, the patient showed substantial clinical worsening characterized by the progressive deterioration of his consciousness state and persistent oral cavity bleeding. Laboratory tests were requested, which showed the prolongation of blood clotting time due to extended partial thromboplastin time (PTT), with the test value for prothrombin time (PT) being 11.9 seconds and that for PTT being 50.1 seconds (normal value until 28 seconds). The mixing study showed PTT fixing with a 50:50 normal plasma sample that lasted for the first and second hour, suggesting intrinsic pathway coagulation factor deficiency. Even though the mixing study was not suggestive of the presence of inhibitors, the medical history of the patient, the presence of an active neoplasm, and the recent beginning of bleeding created a clinical suspicion of acquired hemophilia. For these reasons, a new mixing study, VIII factor assay, and Bethesda assay to measure factor VIII inhibitors were requested. In addition, treatment with prednisone at 1 mg/kg/day and factor VIII at 1700 international unit (IU) every 12 hours was initiated. The results of these assays showed a basal PTT of 67 seconds, which with the 50:50 sample with normal plasma, was reduced to 38,2 seconds and maintained at around normal values two hours afterwards, with a value of 36,3 seconds. Factor VIII was measured at 4% and remained at this same value (4%) 10 minutes after the injection of intravenous factor VIII. The specific factor VIII inhibitor assay reported 1.6 Bethesda units. A diagnosis of acquired hemophilia was made based on the presence of hidden low-titer inhibitors in the mixing study.\nBased on the findings above, the persistence of oral cavity bleeding, and daily transfusion support in the form of two red blood cell units, IV treatment with an activated prothrombin complex like the factor eight (VIII) inhibitor bypassing activity (FEIBA) at a dose of 3500 units/12 h (50 U/kg every 12 hours) was initiated. During the patient’s evolution, hypofibrinogenemia development, the continuous elevation of D-dimer levels, and progressive thrombocytopenia suggested a diagnosis of disseminated intravascular coagulation (DIC). Because of the unresolved bleeding, it was decided to initiate a transfusion of cryoprecipitate and tranexamic acid oral rinse while augmenting the FEIBA dose. The patient developed a low response to the established treatment, along with more profound neurological impairment (central nervous system bleeding was ruled out) and the persistence of red blood cell, platelet, and cryoprecipitate transfusion requirements. Additionally, the patient had severe hyponatremia in the form of an electrolyte imbalance. Electrolyte correction was initiated, and because of the persistence of bleeding, oral cyclophosphamide was added to the immunosuppressive treatment, with the objective of eradicating the inhibitors. Seven days afterward, because of the lack of clinical response to management and the impossibility of providing specific antineoplastic treatment, with the agreement of the patient´s family, transfusion support was suspended, and palliative care was initiated. The patient died one week after.