A 61-year-old man with a past medical history of type II diabetes mellitus, hypertension, hyperlipidemia, hypothyroidism, and obstructive sleep apnea presented to the emergency department (ED) with right lower extremity pain and swelling. His pain began 2 days prior to admission and was initially mild and only behind his knee. Of note, he had noticed increased bruising and was seen by hematology/oncology and vascular surgery outpatient who diagnosed him with B12 and iron deficiency. At home he took levothyroxine 137 µg once daily in the morning (QAM), norvasc 5 mg daily, and aspirin 81 mg daily. He did not have any significant social or family history. He had not had any recent falls or trauma. He came to the ED after his pain worsened to the point that he could not bear weight on his leg and he developed paresthesia and numbness of his toes. He was evaluated by vascular surgery and determined to have compartment syndrome of the posterior compartment. He then went for emergent fasciotomy of his right lower extremity posterior compartment on the day of admission. Postoperatively he continued to have bleeding and received seven units of packed red blood cells (pRBCs) and fresh frozen plasma (FFP). The next day a rapid response was called for diaphoresis, weakness, and right lower extremity pain. He was evaluated by orthopedics and subsequently transferred to the surgical intensive care unit for hemorrhagic shock. At that time, he received three additional units of pRBCs. He went for repeat fasciotomy the following day and was found to be hemorrhaging in his right lower extremity posterior compartment.\nLaboratory values from his admission showed a prolonged activated partial prothrombin time (aPPT) (). On his second day of hospitalization, hematology/oncology was consulted and, based on his laboratory values, it was determined that he had a coagulopathy due to suspected FVIII inhibition and he was administered both FVIII and steroids. Hematology/oncology then ordered FVIII levels which later returned as markedly decreased (). Bethesda inhibitor test was also done which was positive for FVIII inhibitor levels (). His bleeding was not controlled by the combination of FVIII and steroids and thus he was given a trial of recombinant FVII with steroids which, initially, controlled the bleeding of his right lower extremity, but was ultimately not successful. At this time, he remained hemodynamically stable but became blood transfusion dependent. Over the course of 6 weeks he was also trialed on recombinant porcine FVIII, rituximab, intravenous immunoglobulin (IVIG), and plasmapheresis. Of note, during his first 4 weeks of hospitalization he had a total of seven debridements of his right lower extremity in attempt to control his persistent hemorrhaging. However, during his fifth week of hospitalization, he underwent right lower extremity amputation above the knee.\nDuring his sixth week of hospitalization he developed new-onset progressive thrombocytopenia; his platelets rapidly dropped to 32 K/µL. Due to high concern for bacteremia blood cultures were collected and resulted positive for Streptococcus bovis and Escherichia coli. At this time the patient was seen by infectious disease doctor who initiated intravenous ceftriaxone. Colonoscopy was recommended but due to his bleeding risk from AHA and worsening thrombocytopenia it was postponed upon gastrointestinal evaluation. It was suspected that his positive cultures were due to probable gastrointestinal translocation.\nOn his 11th week of hospitalization a code stroke was called for acute right-sided weakness and altered mental status. Computed tomography (CT) of the head was performed and showed multiple hypodensities suspicious for stroke versus possible metastasis. Subsequent magnetic resonance imaging (MRI) of the brain showed innumerable peripheral enhancing mass lesions, highly suspicious for multifocal metastases (). He was ultimately intubated for airway protection and sent to the neurological intensive care unit. Due to high suspicion for malignancy he had an abdomen/pelvis CT which was negative for a mass. As the patient’s mental status did not improve, his family met with palliative care and his code status was changed to “do not resuscitate”. During this same week, he had a pulseless electrical activity (PEA) cardiac arrest and expired.
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.