An 81-year-old woman was admitted to the Mazandaran Heart Center, Sari, Iran in February, 2018 with a 4-day history of nausea, vomiting, and abdominal pain. She had been taking Warfarin (5 mg orally once a day) and aspirin (80 mg/day) for 8 years after aortic valve replacement without close monitoring and had a history of hematochezia caused by Warfarin toxicity one year ago. Colicky pain, an increase in bowel sounds and periumbilical tenderness without distension was determined by physical examination. The primary laboratory findings revealed anemia (Hb: 9.8 g/dl; normal value: 11.5–13.5 g/dl) and elevated INR (6; therapeutic range: 2–3.5), liver function and biochemistry tests were within normal values. Normal left ventricular systolic function, LVEF of 55–60%, septal hypertrophy, normal functioning prosthetic valve, and dilatation of the ascending aorta were reported by echocardiography.\nDuring an abdominal and pelvic ultrasound, long mucosal thickening possibly through the ascending and sigmoid colon was observed, suggestive of intramural hematoma. The patient was placed on\nnil per os, received supportive care and two units of fresh frozen plasma. Due to normal cardiac evaluation and partial relief of symptoms on the second day of admission, the patient was referred to surgical consultation with the possible diagnosis of descending colon and sigmoid intramural hematoma. For re-administration of anticoagulants, heparin infusion (1000 units/hour) began with precise monitoring of prothrombin time.\nOn the fourth day, CT scan was performed with intravenous and oral contrast (\n) and intramural hematoma of ileum was diagnosed. During the CT, a radiologist noticed a mass on the left breast and a lymph node with a malignant feature on the left axilla. With the improvement of abdominal pain and vomiting (on the fourth day), oral feeding was resumed. After mammography and breast biopsy, pathological examination revealed invasive ductal cell carcinoma with lymphatic and perineural invasion. According to the immunohistochemistry staining, tumor cells were strongly ER positive, PR negative, 15% Ki67 positive and equivocal for HER2. The patient was referred to the oncology-hematology department to receive appropriate treatment.\nThe patient was discharged 10 days after admission and Warfarin therapy (5 mg/d) was resumed. The patient was visited 2 weeks later with good general health assessment. Letrozole (2.5 mg/day) was started because the patient refused chemotherapy and radiotherapy.
A 68-year-old Colombian man who worked as an artist was diagnosed with stage IV metastatic melanoma two years prior to presentation after finding a lump in his groin. His past medical history was significant for well-controlled hypertension, hyperlipidemia, insulin-dependent type 2 diabetes, stage III chronic kidney disease, prostate cancer, and gout; he was also born with a single kidney. He experienced partial regression of his melanoma with pembrolizumab but developed acute interstitial nephritis; thus, therapy was suspended and the patient was treated with methylprednisolone followed by high-dose prednisone and furosemide. He then underwent gamma knife resection of a temporal lobe brain metastasis; his recovery was complicated by bilateral lower extremity deep vein thrombosis (DVT) treated with inferior vena cava filter; therapeutic anticoagulation was deferred in the setting of recent brain surgery. One week after discharge to an acute rehabilitation facility, he returned to the hospital complaining of urinary retention.\nOn presentation, the patient was found to have an enterococcal urinary tract infection and an acute kidney injury. He was started on ciprofloxacin for the infection; high-dose prednisone was resumed in light of his recent interstitial nephritis. His presentation was also notable for new acute occlusive DVTs in the bilateral lower extremities. Again, therapeutic anticoagulation was deferred given bleeding risk in the postoperative period. He was given prophylactically dosed enoxaparin, which was changed to heparin on hospital day 8 given worsening renal function. Heparin was administered subcutaneously and dosed TID as per institutional weight-based dosing protocols. Staging imaging revealed progression of his disease with diffuse lymphadenopathy and peritoneal carcinomatosis. Given worsening clinical status, it was decided to start vemurafenib, a B-type Raf (BRAF) inhibitor, and cobimetinib, a mitogen-activated protein kinase (MEK) inhibitor, at reduced doses.\nOn day 16 of hospitalization, the patient became unresponsive while sitting on the edge of his bed. On regaining consciousness, his blood pressure was 80/50 with heart rates ranging 120–130. He reported feeling dizzy and light headed. His vital signs quickly returned to baseline with symptomatic resolution. Physical exam was notable for right-sided supraclavicular fullness and tenderness to palpation, pain with passive range of motion of the right shoulder, and diffuse abdominal ecchymoses at sites of prior heparin injections. Immediate labs demonstrated elevated troponin and lactate. The following morning an acute drop in hemoglobin was noted, from 9.2 g/dL to 6.5 g/dL over 24 hours. Computed tomography (CT) of the chest revealed an expansive subcutaneous hematoma involving the posterior chest wall and right supraclavicular region (). The hematoma appeared to be associated with sites of previously unknown metastatic lesions. Coagulation studies demonstrated markedly elevated aPTT (>200 s), thrombin time (>200 s), and anti-Xa (0.83 IU/mL). The constellation of lab findings indicated heparin toxicity.\nThe patient was supported with transfusions and reversed with several doses of intravenous (IV) protamine sulfate. The aPTT decreased after 20 mg of protamine from >200 s to 129.7 s and then 110.4 s. Two additional 10 mg doses were given with decrease to 68.9 s and 55.9 s, respectively. The aPTT normalized to 35.3 s the following day with no additional doses (). Of note, despite the administration of protamine, the heparin clearance was remarkably delayed ().\nThe patient recovered from his acute bleed, heparin was held indefinitely, and he did not have recurrence of his coagulopathy. Ultimately, however, his liver function worsened with the chemotherapy, requiring drug changes and further dose reductions. There was no reduction in his tumor burden despite trials of multiple agents, and his kidney function again declined. The patient was eventually transitioned to inpatient hospice.