A 71-year-old gentleman was referred by his general practitioner with tachycardia. He reported a 2-day history of nausea, abdominal discomfort, and bloating with three episodes of bilious vomiting. He denied any pain, change in bowel habits or infective symptoms. He passed a normal bowel motion on the day of presentation and had no evidence of upper or lower gastrointestinal bleeding. His comorbid medical conditions were hypertension, hypercholesterolaemia and metallic aortic valve replacement. His regular medications included eplerenone, bisoprolol, fenofibrate and warfarin. The patient admitted taking a double dose of warfarin (4 mg daily) for the past 30 days. On arrival in the Emergency Department, his heart rate was 140 b.p.m., however, other haemodynamic parameters were normal. His abdomen was distended but soft and non-tender with active bowel sounds and no peritonism. Other system examinations were unremarkable and he had no stigmata of active bleeding. Electrocardiogram indicated rapid atrial fibrillation, which was managed with intravenous magnesium sulphate and beta blockade followed by an amiodarone infusion. Laboratory results showed a leukocytosis (white cell count 21 × 109/l), normal haemoglobin 152 g/l, elevated C-reactive protein 77 mg/l, lactate 4.6 mmol/l and supratherapeutic international normalized ratio (INR) of 9.9. The patient received urgent surgical review, fluid resuscitation and INR reversal with intravenous vitamin K, prothrombinex and two units of fresh frozen plasma. Bedside abdominal ultrasound indicated intra-abdominal free fluid which was further investigated with a computed tomography (CT) mesenteric angiogram. This showed circumferential, hyperdense bowel wall thickening involving a long segment of small bowel up to the mid-ileum (Fig. ). The bowel wall density was 50–60 Hounsfield units, consistent with an intramural haematoma. The duodenum and the stomach were dilated with no associated transition point and the distal ileum and the colon were decompressed. Haemoperitoneum was noted adjacent to the liver and spleen (Fig. ). Normal contrast enhancement was demonstrated in the major abdominal vasculature. The patient was admitted to the intensive care unit (ICU) for monitoring and non-operative management with bowel rest, nasogastric decompression and intravenous fluids. Warfarin was withheld and no venous thromboembolism prophylaxis administered due to his high bleeding risk. Repeat INR 5 hours after presentation was 1.5. The patient remained haemodynamically stable in ICU with no evidence of active bleeding. He reverted to sinus rhythm after 2 days of amiodarone infusion and did not require surgical intervention or blood transfusion. Diet was progressed and he was transferred to the ward on Day 3. Cardiology advised that the patient was unsuitable for NOAC (new oral anticoagulant) therapy and he was recommenced on warfarin at 1 mg daily. He was discharged on Day 6 with plan for outpatient warfarin titration. On discharge, the patient was asymptomatic, opening his bowels and tolerating full diet with INR 1.2 and stable haemoglobin of 102 g/l.
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.