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.
The patient is a 52-year-old incarcerated male with a past medical history of diabetes mellitus, chronic pancreatitis, and remote history of open cholecystectomy who was transferred to the hospital for complaint of abdominal pain. He reported three days of worsening epigastric and periumbilical abdominal pain with associated nausea and obstipation. He also reported two days of hematuria without dysuria or frequency. Four days prior, he was awakened by another prisoner who was kicking him in the abdomen.\nOn presentation, he was tachycardic but normotensive. His abdomen was distended and diffusely tender. Initial lab work was notable for leukocytosis of 17 and significant coagulopathy with an unmeasurable international normalized ratio (INR), partial thromboplastin time (PTT) > 200, and prothrombin time (PT) > 120. Repeat labs confirmed the coagulopathy. He denied any ingestions or known exposures. He was given two units of fresh-frozen plasma (FFP) as well as vitamin K and his coagulopathy began to correct.\nA CT scan of the abdomen/pelvis revealed significant bowel dilatation with mural edema and thickened loops of jejunum (Figure ). There was fecalization of the proximal small bowel consistent with high-grade small bowel obstruction. Given his tachycardia, obstructive symptoms, diffuse abdominal pain and CT findings, there was concern for intestinal ischemia and the decision was made to perform an exploratory laparotomy. On inspection, the mid-small bowel was dilated with about 30 centimeters of thickened small bowel with circumferential hematoma. The entirety of the small bowel was examined and the point of obstruction appeared to be the extensive small bowel hematoma. This portion was resected and primarily anastomosed. The abdomen was closed and the patient was brought to the recovery room.\nHis post-operative labs were notable for a normalizing INR of 1.4 and PTT of 30. Given the unclear etiology for his extreme coagulopathy, Hematology was consulted. He had no family history of coagulopathies or hematologic disorders. He reported no history of bleeding symptoms prior to this episode. Coagulation studies were consistent with a deficiency of vitamin K dependent clotting factors that corrected with mixing studies. Differential diagnosis included common pathway factor deficiency, inhibitor exposure, or false result. Disseminated intravascular coagulation (DIC) and liver failure were ruled out. As his coagulopathy quickly corrected with FFP and vitamin K, the most likely etiology was exposure to overdose of a warfarin-based substance. He received additional vitamin K and recovery was otherwise unremarkable. Hematuria had resolved with correction of the coagulopathy. He was discharged on the seventh post-operative day to the prison infirmary. The final pathology was notable for portion of small intestine with transmural hemorrhage with clear resection margins.