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.
A 76-year-old Chinese man complained of acutely worsening abdominal pain after treatment with 4,000 anti-Xa U of LMWH, q12h (low molecular weight heparin calcium injection, 0.4 ml/4000IU) as an anticoagulant for 3 days.\nThe patient was admitted to our hospital because of palpitation and shortness of breath for three days, and diagnosed with atrial fibrillation and heart failure, with cardiac function NYHA grade III at Northern Jiangsu People’s Hospital on March 21, 2018. He had a CHA2DS2-VASc score of 4, which indicated a high risk of stroke. His body mass index was 21.66 kg/m2, and renal function was normal. Therefore, he was given furosemide and spironolactone for diuretic therapy, valsartan capsules for antihypertensive treatment, and LMWH for anticoagulation therapy.\nThe patient had a prior history of hypertension well controlled by treatment with angiotensin-converting enzyme inhibitors.\nThe patient had no specific underlying disease. He had no family history of other significant diseases.\nPhysical examination showed abdomen tenderness and no signs of peritoneal irritation.\nOn March 21, laboratory results showed that N-terminal pro–B-type natriuretic peptide was 1590 pg/ml, international normalized ratio was 1.14, activated partial thromboplastin time (APTT) was 38.20 s, fibrinogen was 1.67 g/L, hemoglobin was 113 g/L, red blood cell count was 3.34 × 1012/L, creatinine was 83 μmol/L, alanine transferase was (ALT) 39.0 U/L, aspartate aminotransferase (AST) was 36.0 U/L, gamma-glutamyltransferase (GGT) was 115.0 U/L, and platelet cell count was 183 × 109/L. After anticoagulation therapy for 3 days, an emergency laboratory test showed that the red blood cell count was 2.56 × 1012/L, and hemoglobin and platelet counts decreased to 82 g/L and 102 × 109/L, respectively. Furthermore, the coagulation function test demonstrated a prolonged APTT of 49.50 s. There was no bleeding per rectum, and his fecal occult blood test was negative. Considering the patient’s symptoms of abdominal pain and the rapid drop in hemoglobin and red blood cell count, there was clinical suspicion for retroperitoneal or gastrointestinal hemorrhage.\nAbdominal computed tomography (CT) showed the thickening areas of the colon up to 110 mm × 78 mm in thickness, which was a symptom of hematoma of the colon ().