A 4-year-old boy was transferred to our pediatric intensive care unit from an outside hospital for further management of a persistent seizure disorder of unknown etiology. A right femoral triple lumen central venous line (CVL) had been placed prior to transfer. Five days after arrival, the patient began to exhibit increased swelling in his right lower extremity, and ultrasonography revealed a catheter-related, acute occlusive deep venous thrombosis in the right common femoral vein. He was started on LMWH (enoxaparin) at 1 mg/kg for a planned course of 3 months. Five days after initiating treatment, the CVL was removed. The patient had no personal or family history of thrombophilia or bleeding diathesis. His anti-Xa level, checked after the second dose, was within the therapeutic range.\nHis hospital course was complicated by multisystem organ failure in the setting of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to anticonvulsive therapy. One week after starting LMWH heparin, the patient experienced gross hematuria. The next day, the injection sites were noted to be slightly oozy, and, in the setting of his anti-Xa levels continuing to rise (0.87), LMWH heparin was held. He required continuous venovenous hemofiltration, during which time anticoagulation was switched to unfractionated heparin. After renal recovery, LMWH therapy was restarted at a lower dose (70% of original dose), but his anti-Xa levels continued to be labile and difficult to control. Eventually, a steady regimen was found with consistently stable and therapeutic anti-Xa levels ().\nOn the 15th day of this regimen, however, he developed signs of bowel obstruction with new onset of copious bilious vomiting. An abdominal ultrasound found a small amount of fluid in the pelvis. A CT of the abdomen and pelvis showed a high-grade small bowel obstruction, with 2 areas of small bowel, suspicious for intussusception (Figures and ). The patient's hemoglobin was found to have dropped from 9.9 to 6.2.\nHe was brought to the operating room for exploratory laparotomy. Intraoperatively, bloody ascites and multiple dilated loops of small bowel were found. Approximately 30 cm of the distal jejunum was found to be tense, heavy, firm, and discolored with a blue hue, with a hematoma that had dissected through the layers of the bowel (). A serosal defect was found on the antimesenteric border of the involved bowel, likely causing the bloody ascites. As the bowel was severely compromised, a resection of the involved segment was performed.\nPathologic analysis of the resected bowel showed an extensive, 35 cm submucosal hematoma causing internal bulging of the mucosa and submucosa, causing attenuation and focal pressure necrosis of the muscularis propria. The serosa was noted to be diffusely purple-red, with a small ovoid defect that was presumably caused by the hematoma. At both ends of the resected bowel, there was evidence of the mucosa and submucosa bulging into the lumen of the bowel as a result of the hematoma.\nThe patient recovered from the operation in the pediatric ICU with no further episodes of emesis or signs of bowel obstruction. He was restarted on LMWH 5 days later and completed his 3-month course without any further signs of bleeding. He was discharged from the hospital 3 weeks later with resolution of his seizures to a rehabilitation facility, without any further complications of bleeding or bowel obstruction.
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.