Guru, Pramod

A 48-year-old male patient requiring extracorporeal membrane oxygenation (ECMO) support for hypoxaemic respiratory failure failed to achieve therapeutic anticoagulation with bivalirudin after continuous dose escalations, and continued to have recurrent fibrin stranding in the circuit over a 6-day course of treatment. Suspecting bivalirudin resistance, the patient was transitioned to argatroban and achieved a therapeutic response in less than 24 hours. The case describes the challenges of anticoagulation in ECMO supported patients. The interplay between bivalirudin metabolism, renal replacement therapy, and immunological effects leading to a heparin-like-effect, inflammatory mediators, and thrombotic burdens may all impact the clinical effect during bivalirudin therapy. The structural biochemistry of thrombin and bivalirudin likely plays a role in the presented patient’s successful response to argatroban. Bivalirudin may fail at achieving therapeutic anticoagulation in patients with genetic thrombin mutations or structural defects that alter the binding pockets at the thrombin exosites.

Pazopanib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) that inhibits the vascular endothelial growth factor receptor A pathway and has the potential to cause ischaemic bowel changes, including perforation. Here we report a case of a 51-year-old man with large, metastatic, retroperitoneal leiomyosarcoma that developed a tumour-bowel fistula after 4 weeks of pazopanib therapy. He presented to the emergency department with sepsis and 1-week history of worsening fever, chills, nausea and diarrhoea. Abdominal CT findings of mesenteric and portal vein gas, commonly found in mesenteric ischaemia and VEGFR modulator-induced bowel toxicity, provided evidence for the causal relation. Unfortunately, the case was not amenable to surgery and patient succumbed to the illness.