Cardiac tamponade is an infrequent but potentially lethal complication related to use of central venous catheters (CVC). We present the case of a 16-year-old female with Diamond-Blackfan anemia (DBA) who developed pericardial tamponade secondary to superior venous caval obstruction caused by CVC thrombosis. The patient presented 3 months after line placement with vomiting, abdominal pain, and cardiomegaly on chest X-ray (CXR). Her condition quickly decompensated with cardiac arrest and subsequent death despite immediate pericardiocentesis. As a result of this case, our center has developed a protocol for the management of CVC problems as a means of facilitating rapid recognition of central line clots.