By: 1 March 2013

Human fibrinogen concentrate restores clotting ability and can significantly reduce the need for blood transfusion when given as an intra-operative, targeted first-line haemostatic therapy in bleeding patients undergoing aortic replacement surgery.

The Phase II prospective study, published in Anesthesiology, performed at the Hannover Medical School, Germany, enrolled 61 patients to assess the ability of fibrinogen concentrate to improve clotting and reduce the need for transfusion following elective aortic replacement surgery with cardiopulmonary bypass (CPB). Patients who received fibrinogen concentrate required fewer allogeneic blood product transfusions than patients receiving placebo (a median of two units in the fibrinogen concentrate group compared with 13 units in the placebo (p<0.001)). In the fibrinogen concentrate group, 45 percent (13 out of 29 patients) avoided transfusion entirely, whereas all 32 patients receiving placebo required transfusion (p<0.001).

The study enrolled patients 18 years or older who were undergoing elective aortic replacement surgery with cardiopulmonary bypass. Patients were excluded from the study if they had undergone previous surgery at the same aortic site, had a congenital or acquired coagulation disorder, had a myocardial infarction or stroke in the previous two months, or if they used aspirin, clopidogrel or vitamin K antagonists before the surgery.

“Aortic replacement surgery puts patients at risk of potentially life-threatening bleeding events because the surgery depletes fibrinogen levels and delays clotting, which may require extensive blood transfusion to restore a patient’s clotting ability,” said Niels Rahe-Meyer, M.D. Ph.D., of the Clinic for Anaesthesiology and Intensive Care Medicine, Hannover Medical School and lead author of the study. “This is the largest study of its kind in patients undergoing aortic replacement surgery and indicates that proactive treatment with fibrinogen concentrate may reduce the need for transfusions, restore clotting ability, and consequently protect aortic surgery patients from possible adverse events associated with donor blood transfusion.”

In the study, reported treatment-emergent adverse events were similar in both groups and typical for patients undergoing cardiac surgery, with the most common being fluid build-up around the lungs (pleural effusion) and abnormal heart rhythm (atrial fibrillation). None of the treatment-emergent adverse events were ascribed to study medication or led to discontinuation from the study. Overall there was no observed safety concern using fibrinogen concentrate during aortic surgery.

In addition to bleeding caused by injury or a surgical intervention itself (surgical bleeding), critical reduction in the level of coagulation factors can lead to additional non-surgical bleeding complications that can be difficult to control (e.g. coagulopathic bleeding). Such patients can have critically low concentrations of many coagulation factors. The first factor to be depleted during CPB is fibrinogen. A simple blood test can detect the level of fibrinogen; the normal range is 150–450mg per decilitre.

“Fibrinogen concentrate has been well characterised for the treatment of specific inherited blood clotting disorders,” said Andrew Cuthbertson, CSL Behring Chief Scientist. “CSL Behring is committed to exploring the use of fibrinogen concentrate in patients at high risk of bleeding, particularly those in the hospital setting where fibrinogen has been shown to be depleted by surgical procedures and where a quick intervention is needed to improve clotting and prevent serious bleeding events.” For more information, visit