A Case of Prekallikrein Deficiency in a Pediatric Patient.

Prekallikrein (also known as Fletcher factor) is described as one of the contact factors, and when converted to its active form, kallikrein, is responsible for the activation of factor XII and initiation of the intrinsic pathway of the coagulation cascade. Kallikrein also converts high-molecular-weight kininogen to bradykinin, which acts as a potent vasodilator. Deficiency of prekallikrein was first described in 1965 as an autosomal recessive disorder. Hereditary deficiency of prekallikrein is not associated with a clinical bleeding disorder, but does result in a prolonged activated partial thromboplastin time (aPTT). Most cases of prekallikrein deficiency are identified through routine screening. We present a young man who was referred to our Hemophilia and Thrombophilia Treatment Center for a significantly prolonged aPTT and subsequently found to have prekallikrein deficiency. NP is a 7 year-old boy who was found to have an aPTT of 209.6 seconds on pre-operative evaluation for PE tubes and adenoidectomy. Prothrombin time (PT) was normal at 14.7 seconds, with an INR of 1.2. There was no personal or family history of bleeding. Past medical history did include bipolar disorder and attention deficit disorder, for which the patient was taking olanzapine and depakote. A 1:1 mixing study with normal plasma led to complete correction of the aPTT to 28.9 sesconds. Levels of factors VIII, IX, XI, and XII were normal at 98%, 92%, 99% and 129%, respectively. High molecular weight kininogen level was also normal. Thrombin time was normal at 17.1 sec. An incubated aPTT was performed over 3 hours with decrease in the aPTT from 179 seconds to 72 seconds, a phenomenon that has been reported previously, and is thought to be due to auto-activation of factor XII. Prekallikrein was measured at less that 15% (normal reference 55–207%). The patient subsequently underwent adeno-tonsillectomy without any excessive bleeding. This case serves as another example of the benign causes for a prolonged aPTT in the pre-operative setting in addition to those such as lupus anticoagulant or factor XII deficiency. Deficiency of prekallikrein should be included in the differential diagnosis of a prolonged aPTT, particularly in the absence of bleeding symptoms.