LAUSR

Dear Editor, High-molecular-weight kininogen (HK) circulates bound to prekallikrein (PK), which can bind to negatively charged phospholipids. It is a non-enzymatic cofactor for kallikrein binding to negatively charged phospholipids. Kallikrein activates factor XII, which then activates factor XI, leading to activation of the intrinsic coagulation pathway [1]. Deficiencies in HK and PK can cause isolated activated partial thromboplastin time (aPTT) prolongation with normal levels of intrinsic coagulation factors (VIII, IX, XI, and XII). In PK deficiency, pre-incubation of patient plasma with an aPTT reagent before aPTT assay shortens the aPTT, whereas in HK deficiency, such pre-incubation does not correct aPTT prolongation [2]. Several cases of HK deficiency have been reported in the Japanese population [3]. Herein we report the first Korean case of congenital HK deficiency that resulted in a prolonged aPTT without a change in the pre-incubation aPTT assay. HK deficiency was confirmed by plasma HK levels and identification of two pathogenic variants, one of which was novel (c.488delG). This study was approved by the institutional review board (IRB) of Seoul National University Hospital (IRB 1911-116-1080). Informed consent for performing genetic testing along with additional coagulation assays was obtained from the patient. A 37-year-old man visited the CHA Bundang Medical Center, Seongnam, Korea, for lipoma surgery. He underwent preoperative assessment, including coagulation assays, during which aPTT prolongation was found. He had suffered from peptic ulcer bleeding in his twenties and had no other medical history related to bleeding or thrombosis. The patient’s peripheral blood specimen was sent to the Seoul National University Hospital (SNUH), Seoul, Korea for further analysis. The results of laboratory workup performed in SNUH are presented in Table 1: Prothrombin time (PT) and aPTT before preincubation were 12.2 and 177.9 s, respectively. Prolonged aPTT was corrected after a mixing study. Factors VIII, IX, and XII were within normal ranges, whereas factor XI was slightly decreased (Table 1). To exclude immunologic causes of aPTT prolongation, lupus anticoagulant, anti-cardiolipin antibody, anti-β2GPI antibody, and anti-nuclear antibody were tested, which all turned out to be negative. Under suspicion of PK deficiency, aPTT was measured after preincubation with an aPTT reagent for 20 minutes. However, aPTT shortening was not observed: the re-tested aPTT was