During my internship, a 56-year old male patient came with the complaints of seizures, calf muscle pain followed by a syncope episode while playing badminton. On taking his history, he reported shortness of breath 3 days back and had no other co-morbidities. He was initially managed at a local hospital where they had treated him with noradrenaline for hypotension and CT brain was performed which was normal. He was referred at out center for further management.
Based upon his presentation physicians suspected pulmonary embolism, and a bolus dose of Inj.Tenecteplase 50mg was administered followed by Inj.Dalteparin 5000 IU twice a day. During his stay his aPTT value was persistently prolonged, even after withholding anticoagulation for 12 hours.
For further investigation a mixing study was performed. A mixing study is done to identify cause of prolonged blood clotting time like aPTT/PT time, it is performed by mixing patient plasma in 1:1 ratio with control plasma to rule out any factor deficiency, if the clotting time becomes normal it indicates factor deficiency and if it does not then lupus anticoagulant panel/ specific factor inhibitors are to be identified. The result showed correction of aPTT, indicating a clotting factor deficiency rather than an inhibitor.
Initially, Factor VIII and Factor IX assays were performed. Factor VIII was found to be borderline elevated. Factor VIII is a procoagulant protein that acts as a cofactor for Factor IXa, enhancing activation of Factor X and promoting thrombin generation. Elevated Factor VIII levels are associated with an increased risk of thrombosis and may shorten aPTT; however, they do not explain a prolonged aPTT. Factor IX levels were within normal limits. Elevated Factor VIII levels can be seen in conditions such as advancing age, inflammation, liver disease, renal disease, stress, and certain blood groups.
Subsequently factor XI and XII assays were performed. Factor XII (Hageman factor) was found to be deficient in this gentleman.
Factor XII deficiency is a rare, inherited autosomal recessive blood disorder. Unlike other clotting deficiencies it typically does not cause bleeding, and may be associated with an increased risk of thrombosis, the mechanism is not fully understood but it is proposed that it results from-
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Impaired fibrinolysis i.e. impaired clot breaking- Factor XII is crucial for plasma kallikrein-kinin system, which helps convert plasminogen into plasmin, an enzyme that breaks down fibrin clots. Without sufficient XII, this clot-dissolving mechanism is impaired, leading to increased persistence of thrombi.
Impaired Inflammation Regulation: FXII bridges coagulation and inflammation. A lack of FXII may lead to a pro-thrombotic state due to altered inflammatory responses that contribute to vascular damage and clot formation.
The patient was referred to a hematologist and initiated on warfarin, with dose titration based on INR monitoring.
MBH/AB