Moderately Severe Homozygous Protein C Deficiency and Dysfunction in a Female with Late Clinical Onset of Venous Thromboembolism

Introduction A 41-year-old female patient with recurrent deep vein thrombosis is reported upon here. As she had suffered from lipoedema and lymphoedema since her childhood in Türkiye, she underwent surgery for lipoedema by liposuction at the age of 16 years ( Y ), subsequently developing deep vein ( DVT ) thrombosis within a week accompanied by skin necrosis in the liposuction area. Thereafter, she received short-term anticoagulation therapy initially with low-molecular-weight heparin ( LMWH ). At age 30 Y , she had a DVT after flight travel, and 3 Y later, she suffered a left calf vein thrombosis and pulmonary embolism. For anticoagulation therapy she received LMWH or fondaparinux, respectively. After popliteal vein DVT at the age of 40, she was treated with the direct oral anticoagulant ( DOAC ) apixaban ( APIX ) twice daily ( b.i.d. ). Now we have fine-tuned the laboratory diagnosis for the development of a long-term treatment strategy. Method The recurrent DVT events were diagnosed using duplex ultrasound techniques. For laboratory diagnosis, coagulation analysis was performed with commercially available assays: e.g., clotting factors F II, V, VII, X, inhibitors and regulators antithrombin, protein C ( PC , chromogenic activity [chrom ], coagulometric activity [ clot ], antigen [ ag ]), protein S ( PS , free ag , clot ). For detailed clotting and fibrinolysis activity detection, the molecular markers ( MM ) D-dimers ( DD ), prothrombin fragments F1+2 , thrombin-antithrombin complexes ( TAT ) and fibrin monomers ( FM ) were analysed. Molecular genetic analysis was performed by direct gene sequencing of PROC gene. The most recent treatment was performed with DOAC , initially with APIX 10 mg b.i.d. , and currently with rivaroxaban ( RIVA ) 20 mg, taken once daily ( qd ). Results The patient suffered from lipoedema grade III and lymphoedema, and also from severe bilateral postthrombotic syndrome. PC ag was found to be 27-34%, PC chrom 24-33% and PC clot 7-12%. The discrepancies between lower PC clot and comparable PC ag and PC chrom levels indicated a PC dysfunction. MM indicated high activity levels for DD : range 1,242-6,823 ng/ml (ref.