Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency

Hereditary thrombophilia due to congenital histidine-rich glycoprotein (HRG) deficiency is an extremely rare inherited blood clotting disorder caused by a deficiency of histidine-rich glycoprotein, a plasma protein that plays a role in the regulation of coagulation and fibrinolysis. HRG normally acts as an anticoagulant by binding to several components of the hemostatic system, including heparin, fibrinogen, plasminogen, and thrombospondin. When HRG levels are reduced due to genetic mutations in the HRG gene (located on chromosome 3q27), the balance between clot formation and clot breakdown is disrupted, leading to an increased tendency to form blood clots (thrombophilia). The condition primarily affects the vascular system, with patients being at elevated risk for venous thromboembolism, including deep vein thrombosis (blood clots in the deep veins, typically of the legs) and pulmonary embolism (blood clots that travel to the lungs). Thrombotic events may occur spontaneously or may be triggered by additional risk factors such as surgery, immobilization, pregnancy, or use of oral contraceptives. The clinical presentation can be variable, and some individuals carrying the deficiency may remain asymptomatic throughout life. Treatment follows general principles for managing hereditary thrombophilia. Acute thrombotic events are treated with anticoagulant therapy, typically heparin followed by oral anticoagulants such as warfarin or direct oral anticoagulants. Long-term anticoagulation may be considered in patients with recurrent thrombotic episodes. Prophylactic anticoagulation may be recommended during high-risk situations. Genetic counseling is advised for affected families. Due to the rarity of this condition, management is largely guided by expert opinion and extrapolation from other hereditary thrombophilias rather than disease-specific clinical trials.

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