Different Risks of Thrombosis in Four Coagulation Defects Associated With Inherited Thrombophilia: A Study of 150 Families

Abstract

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first-and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3.5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.

Thrombophilia in Cardiac Surgery-Patients with Symptomatic Factor V Leiden

“…4,5 The lifetime probability of developing thromboembolic events was increased 2.2-fold in patients with FVL. 6 Surgery and FACTOR V LEIDEN AND CARDIAC SURGERY J CARD SURG 2009;24:379-382 immobilization are periods of increased risk which may trigger the occurrence of thromboembolic events in otherwise healthy persons with thrombophilic diathesis. 1 Indeed, in patients with symptomatic prothrombotic disease, a predisposing factor, such as surgery or immobilization, was reported to be present in 50% of cases.…”

“…3 However, surgery and immobilization are considered to be predisposing factors for the occurrence of a thromboembolic event. 6 In an earlier investigation, no increase in perioperative mortality or in the incidence of perioperative thromboembolic events was observed in cardiac surgical patients with asymptomatic heterozygous FVL. 7 In the present study, we describe our experience with symptomatic FVL patients who underwent a cardiac surgical procedure.…”

Livedoid vasculopathy and popliteal artery occlusion in a patient with protein S deficiency

“…Interestingly, two previous papers showing association between decreased protein S activity and LV reported thrombotic complications of the artery 10,11 similar with this patient, even though protein S deficiency usually causes venous thromboembolisms. 13 Other abnormalities of the protein C pathway, such as factor V Leiden and protein C deficiency, can cause LV, 14 but few patients developed arterial thrombotic events. This difference may be attributed to the mechanism that protein S also has the protein C pathway-independent anticoagulant activity through direct inhibition of the prothrombinase and possibly the Xase complexes.…”

Human plasma‐derived concentrates: preventing thrombosis and controlling haemorrhage

“…Most cases are heterozygous (homozygosity is usually fatal in utero [4]), and affected individuals have a 50-70% lifetime risk of VTE [5,6]. While thrombosis is uncommon during the first two decades of life, by age 50 years, approximately half of all individuals with AT deficiency will have experienced a thrombotic event [7][8][9].…”