Thrombophilic patterns of coagulation factors in lupus

Abstract

Our aim was to better define the coagulation abnormalities in patients with systemic lupus erythematosus who had thrombosis or high-risk clinical settings for thrombosis. Clinical and laboratory data of 111 patients with lupus referred for coagulation assessment because of thrombosis, pregnancy loss or high-risk clinical settings for thrombosis were reviewed retrospectively. Increased activity of procoagulant factors and decreased activity of anti-coagulant factors were observed well above the expected 5% prevalence. All comparisons were significant at the P < 0.001 level. Anticardiolipin antibodies were present in 70.5% of patients tested (55/78) in this high-risk group, but usually in low titres. Platelet hyperfunction was detected in the majority of patients tested (85.7%, 78/91). Hypercoagulability in lupus is complex and is better defined by assessing multiple haemostatic factors in addition to platelet function. Platelet hyperfunction contributes significantly to thrombophilia in lupus and this is the key finding of our study.

Platelets and autoimmunity

“…Furthermore, depletion of platelets improved all measurements of disease activity and overall survival in lupus prone mice . The beneficial effects of statin treatment, which next to its lipid‐lowering effect has a series of anti‐inflammatory effects including a reduction of platelet reactivity and sCD40L, has been confirmed in two randomized double‐blind placebo‐controlled clinical trials . Duffau et al .…”

Thrombophilia in Systemic Lupus Erythematosus: A Review of Multiple Mechanisms and Resultant Clinical Outcomes

“…It is also important to remember that estrogens and pregnancy can induce protein S deficiency and this may compound pregnancy and hormonal therapy management in lupus. Homocysteine has been associated with thrombosis in SLE, and should be measured in lupus patients as part of any hypercoagulable work up [16,[92][93][94]. Interestingly, rheological evaluation of SLE patients with and without thrombosis showed no association of blood viscosity and erythrocyte aggregation with thrombosis [95].…”

“…Venous thrombosis is also associated with smoking in lupus [12]. Other risk factors for thrombosis in lupus include high disease activity, lupus nephritis /nephrotic syndrome, elevated homocysteine, and the presence of antiphospholipid antibodies [11,[13][14][15][16]].…”

“…As discussed in the previous paragraph, inflammation can cause elevations of non-lupus related procoagulant factors. Other factors contributing to hypercoagulability in SLE includes hyperhomocysteinemia [16,[64][65][66], and elevated plasminogen activator inhibitor-1 ( PAI-1) which decreases fibrinolytic activity [16,55], as well as deficiencies of anticoagulant factors such as protein C, protein S and tissue plasminogen activator (tPA)which activates the fibrinolytic system [17,55]. Lupus-specific procoagulant factors include antiphospholipid antibodies.…”

“…Along with the antiphospholipid antibodies discussed above which must be measured in patients with thrombosis or fetal loss in lupus patients with thrombosis or fetal loss, other hemostatic markers should be measured to better assess coagulation risk in SLE, i.e., a coagulation risk laboratory profile. This includes a broad panel of testing to include fibrinogen, factor VII, factor VIII, tPA, PAI-1, plasminogen activity, Von Willebrand factor activity and antigen, protein S activity, protein C activity homocysteine, and high sensitivity C-reactive protein or HSCRP [16]. It is also important to remember that estrogens and pregnancy can induce protein S deficiency and this may compound pregnancy and hormonal therapy management in lupus.…”