Abstract
Patients with systemic lupus erythematosus (SLE) are known to experience thrombosis with higher frequency than the general population, but the demographic and laboratory underpinnings of this phenomenon have been incompletely studied. To characterize clinical and laboratory parameters predisposing to thrombosis in urban systemic lupus patients, medical records of 111 such patients with a history of vascular thrombosis, adverse pregnancy outcome, or considered to be at high risk for thrombosis because of their clinical setting and collagen-vascular disease were reviewed. Extensive investigation of recognized contributors to and markers of inflammation and hypercoagulation, e.g. antiphospholipid antibodies (APLs) had been performed during their clinical evaluation.
Population Demographics Subject # (%) # % # % # % Gender 102F (69) 9M (8) 111 (100) Ethnicity 76 AA (69) 29 Cau (26) 6 Other (5) 111 (100) Organ Damage 59 Major(53) 52 Minor(47) 111 (100) Thrombosis 35 Arterial (31) 14 Venous (13) 15 Both (14) 64 (58) Risk Contributor 24 OB (27) 14 APLs (13) 6 Hi-Risk (5) 44 (40) Bleeding 5 (4) 5 (4)
African-American women, mean age 43.7 years, were predominantly represented in this patient group (69%). More than half the group had major organ involvement (renal, central nervous system) and vascular thrombosis. Obstetrical issues (high-risk pregnancy management or fetal loss, 22%), APLs (13%), and patients referred for high risk settings (pre-organ transplant, vascular surgery, hormone replacement therapy, 5%), and bleeding history (cerebral hemorrhage, vaginal bleeding, 4%) with hypercoagulability characterized the remainder of the study group.
Hemostasis testing further distinguished this population from those previously reported. Neither the Factor V Leiden nor Prothrombin 20210 mutation was identified, while heterozygous (16%) and homozygous (2%) C677T mutations of MTHFR with hyperhomocysteinemia were found. Platelet hyperfunction, either activation threshold lowering (“sticky platelet syndrome”) and/or the homozygous PlA2 genotype, was found in 70% (78/111). Antiphospholipid antibodies were relatively infrequent, and in low concentration when present. Activity of several procoagulant factors (Fibrinogen, Factor VIII, von Willebrand factor, and plasminogen activator inhibitor 1 (PAI-1) was significantly increased, likely reflecting heredity-conditioned response to underlying inflammation. Several patients had mixed results with both pro- and anti-thrombotic tendencies. Platelet dense granule deficiency was associated with bruising/bleeding problems. Thus, in this urban, largely African-American SLE population with thrombosis or clinical settings posing high-risk of thrombosis, platelet hyperfunction and inflammatory procoagulant elevation appear to be of greater importance than antiphospholipid antibodies or the Factor V Leiden or Prothrombin mutations. These differences suggest that strategies for thrombosis prevention in this population should be directed primarily toward suppression of inflammation and modulation of platelet hyperfunction, i.e. toward control of the collagen-vascular disorder and inherited platelet hyperfunction, in the expectation that enlightened prevention may obviate the need for more aggressive life-long anticoagulation measures.
Avascular necrosis in systemic lupus erythematosus: total hip replacement in a patient with mutation in clotting factor V (Leiden) gene, clinical observation