Background/Purpose: Thrombosis in SLE is highly associated with antiphospholipid antibodies, yet the majority of those with antiphospholipid antibodies never have a thrombotic event. Plasma microparticles (PMP) have been identified as a risk factor for atherosclerosis. D-dimers are elevated in the setting of deep venous thrombosis. We investigated both as markers of thrombosis in SLE.

Methods:

We measured plasma microparticles (by their capacity to generate thrombin) and D-dimer levels in 1044 SLE patients. The relationship between these biomarkers and history of, and future risk of, thrombosis was determined.

Results:

The patients were 92% female, 37% African American, 54% Caucasian with mean age 48.1 ±13.1 years. Of the 1044 patients, 270 had at least one thrombotic event, including deep venous thrombosis (122), stroke (77), myocardial infarction (26), other venous (22), and other arterial thrombosis (13). Elevated levels of D-dimer were not associated with thrombosis. Thrombin generated microparticles were associated with history of a thrombotic event (Table 1).  In subanalyses, we found that this association was only found with respect to venous (but not arterial) events (Table 2).  There were 46 patients with a thrombotic event during prospective followup. The adjusted risk ratio for plasma microparticles (adjusted for presence of antiphospholipid antibodies) was 1,6,1.4,1.4 respectively for the 2^nd 3^rd and 4^th quartiles.

 Table 1 :  Life-time Rates of Thrombotic Events in SLE by Biomarker Levels

Group	# events	# of person-years at risk	Rate per 1000 person years	Risk Ratio (95% Confidence Interval)	P-value	Adjusted 1 Risk Ratio (95% Confidence Interval)	P-value
Everyone	270	45,480	5.9
D-dimer    1st quartile   2nd quartile   3rd quartile   4th quartile	76 65 58 71	11,035 11,766 11,712 10.967	6.9 5.5 5.0 6.5	1.0 (Ref. Group) 0.8 (0.6, 1.1) 0.7 (0.5, 1.0) 1.0 (0.7, 1.3)	0.12 0.029 0.79	1.0 (Ref. Group) 0.8 (0.6, 1.1) 0.7 (0.5, 0.9) 0.9 (0.6, 1.2)	0.12 0.022 0.41
PMP   1st quartile   2nd quartile   3rd quartile   4th quartile	54 63 68 62	10,826 10,523 10,233 10,460	5.0 6.0 6.6 5.9	1.0 (Ref. Group) 1.3 (0.9, 1.9) 1.5 (1.1, 2.2) 1.3 (0.9, 1.9)	0.16 0.020 0.19	1.0 (Ref Group) 1.5 (1.0, 2.1) 1.8 (1.3, 2.6) 1.5 (1.0, 2.2)	0.043 0.0014 0.028

¹ Adjusting for ever having a positive anticardiolipin or lupus anticoagulant

 

Table 2:  Life-time rates of Venous Thrombotic Events, by Biomarker Levels

Group	# events	# of person-years at risk	Rate per 1000 person years	Risk Ratio (95% Confidence Interval)	P-value	Adjusted 1 Risk Ratio (95% Confidence Interval)	P-value
Everyone	167	46,489	3.6
D-dimer    1st quartile   2nd quartile   3rd quartile   4th quartile	40 48 35 44	11,403 11,946 11,923 11,216	3.5 4.0 2.9 3.9	1.0 (Ref. Group) 1.1 (0.7, 1.7) 0.8 (0.5, 1.3) 1.2 (0.8, 1.8)	0.55 0.39 0.50	1.0 (Ref. Group) 1.1 (0.7, 1.7) 0.8 (0.5, 1.3) 1.0 (0.7, 1.6)	0.59 0.34 0.94
PMP   1st quartile   2nd quartile   3rd quartile   4th quartile	32 42 33 43	11,085 10,758 10,552 10,652	2.9 3.9 3.1 4.0	1.0 (Ref. Group) 1.5 (0.9, 2.4) 1.2 (0.7, 2.0) 1.6 (1.0, 2.5)	0.093 0.46 0.059	1.0 (Ref. Group) 1.7 (1.1, 2.7) 1.5 (0.9, 2.4) 1.9 (1.2, 3.0)	0.028 0.14 0.0072

¹ Adjusting for ever having a positive anticardiolipin or lupus anticoagulant

Conclusion: Plasma microparticles that generate thrombin increase the risk of venous thrombosis.  These data indicate that hypercoagulability in SLE can be further characterized beyond antiphospholipid antibodies, allowing prophylactic therapy to be given to the subset at greatest risk.

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