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 have been identified as a risk factor for atherosclerosis. D-dimers are elevated in the setting of deep venous thrombosis. Endogenous thrombin potential (ETP) measures the thrombin formation capacity of plasma and may be elevated in hypercoagulable states.

Methods: We measured plasma microparticles by their functional capacity to generate thrombin, ETP, and D-dimer levels in 986 SLE patients. The relationship between these biomarkers and history of thrombosis was estimated.

Results:

The patients were 92% female, 37% African American, 55% Caucasian with mean age 48.1 ±13.1 years. Of the 986 patients, 258 had at least one thrombotic event, including deep venous thrombosis (113), stroke (75), myocardial infarction (26), other venous (21), and other arterial thrombosis (13). Elevated levels of D-dimer (> 0.88 mg/L) were not associated with thrombosis. Thrombin generated microparticles were associated with history of a thrombotic event (Table).  In subanalyses, we found that this association was only found with respect to venous (but not arterial) events.  Low ETP was associated with a higher likelihood of a history of thrombosis. However, controlling for antiocoagulant use, this association disappeared, suggesting that the association was due to the fact that those with a history of thrombosis were put on anticoagulants which reduced their ETP.
Table 1 :  Life-time rates of thrombotic events in SLE patients 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		258	42,513	6.1
Ddimer (High/Low)	<0.88       0.88+	173 85	28,305 14,208	6.1 6.0	1.0 (Ref Group) 1.0 (0.8, 1.3)	.91	1.0 (Ref Group) 0.9 (0.7, 1.2)	.52
Thrombin generated microparticles(High/Low)	<5     5+	76 165	14,262 25,845	5.3 6.4	1.0 (Ref Group) 1.3 (1.0, 1.7)	.044	1.0 (Ref. Group) 1.5 (1.1, 1.9	.0075
ETP quartiles	<343     343-395     395-436     436+	111 42 36 52	9,699 10,486 10,030 10,545	11.4 4.0 3.6 4.9	1.0 (Ref. Group) 0.3 (0.2, 0.5) 0.3 (0.2, 0.4) 0.4 (0.3, 0.6)	<.0001 <.0001 <.0001	1.0 (Ref. Group) 0.9 (0.6, 1.4)2 0.9 (0.6,1.5)2 1.2 (0.8, 1.8)2	.61 .81 .50

¹ Adjusting for ever having a positive ACL or RVVT test unless specified
²Adjusting for ever having a positive ACL or RVVT test and use of anti-coagulants.

Conclusion: Thrombin generated plasma microparticles increase the risk of thrombosis at levels >5.  These data indicated 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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