Previous studies have suggested that aPL antibodies found in PK 11195 patients with venous BMY-14802 thrombosis have increased complement-fixing ability compared to aPL antibodies found in patients with arterial thrombosis and this may be one reason for the increased complement deposition on platelets in patients with aPL antibodies and venous thrombosis. C4d deposition on platelets has been suggested to be highly specific for SLE but it was not known if C1q deposition on platelets could be seen in inflammatory diseases other than SLE. In contrast to a previous investigation increased C4d and C1q deposition could be readily observed on platelets in patients with rheumatoid arthritis, increased C4d deposition on platelets was found in patients with systemic sclerosis, as well as high levels of complement deposition found on platelets in some apparently healthy individuals. Thus, complement activation on platelets is not specific for SLE but associated with platelet activation in general. However, different patterns of C1q and C4d deposition were found in SLE patients and patients with rheumatoid arthritis. Patients with rheumatoid arthritis had a high frequency of elevated C1q levels on platelets but a relatively low frequency of C4d, whereas SLE patients had the opposite with high frequency of elevated C4d levels compared to a relatively low frequency of C1q. This suggests that different mechanisms of complement activation and regulation might be operating in the two diseases. Interestingly, SLE patients with ongoing arthritis had increased C1q deposition on platelets compared to SLE patients with no arthritis. Even though the pathogenesis of arthritis is different between rheumatoid arthritis and lupus, platelet activation has been demonstrated in the joints of patients with rheumatoid arthritis, but the contribution of complement activation on platelets to this is not known. Further studies are needed to elucidate how complement activation on platelets is regulated in different conditions and contributes to disease manifestations. In conclusion, we suggest that aPL antibodies are able to amplify C4d deposition on platelets through two separate mechanisms; amplification of platelet activation, and providing complement-fixing antibodies on platelets. Complement deposition on platelets is associated with venous, but not arterial, thrombosis in SLE patients, independent of traditional cardiovascular risk factors and aPL antibodies.