Antiphospholipid antibodies, proteins C and S, and coagulation changes in sickle cell disease

The significance, interactions, and sources of coagulation abnormalities an d their relationship to clinical severity and painful episodes in sickle ce ll disease are not clear. To evaluate this, we have examined various measur es of coagulation in 37 patients with sickle cell disease (20 patients with HbSS disease and 17 patients with HbSC disease). Measurements have include d isotypes of antiphospholipid antibodies (IgG, IgM, IgA) to specific phosp holipids; proteins C (activity, total antigen) and S (activity, total and f ree antigen); measures of coagulation activation (prothrombin fragment 1.2, thrombin-antithrombin, fibrinopeptide A, d-dimers); indicators of clinical severity; and studies obtained during steady states and painful episodes. Results in HbSS disease showed that antiphospholipid antibodies were increa sed, with IgG phosphatidylserine showing the highest and most frequently in creased levels (37% of patients), Protein C (activity) and protein S (activ ity, total, free antigen) were decreased (P <.01), and all measures of coag ulation activation were increased (P <.001). In HbSC disease, antiphospholi pid antibodies were normal, protein C (activity) and protein S (free antige n) were decreased CP <.001), and all measures of coagulation activation wer e increased (P <.02). A strong correlation was observed in HbSS disease bet ween IgG-PS and d-dimers. Moderate correlations occurred between protein G activity and thrombin-antithrombin and fibrinopeptide A, between protein S activity and prothrombin fragment 1.2 and d-dimers, and between protein C a nd protein S activity In HbSC disease, moderate and fewer correlations occu rred. Significant differences between HbSS disease and HbSC disease were ob served in aPLs, proteins C and S, and measures of coagulation activation. M easurements during steady states and during painful episodes were not signi ficantly different. We conclude that the antiphospholipid antibody IgG-PS m ay contribute to coagulation activation in HbSS disease and that IgG-PS, pr otein C, and protein S relate to each other and jointly to measures of coag ulation activation. The increased level of IgG-PS in HbSS disease most like ly reflects exposure of the procoagulant phosphatidylserine on the surfaces of red cell-shed vesicles and sickle red cells, which would further affect coagulation activation. The significant differences In coagulation measure s between HbSS disease and HbSC disease are consistent with differences in clinical severity between the diseases. The development of painful episodes does not appear to be related to the coagulation changes.