Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura

Abstract

The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 x 10(9)/l) (P = 0.027) and thrombocytopenia (platelet count < 100 x 10(9)/l) (P = 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes.

Figure 1

Relationship between peripheral blood A-IPF and plasma complement activation capacity (CAC) in patients with ITP. Panel A shows A-IPF values for individual patients with either positive(+) or negative (−)plasma CAC. Each data point represents a single patient. The horizontal line reflects an A-IPF cut-off of 15 × 10⁹/L.

Figure 2

Relationship between plasma complement activation capacity (CAC) and ITP patients with thrombocytopenia (n=79). A positive CAC was defined as a complement fixation ratio for C1q, C4d, C3b, and/or C5b-9 ≥ 1.9, relative to an internal assay reference plasma standard.