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 × 109/L) (p = 0.027) and thrombocytopenia (platelet count less than 100K/μl) (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 pharmacologic 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.

Classical complement pathway activation in immune thrombocytopenia purpura: inhibition by a novel C1s inhibitor

“…Increasing evidence suggests a role for complement activation in ITP (Peerschke, et al 2009, Najaoui, et al 2011). Although early work by Frank et al (1975) demonstrated that an intact classical complement pathway was required for damage of antibody sensitized mammalian cell membranes and the development of thrombocytopenia in a guinea pig model, the role for classical pathway (CP) complement activation in human ITP has not been definitively established.…”

Immune thrombocytopenia in children and adults: what's the same, what's different?

“…platelet antibodies the activation of the complement system has been shown to contribute to accelerated decrease in platelets by detection of the degradation components C1q or C4d in platelet-antibody complexes; 4 iii) in addition, in vitro stimulated T cells of some patients with ITP were able to trigger cytotoxic lysis of platelets by either CD3 + CD8 + T cells or CD56 + natural killer cells, 5 eventually in those patients in whom no circulating or plateletbound antibodies can be detected. Taken together, these data provide evidence that both T-and B-cell dependent processes are involved in the pathogenesis of ITP.…”

C3b-Independent Complement Activation in Ischemia/Reperfusion Mesenteric Tissue Injury in Autoimmune Prone (B6.MRL/lpr) Mice

“…The C1q downstream targets are platelets as well as intermediates in the thrombin cascades [32,33]. Soluble CR1 (sCR1) has been produced by recombinant technology and is being used in phase I human trials.…”