Synergistic action in platelet activation induced by an antiplatelet autoantibody in ITP

Yanabu, Mutsumasa; Nomura, Shosaku; Fukuroi, Tsutomu; Soga, Tetsuji; Kawasaki, Koji; Sone, Naoaki; Kitada, Chikaho; Nagata, Hirokazu; Kokawa, Terutoshi; Yasunaga, Kōjirō

doi:10.1111/j.1365-2141.1991.tb04387.x

Cited by 29 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these patients, platelet activation might act as a compensatory mechanism to reduce the bleeding that occurs due to thrombocytopenia; thus, many ITP patients do not have significant bleeding even with severe thrombocytopenia. Platelet auto-antibodies activate normal platelets in patients with ITP [25]. Shao et al [16], Panzer et al [26] and Hayashi et al [27] measured the activated platelets in ITP patients and found that the percentages of CD62p-positive platelets were significantly higher in ITP patients than in other patients.…”

Section: Discussionmentioning

confidence: 99%

Platelet Antibodies, Activated Platelets and Serum Leptin in Childhood Immune Thrombocytopenic Purpura

et al. 2013

View full text Add to dashboard Cite

Background/Aim: The aim of this study was to evaluate the levels of platelet-associated antibodies (PAIgG and PAIgM), activated platelets and serum leptin in children with acute immune thrombocytopenic purpura (ITP). Methods: The study included 40 patients with ITP and 40 healthy age- and sex-matched controls. PAIgG, PAIgM and activated platelet levels were estimated by flow cytometry, and serum leptin levels were estimated by ELISA. Results: Activated platelets and serum leptin were significantly higher in the ITP patients than in the controls. The percentage and mean florescence intensity of PAIgG and PAIgM staining were significantly higher in the patients than in the controls. Serum leptin and activated platelet levels in patients with thrombocytopenia of brief duration were significantly lower than those in patients with thrombocytopenia of prolonged duration. The levels of activated platelets, serum leptin and PAIgG were positively correlated, and the levels of serum leptin, activated platelets and platelet counts were negatively correlated. Conclusion: The increased levels of activated platelets, serum leptin and platelet-associated antibodies in children with acute ITP suggest that these factors could play a role in ITP pathogenesis. Additionally, activated platelets and serum leptin could have prognostic significance in paediatric acute ITP.

show abstract

Section: Discussionmentioning

confidence: 99%

Platelet Antibodies, Activated Platelets and Serum Leptin in Childhood Immune Thrombocytopenic Purpura

et al. 2013

View full text Add to dashboard Cite

show abstract

“…These mechanisms are currently unknown; however, it has been reported that the sera of some patients with ITP activated platelets and enhanced platelet aggregation. [20][21][22] Thus, it is possible that these GPIb-specific antibodies used in our murine model may induce different signaling events in platelets, which could contribute to this heterogeneity. 23 IVIG is a costly therapy, and annual increases in IVIG utilization and limitations in the available volume of humansource plasma may cause IVIG shortages.…”

mentioning

confidence: 99%

Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbα antibodies

Webster

Sayeh

Crow

et al. 2006

Blood

118

101

View full text Add to dashboard Cite

Intravenous immunoglobulin G (IVIG) isused to treat idiopathic thrombocytopenic purpura (ITP). Although many patients benefit from IVIG, some are refractory to this therapy. ITP is characterized by platelet clearance mediated primarily by antiplatelet antibodies against GPIIbIIIa and/or the GPIb␣ complex. These 2 groups of antibodies may induce ITP through different mechanisms. We tested the hypothesis that IVIG may not be equally effective in preventing ITP caused by anti-GPIIbIIIa versus anti-GPIb␣ antibodies in mice. Thrombocytopenia was induced in BALB/c mice using monoclonal antibodies against either mouse GPIIbIIIa (JON1, JON2, and JON3) or GPIb␣ (p0p3, p0p4, p0p5, p0p9, and p0p11). Pretreatment with IVIG significantly ameliorated ITP in all anti-GPIIbIIIainjected animals. Conversely, IVIG failed to prevent ITP in all anti-GPIb␣-treated mice, except for p0p4. These results were repeated in C57BL/6 mice, and with different IVIG preparations. These data in mice suggest that patients with ITP mediated by anti-GPIb␣ antibodies may be less responsive to IVIG treatment. IntroductionIdiopathic thrombocytopenic purpura (ITP) is an autoimmune disease caused by autoantibodies generated against a patients' own platelets, leading to decreased platelet counts and a bleeding diathesis. 1-3 Platelet surface glycoproteins IIbIIIa (GPIIbIIIa, ␣IIb␤3 integrin) and Ib␣ (GPIb␣) are the 2 most common antigenic targets in ITP. [4][5][6] Approximately 70% to 80% of patients have autoantibodies to GPIIbIIIa, 20% to 40% to the GPIb complex, and a significant number of patients simultaneously have antibodies to both or to other glycoproteins (eg, GPIV and Ia/IIa). 2,6,7 Reports that anti-GPIb␣ may cause thrombocytopenia through a different mechanism (Fc-independent pathway) from anti-GPIIbIIIa (Fc-dependent pathway) 8 are intriguing, though the mechanism of Fc-independent platelet clearance is unknown. It is not clear whether pathogenesis and therapeutic responses are different for ITP induced by these 2 groups of antibodies.IVIG is used to treat several autoimmune diseases, including ITP. 9-11 However, the mechanism of action of IVIG is not fully understood. 12 Although IVIG effectively ameliorates thrombocytopenia in many patients with ITP, a significant number (15%-25%) are refractory to this therapy. 13 It is unknown whether refractory cases result from IVIG being less efficacious in ITP caused by certain antibody specificities (ie, anti-GPIb␣). To test this hypothesis, we induced thrombocytopenia in a murine model 14 using well-characterized rat monoclonal antibodies against either mouseGPIIbIIIa or GPIb␣, and tested the ability of IVIG to attenuate ITP induced by these antibodies in this model. Study design AnimalsBALB/c and C57BL/6 mice, 6 to 8 weeks of age, were purchased from Charles River Canada (Montreal, QC, Canada), and maintained in the local research vivarium. Platelet preparation and countingWhole blood (10 L) was obtained from the saphenous vein and immediately diluted 1:100 in 990 L of 1% (vol/vol) EDTA/PBS, pH 7...

show abstract

“…This immunoglobulin may be derived from within the platelet alpha granules ( George et al , 1985 ). The binding of immunoglobulin and immune complexes to the platelet surface has been associated with platelet activation ( Yanabu et al , 1991 ). Platelet activation is associated with alterations in platelet size and shape, alterations in transmembrane molecules, such as GPIIb/IIIa and the release of intraplatelet substances to the cell membrane and plasma.…”

mentioning

confidence: 99%

Protein A immunoadsorption in chronic refractory ITP reverses increased platelet activation but fails to achieve sustained clinical benefit

et al. 1998

View full text Add to dashboard Cite

Adults with chronic relapsing ITP present a difficult therapeutic challenge. The ongoing antibody-mediated platelet destruction in this group might be expected to be associated with increased expression of platelet surface membrane activation antigens. We have studied a group of 10 patients with refractory ITP and 35 healthy controls. Using an immediate, sensitive, unfixed, whole blood, flow cytometric method to detect platelet surface P-selectin and GP53, we have detected markedly increased platelet activation in the ITP group compared with the controls (P-selectin; patient median 24.5% v control median 2.0%. GP53 median 6.5% v 2.1%, P < 0.01 for both). Five patients underwent protein A immunoadsorption therapy. The effect of protein A immunoadsorption on platelet activation before, during and after 18 treatments in these patients was studied and patients were followed-up to assess clinical outcome. Platelet-associated immunoglobulin measurements were made before and at the end of six treatments. Platelet activation decreased after immunoadsorption. P-selectin expression fell significantly; pre- and post-treatment median values differed by 15.5%, P < 0.01, for GP53 the difference was 2.5%, P = NS. A reduction in both platelet-associated IgG (median reduction of 11.8 ng/10(6) platelets, P = 0.08) and IgM (7.6 ng/10(6) platelets, P = 0.06) was recorded.

show abstract

Synergistic action in platelet activation induced by an antiplatelet autoantibody in ITP

Cited by 29 publications

References 29 publications

Platelet Antibodies, Activated Platelets and Serum Leptin in Childhood Immune Thrombocytopenic Purpura

Platelet Antibodies, Activated Platelets and Serum Leptin in Childhood Immune Thrombocytopenic Purpura

Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbα antibodies

Protein A immunoadsorption in chronic refractory ITP reverses increased platelet activation but fails to achieve sustained clinical benefit

Contact Info

Product

Resources

About