Autoantibodies against platelet glycoproteins in critically ill patients with thrombocytopenia

Stéphan, François; Cheffi, Mohamed Ali; Kaplan, C.; Maillet, J; Novara, Ana; Fagon, Jean-Yves; Bonnet, Francis

doi:10.1016/s0002-9343(00)00332-6

Cited by 38 publications

(37 citation statements)

References 30 publications

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“…Antiplatelet antibodies directed against surface gp have also been described in patients with sepsis [11] and SLE [12]. As such, and according to current guidelines, their demonstration is not required for the diagnosis of ITP [13,14].…”

Section: Pathogenic Mechanism Autoantibodiesmentioning

confidence: 99%

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

Kravitz

Shoenfeld

2005

American J Hematol

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Immune thrombocytopenia purpura (ITP), thrombotic thrombocytopenia purpura (TTP), heparin‐induced thrombocytopenia (HIT), and antiphospholipid syndrome (APS) are clinical conditions associated with significant morbidity and mortality. These well‐defined clinical syndromes have in common several properties: (1) their pathogenesis is immune mediated, specifically by autoantibodies; (2) thrombocytopenia is a hallmark in these four conditions; (3) except for the case of ITP, platelet and endothelial cell activation occurs in TTP, HIT, and APS, resulting in a prothrombotic state and an increased risk of thrombosis. Although these four immune‐mediated syndromes are well‐defined diseases, several case reports and studies have documented the association of two diseases in the same patient, illustrating the concept of the kaleidoscope of autoimmunity. Am. J. Hematol. 80:232–242, 2005. © 2005 Wiley‐Liss, Inc.

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Section: Pathogenic Mechanism Autoantibodiesmentioning

confidence: 99%

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

Kravitz

Shoenfeld

2005

American J Hematol

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“…In general, sepsis-associated thrombocytopenia tends to be less severe. In a recent report, the mean platelet count among patients with septic shock was 144 Â 10 9 /L [19]; in a report of critically ill patients with thrombocytopenia, 66% of whom had sepsis, the mean platelet count was 66 Â 10 9 /L [9]. Additional studies have shown that 50% of patients with sepsis had a platelet count > 50 Â 10 9 /L [17], 83% of patients with septic shock and respiratory failure had a platelet nadir > 20 Â 10 9 /L [20], and, among 19 patients with sepsis and thrombocytopenia, platelet counts ranged from 5 Â 10 9 to 140 Â 10 9 /L [8].…”

Section: Discussionmentioning

confidence: 95%

“…Sepsis invokes an immune response that results in nonspecific and specific platelet antibody binding. Elevated levels of nonspecific platelet-associated IgG (PAIgG) have been detected in patients with sepsis and thrombocytopenia [8], and specific platelet antibodies directed against Gp IIb/IIIa or Gp Ib/IX have been detected in a small proportion of critically ill patients with infections [9]. Gp IIb/IIIa reactive antibodies have also been documented during the course of Staphylococcus aureus endocarditis [5].…”

Section: Discussionmentioning

confidence: 99%

“…Gp IIb/IIIa reactive antibodies have also been documented during the course of Staphylococcus aureus endocarditis [5]. The development of platelet autoantibodies during an episode of sepsis may occur as a result of several postulated mechanisms, including the exposure of cryptoantigens on surface proteins [9] and the binding of bacterial products to the platelet surface or the alteration of the platelet membrane [10]. Immune complexes may be an important factor in the development of thrombocytopenia in infective endocarditis; in cases with high levels of circulating immune complexes, a rare TTP-like syndrome has been described with thrombocytopenia, hemolytic anemia, and neurologic and renal impairment [3,10,11].…”

Section: Discussionmentioning

confidence: 99%

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Cardiobacterium hominis endocarditis associated with very severe thrombocytopenia and platelet autoantibodies

et al. 2004

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Severe thrombocytopenia is a life-threatening condition. It is often associated with immune-mediated platelet destruction or myeloablative chemotherapy. Infective endocarditis has been associated with thrombocytopenia, which, as in sepsis, tends to be mild and is often the result of several pathological mechanisms. We report a case of Cardiobacterium hominis endocarditis associated with very severe thrombocytopenia and bleeding in a patient who refused platelet transfusion. Platelet autoantibodies directed against glycoprotein (Gp) IIb/IIIa and Gp Ib/IX were detected during active infection using a glycoprotein-specific assay. Successful treatment of C. hominis endocarditis was associated with loss of platelet autoantibodies and recovery of the platelet count. This report illustrates that the development of platelet autoantibodies can contribute to very severe thrombocytopenia in occasional patients with infective endocarditis. Am.

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“…One such disease is the autoimmune blood coagulation disease ITP, in which the primary molecular targets of autoantibodies are known to be platetelet glycoprotein 1b (pgp 1b) and von Willebrand's factor (VWF, or factor IX) (Kahane et al 1981, He et al 1994, 1995, Hou et al 1997, Wadenvik et al 1998, Stéphan et al 2000, McMillan 2003. Notably, pgp 1b binds to VWF during the normal course of the blood coagulation cascade, and the binding regions of each molecule for the other have been reasonably well characterized: the A1 binding domain of the mature VWF glycoprotein (Gly 479 to Pro 717 ) interacts with the Platelet gp Ib Platelet gp Ib a-chain (His 1 -Arg 293 ) (Titani et al 1987, Vicente et al 1988, Emsley et al 1998, Cruz et al 2000, Shimizu et al 2004.…”

Section: Case Study: Idiopathic Thrombocytopenia Purpuramentioning

confidence: 99%

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

Root‐Bernstein

Couturier

2000

Journal of Immunology Research

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We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self -nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.

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Autoantibodies against platelet glycoproteins in critically ill patients with thrombocytopenia

Cited by 38 publications

References 30 publications

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

Cardiobacterium hominis endocarditis associated with very severe thrombocytopenia and platelet autoantibodies

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

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