Circulating immune complexes in thrombotic thrombocytopenic purpura (TTP) [letter]

The clinical efficacy of plasma exchange with fresh frozen single donor plasma in thrombotic thrombocytopenic purpura (TTP) was evaluated. Six patients with the classical findings of TTP, had plasmapheresis using the Haemonetics Model 30. Treatments were initiated daily. Two to three liters total exchanges were done; 1-1½ liters fresh frozen plasma were infused with each exchange. In five of the six cases, therapy was begun immediately after diagnosis. Steroids and antiplatelet agents were also used. Five of the patients were comatose when treatment was begun; the sixth had neurological symptoms of memory loss and aphasia with severe hemolytic anemia and thrombocytopenia. Circulating immune complex measurements were performed in all patients prior to treatment using the Clq and Raji cell assays.Three patients (2 in coma) responded to therapy. The two comatose patients required more than four daily treatments before beginning to respond (followed by four and six alternate day treatments, respectively). The third patient went into remission after four daily treatments. Three patients in coma died, two deteriorating after the first plasma exchange. The third, treated after a delay due to severe cardiac complications, subsequently died.The three responding patients were younger than the three who died. The two in coma who responded to therapy had a longer course of symptoms (suggesting disease onset prior to onset of coma) than the three who died. Circulating immune complexes by the Clq assay were negative in all six patients. The Raji cell assay was positive in one patient.Even severely ill comatose patients with TTP respond to plasma exchange, but aggressive, persistent therapy may be required before response is seen. More fulminant disease with rapid onset may fail to respond. Circulating immune complexes do not appear to mediate the disease process.

Download Full-text

The Role of ADAMTS13-Specific Circulating Immune Complexes in Prediction of Recurrence of Acquired Thrombotic Thrombocytopenic Purpura

Blood ◽

10.1182/blood.v124.21.1467.1467 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1467-1467

Author(s):

Barbara Ferrari ◽

Carla Valsecchi ◽

Silvia Pontiggia ◽

Ilaria Mancini ◽

Luca Andrea Lotta ◽

...

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Disease Severity ◽

Immune Complexes ◽

Research Funding ◽

Cox Regression ◽

Fold Increase ◽

Circulating Immune Complexes ◽

First Episode ◽

Thrombocytopenic Purpura ◽

Adamts13 Deficiency

Abstract Introduction. Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy due to the development of autoantibodies against the VWF-cleaving protease ADAMTS13. We recently developed and validated a new ELISA method for the detection of ADAMTS13-specific circulating immune complexes (CICs) in acquired TTP patients. This study aims at investigating the clinical relevance of ADAMTS13-specific CICs at disease presentation in a large cohort of acquired TTP patients. Methods. We measured ADAMTS13-specific CICs by ELISA in 51 patients from the Milan TTP Registry, at the first episode of acquired TTP. All patients presented anti-ADAMTS13 autoantibodies by western blotting and severe ADAMTS13 deficiency (i.e., <10% of normal) by FRETS-VWF73 or CBA assays. We studied the associations between ADAMTS13-specific CICs levels and (i) ADAMTS13-related measurements (i.e., ADAMTS13 antigen, anti-ADAMTS13 IgG), (ii) clinical and laboratory markers of disease severity (i.e., muco-cutaneous bleeding, neurological, renal and cardiovascular symptoms, number of platelets, LDH, hemoglobin, creatinine), (iii) short- and long-term clinical outcomes (i.e., number of plasma exchange procedures required to attain remission, recurrence). Statistical analyses were performed using linear, logistic and Cox regression models. Results. The prevalence of ADAMTS13-specific CICs in patients experiencing a first episode of acquired TTP was 39% (95% confidence intervals [CI]: 26-52%). ADAMTS13-specific CICs were only associated with ADAMTS13 antigen levels at regression analyses (beta per 10% increase in ADAMTS13 antigen, 95% CI: 0.05, 0.02-0.08). The presence of ADAMTS13-specific CICs was associated with more than a four-fold increase in the risk of recurrence at 2 years after the first TTP episode (hazard ratio, 95%CI: 4.2, 1.1-16.4). Conclusions. ADAMTS13-specific CICs are neither a biomarker of disease severity, nor a predictor of clinical outcome during acute phase. Conversely, ADAMTS13-specific CICs seem to have relevance in predicting the recurrence of acute TTP episodes. Disclosures Peyvandi: NovoNordisk: Research Funding; Kedrion : Research Funding; NovoNordisk: Speakers Bureau; CSL Behring : Speakers Bureau; Baxter: Speakers Bureau; Bayer: Speakers Bureau.

Download Full-text

CIRCULATING IMMUNE COMPLEXES IN IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

British Journal of Haematology ◽

10.1111/j.1365-2141.1982.tb03944.x ◽

1982 ◽

Vol 52 (4) ◽

pp. 679-680 ◽

Cited By ~ 5

Author(s):

M. G. Ercilla ◽

L. Borche ◽

J. Vives ◽

R. Castillo ◽

A. Gelabert ◽

...

Keyword(s):

Immune Complexes ◽

Immune Thrombocytopenic Purpura ◽

Circulating Immune Complexes ◽

Thrombocytopenic Purpura

Download Full-text

COVID-19 and Thrombotic Thrombocytopenic Purpura: A Case Report

International Journal of Hematology-Oncology and Stem Cell Research ◽

10.18502/ijhoscr.v15i1.5251 ◽

2021 ◽

Author(s):

Maryam Darnahal ◽

Hamed Azhdari Tehrani ◽

Mohammad Vaezi ◽

Shirin Haghighi

Keyword(s):

Case Report ◽

Blood Cell ◽

Thrombotic Thrombocytopenic Purpura ◽

Organ Dysfunction ◽

Red Blood Cell ◽

Immune Complexes ◽

Cell Injury ◽

Coagulation Cascade ◽

Thrombotic Microangiopathies ◽

Thrombocytopenic Purpura

Endothelial injury by toxins, drugs, immune complexes leads to activation of coagulation cascade and thrombosis, which result in platelet consumption and red blood cell injury. These thrombotic microangiopathies can potentially injure numerous organs and result in organ dysfunction. In this case, we present the fourth reported patient with thrombotic thrombocytopenic purpura associated with COVID-19.

Download Full-text

MECHANISMS OF IMMUNOLOGIC THROMBOCYTOPENIA IN INDIVIDUALS AT RISK FOR AIDS

10.1055/s-0038-1644759 ◽

1987 ◽

Author(s):

S Karpatkin

Keyword(s):

Platelet Count ◽

Immune Complex ◽

Immune Complexes ◽

Inverse Correlation ◽

Circulating Immune Complexes ◽

Response To Treatment ◽

Thrombocytopenic Purpura ◽

Atp Level ◽

Healthy Control ◽

Platelet Antibody

HIV-seropositive homosexuals, narcotic addicts and hemophiliacs develop a new syndrome of immunologic thrombocytopenic purpura (ITP) which is clinically indistinguishable from classic autoimmune thrombocytopenic purpura (ATP) with respect to increased megakaryocytes in the bone marrow, peripheral destruction of antibody-coated platelets, negative serology for SLE, response to treatment with prednisone and/or splenectomy. However, their platelet immunologic profiles are different.Homosexuals appear to have an immune complex-mediated mechanism: markedly elevated platelet-bound IgG and C3C4 (3.8 and 4.2-fold greater than classic ATP, respectively), elevated circulating immune complexes (3-fold greater than classic ATP), anti-F(ab')2 antibodies and absence of 7S anti-platelet IgG. There is no inverse correlation between platelet count and platelet-bound IgG or platelet-elutable anti-platelet antibody as in classic ATP.Hemophiliacs appear to have an autoimmune 7S IgG-mediated mechanism similar to classic ATP: inverse relationship betweem platelet count and platelet-bound IgG, r = 0.84, p less than 0.001, 26 df, anti-platelet reactive 7S IgG which reacts by its F(ab')2 domain, (reactive at 60-130 ug/ml compared to control IgG), platelet-elutable anti-platelet antibody. However, these patients also have elevated circulating immune complexes (2.4-fold classic ATP level) and markedly elevated platelet-bound IgG and C3C4 (3.4 and 1.2-fold classic ATP level, respectively). Anti-HIV antibody correlated with circulating immune complexes, r = 0.833, p less than 0.001.Narcotic addicts appear to have a mixture of both mechanisms (immune complex as well as autoimmune 7S IgG): markedly elevated platelet-bound IgG and C3C4 (2.6 and 2.4-fold classic ATP level, respectively), elevated circulating immune complexes (7.3-fold classic ATP level), anti-F(ab')2 antibodies, absence of an inverse correlation between platelet count and platelet-bound IgG. However, these patients do have specific 7S IgG anti-platelet antibody, which reacts by its F(ab')2 domain.F(ab')2antibodies were of the IgG class and correlated with circulating immune complex level. They react with autologous, homologous patient and healthy control F(ab')2 fragments. Some anti-F(ab')2 antibodies have broad reactivity, others are more limited. Some immune complexes were shown to contain HIV antibody. It is postulated that the immune complex platelet deposition noted with homosexual and narcotic addict thrombocytopenia may in part be due to HIV antibody complexes, some of which may exist as anti-antibody complexes.

Download Full-text