A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia

Al‐Samkari, Hanny; Rosovsky, Rachel; Leaf, Rebecca S. Karp; Smith, David B.; Goodarzi, Katayoon; Fogerty, Annemarie E.; Sykes, David B.

doi:10.1182/bloodadvances.2019000868

Cited by 60 publications

(74 citation statements)

References 45 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antibody titers may be important indicators of disease; however, we were unable to reliably compare autoantibody titers between BM and PB because of nonstandardized dilutions and processing methods. Although other investigators have found that the sensitivity of PB platelet autoantibodies was higher than what we found, 19,20 many other studies are in line with our findings. 2 In addition, there was no association between autoantibody profiles of ITP patients and the treatments they received at the time of autoantibody testing (supplemental Tables 1 and 2).…”

Section: Resultssupporting

confidence: 92%

Platelet autoantibodies in the bone marrow of patients with immune thrombocytopenia

Shrestha¹,

Nazy

Smith³

et al. 2020

Blood Advances

View full text Add to dashboard Cite

Autoantibodies cause platelet destruction in patients with immune thrombocytopenia (ITP); yet only 50% to 60% of patients have detectable platelet autoantibodies in peripheral blood. We hypothesized that in some ITP patients, platelet autoantibodies are sequestered in the bone marrow where pathological immune reactions target megakaryocytes or newly formed platelets. In this study, we modified the platelet glycoprotein-specific assay to test bone marrow aspiration samples for free platelet autoantibodies or antibodies bound to bone marrow cells in aspirate fluid from patients with ITP (n = 18), patients with nonimmune thrombocytopenia (n = 3), and healthy donors (n = 6). We found that 10 (56%) of 18 patients with ITP had autoantibodies in the bone marrow, including 5 (50%) of 10 with autoantibodies in bone marrow only, and 5 (50%) of 10 with autoantibodies in bone marrow and peripheral blood. In comparison, 6 (33%) of 18 ITP patients had autoantibodies in peripheral blood, most of whom (5 [83%] of 6) also had autoantibodies in bone marrow. Bone marrow autoantibodies were not detected in patients with nonimmune thrombocytopenia or healthy donors; however, peripheral blood autoantibodies were detectable in 1 (33%) of 3 patients with nonimmune thrombocytopenia. The sensitivity of platelet autoantibodies for the diagnosis of ITP increased from 60% (peripheral blood testing) to 72% (peripheral blood and bone marrow testing). Immune reactions limited to the bone marrow may be characteristic of certain subsets of ITP patients.

show abstract

Section: Resultssupporting

confidence: 92%

Platelet autoantibodies in the bone marrow of patients with immune thrombocytopenia

Shrestha¹,

Nazy

Smith³

et al. 2020

Blood Advances

View full text Add to dashboard Cite

show abstract

“…Unsurprisingly, anti-GPIIb/IIIa antibodies were the most frequently detected, either isolated (24.6%) or associated with anti-GPIb/IX (23.2%), which is consistent with previous studies (10.7-23.5% and 17.5-61.4%, respectively) [18][19][20][21][22][23]. However, the proportion of patients with isolated anti-GPIb/IX was particularly low in our study (1.4%), whereas these antibodies usually account for 3.1-13.3% [18][19][20][21][22][23]. The reason for such a discrepancy was not clear but could be due to a bias of selection as antiplatelet antibodies were not systematically and prospectively measured in our cohort, in accordance with the guidelines [12].…”

Section: Discussionsupporting

confidence: 91%

“…The proportion of patients without antiplatelet antibodies detected by MAIPA was similar to previous papers that reported a frequency around 50% [18][19][20][21], excepted for the last studies that did not detect antiplatelet antibodies in only 20% [22,23]. Unsurprisingly, anti-GPIIb/IIIa antibodies were the most frequently detected, either isolated (24.6%) or associated with anti-GPIb/IX (23.2%), which is consistent with previous studies (10.7-23.5% and 17.5-61.4%, respectively) [18][19][20][21][22][23]. However, the proportion of patients with isolated anti-GPIb/IX was particularly low in our study (1.4%), whereas these antibodies usually account for 3.1-13.3% [18][19][20][21][22][23].…”

Section: Discussionsupporting

confidence: 88%

Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia

Rogier

Samson

Mourey

et al. 2020

JCM

View full text Add to dashboard Cite

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fcγ receptor (FcγR)-dependent manner while anti-GPIb/IX antibodies induce platelet desialylation leading to their destruction by hepatocytes after binding to the Ashwell–Morell receptor, in a FcγR-independent manner. Considering the FcγR-dependent mechanism of action of intravenous immunoglobulins (IVIg), we assumed that the response to IVIg could be less efficient in the presence of anti-GPIb/IX antibodies. We conducted a multicentric, retrospective study including all adult ITP patients treated with IVIg who had antiplatelet antibodies detected between January 2013 and October 2017. Among the 609 identified, 69 patients were included: 17 had anti-GPIb/IX antibodies and 33 had anti-GPIIb/IIIa antibodies. The response to IVIg was not different between the patients with or without anti-GPIb/IX (88.2% vs. 73.1%). The response to IVIg was better in the case of newly diagnosed ITP (odds ratio (OR) = 5.4 (1.2–24.7)) and in presence of anti-GPIIb/IIIa (OR = 4.82 (1.08–21.5)), while secondary ITP had a poor response (OR = 0.1 (0.02–0.64)). In clinical practice, the determination of antiplatelet antibodies is therefore of little value to predict the response to IVIg.

show abstract

“…26,27 Studies, which require confirmation, suggest it may possibly be prognostic for treatment response in the future. 28,29 Anti-phospholipid antibodies. Anti-phospholipid antibodies (APLAs), including anti-cardiolipin antibodies and lupus anticoagulant, can be found in up to 46% of otherwise typical adults with ITP, 30 although most studies report rates of 25% to 30%.…”

Section: Tests Of Potential Utilitymentioning

confidence: 99%

Updated international consensus report on the investigation and management of primary immune thrombocytopenia

et al. 2019

Self Cite

View full text Add to dashboard Cite

Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.

show abstract

A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia

Abstract: Key Points When performed in accordance with modern ASH and ISTH guidelines, PA testing is sensitive and specific for ITP diagnosis. More glycoproteins targeted by autoantibodies predicts for more severe disease, and autoantibodies resolve with clinical remission.

Cited by 60 publications

References 45 publications

Platelet autoantibodies in the bone marrow of patients with immune thrombocytopenia

Platelet autoantibodies in the bone marrow of patients with immune thrombocytopenia

Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia

Updated international consensus report on the investigation and management of primary immune thrombocytopenia

Contact Info

Product

Resources

About