HPA-1a antibody potency and bioactivity do not predict severity of fetomaternal alloimmune thrombocytopenia
Cedric Ghevaert
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorKate Campbell
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorPrachi Stafford
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorPaul Metcalfe
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorAngela Casbard
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorGraham A. Smith
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorDave Allen
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorEdmund Ranasinghe
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorLorna M. Williamson
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorWillem H. Ouwehand
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorCedric Ghevaert
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorKate Campbell
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorPrachi Stafford
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorPaul Metcalfe
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorAngela Casbard
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorGraham A. Smith
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorDave Allen
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorEdmund Ranasinghe
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorLorna M. Williamson
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorWillem H. Ouwehand
From the National Blood Service, Cambridge and Oxford; the Department of Haematology, University of Cambridge, Cambridge; the National Institute for Biological Standards and Control, Potters Bar; and MRC Clinical Trials Unit, London, UK.
Search for more papers by this authorAbstract
BACKGROUND: The antenatal management of fetomaternal alloimmune thrombocytopenia (FMAIT) due to HPA-1a antibodies remains controversial, and a test identifying pregnancies that do not require therapy would be of clinical value.
STUDY DESIGN AND METHODS: The statistical correlation was analyzed between clinical outcome and 1) anti-HPA-1a potency in maternal serum samples determined by a monoclonal antibody immobilization of platelet (PLT) antigen assay with an international anti-HPA-1a potency standard and 2) anti-HPA-1a biological activity measured by a monocyte chemiluminescence (CL) assay.
RESULTS: A total of 133 pregnancies with FMAIT due to anti-HPA-1a were analyzed. In 97 newly diagnosed cases, there was no difference in antibody potency or CL signal between cases with intracranial hemorrhage (ICH; n = 15), those with no ICH but a PLT count of less than 20 × 109 per L (n = 52), and those with a PLT count of at least 20 × 109 per L (n = 30). In 22 previously known pregnancies, the positive predictive value of maternal anti-HPA-1a of greater than 30 IU per mL for a PLT count of less than 20 × 109 per L was 90 percent, but the negative predictive value was only 66 percent. Antibody potency tended to stay stable throughout pregnancy (n = 16) and from one pregnancy to the next (n = 16).
CONCLUSION: Neither severe thrombocytopenia nor ICH in HPA-1a-alloimmunized pregnancies can be predicted with sufficient sensitivity and specificity for clinical application from maternal anti-HPA-1a potency or bioactivity.
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