Continuing controversy in alloimmune thrombocytopenia: Fetal hyperimmunoglobulinemia fails to prevent thrombocytopenia

Nicolini, Umberto; Tannirandorn, Yuen; González, Pedro; Fisk, Nicholas M.; Beacham, J; Letsky, Elizabeth A.; Rodeck, Charles H.

doi:10.1016/0002-9378(90)90674-v

Cited by 66 publications

(34 citation statements)

References 2 publications

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“…Miscarriage is a devastating consequence, and thus, antenatal management is required. In previous work with the β3 -/-model of FNIT, we found that maternal administration of IVIG ameliorated FNIT (34,35), consistent with reported clinical data (1,8), although the clinical data from different groups vary (1,8,47). Here, we investigated whether mice with anti-GPIbα-mediated FNIT similarly responded to IVIG treatment.…”

Section: Figuresupporting

confidence: 80%

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

et al. 2011

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Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder caused by maternal antibody-mediated destruction of fetal/neonatal platelets. It is the most common cause of severe thrombocytopenia in neonates, but the frequency of FNIT-related miscarriage is unknown, and the mechanism(s) underlying fetal mortality have not been explored. Furthermore, although platelet αIIbβ3 integrin and GPIbα are the major antibody targets in immune thrombocytopenia, the reported incidence of anti-GPIbα-mediated FNIT is rare. Here, we developed mouse models of FNIT mediated by antibodies specific for GPIbα and β3 integrin and compared their pathogenesis. We found, unexpectedly, that miscarriage occurred in the majority of pregnancies in our model of anti-GPIbα-mediated FNIT, which was far more frequent than in anti-β3-mediated FNIT. Dams with anti-GPIbα antibodies exhibited extensive fibrin deposition and apoptosis/necrosis in their placentas, which severely impaired placental function. Furthermore, anti-GPIbα (but not anti-β3) antiserum activated platelets and enhanced fibrin formation in vitro and thrombus formation in vivo. Importantly, treatment with either intravenous IgG or a monoclonal antibody specific for the neonatal Fc receptor efficiently prevented anti-GPIbα-mediated FNIT. Thus, the maternal immune response to fetal GPIbα causes what we believe to be a previously unidentified, nonclassical FNIT (i.e., spontaneous miscarriage but not neonatal bleeding) in mice. These results suggest that a similar pathology may have masked the severity and frequency of human anti-GPIbα-mediated FNIT, but also point to possible therapeutic interventions.

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Section: Figuresupporting

confidence: 80%

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

et al. 2011

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“…Three days after each treat ment, FBS and platelet transfusion were performed as before. However, over the next 3 weeks, the fetal plate let count remained below 30 x 109/1, and with no change in fetal serum immunoglobulin levels, despite elevated maternal level (> 20 g/1 [20]) (table 1). Mater nal IVIG treatment was therefore discontinued.…”

Section: Patients and Resultsmentioning

confidence: 99%

“…From 28 weeks, Sandoglobulin (Sandoz, Camberley, UK), 1 g/kg estimated feto-placental weight was administered directly into fetal circulation at each weekly transfusion. Fetal platelet count still remained low over the next 3 weeks, despite high levels of immunoglobulins in fetal serum [20] IVIG was therefore discontinued and weekly platelet transfusions maintained until 32 weeks, when a baby girl weighing 1,325 g was delivered by cesarean section owing to bradycardia, which complicated the last platelet transfusion. The cord platelet count was 35 x 109/1; the baby did not require assisted ventilation, and was normal to both clinical and neurosonographic examinations.…”

Section: Patients and Resultsmentioning

confidence: 99%

“…However, only 30% of the severe cases (pre-treatment platelet count <50 x 109/1) resulted in a platelet count at birth of >50 x 109/1. Several others have reported their experience in the use of mater nal IVIG therapy, some with successful re sults [18,19] and some showing lack of re sponse [20][21][22], The efficacy of such therapy therefore remains controversial. Further more, the estimated cost per pregnancy of weekly gammaglobulin between 20 and 36 weeks, assuming a maternal weight of 70 kg and preparation cost of £23 per g, is over £27,000.…”

Section: Discussionmentioning

confidence: 99%

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Direct Fetal Administration of Immunogíobulins: Another Disappointing Therapy in Alloimmune Thrombocytopenia

Weiner¹,

Zosmer²,

Bajoria³

et al. 1994

Fetal Diagn Ther

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Current management strategies to prevent fetal intracranial haemorrhage in perinatal alloimmune thrombocytopenia (PAIT) include serial platelet transfusion and/or maternal high-dose intravenous immunoglobulin (IVIG) administration. The former involves multiple invasive procedures, while the latter is both expensive and of questionable efficacy. We report the use of direct fetal IVIG in 2 fetuses with PAIT, undergoing serial intrauterine platelet transfusions. Fetal IVIG had no effect on fetal platelet count. We conclude that direct fetal IVIG administration does not appear to have a role in the management of PAIT, and that current management strategies remain far from ideal.

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“…Rodeck/Roberts Successful Treatment of Fetal Cardiac Arrest proved disappointing and the only variable established as having a bearing on the level of the fetal platelet count between transfusions is the absolute value to which that level rises fol lowing transfusion [8].…”

mentioning

confidence: 99%

Successful Treatment of Fetal Cardiac Arrest by Left Ventricular Exchange Transfusion

Rodeck

Roberts²

1994

Fetal Diagn Ther

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A 36-year-old pregnant woman with anti-HPA1a antibodies underwent six fetal platelet concentrate transfusions. During the second, at 28 weeks’ gestation, fetal asystole occurred in association with a post-transfusion platelet count of 813 × 10⁹/l. Asystole was reversed by an intracardiac partial exchange transfusion of normal saline for fetal blood, simultaneously reducing fetal plasma viscosity and enabling re-commencement of the fetal circulation.

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Continuing controversy in alloimmune thrombocytopenia: Fetal hyperimmunoglobulinemia fails to prevent thrombocytopenia

Cited by 66 publications

References 2 publications

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

Direct Fetal Administration of Immunogíobulins: Another Disappointing Therapy in Alloimmune Thrombocytopenia

Successful Treatment of Fetal Cardiac Arrest by Left Ventricular Exchange Transfusion

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