Breast Milk from Immune Thrombocytopenic Mothers Can Contain Anti Platelet Antibodies That Are Associated with Persistent Thrombocytopenia in Neonates

Purpose: Maternal immune thrombocytopenic purpura (ITP) accounts for 5% of all cases of pregnancy associated thrombocytopenia and is a common cause of neonatal thrombo­cytopenia. One of the common mechanism involves transfer of IgG autoantibodies against platelet receptors which are found in the blood samples of affected patients. The neonatal thrombocytopenia usually subsides within 2 months. The autoantibodies are often of the IgG type and therefore can cross the placenta and cause fetal and/or neonatal thrombocytopenia. Recently we observed persistence of neonatal ITP which disappeared following discontinuation of breast feeding. The aim of our current work was to discern whether breast milk of mothers with ITP contains anti-platelet antibodies and whether these antibodies may be the cause for persistent neonatal ITP.

Methods: Breast milk samples were collected from 12 women with ITP. Six of them were thrombocytopenic during pregnancy and their neonates also had thrombocytopenia. The remaining 6 mothers had a history of ITP but not during the current pregnancy, and neither did their neonates. As controls, breast milk from 8 healthy women was also examinied.

The presence of anti-platelet antibodies were evaluated by incubating washed platelets from healthy donors with breast milk or extracted milk – Ig. The type of immune globulin was defined by flow cytometry using fluorescence conjugated anti-human IgA, IgG or total Ig antibodies. To prove that the antibodies were against an antigen that is platelet specific and not against HLA epitopes, we also tested the samples on cultured cells expressing the fibrinogen receptor, αIIbβ3, and compared the results to mock cells (transfected with empty vectors).

Results: In the cases of women with active ITP, 3 were positive for anti-platelet antibodies, 2 were inconclusive and one was negative. In the mothers with a history of ITP, 1 was positive, 1 was inconclusive and 4 were negative. No anti-platelet antibodies were found in breast milk of healthy women. In all 6 cases of active ITP, the cell cultured assay for the fibrinogen receptor αIIbβ3 was positive, indicating that there were anti platelet specific antibodies in their milk. Of the 6 neonates of mothers with active ITP, 4 of them required treatment with oral steroids, and the average time to resolution of thrombocytopenia was 3.5 months.

Conclusion: This study demonstrates that breastmilk of women with active ITP contains anti platelet specific antibodies. The presence of these antibodies demonstrated an association with persistant and prolonged neonatal thrombocytopenia.