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Blood | Fetal and neonatal alloimmune thrombocytopenia

Fetal thrombocytopenia refers to an insufficient number of platelets in the fetal blood circulation. Just like in adults, platelets in the fetus are responsible for forming blood clots to prevent ongoing bleeding after injury or trauma. If there are insufficient circulating platelets, the fetus could develop large bleeds in the brain and this can lead to a stroke while the fetus is still inside the womb.

Essential Information

  • Platelets are small, disk-shaped fragments (or pieces) of cells that are found in large numbers in the fetal and adult circulations. They play an important role in forming blood clots to prevent ongoing bleeding after an injury.
  • Fetal thrombocytopenia refers to a lack of platelets in the fetal blood circulation. Severe thrombocytopenia can make it difficult for the fetal blood to clot, which might lead to serious bleeding in the body or in the fetal brain.
  • Fetal thrombocytopenia may result from a condition called fetal and neonatal alloimmune thrombocytopenia (F/NAIT), where the mother’s immune system forms antibodies that attack and destroy the fetal platelets.
  • When severe thrombocytopenia is diagnosed, weekly immunoglobulin (IVIG) infusions to the mother may be considered, as these have been shown to dramatically improve the outcome for affected fetuses.

Overview

Thrombocytopenia is a lack of platelets in the fetal circulation. Platelets are responsible for blood clotting to prevent ongoing bleeding after an injury.

In a condition called fetal or neonatal alloimmune thrombocytopenia (F/NAIT), the mother’s and fetal platelets are incompatible. The mother’s immune system recognizes the fetal platelets as foreign and mounts an immune attack by forming antibodies to these cells which cross the placenta and reach the fetal circulation. In this way, they can destroy the fetal platelets and cause the fetus to become thrombocytopenic.

Fetal thrombocytopenia cannot be diagnosed on ultrasound, but may present with ultrasound findings of a bleed around the fetal brain (called an intracranial haemorrhage). In these cases, the outcome is very poor, often with significant brain damage. The mother will not have any symptoms.

Sometimes, fetal thrombocytopenia is suspected because of the outcomes of a previous pregnancy, if the mother has delivered a previous child with thrombocytopenia, F/NAIT or a bleed in the brain. Blood from the mother and the father may provide important information about the type of maternal-fetal platelet incompatibility.

Mild and moderate thrombocytopenia usually does not affect fetal wellbeing or cause bleeding, and the long-term outcome for these infants is excellent.

In severe thrombocytopenia, however, fetal blood clotting is significantly impaired and minor trauma may lead to fetal bleeds in the brain (intracranial haemorrhage). These bleeds can lead to a stroke while the fetus is still in the womb, and can result in fetal death or significant long-term developmental delay.

Treatment

Fetuses at high risk for thrombocytopenia due to F/NAIT should be cared for in coordination with a MFM specialist. Preventative treatment with weekly immunoglobulin (IVIG) infusions to the mother, starting in the second trimester of pregnancy, may be indicated. Fetal blood sampling may be considered in the third trimester to document fetal platelet levels and to adjust further treatment. This strategy has significantly reduced the incidence of severe thrombocytopenia and the need for fetal intrauterine platelet transfusions. The risk for severe thrombocytopenia causing intracranial hemorrhage after such preventative therapy is less than 5% and is associated with reassuring long-term outcomes.

Referral Information (for physicians)

Inclusion criteria

  • Confirmed maternal platelet antibodies with or without a history of a previously-affected pregnancy.
  • Incompatible platelet phenotype in partner.
  • History of F/NAIT in a female sibling

Practically

IVIG administration can usually be administered locally and on an outpatient basis, in shared care with Mount Sinai Hospital. Fetal blood sampling at 28 and 36 weeks may be recommended. Local patients will have shared care between the referring centre and Mount Sinai Hospital. Delivery will be usually planned at Mount Sinai Hospital.