Alloimmune thrombocytopenia
| Classification according to ICD-10 | |
|---|---|
| P61.0 | Transient thrombocytopenia in the newborn Thrombocytopenia in the newborn due to: |
| ICD-10 online (WHO version 2019) | |
A alloimmune thrombocytopenia is a rare, fatal disease of the unborn child in the womb or the newborn, which may lead to a bleeding of the child because of reduced platelets. In the first pregnancy it is usually only discovered in the newborn and is then called neonatal alloimmune thrombocytopenia (NAIT). If the risk from previous affected children is already known and the disorder is already detected in the unborn child, it is called fetal alloimmune thrombocytopenia (FAIT). It is caused by an incompatibility between the pregnant woman and the blood platelets ( thrombocytes ) of the child. The mother makes antibodies against features on the surface of the platelets called platelet antigens , which do not have their own platelets but which the child inherited from the father. In this respect, alloimmune thrombocytopenia represents the counterpart to haemolyticus neonatorum disease , in which the child's erythrocytes are attacked by maternal antibodies. The thrombocytes loaded with the antibodies are broken down to a greater extent in the spleen , which leads to a severe shortage of blood platelets ( thrombocytopenia ). Treatment can already be carried out in the womb by transfusing platelet concentrates via the umbilical veins or by appropriate transfusions after birth.
frequency
The incidence of neonatal alloimmune thrombocytopenia is estimated to be approximately one in 800 to 1,000 live births. In up to 60% of the affected mothers, the immunization already takes place in the first pregnancy. The condition is often overlooked as there are no screening programs for this condition. The risk of recurrence in further pregnancies is 50 or 100%, depending on the genotype of the father ( heterozygous or homozygous ). This gives rise to the indication for monitoring a later pregnancy in an institution with experience. The severity often repeats itself in a subsequent pregnancy.
causes
The thrombocytopenia of the unborn child is triggered by blood group antigens (human platelet antigens, or HPA for short) that are found on the child's platelets and are inherited from the father. Antibodies of the specificity anti-HPA 1a (approx. 75%) are found most frequently; those with the specificity anti-HPA 5b (approx. 15%) are rarer. The latter are more likely to be associated with less severe courses. Other HPA antibodies can also cause NAIT. In Asia, alloimmune thrombocytopenia is essentially associated with Group 4 HPA. During pregnancy, the child's mother develops antibodies against these HPA traits, which reach the fetus through the placenta and lead to a significantly shortened life span of the platelets due to increased premature breakdown in the spleen.
Clinical picture
In newborns, only skin bleeding ( purpura ) is usually noticed at first. Bleeding into the intestines such as the gastrointestinal or urinary tract is less common. Occasionally there is clinical deterioration in the first 48 hours after birth. As the most serious complication of alloimmune thrombocytopenia, around 20–30% of affected children suffer from cerebral haemorrhage, around half of them in the womb. Possible consequences are hydrocephalus , blindness, mental and physical disabilities. Cerebral hemorrhages caused by FAIT have already been documented before the 20th week of pregnancy and it is assumed that about every second cerebral hemorrhage in the womb is caused by such a disorder. Cerebral haemorrhage can still occur after birth as long as the platelet deficiency persists. The thrombocytopenia usually lasts a few days to two weeks, in individual cases longer than five weeks.
diagnosis
The diagnosis of neonatal alloimmune thrombocytopenia is a diagnosis of exclusion. First of all, it is necessary to rule out other causes of platelet deficiency in the newborn. These essentially include infections , disseminated intravascular coagulation , autoimmune diseases in the mother in which these autoantibodies against platelets are transferred to the newborn ( idiopathic thrombocytopenic purpura , lupus erythematosus ) and maternal drugs against which cross-reacting antibodies are formed. In the presence of alloimmune thrombocytopenia, corresponding alloantibodies can be detected in the mother's blood ( serum ). A failed serological detection of the antibody does not rule out FAIT / NAIT, because even in severe FAIT / NAIT cases the antibody detection is sometimes only successful after several days - and in up to 10% of cases not at all. The level of the antibody is also no indication of the severity of the NAIT / FAIT. During pregnancy, the child's thrombocytopenia can only be clearly diagnosed with a fetal blood sample obtained via an umbilical cord puncture ( cordocentesis ). The genotype for the platelet antigens can also be determined in both parents, which is particularly important for genetic counseling on the risk of recurrence.
therapy
a) of the newborn
Treatment depends on the severity of the disease. If there are clinical signs of bleeding or the number of blood platelets is below 30,000 / µl, platelets must be quickly replaced by a transfusion because of the risk of cerebral hemorrhage. The mother is the best donor for this, as their platelets do not carry the corresponding antigen and these are not immediately destroyed by the antibodies still present in the child after the transfusion. For this purpose, the platelet concentrate must be washed to remove the antibodies formed by the mother. It should also be irradiated to avoid a graft-versus-host reaction . If such platelet concentrates are not available in time, the blood bank can also provide concentrates from HPA 1a-negative donors, as this antigen is by far the most common cause of the disease. With platelet counts> 30,000 / µl without clinical signs of bleeding, close blood counts and ultrasound examinations of the head are usually sufficient because the platelet count usually increases rapidly on its own. In the event of a sudden drop, a transfusion as described above may still be necessary. In individual cases, treatment with immunoglobulins could also increase the number of platelets in the affected children.
b) of the fetus
In science, the optimal therapy for increasing the platelet count in children is controversial. The main problem here is that the small number of cases means that comprehensive clinical studies cannot be carried out. One possible form of therapy is the intrauterine transfusion of platelets. In addition, if a severe course is suspected, from around the 20th week of pregnancy, platelet concentrates can be transfused directly via the umbilical cord. The aim is to achieve a fetal platelet count of> 200,000 / µl. The transfused platelets should not carry the antigens against which the antibodies transferred from the mother are directed. However, the lifespan of the transfused platelets is short (no more than a week), which means that multiple transfusions are necessary before birth. Every umbilical cord puncture carries the risk of miscarriage or premature birth, which is stated in the literature with a probability of 1 to 2% per puncture (5 - 8% per pregnancy). An alternative therapy consists in the administration of high-dose immunoglobulins (1–2 g / kg / week), if necessary with concomitant administration of a glucocorticoid . In particular, if the platelet count was <20,000 / µl at the time of the first puncture or if there was a severe course in the previous pregnancy (e.g. occurrence of cerebral haemorrhage in the case of severe thrombocytopenia (<20,000 / µl) in the sibling), the administration seems to be not always having a positive influence on the child's platelets. In addition, the women affected report treatment-related side effects in the form of e.g. B. severe headaches, fatigue and gestational diabetes.
It is recommended to deliver by caesarean section in the 32nd to 37th week of gestation so that the platelet transfusion can be carried out on the born child with little risk. An early delivery is particularly advisable for patients who do not react or react insufficiently to the therapy (presence of fetal platelet counts of <20,000 / µl).
Individual evidence
- ↑ a b c d e f Kaplan C: Fetal and neonatal alloimmune thrombocytopenia . In: Orphanet Encyclopedia 2006 full text online (English, pdf)
