Neonatal alloimmune thrombocytopenia

Thrombocytopenia in neonates by: isoimmunization

An alloimmune thrombocytopenia is a rare, serious disease of the unborn child in the womb or of the newborn, which may lead to a bleeding tendency of the child due to reduced platelets. In the first pregnancy, it is usually only discovered in the newborn and is then called Alloimmune Neonatal thrombocytopenia ( NAIT ). If the risk by previous affected children already known and the fault is already found in the unborn, they are 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 produces antibodies against features on the surface of platelets, called platelet antigens that do not have their own platelets, which, however, has inherited from his father the child. To this extent, an alloimmune thrombocytopenia, the counterpart of a rhesus incompatibility based on platelet represents the laden with the antibodies platelets are increasingly degraded in the spleen, causing a serious shortage of blood platelets ( thrombocytopenia ) results. A treatment can be carried in the womb by transfusion of platelet concentrates through the umbilical vein or with the appropriate transfusions after birth.

Frequency

The incidence of neonatal alloimmune thrombocytopenia is estimated to be about one of 800 to 1,000 live births. With up to 60 % of affected mothers, immunization is carried out in the first pregnancy. The disease is often overlooked, as there are no screening programs for this disease. The risk to subsequent pregnancies is dependent on the genotype of the father ( heterozygous or homozygous ) at 50 or 100%. It is therefore crucial to monitor later pregnancies in a so experienced a subsequent pregnancy Einrichtung.Bei the severity repeated often.

Causes

The thrombocytopenia of the unborn child is by blood group antigens (human platelet antigens, human platelet antigen HPA short called ), which are located on the platelets of the child and were inherited from the father raised. Most frequently found antibodies of specificity anti -HPA 1a (ca. 75 %); rare are those of specificity anti -HPA 5b (about 15 %). The latter are likely to be associated with less severe disease. Also other HPA antibodies can cause NAIT. In Asia, the alloimmune thrombocytopenia is significantly associated with the HPA Group 4. During pregnancy, the child's mother forms antibodies against these HPA characteristics that pass through the placenta ( the placenta ) to the fetus and result in a significantly shorter survival time of platelets by increased premature degradation in the spleen.

Disease

For the newborn, usually initially only skin bleeding ( purpura). Bleeding in the intestines, such as the gastrointestinal or urinary tract are rare. Occasionally, a worsens during the first 48 hours after birth. As a serious complication of alloimmune thrombocytopenia suffer about 20-30 % of affected children cerebral hemorrhage, about half of them in the womb. Possible consequences include hydrocephalus (hydrocephalus ), blindness, mental and physical disability. There were already bleeding in the brain that were caused by a FAIT documented before the 20th week of pregnancy and it is believed that about every second cerebral hemorrhage caused by such a disturbance in the womb. Intracranial bleeding may still occur as long as the lack of platelets persists even after birth. The thrombocytopenia usually lasts a few days to two weeks, in some cases for more than five weeks.

Diagnosis

The diagnosis of neonatal alloimmune thrombocytopenia is a diagnosis of exclusion. First, other causes of a lack of blood platelets must be excluded in the neonatal period. This mainly includes infections, disseminated intravascular coagulation, autoimmune diseases of the mother, with whom these autoantibodies against platelets on the newborn transfers ( Idiopathic thrombocytopenic purpura, lupus erythematosus ) and maternal medications are formed against the cross-reacting antibodies. In the presence of alloimmune thrombocytopenia corresponding alloantibodies (serum ) of the mother can be detected in blood. A negative serological antibody includes a FAIT / NAIT is not sufficient, because even in severe FAIT / NAIT cases, the antibody detection succeeds sometimes only after several days - not at all, and in up to 10 % of cases. Also the height of the antibody level is not indicative of the severity of NAIT / FAIT. In pregnancy can only be through a fetal blood sample via an umbilical puncture ( cordocentesis ) is obtained, the thrombocytopenia of the child are clearly diagnosed. And the genotype for the platelet antigens can be determined for both parents, which is particularly important for genetic counseling about the risk of recurrence.

Therapy

A) of the newborn

Treatment depends on the severity of the disease. Existence of clinical signs of bleeding or the platelet count is below 30000/μl, must be replaced by a transfusion because of the risk of cerebral hemorrhage rapidly platelets. The best donor for this is the mother because their platelets do not carry the corresponding antigen and these are destroyed after the transfusion immediately by the remaining antibodies in the child again. For this, the platelet concentrate must be washed to remove the antibodies produced by the mother. Moreover, it is to be irradiated in order to avoid graft-versus- host reaction. If such platelet concentrates not available in time, even such concentrates may be provided by the blood bank, which originate from HPA 1a - negative donors, since this antigen is by far the most common cause of the disease. When platelet counts > 30000/μl without clinical signs of bleeding close monitoring of blood counts and ultrasound scans of the head are usually sufficient, because the platelet count usually rises by yourself quickly. Event of a sudden drop can still transfusion as described above are required. In individual cases, treatment with immunoglobulins was able to increase the number of platelets in the affected children in these cases.

B ) the fetus

In science, the optimal therapy for increasing the child's platelets is controversial. The problem here is mainly that no comprehensive clinical studies can be performed by the small number of cases. One possible form of therapy is intrauterine transfusion of platelets. These 20 weeks platelet concentrates can be transfused directly through the umbilical cord on suspicion of a severe course from approx. The aim is to achieve a platelet count of fetal > 200.000/μl. The transfused platelets should be negative for the data transmitted from the mother's antibodies. However, the life of the transfused platelets is low ( not more than a week), so multiple transfusions are necessary to birth. Each umbilical cord puncture carries the risk of miscarriage or premature birth, which in the literature with a probability of 1 to 2% per puncture ( 5-8 % per pregnancy ) is specified. An alternative therapy consists of the administration of high-dose immunoglobulins (1-2 g / kg / week ) with or without cortisone. In particular, in the presence of a platelet count of <20,000 at the time of the first puncture or in the presence of severity in the previous pregnancy (eg appearance of a brain haemorrhage in severe thrombocytopenia ( <20,000 ) of the sibling ) but the gift does not always have a positive influence on the child's platelets to have. In addition, the affected women report of treatment-related side effects in the form of eg severe headache, fatigue, and gestational diabetes.

There is a delivery by Caesarean section after 32 to 37 weeks is recommended so that the platelet transfusion can be done at low risk born child. An early birth is particularly important for patients who do not or insufficiently respond to therapy (presence of fetal platelet counts <20,000 ), attached.