What are blood cell antigens and alloimmunization during pregnancy ?
On the surface of blood cells (red blood cells, platelets and granulocytes) there are several types of proteins called antigens. Antigens on red blood cells /erythrocytes define blood groups (e.g., ABO, Rh, Kell , Duffy, Kidd , etc.); antigens on platelets are called platelet antigens (HPA from Human Platelet Antigens). People differ in terms of both blood groups and platelet antigens. If an antigen is present the person is called positive for the antigen; if it is absent , the person is called negative for the antigen; for example, RhD negative and RhD positive or HPA -1a positive and HPA -1a negative.
Platelet alloimmunization happens when a mother's body produces antibodies (a protein substance that reacts to unrecognized proteins in the body) in reaction to fetal antigens that are different from her own. Maternal antibodies cross the placenta, attach to the platelets in the baby's blood and cause diseases such as : anemia (eg. hemolytic disease of the fetus / newborn - (FNHD in case of mismatch in the red blood cell antigens or fetal neonatal alloimmune thrombocytopenia ( FNAITP) - in the case of platelet antigens.
Alloimmunization by platelet antigens
What are the functions of platelets and the consequences of reduced platelet count?
Platelets are responsible for blood clotting. Reduced platelet count i.e. thrombocytopenia may lead to extravasations and strokes, the most dangerous of which and sometimes fatal are strokes to the central nervous system.
What is platelet alloimmunization during pregnancy?
When a child inherits (from the father) a platelet antigen which is not present on platelets of the mother the risk of alloimmunization occurs (for example, the child is HPA1a positive, the mother HPA1a negative). During pregnancy the mother's immune system can produce antibodies to child's antigen. These antibodies may destroy fetal platelets and cause diseases such as fetal neonatal alloimmune thrombocytopenia and serious complications ( stroke and fatal intracranial hemorrhage). The onset of the disease of the fetus occurs presents no symptoms in the mother and can occur in the first pregnancy.
Does the feto-maternal antigen incompatibility always induce alloimmunization and the disease of the fetus?
Incompatibility of maternal and fetal antigens does not always induce the production of antibodies and antibodies do not always lead to a serious disease of the fetus /baby. However, there are no reliable tests to predict antibody production and development of thrombocytopenia in the child. Sometimes bleeding may cause brain damage in child or infant, and may sporadically be fatal. In most born with low platelet count no serious bleedings are observed , in some however bleeding does occur.
How often does platelet antigen alloimmunization occur and how often it is responsible for serious consequences to the fetus?
The alloimmunization between the mother and the fetus in terms of platelet antigens is rare. Thrombocytopenia in fetuses or newborns due to anti-HPA1a production is observed in approximately 1/1000 - 1500 live births. For about 10% the consequences of "the conflict" are severe and may lead to hemorrhage into the central nervous system potentially fatal for the child. Pregnancies of mothers with antibodies to platelet antigens should be under special care so early treatment of the fetus or new born can be launched.
Thrombocytopenia as result of platelet alloimmunization most often occurs when a mother with no HPA-1a antigen (HPA-1a negative) produces antibodies to this antigen which the baby inherited from its father.
What special attention do HPA-1a negative women require?
Regular investigation of HPA-1a negative women for the presence of such antibodies, as well as regular fetal ultrasonography are necessary.
In subsequent pregnancies should HPA-1a negative women be subjected to special diagnostics and gynecological care ?
A woman who gave birth to a baby with a low platelet count due to the presence of platelet antibodies is at high risk of the same complication during the next pregnancy. There is also the risk that a HPA-1a negative woman, who developed no antibodies in the current pregnancy and gave birth to a healthy baby may produce such antibodies in subsequent pregnancies at risk to the baby. HPA-1a negative women during pregnancy should therefore be under special care; tests for antibodies and ultrasound should be performed on regular basis in each subsequent pregnancy. These women should be provided with highly specialized gynecological and obstetric care.
How we can tell that a woman is at risk of alloimmunization by platelet antigens? Where are such tests performed?
The presence of HPA -1a antigen can be determined due to recently developed appropriate serological and DNA-based methods. HPA -1a negative women at risk of alloimmunization represent 2 % of the population. Tests are performed in 8 - 20 week of pregnancy on a small blood samples collected during routine/mandatory blood group and RhD testing. The study involves pregnant women from Warsaw and the surrounding areas and is performed in cooperation with the University of Tromsø, in Norway. It is financed by the Polish-Norwegian Research Programme operated by the National Centre for Research and Development under the Norwegian Financial Mechanism 2009-2014 in the frame of Project Contract No Pol-Nor/203111/69/2013
HPA -1a negative women are subjected to special care in the Second Department of Gynecology and Obstetrics in Warsaw, the only center in Poland to provide treatment for fetus and newborn of women with antibodies to platelets.
What are the benefits of joining the PREVFNAIT program?
The study will determine whether the women enrolled are HPA -1a positive or HPA- 1a negative. Antigen identification is performed only once ( antigens never change during a life-time).
HPA -1a positive women are at no risk of the most common and dangerous platelet alloimmunization, unlike HPA -1a negative women who belong to a group of higher risk. All pregnancies of HPA -1a negative women should be under special gynecological and diagnostic care of IHTM.
The PREVFNAIT project provides all applicable diagnostic tests to HPA- 1a negative women free of charge. The results will help to predict and prevent disease of the fetus/newborn. If indicated, appropriate treatment will be launched to prevent life-threatening bleedings in fetus.
Pregnant women in 8-20 week of gestation are invited to participate in antigen HPA -1 tests.