Platelet Isoimmunization (Obstetrics - Normal and Problem Pregnancies)

Gabbe: Obstetrics - Normal and Problem Pregnancies, 3rd ed., Copyright c 1996 Churchill Livingstone, Inc.

Platelet Isoimmunization

Like erythrocytes, platelets contain specific surface antigens, and maternal sensitization to platelet antigens can occur when there is an incompatibility between fetus and mother. In a situation analogous to Rh isoimmunization, alloimmune thrombocytopenia is the result of maternal sensitization to incompatible fetal platelets and transfer of antiplatelet antibody to the fetus with subsequent sequestration of platelets in the reticuloendothelial system. [206] In affected cases, the maternal platelet count is normal, with fetal-neonatal thrombocytopenia ranging from mild to profound.

Five biallelic systems of platelet-specific antigens have been well described: PlA1 /PlA2 , Kob /Koa , Baka /Bakb (Leka /Lekb ), Pena /Penb (Yukb /Yuka ), and Brb /Bra . A new and simplified system of nomenclature for the human platelet antigens has been suggested, [207] numbering the antigen families in chronological order of discovery (HPA-1 through HPA-5), but many clinicians continue to use the older system. Platelets also express HLA class I antigens but not those of class II. [208] [209]

Sensitization to the PlA1 antigen is the etiology in about three-fourths of cases of neonatal alloimmune thrombocytopenia. Approximately 2 percent of whites, 0.4 percent of blacks, and less than 0.1 percent of Asians are negative for PlA1 . Sensitization to Bra is the second most common cause of neonatal alloimmune thrombocytopenia, about 10 to 15 percent of cases; less than 1 percent of whites are negative for Bra . [208] [209]

Although HLA antigens are less immunogenic on platelets than on other cells, anti-HLA antibodies may rarely cause neonatal isoimmune thrombocytopenia. [210] Also, maternal HLA class II type appears to influence susceptibility to platelet isoimmunization; HLA-DR3 is associated with PlA1 isoimmunization, and HLA-DRw6 is associated with sensitization to Bra . [211]

Neonatal alloimmune thrombocytopenia occurs in about 1:1,000 to 1:2,000 births and is probably the most common reason for severe thrombocytopenia in the newborn. [206] [212] [213] [214] The clinical severity of neonatal alloimmune thrombocytopenia varies widely. Approximately 90 percent of affected newborns have diffuse petechiae, and 9 to 12 percent suffer intracranial bleeding, with a neonatal mortality of 5 to 13 percent. [208] [212] About 45 percent of cases of central nervous system hemorrhage occur before birth, often resulting in porencephalic cysts. [215] Fetal thrombocytopenia appears to be most common in the third trimester, but has been detected as early as 20 weeks gestation. [216] [217]

Unlike Rh isoimmunization, maternal titers of antibody to the platelet antigen are not predictive of clinical outcome, anti-platelet IgG production can occur in the first pregnancy, and firstborn children are often affected. Primiparas account for between 20 and 60 percent of identified cases, [208] [218] and mothers at risk are usually identified only after the birth of an affected newborn. There are several reasons why all pregnant women are not screened for the presence of antiplatelet antibodies: (1) at least one-fourth of cases of alloimmune neonatal thrombocytopenia are not due to the PlA1 antigen; (2) the maternal immune response seems to be influenced by other factors such as HLA type, and only a minority of infants of mothers negative for the PlA1 antigen will develop significant thrombocytopenia; and (3) no relationship exists between the level of antibody to PlA1 and the degree of thrombocytopenia. Following delivery of an affected newborn, though, the incidence of recurrent fetal-neonatal thrombocytopenia of equal or greater severity is up to 95 percent in the next pregnancy. [208] [209]

The management of patients at risk for neonatal isoimmune thrombocytopenia is directed at preventing hemorrhage in the fetus and neonate. Before the availability of umbilical cord blood sampling, the management strategy for pregnancies at risk for alloimmune thrombocytopenia was to avoid fetal trauma with bedrest during the pregnancy and cesarean delivery before labor. [219] [220] However, since approximately half of fetuses who suffer intracranial bleeding do so before labor, avoidance of labor and vaginal delivery only partially reduces the associated morbidity and mortality. As mentioned, maternal platelet counts are normal, and maternal antibody levels are not predictive of fetal platelet count. Umbilical cord blood sampling and direct measurement of fetal platelet count is currently the only method to assess fetal status accurately.

Several strategies have recently been proposed for the management of pregnancies at risk for alloimmune thrombocytopenia. Transfusions of maternal (antigen-negative) platelets into the fetal circulation and maternally administered high-dose immunoglobulin (with and without concurrent administration of corticosteroids) both appear to raise the fetal platelet count in utero, and each therapy has its supporters.

One group has suggested that the diagnosis of fetal thrombocytopenia be made by cordocentesis at 20 to 22 weeks' gestation, and patients with an affected fetus should be advised to rest carefully and avoid abdominal trauma. [221] [222] At 37 weeks gestation, umbilical cord blood sampling can be repeated, and if the fetal platelet count is normal, labor can be induced; if the platelet count is less than 50,000 cells/mul, maternal platelets are transfused into the fetal circulation using the following formula, allowing safe induction of labor and vaginal delivery:

V=(EFBV x (desired FPC – pretransfusion FPC)) / count of platelet concentrate

where V is volume of platelet concentrate to be transfused, EFBV is estimated fetal blood volume, and FPC is fetal platelet count. [222] This approach, with a single fetal platelet transfusion immediately before delivery, does not address the possibility of spontaneous hemorrhage in utero, but may be the most reasonable management plan for fetuses considered to be at low risk for antepartum bleeding.