Fetal Platelet Count Research Articles

Bleeding after intravascular transfusion: Experimental and clinical observations

Characteristics of postpuncture bleeding of umbilical vessels were evaluated with an in vitro cord perfusion model and in vivo by ultrasonographic observation of bleeding duration after intravascular transfusion. Ultrasonographic determination of blood loss in vitro was very sensitive (0.01 ml/sec). In vitro blood loss varied directly with perfusion rate, but there were wide variations between cord specimens. Observed clinical bleeding occurred in 43% of cases; the duration of bleeding varied by vessel punctured, needle size, and fetal platelet count. The combined in vitro and clinical data help define the range of duration of bleeding and the probable volume of loss.

Prenatal Diagnosis of Neonatal Alloimmune Thrombocytopenia Using Allele-Specific Oligonucleotide Probes

The prediction of neonatal alloimmune thrombocytopenia (NATP) in affected families has, in the past, been based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. We explored the feasibility of allele-specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP. A total of eight families at risk for delivering an affected fetus were studied with both serologic and oligonucleotide typing. The correlation between serologic and oligonucleotide PIA types was 100%. Similarly, in an additional eight families not at risk for PIA1-mediated NATP, serologic and oligonucleotide typing maintained a perfect correlation. DNA isolated from fetal leukocytes as well as fetal amniocytes was successfully typed using this technology. Oligonucleotide-based typing of fetuses at risk for NATP whose fathers are heterozygous for the PIA antigens allows early recognition of affected fetuses so that prenatal therapy of mothers can be instituted if necessary. When fetuses are found to be unaffected, invasive, and/or expensive, prenatal interventions can be avoided.

False‐negative prenatal exclusion of Wiskott‐Aldrich syndrome by measurement of fetal platelet count and size

The study of the fetal platelet count and size can, according to the literature, be used for the prenatal diagnosis of the Wiskott-Aldrich syndrome (WAS). So far, no affected fetuses have been identified by this method. All pregnancies in which this method had been applied to resulted, as correctly predicted, in the birth of normal children. Here we report on a familial case of WAS where the haematological parameters failed to reveal the affected second child. Hence we assume that the platelet count and size of platelets remain normal in fetuses with WAS to the gestational age of 22 weeks and cannot be used for prenatal diagnosis.

Bleeding after intravascular transfusion: Experimental and clinical observations

Characteristics of postpuncture bleeding of umbilical vessels were evaluated with an in vitro cord perfusion model and in vivo by ultrasonographic observation of bleeding duration after intravascular transfusion. Ultrasonographic determination of blood loss in vitro was very senstitive (0.01 ml/sec). In vitro blood loss varied directly with perfusion rate, but there were wide variations between cord specimens. Observed clinical bleeding occurred in 43% of cases; the duration of bleeding varied by vessel punctured, needle size, and fetal platelet count. The combined in vitro and clinical data help define the range of duration of bleeding and the probable volume of loss.

Misdiagnosis of a Normal Fetal Platelet Count After Coagulation of Intrapartum Scalp Samples in Autoimmune Thrombocytopenic Purpura

Intrapartum fetal scalp sampling for platelet counts in maternal autoimmune thrombocytopenia has been advocated for determining route of delivery. We report a case in which two coagulated scalp samples were believed to indicate a normal fetal platelet count. As a result, vaginal delivery of a severely thrombocytopenic fetus was allowed.

Fetal Platelet Counts in Thrombocytopenic Pregnancy

KAPLAN, CECILE; DAFFOS, FERNAND; FORESTIER, FRANCOIS; TERTIAN, GERARD; CATHERINE, NICOLE; PONS, JEAN CLAUDE; TCHERNIA, GIL Author Information

Fetal platelet counts in thrombocytopenic pregnancy

Fetal platelet counts were assessed by percutaneous umbilical blood sampling in 64 pregnancies (62 women) with maternal thrombocytopenia. In 33 pregnancies associated with chronic immune thrombocytopenia, 11 of the fetuses had platelet counts below 150 × 10 9/l and 4 were severely thrombocytopenic ( < 50 × 10 9/l). In 31 pregnancies with symptomless maternal thrombocytopenia as an incidental finding, 4 fetuses were thrombocytopenic, 1 of them severely. Maternal indices, including antiplatelet antibodies, did not correlate with risk of fetal thrombocytopenia; and in those with repeat measurements there was no evidence of benefit from treatment with either corticosteroids (4 cases) or intravenous immunoglobulin (3 cases). Percutaneous umbilical blood sampling, a safe procedure in experienced hands, provides accurate platelet counts in thrombocytopenic pregnancy, as an aid to decisions on mode of delivery and to assessment of treatments.

Continuing controversy in alloimmune thrombocytopenia: Fetal hyperimmunoglobulinemia fails to prevent thrombocytopenia

Two patients with severe alloimmune thrombocytopenia were managed by weekly intrauterine platelet transfusions at 25 to 36 weeks. In one patient high-dose immunoglobulin was also administered weekly to the mother, and high maternal and fetal immunoglobulin levels were achieved. Fetal platelet counts were similar in both patients. The only variable that affected fetal platelet concentration was the posttransfusion platelet count from the previous transfusion.

Pregnancy in Women With Immune Thrombocytopenic Purpura

Thirty-six women with immune thrombocytopenic purpura were studied during 37 pregnancies, and maternal characteristics with predictive value for the fetal platelet count were determined. Nine neonates were thrombocytopenic, with a platelet count of less than 50 x 10(9)/L in eight. Four of these nine neonates delivered to a subgroup of 31 mothers were studied prospectively; the frequency of thrombocytopenia in neonates of women with immune thrombocytopenic purpura was thus 13%. Only two of these nine neonates presented with hemorrhagic syndromes (two, petechial purpura; one, intracranial bleeding). The frequency of neonatal thrombocytopenia was higher in mothers with deep thrombocytopenia and in those who had not responded to corticosteroid treatment following diagnosis. No prognostic value could be assigned to the other maternal characteristics studied, such as a history of splenectomy, maternal treatment at the time of delivery, or the presence of platelet autoantibodies evaluated either with the platelet immunofluorescence test or the platelet Western blot immunoassay.

Immune thrombocytopenia in pregnancy

Autoimmune thrombocytopenia (ITP)1) The risks to mother and fetus have previously been overstated.2) There is no maternal test which will accurately determine fetal thrombocytopenia.3) The only reliable test for fetal thrombocytopenia is cordocentesis – this carries a higher morbidity than that of fetal intracerebral haemorrhage from ITP.4) Contrary to received wisdom, there is no evidence that, even for the most severely thrombocytopenic infant, abdominal delivery protects against intracranial haemorrhage.5) Management therefore involves keeping the maternal platelet count above 50 × 1091 and choosing the route of delivery on normal obstetric grounds.Alloimmune thrombocytopenia1) Alloimmune thrombocytopenia is commoner than hitherto believed (0.15% all neonates).2) The fetal risks are considerable: intracranial haemorrhage occurs in 4% of cases antenatally and in 10% in labour. The risks are virtually confined to those with a platelet count of less than 30 × 109l−1.3) Cordocentesis is justified for the ‘at risk’ fetus; fetal immunoglobulin or platelet therapy can be given.4) When the fetal platelet count is below 50 × 109l−1, abdominal delivery should be planned.5) A maternal screening test for neonatal alloimmune thrombocytopenia exists (lack of P1A1 antigen).

Platelet count in normal, small, and anemic fetuses

A reference range for fetal platelet count with gestation was established from the study of samples obtained by cordocentesis from 229 pregnancies that had prenatal diagnosis. The mean platelet count increased from 187 ± 47 x 10 9/L at 15 weeks to 274 ± 47 x 10 9/L at 40 weeks' gestation. In 113 red cell -isoimmunized pregnancies, the moderately anemic fetuses were significantly thrombocythemic, whereas the severely anemic fetuses were thrombocytopenic. In 136 small-for-gestational-age fetuses the platelet count was reduced and there were significant correlations between the magnitude of the thrombocytopenia and the degree of fetal smallness, hypoxemia, and acidemia.

Management of Fetal Alloimmune Thrombocytopenia by Weekly in utero Platelet Transfusions

Alloimmune neonatal thrombocytopenia (ANT) may cause intracranial haemorrhage in utero as well as at delivery. Recent management has concentrated on attempts to minimise fetal thrombocytopenia and prevent its complications. This report describes further experience with the use of repeated intravascular transfusions of compatible platelets in utero. The patient studied had already had one infant with intracranial haemorrhage due to ANT. In her next pregnancy, weekly intra-uterine platelet transfusions were given from 26 weeks, but intra-uterine death occurred at 30 weeks after the mother had a heavy fall. In her most recent pregnancy, weekly intravascular transfusions of platelets were given by cordocentesis from 29 to 34 weeks. The fetal platelet count was maintained above 30 X 10(9)/l for almost all of the last 6 weeks of pregnancy before delivery of a normal infant by Caesarean section at 35 weeks' gestation. This approach is effective in preventing severe fetal thrombocytopenia in the last trimester of pregnancy and is contrasted with alternative treatments of ANT. Further data are required to determine the efficacy and risks of these treatments.

Neonatal Uses of Intravenous Immunoglobulin

Intravenous gamma-globulin (IVGG) has several potential uses in neonates. A considerable amount of study is going into the evaluation of its role in neonatal sepsis. Preliminary results from two large controlled trials suggest that there may be a reduction in nosocomial sepsis following infusion of intravenous immunoglobulin (IVIG) in small premature infants, but the data are still incomplete. It is important to distinguish the two types of neonatal immune thrombocytopenia. In maternal autoimmune disease, neonatal intracranial hemorrhage has an incidence of only 1-2%, and treatment can be initiated postnatally in the thrombocytopenic neonate. Since antenatal hemorrhage is very rare, treatment of the mother for the sake of the fetus seems unnecessary. In alloimmune thrombocytopenia, on the other hand, intracranial hemorrhages occur in approximately 20% of all identified cases, and as many as one-half of these occur antenatally. Pilot studies of maternally administered IVGG have indicated that it may elevate the fetal platelet count and prevent intracranial hemorrhage.

ITP in pregnancy: use of the bleeding time as an indicator for treatment.

ITP is a relatively common disorder seen in pregnancy. Current recommendations for management of patient with ITP recommend maintaining the platelet count above 50 x 10(9)/L and the bleeding time less than 20 min. It has been well documented that the bleeding time in ITP is disproportionately shortened in many patients relative to the platelet count. We present a prospective study of 24 ITP patients in whom the bleeding time was used as an indicator for therapeutic intervention in pregnancy. Indications for therapy with prednisone and/or intravenous gammaglobulin were the following: significant clinical hemorrhage due to thrombocytopenia; bleeding time of greater than 20 min at the baseline platelet count; for normalization of hemostasis prior to delivery or surgical procedure. Caesarean section was performed only in cases in which there were obstetrical indications for this mode of delivery or when the fetal platelet count (obtained by fetal scalp vein sample) was less than 50 x 10(9)/L. Of 24 patients with ITP, eight had significant thrombocytopenia (platelet count less than 50 x 10(9)/L) throughout pregnancy. Only two patients required prolonged prednisone therapy. Both suffered side effects of chronic prednisone administration. Four patients were treated with prednisone for a short course (10-14 days) at term to improve hemostasis for delivery. One patient was treated with intravenous gammaglobulin at term in an effort to prevent severe neonatal thrombocytopenia. Seven patients required caesarean section; the remaining 17 patients underwent vaginal delivery. Only one minor bleeding complication was seen - a small wound hematoma post caesarean section. In summary, using the bleeding time as an indicator for therapeutic intervention, treatment of ITP in pregnancy can be minimized. Thus, therapy related toxicity can be avoided.

ITP in pregnancy and the newborn: introduction.

Idiopathic thrombocytopenic purpura (ITP) occurs more commonly in young women and is one of the commonest immune mediated disorders in pregnancy. It may exist as an incidental finding in an otherwise healthy pregnant woman or may be associated with symptomatic reduction in the platelet count and varying degrees of clinical hemorrhage. The condition termed incidental thrombocytopenia of pregnancy is invariably associated with a platelet count of greater than 100 x 10(9)/L and a very low incidence of fetal thrombocytopenia. Symptomatic thrombocytopenia is more commonly associated with low platelet counts in the fetus (estimated between 20%-40%). It has recently been suggested that the incidence of fetal thrombocytopenia is substantially lower than this figure. The management of ITP in pregnancy is complicated by the fact that fetal thrombocytopenia is difficult to diagnose and carries substantial risks during the delivery process with rare cases of fetal hemorrhage occurring spontaneously in utero. Unfortunately there are no laboratory studies that can be performed precisely in the mother that may predict the occurrence of fetal thrombocytopenia. Maternal management is usually directed towards treatment of maternal symptoms. Maternal treatment or response to treatment is inconsistently associated with predictable changes in the fetal platelet count. Obstetric management is aimed at reducing the risks of life threatening fetal hemorrhage occurring at the time of delivery, and fetal management is directed towards the obtaining of fetal platelet samples in order to plan an appropriate strategy for obstetrical delivery. Fetal blood samples are obtained either by a scalp vein puncture at the time of delivery or earlier in gestation by the use of the newer technique termed percutaneous umbilical blood sampling. Fetuses with platelet counts of less then 50 x 10(9)/L are generally delivered by cesarean section whereas those with counts greater than 50 x 10(9)/L are allowed to proceed with vaginal delivery assuming no obstetrical contraindications exist. The use of IVIgG therapy during pregnancy has theoretical implications on improving platelet counts in the mother in situations of severe hemorrhage, however cannot be considered to be appropriate treatment for the prevention of fetal thrombocytopenia, since the exogenous transport of IVIgG across the placenta appears to be inconsistent and unpredictable.(ABSTRACT TRUNCATED AT 400 WORDS)

Antenatal treatment of fetal alloimmune cytopenias.

The antenatal use of intravenous immunoglobulin (IVG) was explored in 9 cases of alloimmune cytopenias affecting fetuses. In 7 cases of alloimmune thrombocytopenia, IVG at a dose of 1 gm/kg/week appeared to be uniformly effective in elevating the fetal platelet count and preventing a recurrence of antenatal intracranial hemorrhage (2 cases). In 2 cases of Rh disease the results were more equivocal. There did not appear to be any significant toxicity associated with its use. The mechanism of IVG effect in the successfully treated cases remains uncertain.

Perinatal diagnosis of passive ITP: use of percutaneous umbilical blood sampling (PUBS).

Fetal blood samples can be obtained in utero by direct sampling of the umbilical cord vessels, using an ultrasound guided technique termed percutaneous umbilical sampling (PUBS). This procedure is being used more frequently in high risk pregnancies to obtain direct fetal laboratory data. In specialized centers, with trained personnel, the technique can be used with a high degree of safety and efficiency. Direct access to the fetal circulation can also allow an accurate determination of the fetal platelet count in cases of suspected fetal thrombocytopenia. The technique may be used to plan appropriate clinical management of maternal ITP as well as to diagnose the presence of fetal alloimmune thrombocytopenia. A logical strategy for obstetric management and evaluation of fetal risk can be planned. The procedure also has the potential to allow direct fetal treatment as has been the case in the management of severe fetal anemia.

Percutaneous Umbilical Cord Blood Sampling in the Evaluation of Fetal Platelet Counts in Pregnant Patients With Autoimmune Thrombocytopenia Purpura

Autoimmune thrombocytopenia purpura in pregnancy is associated with fetal thrombocytopenia. Twenty-one patients with autoimmune thrombocytopenia purpura (22 fetuses) underwent 26 umbilical cord punctures to assess the fetal platelet count. Blood could not be obtained from one fetus. Thrombocytopenia (less than 150,000/microL) was found in five cases, but in none was it of sufficient degree to preclude vaginal delivery. Persistent fetal bradycardia necessitating emergency cesarean delivery occurred in two cases. Umbilical cord puncture was found to be technically more difficult in the term fetus than in the second-trimester fetus studied in previous investigations.

Antenatal Treatment of Neonatal Alloimmune Thrombocytopenia

Neonatal alloimmune thrombocytopenia results from the formation of a maternal antibody to a paternal antigen on fetal platelets. Intracranial hemorrhage, which may be antenatal, occurs in approximately 15 to 20 percent of infants with this form of thrombocytopenia. In families with an affected infant, 75 percent of subsequent infants are affected. We report the results of antenatal treatment with intravenous gamma globulin, with or without dexamethasone, in seven pregnant women who had previously had infants who had severe alloimmune thrombocytopenia. The platelet count increased by a mean (+/- SD) of 72.5 +/- 62 x 10(9) per liter in the six fetuses in whom periumbilical blood sampling was performed. All seven treated fetuses had platelet counts above 30 x 10(9) at birth, and none had an intracranial hemorrhage, in contrast to all seven of their respective untreated siblings, who had lower platelet counts and three of whom had intracranial hemorrhages (antenatal in two infants). Mild intrauterine growth retardation was observed in one treated infant; all seven infants have developed normally in the two months to four years since birth. We conclude that intravenous gamma globulin, with or without dexamethasone, is effective in elevating the fetal platelet count in severe cases of neonatal alloimmune thrombocytopenia and in helping to avoid intracranial hemorrhage.

The use of percutaneous umbilical blood sampling in immune thrombocytopenic purpura

Maternal immune thrombocytopenic purpura has been associated with profound fetal and neonatal thrombocytopenia. Percutaneous umbilical blood sampling offers a reliable method of determining the fetal platelet count antenatally and optimizing obstetric management. We present our experience with this technique in 19 gestations.