How I diagnose and treat neonatal thrombocytopenia.

Neonatal thrombocytopenia, defined as the presence of a circulating platelet count <150 × 109/L, is a common abnormality in babies admitted to neonatal intensive care units. Thrombocytopenia that is typically mild and self-limiting often accompanies neonatal stress in scenarios such as premature delivery or intrauterine growth restriction. However, the differential diagnosis of neonatal thrombocytopenia is wide and includes potentially life-threatening disorders, such as bacterial sepsis, viral infection, and necrotizing enterocolitis. Distinguishing these causes of thrombocytopenia from entities such as genetic thrombocytopenia and fetal and neonatal alloimmune thrombocytopenia is critical for the accurate quantitation of significant adverse events, such as intracranial bleeding, and for the selection of treatments, such as platelet transfusion. In this review, we focus on common differential diagnoses of neonatal thrombocytopenia and highlight how the landscape of diagnosis and management is changing with recent advances in genomic technology and the completion of pivotal clinical trials of platelet transfusion practice. Increasing evidence highlights the need for judicious and restrictive use of platelet transfusions in neonates.

Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study.

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP.

How I manage pregnancy in women with Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare inherited platelet function disorder caused by a quantitative and/or qualitative defect of the αIIbß3 integrin. Pregnancy and delivery are recognized risk periods for bleeding in women with GT. The newborn may also be affected by fetal and neonatal immune thrombocytopenia induced by the transplacental passage of maternal anti-αIIbß3 antibodies, which can lead to severe hemorrhage and fetal loss. Pregnancy in women with GT thus requires a multidisciplinary approach, including prepregnancy counseling and a treatment plan for delivery for both the mother and child. In this article, we summarize the current knowledge on pregnancy in women with GT and describe how we manage this severe platelet disorder in our clinical practice.

Does anti-HPA-1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) ensues from parental incompatibility for platelet alloantigens with maternal sensitization. HPA-1a/1b incompatibility is the most common cause of FNAIT in Caucasians. Placental villitis and lower birthweight in FNAIT suggest anti-HPA-1a may have effects beyond inducing thrombocytopenia. OBJECTIVES: Does FNAIT secondary to anti-HPA-1a result in smaller newborns and, the corollary, does antenatal management of FNAIT increase birthweight? STUDY DESIGN: Birthweights of 270 FNAIT-affected newborns from a randomized clinical trial and a NAITbabies.org survey (135 paired siblings) were compared with those of published controls and treated to untreated FNAIT-affected siblings. Birthweights were converted to percentiles to account for gestational age, sex, and role of birth order in birth weight. Body weights of FNAIT-affected and -unaffected pups in a mouse FNAIT model were analyzed. RESULTS: Untreated siblings in both the clinical trial and NAITbabies.org cohorts were not small, compared with normal controls. However, treated siblings in both cohorts had significantly higher birthweight percentiles compared with their previous untreated affected sibling. After accounting for gestational age, sex, and birth order, increased birthweight percentile in treated compared with the untreated siblings remained significant in both cohorts. FNAIT-affected neonatal mice had lower bodyweights than FNAIT-unaffected pups. CONCLUSIONS: Untreated FNAIT-affected newborns were not small; however, treatment of FNAIT-affected pregnancies increased newborn birthweights despite corrections to account for other factors that might have influenced the results. High dose IVIG is believed to "block" FcRn and lower maternal anti-HPA-1a levels, and thus increase birthweights by reducing levels of maternal anti-HPA-1a and reducing placental villitis.

New Horizons in Fetal and Neonatal Alloimmune Thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a common cause of severe thrombocytopenia in newborns. Intracranial bleeding may lead to severe neurological sequelae and mortality. Current management of pregnancies at risk is suboptimal. Prenatal FNAIT diagnosis commonly requires invasive procedures and therapy is associated with a high treatment burden. The present review explores advances in the field and their potential contribution to modification of the diagnostic and therapeutic landscape. Topics addressed include the role of noninvasive prenatal testing using fetal cell free DNA, insights into novel and prospective therapeutic options achieved through the development of murine models of FNAIT as well as the forecast for the progress in pregnancy risk stratification through advancement in the investigation of biological characteristics of alloantibodies and their association with the risk of fetal bleeding.

Neonatal Thrombocytopenia: Factors Associated With the Platelet Count Increment Following Platelet Transfusion.

OBJECTIVE: To understand better those factors relevant to the increment of rise in platelet count following a platelet transfusion among thrombocytopenic neonates. STUDY DESIGN: We reviewed all platelet transfusions over 6 years in our multi-neonatal intensive care unit system. For every platelet transfusion in 8 neonatal centers we recorded: (1) platelet count before and after transfusion; (2) time between completing the transfusion and follow-up count; (3) transfusion volume (mL/kg); (4) platelet storage time; (5) sex and age of platelet donor; (6) gestational age at birth and postnatal age at transfusion; and magnitude of rise as related to (7) pre-transfusion platelet count, (8) method of enhancing transfusion safety (irradiation vs pathogen reduction), (9) cause of thrombocytopenia, and (10) donor/recipient ABO group. RESULTS: We evaluated 1797 platelet transfusions administered to 605 neonates (median one/recipient, mean 3, and range 1-52). The increment was not associated with gestational age at birth, postnatal age at transfusion, or donor sex or age. The rise was marginally lower: (1) with consumptive vs hypoproductive thrombocytopenia (P < .001); (2) after pathogen reduction (P < .01); (3) after transfusing platelets with a longer storage time (P < .001); and (4) among group O neonates receiving platelets from non-group O donors (P < .001). Eighty-seven neonates had severe thrombocytopenia (<20 000/µL). Among these infants, poor increments and death were associated with the cause of the thrombocytopenia. CONCLUSION: The magnitude of post-transfusion rise was unaffected by most variables we studied. However, the increment was lower in neonates with consumptive thrombocytopenia, after pathogen reduction, with longer platelet storage times, and when not ABO matched.

Successful prenatal therapy for anti-CD36-mediated severe FNAIT by deglycosylated antibodies in a novel murine model.

Recent studies have shown that maternal anti-CD36 antibodies represent a frequent cause of fetal/neonatal alloimmune thrombocytopenia (FNAIT) in Asian and African populations. However, little is known about the pathomechanism and antenatal treatment of anti-CD36-mediated FNAIT. Here, we established a novel animal model to examine the clinical features of pups from immunized Cd36-/- female mice after breeding with wild-type male mice. Mild thrombocytopenia was observed, but high pup mortality was also documented (40.26%). Administration of intravenous immunoglobulin (IVIG) (1 g/kg) on days 7, 12, and 17 to immunized Cd36-/- mothers after breeding reduced fetal death (12.70%). However, delaying the IVIG administration series on days 10, 15, and 20 did not reduce fetal death (40.00%). In contrast, injection of deglycosylated anti-CD36 (deg-anti-CD36) polyclonal antibodies (5 mg/kg) on days 10, 15, and 20 significantly reduced fetal death (5.26%). Subsequently, monoclonal antibodies (mAbs) against mouse CD36 were developed, and one clone producing high-affinity anti-CD36 (termed 32-106) effectively inhibited maternal antibody binding and was therefore selected. Using the same approach of deg-anti-CD36, the administration of deg-32-106 significantly reduced fetal death (2.17%). Furthermore, immunized Cd36-/- mothers exhibited placental deficiency. Accordingly, maternal anti-CD36 antibodies inhibited angiogenesis of placenta endothelial cells, which could be restored by deg-32-106. In summary, maternal anti-CD36 antibodies caused a high frequency of fetal death in our animal model, associated with placental dysfunction. This deleterious effect could be diminished by the antenatal administration of IVIG and deg-mAb 32-106. Interestingly, treatment with deg-32-106 seems more beneficial considering the lower dose, later start of treatment, and therapy success.

Neonatal Thrombocytopenia: Differing Characteristics of NAIT Versus Non-NAIT.

While neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe neonatal thrombocytopenia good clinical predictors are lacking. We analyzed cases of neonatal thrombocytopenia in Schneider Children's Medical Center of Israel to pinpoint qualifiers of NAIT (NAIT+) in comparison to non-NAIT (NAIT-) thrombocytopenia. Patient and maternal data were retrospectively collected on all thrombocytopenic newborns undergoing a workup for NAIT in our tertiary center between 2001 and 2016. Among 26 thrombocytopenic neonates, the mean nadir in NAIT+ patients (25×10 9 /L) was significantly lower than NAIT- patients (64×10 9 /L) ( P <0.001). 61.5% of NAIT+ infants required treatment compared with 23% of non-NAIT ( P =0.015). NAIT+ patients also required more therapeutic modalities than infants with NAIT- thrombocytopenia. Human platelet antigen (HPA)-1a and HPA-5b alloantibodies most frequently caused NAIT. In summary, thrombocytopenia in NAIT+ was significantly more severe compared with NAIT- and more likely to require treatment. In addition, despite the varied ethnic population in Israel, the HPA alloantibodies found in our population were most similar to those common in Western countries. In the absence of rigorous prenatal screening options, we suggest platelet counts below 40 to 50×10 9 /L in a healthy newborn be considered most suggestive for NAIT and warrant urgent NAIT-specific analysis.

Neonatal Thrombocytopenia Due to Dual Alloimmune and Autoimmune Mechanisms.

Alloantibody-mediated and autoantibody-mediated immune destruction are common causes of early neonatal thrombocytopenia. The authors report a case of severe, early-onset thrombocytopenia with mucocutaneous bleeding in an otherwise well-appearing full-term neonate. Recurrence of thrombocytopenia following initial treatment and its persistence after 2 weeks of life suggested a dual immune mechanism. This is a rare case of immune thrombocytopenia caused by human platelet antigen-5b alloimmunization and passive transfer of maternal antiplatelet antibodies. Appropriate, timely treatment and absence of severe bleeding complications, namely intracranial hemorrhage, conferred a good overall prognosis.

Severe intracranial haemorrhage in neonatal alloimmune thrombocytopenia due to antibodies against human platelet antigen 1b: Case report and literature review.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare life-threatening disorder, leading to severe thrombocytopenia and potentially bleeding, with intracranial haemorrhage (ICH) being the most serious complication. We report on a FNAIT case with fourth-degree ICH that arose due to antibodies against human platelet antigen (HPA)-1b. The male infant, born to an otherwise healthy mother, presented with severe signs of ICH soon after delivery. Since only moderate thrombocytopenia was noted and there were no active signs of bleeding, the infant did not receive intravenous immunoglobulins (IVIg) or platelet transfusion. Spontaneous recovery of platelets was noted on the eighth day of life, but permanent neurological impairment remained as a consequence of ICH. We report the results of HPA and human leukocyte antigen (HLA) antibodies in the mother's and the infant's sera, the family's HPA genotype and the mother's HLA genotype, and summarise previously described cases of FNAIT due to anti-HPA-1b antibodies in the literature. FNAIT with severe ICH due to anti-HPA-1b antibodies is rarely diagnosed. An association between HLA genes and sensitization to HPA-1b antibodies was not demonstrated. The severity of FNAIT and the occurrence of ICH is often difficult to predict. In this case, the infant presented with moderate thrombocytopenia and ICH, with subsequent permanent consequences.

Risk factors for severe neonatal thrombocytopenia in cases of maternal immune thrombocytopenia.

AIM: Maternal immune thrombocytopenia (ITP) may induce neonatal thrombocytopenia (nTP), which carries a risk of neonatal haemorrhagic complications. Some risk factors for nTP have reached consensus such as maternal splenectomy and previous severe nTP, while others such as maternal platelet count have not. METHODS: We conducted a retrospective cohort study in a university hospital, including 145 neonates of mothers with ITP. We assessed the risk of severe nTP and bleeding complications. RESULTS: Severe nTP in the first 24 h after birth was more common in case of maternal splenectomy (OR = 4.4) and a previous severe nTP (OR = 46.9). Severe nTP at nadir (lowest platelet count during the initial postnatal days) was more frequent in cases of a previous neonate with severe nTP (OR = 42), maternal treatment during pregnancy (OR = 2.4) and a low maternal platelet count during pregnancy or at delivery. These risk factors were not significantly associated with an increased risk of neonatal haemorrhagic complications. CONCLUSION: In our population, we confirm the risk of severe nTP in case of maternal splenectomy or previous nTP. By monitoring the platelet count to its nadir, we identified three additional risk factors: maternal treatment during pregnancy and low maternal platelet count during pregnancy or low maternal platelet count at delivery.

Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death.

The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25 × 109/L compared with 50 × 109/L for major bleeding and/or mortality in preterm neonates (7% absolute-risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25 × 109/L threshold. We wanted to assess this heterogeneity of treatment effect in the PlaNet-2 trial, to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariate logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into 4 risk quartiles. Within these quartiles, we assessed absolute-risk difference between the 50 × 109/L- and 25 × 109/L-threshold groups. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval, 0.58-0.68). The 25 × 109/L threshold was associated with absolute-risk reduction in all risk groups, varying from 4.9% in the lowest risk group to 12.3% in the highest risk group. These results suggest that a 25 × 109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. This trial was registered at www.isrctn.com as #ISRCTN87736839.

New developments in fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia, the platelet equivalent of hemolytic disease of the fetus and newborn, can have devastating effects on both the fetus and neonate. Current management of fetal and neonatal alloimmune thrombocytopenia in a subsequent affected pregnancy involves antenatal administration of intravenous immune globulin and prednisone to the pregnant woman to prevent the development of severe fetal thrombocytopenia and secondary intracranial hemorrhage in utero. That therapy has proven to be highly effective but is associated with maternal side effects and is expensive. This commentary describes 4 advances that could substantially change the current approach to detecting and managing fetal and neonatal alloimmune thrombocytopenia in the near future. The first would be an introduction of a program to screen all antepartum patients in this country for pregnancies at risk of developing fetal and neonatal alloimmune thrombocytopenia. Strategies to implement this complex process have been described. A second advance is testing of cell-free fetal DNA obtained from maternal blood to noninvasively determine the fetal human platelet antigen 1 genotype. A third, in preliminary development, is creation of a prophylactic product that would be the platelet equivalent of Rh immune globulin (RhoGAM). Finally, a fourth major potential advance is the development of neonatal Fc receptor inhibitors to replace the current medical therapy administered to pregnant women with an affected fetus. Neonatal Fc receptor recycles plasma immunoglobulin G to increase its half-life and is the means by which immunoglobulin G crosses the placenta from the maternal to the fetal circulation. Blocking the neonatal Fc receptor is an ideal way to prevent maternal immunoglobulin G antibody from causing fetal and neonatal alloimmune thrombocytopenia in a fetus at risk of developing that disorder. The pertinent pathophysiology and rationale for each of these developments will be presented in addition to our thoughts relating to steps that must be taken and difficulties that each approach would face for them to be successfully implemented.

Neonatal Alloimmune Thrombocytopenia: A Concise Review.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is defined as an uncommon platelet disorder caused by maternal alloimmunization to human-specific antigens (HPAs) that are paternally inherited, resulting in low fetal/neonatal platelet levels and debilitating effects on the newborn. The incidence of NAIT is 1 in every 1000 live births within the United States; it is the most common cause of severe thrombocytopenia (<30 × 109/L) and intracranial hemorrhage in term newborns. PURPOSE: The purpose of this article is to discuss the pathophysiology, clinical manifestations, diagnosis, and treatment of NAIT and its implications upon the lifespan of the neonate. METHODS: A literature review was conducted using PubMed, CINAHL, and Google Scholar (2014-2019). Search terms included NAIT, neonatal/fetal alloimmune thrombocytopenia, newborn platelets, and intracranial bleeding and NAIT. RESULTS: NAIT can affect first pregnancies and often goes undiagnosed until delivery. Universal screening tools with a focus on HPA-1a typing via noninvasive testing have been successfully trialed and have yielded promising results indicating a 75% reduction in risks associated with NAIT; however, none have been incorporated into practice and prophylactic treatment remains unavailable. IMPLICATIONS FOR RESEARCH: Adopting a universal screening tool and prophylaxis for NAIT would allow for early diagnosis and treatment in utero. IMPLICATIONS FOR PRACTICE: Many healthcare providers are not familiar with NAIT often focusing on other causes of thrombocytopenia as a potential diagnosis.

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.

Murine models for studying treatment, prevention and pathogenesis of FNAIT.

Maternal alloimmunization to paternally inherited antigens on fetal/neonatal platelets can cause fetal/neonatal alloimmune thrombocytopenia (FNAIT) after antibody-mediated removal of platelets from the fetal circulation. The complications vary from mild bleeding symptoms to severe intracranial hemorrhage and subsequent neurological impairment or death. Studies on in vivo mechanisms are challenging to measure directly in pregnant women, rendering murine models as valuable and attractive alternatives, despite some critical differences between mice and men affecting the translational value. Here we present and discuss, the different murine models that substantially have increased our knowledge and understanding of FNAIT pathogenesis - as well as pre-clinical evaluation of therapeutic and preventive strategies.

Hydrops fetalis associated with anti-CD36 antibodies in fetal and neonatal alloimmune thrombocytopenia: Possible underlying mechanism.

OBJECTIVES: In the present study, we asked whether anti-CD36 antibodies impair the maturation of erythropoietic stem cells to mature red blood cells (RBCs), leading to anaemia and hydrops fetalis (HF). BACKGROUND: Recent studies have shown the importance of anti-CD36 antibodies in the development of Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT). In comparison to other types of antibody-mediated FNAIT, anti-CD36 antibodies are frequently associated with anaemia and HF. As mature RBCs do not express CD36, the reason for this phenomenon is currently not fully understood. MATERIAL AND METHODS: A case of FNAIT with signs of HF was characterised in this study. Maternal anti-CD36 antibodies were isolated by an absorption/elution approach. We cultured haematopoietic stem cells (HSCs) with purified anti-CD36 antibodies, and the formation of burst-forming unit-erythroid and colony-forming unit-erythroid (CFU-E/BFU-E) cells was analysed. Apoptosis of HSCs was also investigated. RESULTS: Analysis of the mother showed type-1 CD36 deficiency. Anti-CD36 antibodies were found in maternal serum, as well as on fetal platelets, by ELISA, and the specificity of these antibodies was further substantiated by flow cytometry. In comparison to control IgG, incubation of HSCs with purified anti-CD36 antibodies led to a significant reduction in CFU-E/BFU-E cell formation, and this result was associated with an increased number of apoptotic CD34+ erythroid/myeloid precursor cells. Administration of intra-uterine transfusion with washed RBCs was effective in improving fetal anaemia. CONCLUSIONS: Anti-CD36 antibodies may cause anaemia and trigger HF through apoptosis of CD34+ erythroid/myeloid precursor cells. However, the contribution of other cells must also be taken into account.

Non-invasive risk-assessment and bleeding prophylaxis with IVIG in pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia: management to minimize adverse events.

INTRODUCTION: In pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT), prenatal intervention in subsequent pregnancies may be required to prevent fetal bleeding. Several invasive and non-invasive protocols have been published: amniocentesis for fetal genotyping, fetal blood sampling for the determination of fetal platelet count, intrauterine platelet transfusions, and weekly maternal i.v. immunoglobulin (IVIG) infusion with or without additional corticosteroid therapy. This is the first retrospective study that report the experience with a non-invasive protocol focused on side effects of maternal IVIG treatment and neonatal outcome. METHODS: Pregnant women with proven FNAIT in history and an antigen positive fetus were treated with IVIG (1 g/kg/bw) every week. To identify potential IVIG-related hemolytic reactions isoagglutinin titer of each IVIG lot and maternal blood count were controlled. IVIG-related side effects were prospectively documented and evaluated. Furthermore, ultrasound examination of the fetus was performed before starting IVIG administration and continued regularly during treatment. Outcome of the index and subsequent pregnancy was compared. Corresponding data of the newborns were analyzed simultaneously. RESULTS: IVIG was started at 20 weeks of gestation (median). Compared to the index pregnancy, platelet counts of the newborns were higher in all cases. No intracranial hemorrhage occurred (Index pregnancies: 1 case). Platelet counts were 187 × 109/l (median, range 22-239, 95% CI) and one newborn had mild bleeding. No severe hemolytic reaction was observed and side effects were moderate. CONCLUSION: Among pregnant women with FNAIT history, the use of non-invasive fetal risk determination and maternal IVIG resulted in favorite outcome of all newborns. Invasive diagnostic or therapeutic procedures in women with a history of FNAIT should be abandoned.

Flow cytometry for near-patient testing in premature neonates reveals variation in platelet function: a novel approach to guide platelet transfusion.

BACKGROUND: Neonatal haemorrhaging is often co-observed with thrombocytopenia; however, no evidence of a causal relationship with low platelet count has been reported. Regardless, the administration of a platelet transfusion is often based upon this parameter. Accurate measurement of platelet function in small volumes of adult blood samples by flow cytometry is well established and we propose that the use of the same technology could provide complementary information to guide the administration of platelet transfusions in premature neonates. METHODS: In 28 neonates born at 27-41 weeks gestation, platelet function after stimulation agonists was measured using fibrinogen binding and P-selectin expression (a marker of degranulation). RESULTS: Platelets of neonates with gestation of ≤36 weeks (n = 20) showed reduced fibrinogen binding and degranulation with ADP, and reduced degranulation with CRP-XL. Degranulation Scores of 7837 ± 5548, 22,408 ± 5301 and 53,131 ± 12,102 (mean ± SEM) identified significant differences between three groups: <29, 29-36 and >36 weeks gestation). Fibrinogen binding and degranulation responses to ADP were significantly reduced in suspected septic neonates (n = 6) and the Fibrinogen Binding scores clearly separated the septic and healthy group (88.2 ± 10.3 vs 38.6 ± 12.2, P = 0.03). CONCLUSIONS: Flow cytometric measurement of platelet function identified clinically different neonatal groups and may eventually contribute to assessment of neonates requiring platelet transfusion.

Marked thrombocytopenia in a neonate is associated with anti-HPA-5b, anti-HLA-A31, and anti-HLA-B55 antibodies.

Maternal antibodies against human platelet antigen (HPA) and/or human leukocyte antigen (HLA) cause fetal and neonatal alloimmune thrombocytopenia (FNAIT) in 0.09-0.15% of live births. Severe cases account for 5-31% and the frequency of multiple kinds of alloantibodies is 6.9-9% of FNAIT. We present a case of severe FNAIT associated with anti-HPA-5b, anti-HLA-A31, and anti-HLA-B55 antibodies, successfully treated with immunoglobulin and platelet transfusion. The anti-HLA-B55 antibody was detected in the newborn's serum, but disappeared on the 20th day, which was followed by an increase of the platelet count. These findings suggested the potential involvement of an anti-HLA antibody in the pathogenesis of FNAIT.