Colegio San Agustin-Bacolod

College of Health and Allied Professions

Medical Technology Program

“Pregnancy Complicated by Anti-HPA-1a with Sequential Development of Fetal and

Neonatal Alloimmune Thrombocytopenia”

In partial fulfillment of the requirements

for the course MLS 118B: Seminar 2

MAJOR GROUP 2

Group 3: Biatingo, Dale Jeric, Dequiña, Joannie Daisy, & Palencia, Meryl

Group 14: Espos, Charise, Jabagat, Josh Thadeo, Mudoc, Emily, & Sayam, Ericka Jayne

Group 21: Gegato, Julie Ann, Recto, Erl Wyn Bee, & Tejada, Ariane Ruth

Group 37: Bañares, Kyla Shan, Castillanes, Colby, Mirasol, Marinuel, & Panganiban, Fritzel

March 15, 2025

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TABLE OF CONTENTS
Page
TITLE PAGE i
TABLE OF CONTENTS ii
LIST OF TABLES iii
LIST OF FIGURES iv
CASE 1
INTRODUCTION 1
MEDICAL HISTORY 3
PERSONAL HISTORY 3
OBSTETRIC AND GYNECOLOGIC HISTORY 4
FAMILY HISTORY 4
SIGNS AND SYMPTOMS 4
LABORATORY DIAGNOSIS 7
OTHER SIGNIFICANT FINDINGS: IMAGING STUDIES 17
Obstetric Ultrasound 17
Cranial MRI 17
DIFFERENTIAL DIAGNOSIS & FINAL DIAGNOSIS 18
DIAGNOSTIC WORKUP 25
PATHOPHYSIOLOGY 26
Intracranial Hemorrhage 29
PREVALENCE 31
TREATMENT 33
Neonatal Management 34
Long-Term Follow-Up and Management of FNAIT 38
Maternal Management for Future Pregnancies 40
RECOMMENDATIONS 42
PROGNOSIS 45

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SUMMARY AND CONCLUSION 45

REFERENCES 47

LIST OF TABLES

Table 1 Medical History of the Patient 8

Table 2 Vital Signs Record 9

Table 3 Chemistry Test Results 11

Table 4 Routine Urinalysis Result 11

Table 5 Coagulation Panel 12

Table 6 Postnatal Coagulation Panel 15

Table 7 Platelet crossmatch, HPA antibody screening and 15

HPA genotyping results

Table 8 Blood Typing between Mother and Offspring 16

Table 9 Comparisons of possible diagnosis based on their 18

key features and supporting tests

Table 10. Diagnostic Workup for FNAIT 25

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LIST OF FIGURES

Figure 1 Fetal Intracranial Hemorrhage 5

Figure 2 Petechiae 6

Figure 3 Purpura 6

Figure 4 Left eye proptosis and hemorrhage in the anterior 6

chamber of the eye of the patient.

Figure 5 Bleeding at the infusion site 7

Figure 6 Maternal Complete Blood Count 10

Figure 7 Postnatal Complete Blood Count 13

Figure 8 Peripheral Blood Smear Result 14

Figure 9 Intracerebral Hemorrhage 17

Figure 10 Right Sided-Intraparenchymal Hemorrhage 18

Figure 11 Pathophysiology of FNAIT 29

Figure 12 Pathophysiology of ICH due to FNAIT 33

Figure 13 Platelet Transfusion Guideline 35

Figure 14 Indications for IVIg 44

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“PREGNANCY COMPLICATED BY ANTI-HPA-1A WITH SEQUENTIAL

DEVELOPMENT OF FETAL AND NEONATAL ALLOIMMUNE
THROMBOCYTOPENIA”

CASE

Karla, a 27-year-old primigravida woman with no significant medical history reported a

decrease in fetal movement and was referred to the Department of Obstetrics and Gynecology at

34 weeks’ gestation for an ultrasound to check for fetal well-being. The ultrasound revealed a

possible fetal intracranial hemorrhage and signs of fetal distress. Moreover, Karla exhibited mildly

elevated blood pressure, raising concerns for the fetus and the mother. The pregnancy was regarded

as low-risk prior to this discovery with no obvious clinical symptoms that would point to an

underlying illness. On the same day, Karla had an emergency cesarean section. Upon birth, the

neonate exhibited respiratory distress, lethargy, and diffuse petechiae and purpura on the face and

trunk. Vital signs were recorded immediately, with the fetal heart rate at 145 bpm, respirations at

65 breaths per minute, and blood pressure at 55/35 mmHg. Physical examination also revealed the

presence of left eye proptosis and hemorrhage in the anterior chamber of the eye, at the same time,

prolonged bleeding on the infusion site was also noted.

INTRODUCTION

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition and the

primary cause of thrombocytopenia in newborns. It arises when the mother becomes

alloimmunized against fetal platelet antigens inherited from the father, which are absent on

maternal platelets, leading to a significant reduction in platelet count (<150,000/uL). While most

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cases present with mild symptoms, such as widespread petechiae and other skin lesions, severe

cases can lead to intracranial hemorrhage (ICH), potentially causing death or long-term disability

(Espinoza et al., 2013).

The most frequent and severe cases of FNAIT recorded in white populations result from

alloantibodies targeting human platelet antigen 1a (HPA-1a), which is absent in 2.3% of women.

Currently, early screening and predictive tools to forecast FNAIT are not available; hence, it is not

suspected until an otherwise healthy child born at term presents with thrombocytopenia, leading

to delayed diagnosis and increased risk of preventable complications. Approximately 25 to 50%

of FNAIT cases occur without warning during the gestation period of the first pregnancy, affecting

the majority of subsequent pregnancies (Zhi et al., 2021).

FNAIT is often regarded as the platelet counterpart of hemolytic disease of the fetus and

newborn (HDFN). In this condition, maternal alloantibodies targeting paternally inherited platelet

antigens cross the placenta, leading to thrombocytopenia in the fetus or newborn (Kjeldsen-Kragh

& Bengtsson, 2020). Significant differences between HDFN and FNAIT extend beyond the source

of fetal antigen. These differences primarily involve the timing of maternal alloimmunization and

the strategies for clinical management. In HDFN, first pregnancies are rarely affected, and fetuses

are more progressively affected in subsequent pregnancies. Furthermore, screening programs in

place for Rh incompatibility have greatly reduced the incidence of HDFN. In contrast, FNAIT can

present with severe clinical symptoms during a first pregnancy, often remaining undiagnosed until

after delivery. Currently, no routine antenatal screening is available to identify patients at risk of

developing FNAIT (Semple & Kapur, 2022).

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Fetal and neonatal alloimmune thrombocytopenia is characterized by the binding of

maternal alloantibodies to the infant’s platelets, causing their destruction during pregnancy and

even after birth. Approximately 80% of FNAIT cases are induced by antibodies against human

platelet antigen 1a (HPA-1a), with approximately 2000 out of 100,000 pregnancies occurring in

women who do not carry the HPA-1a antigen (Sachs, 2020).

FNAIT is a rare condition often not recognized by clinicians, resulting in difficulties in

determining the burden of the disease. Furthermore, since the diagnosis is almost established after

the birth of a symptomatic child, only a minority of FNAIT cases are detected (Tiller et al., 2017).

MEDICAL HISTORY

During the course of pregnancy, Karla adhered to regular prenatal visits, showing normal

fetal growth with no signs of preeclampsia, gestational diabetes, or other conditions. No reports of

any history of bruising, bleeding, or fatigue and concerns about placental or fetal well-being were

noted, accompanied by normal vital signs. However, a notable observation during the pregnancy

was a slight increase in maternal platelet count during the first trimester, which resolved during

mid-pregnancy, not raising any concern. Overall, the pregnancy had been uneventful, with no

apparent maternal symptoms until the 34th week of gestation, wherein a routine ultrasound showed

mild ventriculomegaly.

PERSONAL HISTORY

Karla has been working as a virtual assistant for the past 3 years. She reported no significant

past medical history of chronic illnesses, hematologic disorders, or autoimmune conditions. Karla

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also noted that she had never undergone major surgeries or blood transfusions and had no known

drug allergies.

OBSTETRIC AND GYNECOLOGIC HISTORY

This was the patient’s first pregnancy, with no previous history of miscarriages, infertility

treatments, and stillbirths. She had her regular monthly menstrual cycles before conception and

had never been diagnosed with reproductive disorders such as polycystic ovarian syndrome

(PCOS), endometriosis, or uterine anomalies.

FAMILY HISTORY

Karla and her husband reported no known family history of autoimmune disorders,

bleeding disorders, or any hematologic disorders. Both parents were healthy and had no siblings

that presented with a history of neonatal complications.

SIGNS AND SYMPTOMS

Fetal and neonatal alloimmune thrombocytopenia may vary from asymptomatic

thrombocytopenia to a very severe, lethal intracranial hemorrhage. In most cases, the disease

manifests in neonates as petechiae, hematomas, melena, hemoptysis, retinal bleeding, and

hematuria, with platelet count continuing to fall for some days after delivery (Brojer et al., 2015).

The clinical presentation of FNAIT in this case was first suggested by a reported decrease

in fetal movement at 34 weeks’ gestation, despite an otherwise uneventful pregnancy.

Subsequently, the ultrasound examination showcased signs of fetal distress and a possible

intracranial hemorrhage, advising an emergency cesarean section.

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Fetal distress is a general term for signs and symptoms that indicate the fetus is unwell,

including changes in fetal movement, heart rate, or biochemistry. It is a medical condition that

indicates a low level of oxygen in a fetus, commonly detected through an abnormal heart rate,

decrease in fetal movement, maternal cramping, vaginal bleeding, and meconium in amniotic fluid

(Steinweg et al., 2020).

Intracranial hemorrhage is characterized as spontaneous bleeding within the brain, leading

to blood accumulation between the brain and the skull. This condition occurs when maternal

alloantibodies attack fetal platelets due to an incompatibility in human platelet antigens. FNAIT is

primarily associated with severe bleeding, leading to intracranial hemorrhage in the fetus and or

newborn (Tiller et al., 2013).

Figure 1. Fetal Intracranial Hemorrhage

At birth, the neonate exhibited multiple signs of thrombocytopenia and hemorrhagic

complications, including cutaneous manifestations, ophthalmic findings, neurological conditions,

and bleeding manifestations. Fetal thrombocytopenia is characterized by platelet counts less than

150 x10^9/L, regardless of gestational age. Meanwhile, for severe thrombocytopenia, a cut-off

level of 50 x10^9/L is commonly considered (Constantinescu et al., 2012).

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The cutaneous manifestations exhibited by the fetus are petechiae and purpura, which occur

from bleeding under the skin. Petechiae are pinpoint hemorrhages on the skin that are often redder

in color than purpura, which manifests as larger areas of skin discoloration that are more purple in

color. In addition, these discolorations occur on much of the body and appear within a few hours

after birth (National Organization for Rare Disorders, 2023).

Figure 2. Petechiae Figure 3. Purpura

Upon physical examination, the neonate presented with retinal hemorrhage, which refers

to hemorrhage within the retina and is commonly observed in neonates with severe

thrombocytopenia. This is brought about by the functional impairment of platelets and endothelial

cells caused by the various subtypes of anti-HPA-1a binding to the fibrinogen and fibronectin

receptors on these cells (de Vos et al., 2021). Left eye proptosis was also noted, which is the

protrusion of one or both eyes from their natural position induced by increased venous pressure or

bleeding disorders (Pujari et al., 2018).

Figure 4. Left eye proptosis and hemorrhage in the anterior chamber of the eye of the patient.

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Upon delivery, the neonate appeared weak and exhibited reduced activity and

responsiveness. According to Nall (2019), lethargy refers to fatigue, sluggishness, and lack of

mental or physical motivation. Moreover, despite standard hemostatic measures, the neonate

continued to present with prolonged bleeding at the infusion site as a consequence of reduced

platelet count. As platelet levels drop, there may be insufficient platelets to form an effective clot,

leading to prolonged bleeding. In neonates affected by FNAIT, this is commonly observed as

maternal anti-HPA-1a antibodies target and destroy fetal or neonatal platelets, further impairing

clot formation (Baykara, 2024).

Figure 5. Bleeding at the infusion site.

LABORATORY DIAGNOSIS

As the mother presented to the Department of Obstetrics and Gynecology, the patient was

assisted by a nurse who took note of the patient’s personal information, medical history, weight,

temperature, blood pressure, pulse rate, and respiration rate. The recorded data was taken note on

the medical chart of the patient and was referred to the attending in-charge.

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Hospital ID: 1112233

Name of Patient: Karla Buenavista Torres Age: 27
Date of Admission: 1/31/2025 Sex: Female
Date of Birth: 12/12/1997 Attending Physician: Juan De la Cruz
Gravida/Parity: G1P0 (Primigravida) Gestational Age: 34 weeks
Chief Complaint: Decreased Fetal Movement

—-----------------------------------------MEDICAL HISTORY—---------------------------------------
Presenting Symptoms:
● Primary Concern: Decreased Fetal Movement
● Mildly Elevated Blood Pressure
● No history of infections, fever, or recent illness

Past Medical History

● No known chronic illnesses or conditions

Obstetric History
● First pregnancy (G1P0)

Family History
● No history of bleeding disorders, autoimmune diseases, or thrombocytopenia.

Medication History
● No regular medications
● Prenatal Supplements

Allergies
● No known drug allergies

Social History
● Non-smoker, no alcohol, or illicit drug use.

Table 1. Medical History of the Patient

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Hospital ID: 1112233

Name of Patient: Karla Buenavista Torres Age: 27
Date of Admission: 1/31/2025 Sex: Female
Date of Birth: 12/12/1997 Attending Physician: Juan De la Cruz
Gravida/Parity: G1P0 (Primigravida) Gestational Age: 34 weeks
Chief Complaint: Decreased Fetal Movement

Date Weight Height BP Pulse Respiration Temp Nurse

Initials

1/31/2025 60kg 5’ 3 140/90 88 bpm 28/min 36.8°C J.D.

mmHg

Table 2. Vital Signs Record

Vital sign records showcased a normal BMI, pulse rate, respiration, and temperature.

However, maternal blood pressure was mildly elevated, raising suspicion for possible hypertensive

disorders of pregnancy. Furthermore, to assess maternal health and fetal well-being, the doctor

ordered a series of laboratory and imaging studies, including an obstetric ultrasound, complete

blood count, liver function tests (AST, ALT), routine urinalysis, and coagulation panel.

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Complete Blood Count

Figure 6. Maternal Complete Blood Count

Based on the patient's complete blood count (CBC) results, the hemoglobin and hematocrit

levels indicate the absence of maternal anemia. This finding is consistent with the red cell indices

and total RBC count, confirming no evidence of maternal polycythemia or anemia. Additionally,

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the total white blood cell (WBC) count falls within the normal range, suggesting no signs of

infection or leukocytosis. Furthermore, the platelet count is within normal limits, indicating the

absence of maternal thrombocytopenia.

Test Result Reference Interpretation

ALT/SGPT 16 U/L <50 U/L NORMAL

AST/SGOT 22 U/L 5-37 U/L NORMAL

LDH 115 U/L 100-220 U/L NORMAL

Table 3. Chemistry Test Results

Hospital ID: 1112233

Name of Patient: Karla Buenavista Torres Age: 27
Date of Admission: 1/31/2025 Sex: Female
Date of Birth: 12/12/1997 Attending Physician: Juan De la Cruz
Gravida/Parity: G1P0 (Primigravida) Gestational Age: 34 weeks
Chief Complaint: Decreased Fetal Movement
—---------------------------------------------URINALYSIS—-------------------------------------------
PHYSICAL CHEMICAL
Color Straw Albumin Negative
Reaction pH - 6.5 Glucose Negative
Transparency Hazy Bilirubin
Specific Gravity 1.020 Leukocytes
Blood
MICROSCOPIC CELLS: Nitrite
Pus Cells 0-2/HPF Urobilinogen
RBC 0-2/HPF
Yeast Cells
Bacteria OCCASIONAL/HPF
Epithelial Cell
Casts

Table 4. Routine Urinalysis Result

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Maternal chemistry assays were performed to evaluate liver function, revealing normal

levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore,

LDH, a marker for hemolysis, showcased a normal value. These findings indicate no evidence of

liver damage or inflammation and hemolysis, effectively ruling out HELLP syndrome.

Additionally, routine urinalysis results were within normal limits, particularly concerning protein

levels, further reducing the likelihood of preeclampsia.

Test Result Reference Interpretation

PT 12.5 sec 11-16 sec NORMAL

aPTT 30.2 sec 30-40 sec NORMAL

Table 5. Coagulation Panel

Maternal coagulation panels were conducted to evaluate potential coagulation disorders

and assess the risk of hemorrhage or thrombosis, particularly in preparation for an emergency

cesarean section. The results indicated normal maternal coagulation function, with no evidence of

clotting disorders or coagulation factor deficiencies.

Given the combination of fetal distress, suspected ICH, and mildly elevated maternal blood

pressure, an emergency C-section was performed to prevent further fetal compromise. Following

the delivery of a male neonate, a physical examination revealed prominent petechiae and purpura

on the face and trunk, left eye proptosis with hemorrhage on the anterior chamber of the left eye,

lethargy, and prolonged bleeding at the infusion site. Immediate postnatal laboratory investigations

were performed 1-hour post-birth, including a complete blood count, peripheral blood smear, and

coagulation panel.

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Figure 7. Postnatal Complete Blood Count

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Figure 8. Peripheral Blood Smear Result

The postnatal complete blood count (CBC) revealed a significantly low platelet count,

prompting a manual blood workup through a peripheral blood smear to confirm neonatal

thrombocytopenia. The smear was performed to assess morphological abnormalities in blood cells,

particularly platelets, and to aid in differentiating potential causes of thrombocytopenia. The

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peripheral blood smear findings demonstrated a marked reduction in platelet count, with no

evidence of schistocytes ruling out hemolytic diseases.

Test Result Reference Interpretation

PT 13.2 sec 11-16 sec NORMAL

aPTT 32.2 sec 30-40 sec NORMAL

Table 6. Postnatal Coagulation Panel

A postnatal coagulation panel was conducted to assess the neonate's coagulation function

and rule out potential neonatal coagulation disorders, given the physical symptoms observed after

birth, which were suggestive of a coagulation abnormality. The results indicated normal

coagulation function, effectively excluding coagulation factor deficiencies as a cause.

Tests Results

Maternal Serum Antibody Testing Positive for anti-HPA-1a antibodies

(ELISA/MAIPA)

Maternal Platelet Antigen Genotyping Negative for HPA-1a

Neonatal Platelet Antigen Genotyping Positive for HPA-1a

Maternal Serum Crossmatch with Neonatal Strongly Reactive

Platelets

Abbreviation: HPA, human platelet antigen.

Table 7. Platelet crossmatch, HPA antibody screening and HPA

genotyping results

Confirmatory testing for neonatal alloimmune thrombocytopenia was performed

postnatally due to the newborn's severely decreased platelet count with normal maternal platelet

count. Maternal serum antibody testing identified the presence of anti-HPA-1a antibodies, as well

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as the absence of HPA-1a in maternal platelet antigen genotyping. Furthermore, neonatal platelet

antigen genotyping confirmed the inheritance of the paternal HPA-1a antigen, which correlated

with the strong reactivity observed in the neonatal platelet crossmatch with maternal serum.

FORWARD TYPING REVERSE TYPING BLOOD

TYPE

A Rh B A1 B

Mother 4+ 4+ 0 0 4+ A positive

Baby 0 4+ 0 O positive

Table 8. Blood Typing between Mother and Offspring

The neonate’s blood group is O Rh-positive, while the mother’s blood group is A Rh-

positive, and the father’s is O Rh-positive. Blood group compatibility is not a significant concern,

as there is no ABO or Rh incompatibility between the mother and the baby. However, the

pregnancy is complicated by anti-HPA-1a alloimmunization, in which the mother lacks the HPA-

1a antigen and has developed anti-HPA-1a antibodies. These maternal antibodies target fetal

platelets that have inherited the HPA-1a antigen from the father, leading to neonatal alloimmune

thrombocytopenia (NAIT).

Collectively, these findings present a complex case of maternal anti-HPA-1a

alloimmunization, in which maternal antibodies target fetal platelets expressing the HPA-1a

antigen. The intracranial hemorrhage detected on ultrasound, along with the presence of petechiae,

purpura, left eye proptosis, and hemorrhage in the anterior chamber of the eye at birth, is likely

associated with severe thrombocytopenia. This thrombocytopenia is induced by maternal anti-

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HPA-1a antibodies, which mediate the destruction of fetal platelets, leading to significant bleeding

complications.

OTHER SIGNIFICANT FINDINGS: IMAGING STUDIES

Obstetric Ultrasound

Obstetric ultrasound revealed evidence of possible fetal intracranial hemorrhage (ICH) and

signs of fetal distress, raising concerns for fetal compromise requiring urgent intervention. Aside

from that, no structural abnormalities were noted. The sonographic image revealed intracerebral

hemorrhage, which is often associated with alterations in maternal blood pressure, placental

abruption, severe abdominal trauma, hereditary coagulation disorders, and alloimmune platelet

disorders (Bianchi et al., 2010).

Figure 9. Intracerebral Hemorrhage

Cranial MRI

While prenatal ultrasound detected a possible intracranial hemorrhage, a cranial MRI was

performed on the neonate to determine the extent of the hemorrhage. The MRI revealed a right-

sided intraparenchymal hemorrhage with associated ventricular dilation, consistent with severe

thrombocytopenia-induced bleeding. However, no evidence of congenital brain malformations

was noted.

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Figure 10. Right Sided-Intraparenchymal Hemorrhage

DIFFERENTIAL DIAGNOSIS & FINAL DIAGNOSIS

Frequent scenarios of fetal and neonatal alloimmune thrombocytopenia, shortly post-birth

event, involves a neonate presenting with intracranial hemorrhage, respiratory distress, lethargy,

diffuse petechiae and purpura on the face and trunk, left eye proptosis and hemorrhage in the

anterior chamber of the eye, at the same time, prolonged bleeding on the infusion site upon birth,

necessitating a thorough evaluation to determine the underlying etiology.

POSSIBLE DIAGNOSIS KEY FEATURES SUPPORTING TESTS

Fetal and Neonatal ● Marked ● Maternal anti-HPA

Alloimmune thrombocytopenia antibody screening
Thrombocytopenia ● Petechiae and identification.
● Purpura ● HPA genotyping of
● Retinal bleeding mother, father and/or
● Overt bleeding neonate.
● Intracerebral ● Confirmation of
hemorrhage antibody specificity
● Major lung bleed and reactivity with the
● Presence of maternal monoclonal antibody
anti-HPA-1a antibodies. immobilization of
platelets.

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Immune Thrombocytopenia ● Maternal autoimmune ● Detection of

(Maternal ITP-Related) disorder with platelet autoantibodies against
destruction platelet antigens to
● Neonatal confirm maternal ITP
thrombocytopenia due using Maternal
to passive transfer of Antibody Testing.
maternal autoantibodies
● Maternal
thrombocytopenia often
present
● No response to IVIG in
neonate (distinguishes
from FNAIT)
thrombocytopenia
● Petechiae or bruising in
neonate may show
several days after birth

HELLP Syndrome ● Severe form of ● Liver Function Tests

preeclampsia (often in ● Coagulation Studies
3rd trimester) ● Complete Blood
● Hemolysis → anemia, Count
schistocytes
● Elevated liver enzymes
(AST, ALT)
● Low platelets
(<100,000/µL)

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TORCH Infection ● Fever and Sluggishness ● Amniotic fluid culture

● Eye abnormalities to identify specific
● Potential cardiac defects pathogens.
● Congenital infections ● Specific IgM and IgG
causing antibody tests for each
thrombocytopenia, TORCH pathogen to
hepatosplenomegaly, confirm active or past
jaundice, intracranial infections.
calcifications, and ● Ultrasound to detect
petechiae/purpura structural anomalies
("blueberry muffin associated with
rash") TORCH infections,
● Specific findings vary such as microcephaly
by pathogen (e.g., CMV or cardiac defects.
→ periventricular
calcifications,
Toxoplasmosis →
diffuse calcifications)

Congenital ● Severe ● Assessment of blood

Amegakaryocytic thrombocytopenia cell indices, and
Thrombocytopenia ● Bruising platelet size-
● Petechiae morphology through
● Severe bleeding platelet count,
manifestations complete blood count
● Intracranial hemorrhage (CBC), and peripheral
● Pulmonary hemorrhage blood smear (PBS)
● Bone marrow failure ● Bone Biopsy

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● Genetic Testing

Table 9. Comparisons of possible diagnosis based on their key features and supporting tests.

The differential diagnosis included Immune Thrombocytopenia (Maternal ITP-Related),

HELLP Syndrome, TORCH Infections, and congenital amegakaryocytic thrombocytopenia, all of

which were systematically ruled out based on laboratory and clinical findings.

A key distinction between fetal and neonatal alloimmune thrombocytopenia (FNAIT) and

immune thrombocytopenia (ITP) in pregnant individuals lies in their underlying immune

mechanisms. In FNAIT, maternal alloantibodies are directed against fetal platelet-specific

antigens, such as HPA-1a, whereas in ITP, maternal autoantibodies—commonly directed against

GPIIb/IIIa or GPIb/IX—attack both maternal and fetal platelets. As a result, maternal

thrombocytopenia is a characteristic feature of ITP but is absent in FNAIT. Furthermore, neonates

with ITP-related thrombocytopenia are often less severely affected than those with FNAIT, as

FNAIT poses a higher risk of intracranial hemorrhage (ICH) due to more severe

thrombocytopenia, often with platelet counts below 100,000/µL. Unlike FNAIT, ITP-related

neonatal thrombocytopenia typically resolves within weeks without aggressive intervention

(Kashyap et al., 2021 and Pishko et al., 2022). Maternal Immune Thrombocytopenia (ITP)-related

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neonatal thrombocytopenia was a possibility, given that maternal autoantibodies can cross the

placenta and destroy fetal platelets. However, the mother had a normal platelet count and no history

of immune thrombocytopenia, making this diagnosis unlikely.

Similarly, HELLP Syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets) can

lead to neonatal thrombocytopenia, but its primary pathology is linked to maternal endothelial

dysfunction and placental insufficiency rather than direct immune-mediated platelet destruction.

The presence of maternal thrombocytopenia, hemolysis, and elevated liver enzymes serves as a

hallmark of HELLP, differentiating it from FNAIT. Unlike FNAIT, where the neonate is otherwise

well aside from thrombocytopenia, neonates affected by HELLP syndrome often suffer from

intrauterine growth restriction (IUGR), preterm birth, and perinatal complications due to placental

insufficiency and systemic inflammation (Khalid and Tonismae, 2023). HELLP Syndrome, a

hypertensive disorder of pregnancy characterized by hemolysis, elevated liver enzymes, and low

platelets, was ruled out due to normal maternal liver function tests (AST, ALT), lactate

dehydrogenase (LDH), and platelet count.

On the other hand, TORCH infections represent a non-immune cause of neonatal

thrombocytopenia that mimics FNAIT but is associated with congenital infections leading to

systemic involvement, including hepatosplenomegaly, jaundice, microcephaly, and intracranial

calcifications. Unlike FNAIT, which typically presents with isolated thrombocytopenia, neonates

with TORCH infections have multisystem involvement and signs of congenital infection, such as

petechiae ("blueberry muffin rash"), anemia, and organomegaly. The TORCH panel and PCR

testing help distinguish these cases from FNAIT, whereas maternal alloantibody screening (e.g.,

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anti-HPA-1a testing) confirms FNAIT (Jaan and Rajnik, 2023). Congenital infections such as

TORCH (cytomegalovirus (CMV), toxoplasmosis, rubella, and herpes simplex virus) were

considered in the differential diagnosis due to their potential to cause neonatal thrombocytopenia.

However, the absence of maternal symptoms and history of infection, laboratory findings, and the

lack of additional systemic manifestations made congenital infections unlikely.

Meanwhile, congenital amegakaryocytic thrombocytopenia (CAMT) is an inherited

condition arising from deficient thrombopoietin signaling due to a biallelic mutation of c-MPL.

Affected individuals primarily experience severe thrombocytopenia at birth, with an elevated risk

of intracranial bleeding and an early onset of bone marrow failure. Rarely, affected neonates

develop findings during fetal development, with common manifestations of purpura, intracranial

bleeding, recurrent rectal bleeding, or pulmonary hemorrhage within hours of birth. However, a

family history of thrombocytopenia may be present, distinguishing it from FNAIT (Tirthani,

2024). In the neonate's case, congenital amegakaryocytic thrombocytopenia (CAMT) was initially

considered due to the presence of severe thrombocytopenia at birth. However, CAMT is typically

associated with progressive bone marrow failure and pancytopenia, which were not observed. The

absence of other cytopenias in the patient's complete blood count further indicated that CAMT was

unlikely.

Given these exclusions, further investigation focused on FNAIT, a condition caused by

maternal alloimmunization against fetal platelet antigens inherited from the father. The neonate’s

markedly reduced platelet count, presence of petechiae, purpura, prolonged bleeding at the

infusion site, and intracranial hemorrhage raised strong clinical suspicion. Postnatal laboratory

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confirmation included maternal antibody testing, which identified anti-HPA-1a antibodies, and

neonatal platelet antigen genotyping, which confirmed the inheritance of the paternal HPA-1a

antigen. This demonstrated maternal-fetal platelet incompatibility, confirming FNAIT as the

underlying cause (Stam et al., 2022).

As stated by (Tiller et al., 2013), in cases of FNAIT, ICH is estimated to occur in 10% to

20% of affected pregnancies, often detected in utero during late pregnancy. Importantly, the

presence of intracranial hemorrhage (ICH) detected via prenatal ultrasound and confirmed by

neonatal MRI further supports the diagnosis, as severe thrombocytopenia in FNAIT can lead to

life-threatening bleeding, particularly in the brain. The MRI findings of a right-sided

intraparenchymal hemorrhage with ventricular dilation align with hemorrhagic complications seen

in severe cases of FNAIT. The absence of schistocytes on a peripheral blood smear ruled out

microangiopathic hemolytic processes, reinforcing the diagnosis of antibody-mediated platelet

destruction.

Overall, the combination of severe neonatal thrombocytopenia, normal maternal platelet

count, presence of anti-HPA-1a antibodies, and neonatal platelet antigen-genotyping confirming

HPA-1a inheritance from the father confirms that this case is Fetal and Neonatal Alloimmune

Thrombocytopenia (FNAIT). The clinical complications, particularly intracranial hemorrhage,

highlight the severity of this condition, necessitating immediate postnatal management with

platelet transfusions and intravenous immunoglobulin (IVIG) to reduce further bleeding risk.

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DIAGNOSTIC WORKUP

Findings Interpretation Ruled Out Diagnosis

Initial ● Decreased fetal ● Suggests a possible

Presentation movement hemorrhagic or
● ICH and fetal ischemic event
distress evident on affecting the fetus.
ultrasound.

Postnatal Signs ● Petechiae ● Suggests

● Purpura thrombocytopenia,
● Left eye proptosis likely immune-
with hemorrhage mediated.
on the anterior
chamber of the
eye.
● Prolonged
bleeding at the
infusion site.

Maternal CBC ● Platelet count is ● No maternal Maternal Immune

within range. thrombocytopenia. Thrombocytopenic
● Fetal platelet Purpura
destruction is not
due to maternal
ITP.

Maternal ● Normal ● No evidence of HELLP Syndrome

Chemistry Test liver dysfunction
(AST, ALT, LDH) or hemolysis.

TORCH ● No maternal ● No features TORCH Infection

Symptoms symptoms and suggestive of
history of congenital
infection. infections.

Neonatal CBC ● Severe ● No ● HELLP Syndrome

and PBS thrombocytopenia microangiopathic ● Congenital
● No Schistocytes hemolysis and Amegakaryocytic
other cytopenias, Thrombocytopenia
suggesting
immune-mediated

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platelet
destruction.

Maternal and ● Mother: HPA-1a ● Confirms

Neonatal HPA negative maternal-fetal
Genotyping ● Neonate: HPA-1a platelet
positive incompatibility.

Platelet ● Strongly reactive ● Confirms

Crossmatch maternal serum destruction of
with neonatal neonatal platelet by
platelets. maternal
antibodies.

Final Diagnosis Fetal and Neonatal Alloimmune Thrombocytopenia

Table 10. Diagnostic Workup for FNAIT

PATHOPHYSIOLOGY

Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) arises when a mother who is

negative for a specific human platelet antigen (HPA) carries a fetus found to be positive for the

antigen due to paternal inheritance. An individual can be HPA-1a negative when they inherit two

b alleles making them HPA1b/b, while an individual can be HPA-1a positive when they inherit at

least one a allele from their parents (Partners in Care, 2023). According to the study conducted by

Tiller et al., (2017), HPA-1a is the most commonly implicated antigen, which is responsible for

about 80-90% of FNAIT cases. The HPA-1a antigen is located on the β3 integrin GPIIIa on the

platelet surface as early as 16 weeks of intrauterine life (Jens Kjeldsen-Kragh et al., 2020).

Normally, the maternal immune system is tolerant to fetal cells, but not until cells (HDFN) or

platelets (FNAIT) carrying the paternally inherited HPA-1a antigen will cross the placenta,

allowing them to enter the maternal circulation. This can occur due to fetomaternal hemorrhage

(FMH), which can happen during specimen collection to assess fetus health (amniocentesis) or

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even during labor and delivery. Incompatibility for human platelet antigens (HPAs) can induce

antibodies against fetal platelets, leading to FNAIT and hemorrhagic complications (Tiller et al.,

2017).

According to Garraud and Chiaroni (2022), in cases of FNAIT, the HPA-1a antigen present

on fetal platelets enters the maternal circulation. The maternal immune system recognizes HPA-

1a as a foreign antigen, triggering the activation of B lymphocytes. These B lymphocytes then

differentiate into plasma cells, which produce IgG alloantibodies specifically targeting HPA-1a.

Initially, this immune response is relatively mild and may not cause significant fetal complications

in the first affected pregnancy (Vander Haar et al., 2023). However, during subsequent

pregnancies, if the mother carries another HPA-1a-positive fetus, the immune system rapidly

reacts with the antigen due to immunological memory and responds with a much stronger and

quicker production of anti-HPA-1a antibodies. As claimed by Tiller et al. (2017), the intensity of

the immune response in later pregnancies can lead to earlier and more severe fetal

thrombocytopenia, increasing the risk of complications.

As explained by Zoltán Szittner et al. (2023), once alloimmunization occurs, unlike IgM

antibodies, which cannot cross the placenta, maternal IgG antibodies-directed HPA-1a are actively

transported across the placenta via Fc receptors, starting 13th week to 16th week of gestation. In

fetal circulation, these anti-HPA-1a IgG bind to fetal platelets that express the HPA-1a antigen.

The bound antibodies opsonize the platelets, marking them for destruction. The macrophage of the

reticuloendothelial system (RES) recognizes the antibody-coated platelets as foreign, removing

them through Fc receptor-mediated phagocytosis. As this continues to happen, the rate of platelet

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destruction increases, exceeding the capacity of the fetal bone marrow to compensate for the loss

of platelets. This can lead to progressive thrombocytopenia (low platelet count) and results in poor

clot formation, leading to increased spontaneous hemorrhage. This often worsens with advancing

gestation as the maternal antibody titers increase (Ni, 2013).

The antigens capable of causing FNAIT are spread across six different glycoproteins found

on the surface membrane of platelets. These glycoproteins, such as GPIIIa, GPIb, GPIa, and

GPIIa, play a significant role in platelet functions such as adhesion, aggregation, and plug

formation, processes important in maintaining hemostasis. As of today, 35 HPAs are known and

described. The first described antigen, which is also important in the pathogenesis of FNAIT, was

HPA-1a (Novak et al., 2017). The β3 integrin subunit, carrying the HPA-1a antigen, can dimerize

with either the αv or the αIIb subunit. The integrin αIIbβ3 complex is abundantly expressed on

platelets and megakaryocytes and is a receptor for fibrinogen, vWF, fibronectin, and vitronectin,

which is vital for platelet aggregation (Bennett, 2005). Consequently, any abnormalities that can

preclude platelet aggregation result in prolonged bleeding. The mechanism of platelet destruction

and clearance in FNAIT involves maternal exposure to paternally-inherited HPA. According to

Chen et al. (2019), fetal microparticles may have been the potential source of foreign antigens for

the mother's immune system to produce antibodies as they have been detected in maternal serum

as early as 7 weeks. Kjaer et al. (2020) also speculated that maternal immunization could be caused

by invasive trophoblast cells that express integrin β3, which harbor the HPA-1a antigen. Following

alloimmunization, the maternal alloantibodies are generated and enter the fetal circulation through

the placental trophoblasts, which is mediated by the neonatal Fc-receptor, allowing active placental

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transport. Subsequent antibody opsonization of fetal platelets leads to their destruction, resulting

in low platelet counts in the fetus/neonate (Stam et al., 2023).

A study conducted by Kjeldsen-Kragh et al. (2019) stated four factors that influence the

neonatal platelet count such as the rate of placental transport of anti-HPA-1a, the density of anti-

HPA-1a on fetal platelets, glycosylation pattern of the Fc-part of anti-HPA-1a IgG, and the extent

to which fetal thrombopoiesis can compensate for the destruction brought about by the

sensitization of platelets.

Figure 11. Pathophysiology of FNAIT (Wolf, 2024).

Intracranial Hemorrhage

Intracranial hemorrhage is one of the most severe complications of FNAIT, which arises

due to a significant decrease in fetal platelet count, causing the inability of the platelet to form a

stable blood clot. The pathological mechanism of ICH caused by FNAIT is not only limited to

simple platelet depletion but also involves multiple interconnected processes, including impaired

angiogenesis, endothelial dysfunction or cell apoptosis, and vascular instability (Kjeldsen-Kragh

& Bengtsson, 2020).

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In FNAIT, the maternal immune response to the fetal platelet antigens, HPA-1a being the

most common human platelet antigen involved, is the primary cause of ICH. This happens when

a mother who is negative for HPA carries a fetus that is positive for HPA-1a, producing antibodies

against fetal platelets (Jens Kjeldsen-Kragh et al., 2020). Consequently, this leads to

thrombocytopenia in the fetus, reducing the number of platelets available for clot formation. As a

result, the fetus becomes highly susceptible to spontaneous bleeding, particularly in high-pressure

vascular regions like the brain. However, recent research studies claim that thrombocytopenia

alone does not fully explain the high incidence of ICH in FNAIT.

As explained by Issaka Yougbaré et al., (2018), anti-β3 integrin antibodies produced by

the mother, which target αIIbβ3 on platelets, can also cross-react with αVβ3 integrins expressed

on endothelial cells (ECs) of the fetus. These integrins play an important role in angiogenesis as

well as in maintaining vascular integrity. The reaction of maternal antibodies and αVβ3 integrins

on fetal endothelial cells leads to cell apoptosis. Since endothelial cells need αVβ3 integrins

signaling for the smooth migration and proper formation of the blood vessels, their loss results in

fragile and underdeveloped vasculature that is prone to rupture. In addition, the obstruction of

angiogenesis results in decreased blood vessel density and weakened blood vessel networks,

especially in the fetal brain and retina, increasing the likelihood of hemorrhage (Kjeldsen-Kragh

& Bengtsson, 2020). During fetal development, the blood-brain barrier, which primarily protects

the brain from circulating immune cells and toxins, is still developing and maturing–weakening

this barrier. As a consequence, there will be an increased permeability of plasma components into

the brain, making hemorrhagic events even more likely (Issaka Yougbaré et al., 2018).

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The severity of hemorrhage is not only associated with maternal antibodies coating the

fetal platelets, but it is more on the binding affinity of the maternal anti-HPA-1a antibodies to the

fetal endothelial integrins. The stronger the reaction or the binding to the integrins, the higher the

risk of ICH, making antibody screening a potential predictive tool for identifying at-risk

pregnancies. In cases where the neonates are able to survive ICH, neurological impairments can

still arise because of the brain damage from hemorrhagic events. Cerebral palsy, seizures, epilepsy,

cognitive and developmental delays are some of the neurological problems the neonates may

develop. Also, vision impairment is possible due to the anti-angiogenic effects on retina vessels.

The disruption of angiogenesis in the brain and retina may have lifelong consequences for

cognitive and sensory development (Issaka Yougbaré et al., 2018).

PREVALENCE

It has been reported that 1.6% - 4.6% of the general population are HPA-1a negative, which

means that they carry two alleles of the HPA-1 b antigen (Nowak et al., 2017). However, only

10% of HPA-1a-negative women bearing an HPA-1a-positive fetus will likely develop

alloantibodies. FNAIT is considered the most common and leading cause of severe

thrombocytopenia, particularly among white people, in which 2.3% of the population of women

do not have the human platelet antigen 1a (Kjeldsen-Kragh & Bengtsson, 2020). Kjeldsen-Kragh

& Ahlen (2020) further stated that 80% of FNAIT cases among Caucasians and noted as the most

severe ones were caused by alloantibodies against the human platelet antigen 1a (HPA-1a). Zhi et

al. (2022) gave a rough estimate of 25% or more of the FNAIT cases occurring during the first

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pregnancy without any warnings brought about by alloimmunization as early as the 17th

gestational week.

According to Peterson (2020), about one-third of those HPA-1a negative women are

positive for HLA-DR antigen B3*0101 gene and are at high risk of becoming immunized against

HPA 1a when they carry an HPA- 1a positive child, which occurs in 35% of cases. Of these,

approximately 1 in three of them will give birth to an HPA- 1a positive child with significant

thrombocytopenia (Peterson, 2020).

Additionally, severe thrombocytopenia affects 1 in 700 newborns, and 27% of the cases

are caused by FNAIT, making the condition the most common cause of isolated thrombocytopenia

in newborns (Nowak et al., 2017). In patients with FNAIT, intracranial hemorrhage is estimated

to affect 6% of newborns and could rise to 26% in those without treatment, resulting in fatal

outcomes.

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Figure 12. Pathophysiology of ICH due to FNAIT

TREATMENT

In the absence of population-based screening for FNAIT, diagnosis is primarily based on

the presentation of symptoms, presenting a clinical challenge, as management must focus on

treating the thrombocytopenic neonate with newly diagnosed FNAIT while also preventing similar

bleeding complications in future pregnancies through appropriate antenatal therapy (Winkelhorst

et al., 2017). According to current medical guidelines, FNAIT is typically not suspected until after

birth, when an otherwise healthy neonate presents with thrombocytopenia or bleeding

complications. This occurs because routine screening for maternal alloantibodies against fetal

platelets and, in this case, due to anti-HPA-1a, is not yet established in standard prenatal care. In

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the first affected pregnancy, the maternal immune system is exposed to fetal platelet antigens for

the first time, and alloantibody production usually occurs too late in gestation to be detected or

managed before birth (Kjeldsen-Kragh & Bengtsson 2020). As a result, prenatal interventions are

only applicable in subsequent pregnancies, where maternal alloantibodies are already present and

capable of crossing the placenta early enough to affect fetal platelet levels.

Given that prenatal treatment was not an option since no complication was observed until

the latter part of the pregnancy and an emergency delivery had already been performed, the

physician can only start on postnatal management, which is focused on stabilizing the neonate’s

platelet count and preventing further complications such as intracranial hemorrhage (ICH). The

following was the order in which postnatal care was administered:

Neonatal Management

Platelet Transfusion. Platelet transfusions are primarily indicated for the prevention and

treatment of bleeding in patients with acquired thrombocytopenia across a range of clinical

contexts (Stanworth & Shah, 2022). In this case, a term neonate presented with severe

thrombocytopenia (defined as a platelet count below 20 × 10⁹/L), wherein the laboratory analysis

revealed a platelet count of 19 × 10⁹/L. Given the significant risk of hemorrhagic complications

associated with this level of thrombocytopenia, immediate postnatal intervention with platelet

transfusion was deemed necessary. To minimize the risk of alloimmunization and subsequent

transfusion refractoriness, HPA-1a-negative platelets were the preferred choice for transfusion.

This approach prioritizes the use of platelets lacking the human platelet antigen (HPA)-1a, which

is a common cause of neonatal alloimmune thrombocytopenia (NAIT). If HPA-1a-negative

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platelets were unavailable, an alternative strategy involves the initial administration of random

donor platelets followed by intravenous immunoglobulin (IVIG) therapy. IVIG administration

aims to enhance platelet survival and reduce the risk of further bleeding. The therapeutic goal was

to achieve and maintain a platelet count exceeding 50 × 10⁹/L (50,000/µL) to effectively mitigate

the risk of clinically significant hemorrhage. This target platelet count is based on established

clinical guidelines and reflects a balance between the risk of bleeding and potential adverse effects

associated with excessive platelet transfusion. It is important to note that the physician carefully

considered the potential risks associated with high-dose platelet transfusion. Studies have indicated

a correlation between increased platelet transfusion doses and elevated 28-day mortality rates

(Curley et al., 2018). Therefore, a conservative approach to platelet transfusion was adopted,

guided by the clinical status of the neonate and regular monitoring of platelet counts.

Figure 13. Platelet Transfusion Guideline (de Vos et al., 2020).

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Intravenous Immunoglobulin (IVIG) Therapy. The neonate's severe thrombocytopenia,

with a platelet count of 19 x 10⁹/L, necessitated immediate treatment to prevent life-threatening

hemorrhage. While platelet transfusion was the primary intervention, intravenous immunoglobulin

(IVIG) therapy was concurrently administered as an adjunct treatment to enhance its effectiveness.

The IVIG regimen consisted of 1 g/kg/day for two consecutive days. This dual approach aims to

address two critical aspects of the condition: neutralization of maternal antibodies and improved

platelet recovery and survival. The IVIG infusion provides a high concentration of polyclonal IgG

antibodies that competitively inhibit the binding of these maternal antibodies to the neonate's

platelets, thereby reducing their destructive effect, and preventing further platelet destruction.

Beyond its direct effect on maternal antibody neutralization, IVIG may also indirectly improve

platelet survival. Research suggests a nonspecific effect of IVIG on antibody clearance (Hansen,

2002). This means that IVIG may promote the removal of pathogenic antibodies, including the

maternal alloantibodies present in the neonate's circulation, leading to improved platelet recovery

and a longer lifespan for the transfused platelets. This secondary mechanism complements the

primary effect of antibody neutralization, maximizing the benefit of the platelet transfusion.

Corticosteroid Therapy. In this case of neonatal alloimmune thrombocytopenia,

corticosteroid therapy was considered a potential third-line treatment option in the event of platelet

refractoriness—a situation where the platelet transfusions proved insufficient to raise or maintain

the platelet count to a safe level. Platelet refractoriness can occur due to the continued destruction

of transfused platelets by maternal antibodies despite the administration of IVIG. Should platelet

refractoriness have developed, corticosteroids, specifically prednisone, at a dosage of

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approximately 1-2 mg/kg/day, would have been considered. The rationale for using corticosteroids

in such situations is based on their established immunomodulatory effects (Neunert et al., 2017).

Corticosteroids exert their therapeutic effect by inhibiting immune-mediated platelet destruction.

Corticosteroids suppress the immune response by reducing the production and activity of

inflammatory mediators, including cytokines and antibodies. This immunosuppressive effect can

help to decrease the destruction of platelets mediated by maternal alloantibodies. By reducing the

inflammatory response, corticosteroids create a more favorable environment for platelet survival.

However, in this particular case, the neonate demonstrated a favorable response to the combined

therapy of IVIG and platelet transfusions. The platelet count increased to a safe level, thus

eliminating the need to initiate corticosteroid therapy. The successful response to the initial

treatments suggests that the maternal antibody-mediated platelet destruction was effectively

controlled without the need for additional immunosuppression. This avoided the potential side

effects associated with corticosteroid use in neonates, which can include growth retardation,

increased risk of infections, and other adverse effects. Therefore, the decision to forgo

corticosteroid therapy was based on the successful response to the initial treatment strategy and

the avoidance of unnecessary immunosuppression.

NICU Admission and Supportive Care. NICU care provides immediate stabilization, close

monitoring, and targeted interventions to prevent life-threatening complications. The neonate's

admission to the neonatal intensive care unit (NICU) necessitated comprehensive supportive care

to address the physiological consequences of severe thrombocytopenia, including the risk of

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hemorrhage. Two key aspects of this supportive care were respiratory management and blood

pressure control.

Respiratory Management. The neonate experienced respiratory distress, necessitating the

initiation of continuous positive airway pressure (CPAP) to maintain adequate oxygenation. The

goal of CPAP therapy was to improve oxygen saturation (SpO2) levels, aiming for a target range

of 90-95%, while minimizing the risk of respiratory complications. The specific CPAP settings

(pressure level, flow rate) would be adjusted based on the neonate's clinical response, including

oxygen saturation, respiratory rate, and work of breathing. Regular monitoring of arterial blood

gases (ABGs) would provide an objective assessment of oxygenation and ventilation.

Blood Pressure Management. Maintaining stable blood pressure is paramount to minimize

the risk of intracranial hemorrhage (ICH). Fluctuations in blood pressure can disrupt cerebral

perfusion, increasing the risk of bleeding in a vulnerable neonate with thrombocytopenia

(Rajashekar & Liang, 2023). The goal of blood pressure management was to maintain cerebral

perfusion pressure (CPP) within a safe range, typically considered to be between 40-60 mmHg.

Close monitoring of blood pressure and clinical signs of ICH, such as altered level of

consciousness and bulging fontanelle, is crucial. Medications to support blood pressure, if

necessary, would be chosen based on the neonate's hemodynamic status and overall clinical

picture.

Long-Term Follow-Up and Management of FNAIT:

Following stabilization of the neonate's platelet count, continued neuroimaging assessment

is essential to monitor for the development of intracranial hemorrhage (ICH)-related complications

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and the persistence of thrombocytopenia. Given the neonate's diagnosis of ICH, neuroimaging, in

the form of cranial ultrasound or magnetic resonance imaging (MRI), was performed to assess the

extent of the hemorrhage and to evaluate for any associated complications. The importance of this

ongoing monitoring cannot be overstated, as ICH can lead to severe and potentially irreversible

neurological sequelae. The presence of ICH necessitates meticulous ongoing neurological

monitoring to detect potential complications such as seizures (requiring appropriate anticonvulsant

management), developmental delays (necessitating early intervention programs), and motor

deficits (potentially requiring physical therapy and rehabilitation). Early detection of these

complications is vital for optimizing neurodevelopmental outcomes (Espinoza et al., 2018). Most

patients can be managed without surgical interventions but in cases of severe ICH, neonates may

demand neurological procedures such as external ventricular drainage and/or ventriculoperitoneal

shunt/s (Huseynov et al., 2023). To determine the severity of the case, ultrasound or the use of

CT/MRI is needed to assess the extent of brain damage and guide future medical interventions

(Jain et al., 2021). The neonate, in this case, was discovered to be mildly affected by ICH thus,

there was no need for complicated medical treatment except for the need of platelet transfusions

to maintain and eventually increase the platelet count (De Vos et al., 2019).

Continuous platelet monitoring monitors the clearance of maternal alloantibodies and the

subsequent recovery of platelet production. This close monitoring is critical because the

persistence of thrombocytopenia beyond the expected resolution period might indicate ongoing

immune-mediated platelet destruction or other underlying conditions. The expected resolution of

thrombocytopenia, following the clearance of maternal antibodies, is generally within 2-4 weeks

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postpartum; however, this timeframe can vary (Sillers, Van Slambrouck, & Lapping-Carr, 2015).

Persistent thrombocytopenia beyond this period warrants further investigation and may necessitate

additional interventions, such as repeat IVIG administration or other supportive therapies as

clinically indicated.

Prophylactic measures are recommended to reduce the risk of bleeding in neonates with

FNAIT. Invasive procedures, such as circumcision, should be postponed until platelet levels reach

a safe threshold to prevent significant bleeding complications. Additionally, close monitoring for

signs of bleeding—including petechiae, purpura, hematomas, and occult bleeding—should be

maintained throughout the follow-up period. This proactive approach is essential in minimizing

morbidity and ensuring optimal patient outcomes.

Maternal Management for Future Pregnancies:

The high recurrence risk of fetal/neonatal alloimmune thrombocytopenia (FNAIT) in subsequent

pregnancies, estimated at 90% (Constantinescu, 2012), necessitates a proactive and

multidisciplinary approach to management. This approach involves meticulous prenatal

surveillance, targeted prophylactic therapies, and optimized delivery planning to minimize the risk

of severe complications in subsequent offspring.

Prenatal Surveillance and Risk Assessment. Early identification of at-risk pregnancies is

crucial. Maternal screening for anti-HPA-1a antibodies should be initiated early in subsequent

pregnancies, ideally before 12 weeks of gestation. The detection of these antibodies signifies a

heightened risk of FNAIT in the developing fetus. To confirm fetal involvement and quantify the

risk, fetal HPA genotyping is essential. This can be achieved using non-invasive prenatal testing

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(NIPT) analyzing cell-free fetal DNA (cffDNA) from maternal blood, offering a less invasive

alternative to amniocentesis (Kjaer et al., 2018). Amniocentesis, while providing definitive results,

carries a small risk of complications and should be reserved for cases where NIPT is inconclusive

or high-risk. The results of these tests inform the intensity and timing of prophylactic interventions.

Prophylactic Interventions. To mitigate the risk of fetal thrombocytopenia, prophylactic

treatment is often recommended. Intravenous immunoglobulin (IVIG) therapy, typically initiated

between 12 and 16 weeks of gestation if maternal anti-HPA-1a antibodies are present, plays a

central role in preventing fetal platelet destruction. The recommended dosage is 1-2 g/kg/week

(Giouleka et al., 2023). The rationale behind early initiation is to prevent the development of

significant fetal thrombocytopenia before it becomes clinically apparent. In some cases,

corticosteroids such as prednisone (0.5-1 mg/kg/day) may be added as an adjunct to IVIG,

particularly if fetal thrombocytopenia is suspected or if the maternal antibody titer is high

(Giouleka et al., 2023). The combined use of IVIG and corticosteroids aims to further suppress

maternal antibody activity, thereby reducing the risk of fetal platelet destruction. However, the

decision to use corticosteroids should be carefully weighed against potential adverse effects,

particularly in early pregnancy.

Optimized Delivery Planning. Given the increased risk of intracranial hemorrhage (ICH)

in neonates with FNAIT, a planned cesarean delivery at 36-38 weeks’ gestation is frequently

recommended. This approach aims to minimize the risk of birth trauma, which can exacerbate

bleeding complications. The timing of delivery balances the risks of prematurity with the risks

associated with continued antibody exposure and the potential for ICH. Close collaboration among

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a multidisciplinary team, including obstetricians, hematologists, neonatologists, and potentially

other specialists, is paramount for optimal management of these high-risk pregnancies and

subsequent neonatal care (Regan et al., 2019).

RECOMMENDATIONS

Current practices for managing fetal and neonatal alloimmune thrombocytopenia (FNAIT)

are largely reactive, with diagnosis often delayed until a term neonate presents with

thrombocytopenia. To improve early detection and intervention, a multifaceted approach

incorporating the following recommendations is crucial:

Implementation of Routine Maternal Screening for Anti-HPA Antibodies. Currently,

FNAIT is often not suspected until a term neonate presents with unexplained thrombocytopenia.

This delayed diagnosis necessitates a paradigm shift towards proactive screening. Implementing

routine maternal screening for anti-HPA antibodies (specifically anti-HPA-1a, the most common

cause of FNAIT) in women identified as high-risk would significantly improve early diagnosis.

High-risk criteria should include women with a history of unexplained neonatal thrombocytopenia,

a prior pregnancy complicated by fetal intracranial hemorrhage (ICH), or a family history of

FNAIT. This targeted approach in high-risk populations would allow for the timely initiation of

prenatal management strategies, such as intravenous immunoglobulin (IVIG) therapy, reducing

the severity of thrombocytopenia and the risk of ICH.

Routine HPA-1a Genotyping and Risk Assessment. For mothers with a history of affected

pregnancies, genetic testing for fetal HPA-1a status using non-invasive methods such as cell-free

fetal DNA (cffDNA) analysis is recommended. This allows for precise identification of fetuses at

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high risk of developing severe FNAIT, guiding appropriate prenatal interventions (Nogués, 2020).

While challenges remain in reliably identifying fetal HPA-1a genotype due to the single nucleotide

polymorphism (SNP) between HPA-1a and HPA-1b alleles, advancements in technologies like

next-generation sequencing (NGS) and digital PCR offer improved sensitivity and accuracy for

early pregnancy assessment.

Enhanced Neonatal Monitoring. Neonates born to mothers with a history of FNAIT or

those identified as high-risk require close monitoring for thrombocytopenia and bleeding

complications, regardless of their apparent health at birth. This comprehensive monitoring strategy

includes Serial Platelet Counts. Routine platelet counts should be performed immediately after

birth and repeated as clinically indicated based on the initial platelet count and clinical findings.

Neonates presenting with a low platelet count warrants close observation and potentially further

interventions. Moreover, Cranial ultrasound must be performed as it is essential to detect

intracranial hemorrhage (ICH), a potentially life-threatening complication of FNAIT. The timing

of the ultrasound should be determined based on the clinical assessment of the neonate and the

results of the platelet count. Furthermore, meticulous clinical assessment for signs of bleeding,

including petechiae, purpura, mucosal bleeding, and hematomas, is crucial. Any evidence of

bleeding necessitates prompt evaluation and management. Lastly, a thorough neurological

examination is important to detect subtle neurological signs that may indicate ICH or other

complications. This should be performed regularly throughout the neonatal period. This

multifaceted approach to neonatal monitoring ensures early detection and management of

complications associated with FNAIT, improving neonatal outcomes.

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Standardized Prenatal Management Protocols. The development and implementation of

standardized protocols for prenatal management in subsequent pregnancies are vital. These

protocols should clearly outline indications for IVIG prophylaxis and/or corticosteroid therapy to

minimize fetal platelet destruction and optimize maternal and fetal outcomes. This approach

ensures consistent and evidence-based care across different healthcare settings. Women with a

history of FNAIT-affected pregnancies should receive prophylactic treatment in subsequent

pregnancies to reduce the risk of fetal platelet destruction. This may involve IVIG therapy

(typically 1-2 g/kg/week, starting ideally between 12-16 weeks gestation) and/or corticosteroids

(such as prednisone, 0.5-1 mg/kg/day) as clinically indicated. Standardized protocols for early

prenatal management should be developed to optimize maternal and fetal outcomes. The decision

to use corticosteroids should be made on a case-by-case basis, weighing the potential benefits

against potential risks.

Figure 14. Indications for IVIg (de Vos et al., 2020).

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PROGNOSIS

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of

severe neonatal thrombocytopenia. It is typically suspected in neonates presenting with bleeding

or severe, unexplained, and/or isolated postnatal thrombocytopenia. Although rare, FNAIT is a

potentially devastating condition and a leading cause of severe isolated thrombocytopenia and

intracranial hemorrhage in fetuses and term neonates. The most serious complication is intracranial

hemorrhage due to severe thrombocytopenia, which can result in death in approximately 10% of

cases or major neurological impairment in 20% of cases. This may lead to long-term consequences

such as cognitive and physical disabilities, blindness, and hydrocephalus. However, in the absence

of cerebral bleeding, FNAIT is a self-limiting and transient condition with an excellent prognosis,

as thrombocytopenia typically resolves within 2 to 6 weeks.

SUMMARY AND CONCLUSION

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is primarily caused by maternal

immunization against paternally inherited HPA, leading to the destruction of fetal platelets. It

represents a critical area in obstetric care that requires a thorough understanding and careful

clinical management. It is crucial to rule out other causes of thrombocytopenia, such as infections

or congenital disorders, by considering clinical history and conducting appropriate tests. Diagnosis

is often made after observing severe symptoms in the neonate, such as intracranial hemorrhage

(ICH). The condition typically presents with severe bleeding or low platelet counts shortly after

birth, making it critical to differentiate it from other hematological disorders.

FNAIT is a complex but manageable condition requiring careful diagnosis through

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maternal antibody screening, genetic testing, and specific assays. Understanding its

pathophysiology and ruling out alternative diagnoses are vital for effective management and

treatment, particularly in preventing severe complications like ICH in affected neonates. Early

identification and intervention can significantly improve outcomes for both the infant and future

pregnancies.

Despite its clinical significance, FNAIT remains an underdiagnosed condition that can

result in severe neonatal thrombocytopenia and life-threatening complications, including ICH. In

this case, postnatal management is crucial in stabilizing the neonate’s platelet levels and preventing

further hemorrhagic-related complications. Long-term follow-up and parental counseling are

essential to prepare for future pregnancies, given the high recurrence risk of FNAIT. Moving

forward, advancements in early screening, routine genetic testing, and standardized treatment

protocols will be key to improving outcomes for affected infants.

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REFERENCES

Baykara, O. (2024). Molecular basis and genetics of Coagulopathies. Comprehensive Hematology

and Stem Cell Research, 250–263. https://doi.org/10.1016/b978-0-443-15717-2.00033-0

Bennett, J. S. (2005). Structure and function of the platelet integrin IIb 3. Journal of Clinical

Investigation, 115(12), 3363–3369. https://doi.org/10.1172/jci26989

Bianchi, D. W., Crombleholme, T. M., D’Alton, M. E., & Malone, F. D. (2010). Intracranial

hemorrhage. In Fetology: Diagnosis and Management of the Fetal Patient (2nd ed.). essay,

McGraw-Hill Education. Retrieved February 24, 2025, from

https://obgyn.mhmedical.com/content.aspx?bookid=1306&sectionid=75204758#:~:text=

Factors%20that%20may%20place%20the,Koml%C3%B3si%20et%20al.%2C%202005).

Brojer, E., Husebekk, A., Dębska, M., Uhrynowska, M., Guz, K., Orzińska, A., Dębski, R., &

Maślanka, K. (2015). Fetal/neonatal alloimmune thrombocytopenia: Pathogenesis,

Diagnostics and prevention. Archivum Immunologiae et Therapiae Experimentalis, 64(4),

279–290. https://doi.org/10.1007/s00005-015-0371-9

Chen, Z. Y., Oswald, B. E., Sullivan, J. A., Dahmani, F. Z., Pasman, Y., Liu, Z., Chen, P., & Ni,

H. (2019). Platelet physiology and immunology: pathogenesis and treatment of classical

and non-classical fetal and neonatal alloimmune thrombocytopenia. Annals of Blood, 4,

29–29. https://doi.org/10.21037/aob.2019.12.04

Constantinescu, S., Zamfirescu, V., & Vladareanu, P. R. (2012). Fetal and neonatal alloimmune

thrombocytopenia. Maedica, 7(4), 372–376.

47
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

Curley, A., Stanworth, S. J., Willoughby, K., Fustolo-Gunnink, S. F., Venkatesh, V.,

Hudson, C., Deary, A., Hodge, R., Hopkins, V., Santamaria, B. L., Mora, A., Llewelyn, C.,

D’Amore, A., Khan, R., Onland, W., Lopriore, E., Fijnvandraat, K., New, H., Clarke, P.,

& Watts, T. (2018). Randomized trial of Platelet-Transfusion thresholds in neonates. New

England Journal of Medicine, 380(3), 242–251. https://doi.org/10.1056/nejmoa1807320

de Vos, T.W., Winkelhorst, D., de Haas, M., Lopriore, E., & Oepkes, D. (2020). Epidemiology

and management of fetal and neonatal alloimmune thrombocytopenia. Transfusion and

Apheresis Science, 59(1), 102704. https://doi.org/10.1016/j.transci.2019.102704

de Vos, T. W., Porcelijn, L., Hofstede‐van Egmond, S., Pajkrt, E., Oepkes, D., Lopriore, E., van

der Schoot, C. E., Winkelhorst, D., & de Haas, M. (2021). Clinical characteristics of human

platelet antigen (HPA)‐1a and HPA‐5B alloimmunised pregnancies and the association

between platelet HPA‐5B antibodies and symptomatic fetal neonatal alloimmune

thrombocytopenia. British Journal of Haematology, 195(4), 595–603.

https://doi.org/10.1111/bjh.17731

Espinoza, J. P., Caradeux, J., Norwitz, E. R., & Illanes, S. E. (2013). Fetal and neonatal

alloimmune thrombocytopenia. Reviews in obstetrics & gynecology, 6(1), e15–e21.

Garraud, O., & Chiaroni, J. (2022). An overview of red blood cell and platelet alloimmunisation

in transfusion. Transfusion Clinique et Biologique, 29(4), 297–306.

https://doi.org/10.1016/j.tracli.2022.08.140

48
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

Huseynov, O., Huisman, T., Hassan, A., & Huseynova, R. (2023). Intracranial Hemorrhage

in Neonates: Causes, Diagnosis, and Management. Newborn, 3(2), 111–123.

https://www.newbornjournal.org/abstractArticleContentBrowse/JNB/36327/JPJ/fullText

Jaan, A., & Rajnik, M. (2021). TORCH Complex. PubMed; StatPearls Publishing.

https://www.ncbi.nlm.nih.gov/books/NBK560528/

Jain, A., Malhotra, A., & Payabvash, S. (2021). Imaging of spontaneous intracerebral

hemorrhage. Neuroimaging Clinics of North America, 31(2), 193–203.

https://doi.org/10.1016/j.nic.2021.02.003

Jens Kjeldsen-Kragh, Fergusson, D. A., Kjaer, M., Lieberman, L., Greinacher, A., Murphy, M. F.,

Bussel, J., Tamam Bakchoul, Corke, S., Bertrand, G., Oepkes, D., Baker, J. M., Hume, H.,

Massey, E., Kaplan, C., Arnold, D. M., Shoma Baidya, Ryan, G., Savoia, H. F., & Landry,

D. (2020). Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of

HLA-DRB3*01:01 on fetal/neonatal outcome. Blood Advances, 4(14), 3368–3377.

https://doi.org/10.1182/bloodadvances.2020002137

Kashyap, R., Garg, A., & Pradhan, M. (2021). Maternal and Fetal Outcomes of Pregnancy in

Patients with Immune Thrombocytopenia. Journal of obstetrics and gynaecology of India,

71(2), 124–130. https://doi.org/10.1007/s13224-020-01390-w

Khalid, F., & Tonismae, T. (2023, July 29). HELLP Syndrome. PubMed; StatPearls Publishing.

https://www.ncbi.nlm.nih.gov/books/NBK560615/

49
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

Kjær, M., Geisen, C., Akkök, Ç. A., Wikman, A., Sachs, U., Bussel, J. B., Nielsen, K., Walles, K.,

Curtis, B. R., Vidarsson, G., Järås, K., & Skogen, B. (2020). Strategies to develop a

prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune

thrombocytopenia. Transfusion and Apheresis Science, 59(1), 102712.

https://doi.org/10.1016/j.transci.2019.102712

Kjeldsen-Kragh, J., & Ahlen, M. T. (2020). Foetal and neonatal alloimmune thrombocytopenia -

The role of the HLA-DRB3*01:01 allele for HPA-1a-immunisation and foetal/neonatal

outcome. Transfusion and apheresis science : official journal of the World Apheresis

Association : official journal of the European Society for Haemapheresis, 59(1), 102707.

https://doi.org/10.1016/j.transci.2019.102707

Kjeldsen-Kragh, J., & Bengtsson, J. (2020). Fetal and neonatal alloimmune thrombocytopenia—

new prospects for fetal risk assessment of HPA-1A–negative pregnant women. Transfusion

Medicine Reviews, 34(4), 270–276. https://doi.org/10.1016/j.tmrv.2020.09.004

Kjeldsen-Kragh, J., Titze, T. L., Lie, B. A., Vaage, J. T., & Kjær, M. (2019). HLA-DRB3*01:01

exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a-immunized

women. Blood advances, 3(7), 945–951.

https://doi.org/10.1182/bloodadvances.2019032227

McGuinn, C., & Bussel, J. B. (2021). Disorders of platelets. In Elsevier eBooks (pp. 237–

285). https://doi.org/10.1016/b978-0-12-821671-2.00016-7

Nall, R. (2019, August 2). What you should know about lethargy. Healthline.

https://www.healthline.com/health/lethargy

50
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

National Organization for Rare Disorders. (2023, November 20). Fetal and neonatal alloimmune

thrombocytopenia - symptoms, causes, treatment. https://rarediseases.org/rare-

diseases/fetal-and-neonatal-alloimmune-thrombocytopenia/

Ni, H. (2013). Fetal and Neonatal Alloimmune Thrombocytopenia: Lessons Learned from Animal

Models. Blood, 122(21), SCI-50-SCI-50. https://doi.org/10.1182/blood.v122.21.sci-

50.sci-50

Nogués N. (2020). Recent advances in non-invasive fetal HPA-1a typing. Transfusion and

apheresis science : official journal of the World Apheresis Association : official journal of

the European Society for Haemapheresis, 59(1), 102708.

https://doi.org/10.1016/j.transci.2019.102708

Nowak, I., Kubiak-Prałat, W., Minta, M., Szymankiewicz, M., Gadzinowski, J., & Szpecht, D.

(2017). Alloimmunologiczna małopłytkowość noworodków. Acta Haematologica

Polonica, 48(2), 119–124. https://doi.org/10.1016/j.achaem.2017.01.004

Platelet alloimmunization is treated in the Comprehensive Fetal Center. (2023, August

11). Partners in Care. https://partnersincare.health/conditions/platelet-

alloimmunization#:~:text=On%20the%20surface%20of%20a,1a%20or%20HPA%2D1b).

Peterson, J. A., McFarland, J. G., Curtis, B. R., & Aster, R. H. (2013). Neonatal alloimmune

thrombocytopenia: pathogenesis, diagnosis and management. British Journal of

Haematology, 161(1), 3–14. https://doi.org/10.1111/bjh.12235

Pishko, A. M., & Marshall, A. L. (2022). Thrombocytopenia in pregnancy. Hematology, 2022(1),

303–311. https://doi.org/10.1182/hematology.2022000375

51
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

Pujari, A., Mukhija, R., Shashni, A., Obedulla, H., Meel, R., & Bajaj, M. (2018). Bilateral

hemorrhagic proptosis due to an uncommon cause in ocular emergency. Indian Journal of

Ophthalmology, 66(9), 1370. https://doi.org/10.4103/ijo.ijo_399_18

Sachs, U. J. (2020). Prospects for risk stratification of anti-hpa-1a alloimmunized pregnant women.

Transfusion and Apheresis Science, 59(1), 102709.

https://doi.org/10.1016/j.transci.2019.102709

Semple, J. W., & Kapur, R. (2022). Protecting the fetus from FNAIT. Blood, 140(20), 2097–2099.

https://doi.org/10.1182/blood.2022017937

Stam, W., Wachholz, G. E., de Pereda, J. M., Kapur, R., van der Schoot, E., & Margadant, C.

(2022). Fetal and neonatal alloimmune thrombocytopenia: Current pathophysiological

insights and perspectives for future diagnostics and treatment. Blood Reviews, 101038.

https://doi.org/10.1016/j.blre.2022.101038

Stanworth, S. J., & Shah, A. (2022). How I use platelet transfusions. Blood, 140(18), 1925–1936.

https://doi.org/10.1182/blood.2022016558

Steinweg, K., Nippita, T., Cistulli, P. A., & Bin, Y. S. (2020). Maternal and neonatal outcomes

associated with restless legs syndrome in pregnancy: A systematic review. Sleep Medicine

Reviews, 54, 101359. https://doi.org/10.1016/j.smrv.2020.101359

Tiller, H., Kamphuis, M. M., Flodmark, O., Papadogiannakis, N., David, A. L., Sainio, S.,

Koskinen, S., Javela, K., Wikman, A. T., Kekomaki, R., Kanhai, H. H., Oepkes, D.,

Husebekk, A., & Westgren, M. (2013). Fetal intracranial haemorrhages caused by fetal and

neonatal alloimmune thrombocytopenia: An observational cohort study of 43 cases from

52
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

an international multicentre registry. BMJ Open, 3(3). https://doi.org/10.1136/bmjopen-

2012-002490

Tiller, H., Husebekk, A., Ahlen, M. T., Stuge, T. B., & Skogen, B. (2017). Current perspectives

on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new

treatment opportunities. International Journal of Women’s Health, 9, 223–234.

https://doi.org/10.2147/IJWH.S90753

Tiller, H., Kamphuis, M. M., Flodmark, O., Papadogiannakis, N., David, A. L., Sainio, S.,

Koskinen, S., Javela, K., Wikman, A. T., Kekomaki, R., Kanhai, H. H. H., Oepkes, D.,

Husebekk, A., & Westgren, M. (2013). Fetal intracranial haemorrhages caused by fetal and

neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an

international multicentre registry. BMJ Open, 3(3), e002490.

https://doi.org/10.1136/bmjopen-2012-002490

Tirthani, E. (2024, May 1). Amegakaryocytic thrombocytopenia. StatPearls [Internet].

https://www.ncbi.nlm.nih.gov/books/NBK568795/

Vander Haar, E., Abshier Ware, C., Allen, G., Armstrong, R., Black, D., Bombara, M., Dhanraj,

D., Lawrence, L., Miller, R., Nanda, S., Paidas, M. J., Patki, K. C., Sitras, V., Skupski, D.,

Swarup, M., Thorp, J., Tiller, H., Verweij, J., & Bussel, J. B. (2023). Identifying

Pregnancies at Higher Risk for HPA-1a Alloimmunization and Fetal/Neonatal

Alloimmune Thrombocytopenia (FNAIT): An International, Prospective, Natural History

Study. Blood, 142(Supplement 1), 1224–1224. https://doi.org/10.1182/blood-2023-

177657

53
 Colegio San Agustin-Bacolod
College of Health and Allied Professions
Medical Technology Program

Winkelhorst, D., Oepkes, D., & Lopriore, E. (2017). Fetal and neonatal alloimmune

thrombocytopenia: Evidence based antenatal and Postnatal Management Strategies. Expert

Review of Hematology, 10(8), 729–737. https://doi.org/10.1080/17474086.2017.1346471

Wolf, E. K. (2024, November 26). What is FNAIT? Fetal Health Foundation.

https://www.fetalhealthfoundation.org/blogs/what-is-fnait/

Zhi, H., Ahlen, M. T., Skogen, B., Newman, D. K., & Newman, P. J. (2021). Preclinical evaluation

of immunotherapeutic regimens for fetal/neonatal alloimmune thrombocytopenia. Blood

Advances, 5(18), 3552–3562. https://doi.org/10.1182/bloodadvances.2021004371

Zhi, H., Sheridan, D., Newman, D. K., & Newman, P. J. (2022). Prophylactic

administration of HPA-1a–specific antibodies prevents fetal/neonatal alloimmune

thrombocytopenia in mice. Blood, 140(20), 2146–2153.

https://doi.org/10.1182/blood.2022015666

Zoltán Szittner, Arthur, A. Robin Temming, Schmidt, D. E., Visser, R., Lissenberg-Thunnissen,

S., Mok, J. Y., Esch, van, Sonneveld, M. E., Erik, Manfred Wuhrer, Leendert Porcelijn,

Haas, M. de, Ellen, & Gestur Vidarsson. (2023). Cellular surface plasmon resonance-based

detection of anti-HPA-1a antibody glycosylation in fetal and neonatal alloimmune

thrombocytopenia. Frontiers in Immunology, 14.

https://doi.org/10.3389/fimmu.2023.1225603

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