1. Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
Christine Wheeler, MD
Transfusion Medicine Fellow

2. Overview
Neonatal alloimmune thrombocytopenia (NAIT): most common etiology of severe thrombocytopenia and intracranial hemorrhage in term neonates
Incidence: 1/1000 live births

3. Pathophysiology
Incompatibility between mother and fetus for human platelet antigens (HPAs)
Fetus inherits a platelet antigen from the father, which the mother does not possess and to which the mother becomes immunized
Human platelet antigens (HPAs) are located on platelet membrane glycoproteins: GPIb-V-IX (von Willebrand receptor), GPIIb/IIIa (fibrinogen receptor), GPIa/IIa ( a collagen receptor) and CD109

4. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. British Journal of Haematology 2013;161(1):3-14.

5. Alloimmunization to HPA Antigens
Six bi-allelic platelet alloantigen systems are responsible for the majority of cases of NAIT due to platelet-specific alloantibodies: HPA-1, -2, -3, -4, -5 and -15 (a: high frequency allele, b: low frequency allele)
Caucasians and Africans: 80-85% of cases due to anti-HPA-1a (2.5% of mothers are HPA-1a negative)
Other platelet antigens more frequently implicated in NAIT:
- HPA-5b: 8-15%
- HPA-1b: 1-4%
- HPA-3a: 1-2%
- HPA-5a: about 1%
- HPA-15b: 4%

6. Alloimmunization to HPA-1a
Presence of the DRB3*0101 allele increases immunization risk: this allele is important in the presentation of the HPA-1a peptide in antibody production
Women with the DRB3*0101 allele generate more than 90% of HPA-1a antibodies
10% of HPA-1b1b mothers with an HPA-1a fetus produce anti-HPA-1a
30% of fetuses associated with HPA-1a alloimmunized pregnancies have severe thrombocytopenia (<50,000/mcL)

7. Alloimmunization to HPA Antigens
Low-frequency antigens (HPA-6b to -14b and HPA-16b) may also be involved
Asians: alloimmunization to HPA-4b, -6b and - 21b occurs more frequently than in Caucasians

8. Alloimmunization to Glycoprotein IV
Glycoprotein IV (CD36, Nak) is a class B scavenger receptor protein
Approximately 5% of Africans and Asians lack CD36 expression and can become immunized if exposed to CD36 by pregnancy or transfusion
FNAIT can be caused by maternal alloimmunization to CD36

9. Alloimmunization to HLA Antigens
Class I HLA antigens are present on platelets
Alloimmunization to class I HLA antigens is present in one third of multiparous women
Infants born to these alloimmunized women usually have normal platelet counts
One study did not demonstrate correlation between the presence or absence of HLA antibodies and neonatal platelet counts
There are reports of apparent FNAIT possibly due to HLA antibodies
It is possible that high titer HLA antibodies or antibodies directed against potent HLA antigens may cause FNAIT

10. Case Study: NAIT Due to HLA Antibodies?
Term (39 weeks), small for gestational age, O positive male born of a 24 year old G1P0 (now P1) O positive female by normal spontaneous vaginal delivery: meconium stained amniotic fluid, Apgar scores 8/9
Baby was thrombocytopenic (platelet count <9000/mcL, repeat 2 hours later without platelet transfusion was 46,000/mcL)
No evidence of bleeding including no intracerebral bleed identified on imaging study
24 mL of platelets transfused: platelet count 55,000/mcL (6 hours after issue); platelet count 87,000/mcL (20 hours later) with a subsequent fall to 64,000/mcL (12 hours later)

11. Case Study: NAIT Due to HLA Antibodies?
Bonfils Blood Center was informed that NAIT was in the differential diagnosis and that maternal platelets might need to be collected by apheresis
Requested blood sample from the mother to evaluate for the presence of anti-platelet antibodies

12. Case Study: PakPlus Results
No antibodies to GPIIb/IIIa (HPA-1a/1a, HPA- 3a/3a, HPA-4a/, HPA-1b/1b, HPA-3b/3b), GPIa/IIa (HPA-5a/5a, HPA-5b/5b), GPIb/IX or GPIV detected
Antibodies to Class I HLA antigens (HLA-A -B) detected: mother had history of VSD repair before age 10 years

13. Case Study: HLA Antibody Specificity
Clinimmune Laboratory performed Luminex Single Ag HLA Class I test to determine HLA antibody specificity.
Defined specificities: A25, A26, A33, A34, A66, A68, A69, B27, B38, B63, Cw1, Cw14
Tentative specificities: A29, A31, A32, A43, A74, B8, B39, B46, B73, B2708, Cw8, Cw9, Cw10

14. Case Study: NAIT Due to HLA Antibodies?
Follow-up information indicated thrombocytopenia not likely due to NAIT
Hypoglycemia, leukopenia/neutropenia, and coagulopathy (decreased fibrinogen, elevated PT/INR/ PTT/D-dimers) present : cryoprecipitate and FFP transfused, vitamin K given; blood cultures negative at time of transfer
Liver dysfunction with decreased albumin and hyperammonemia present: abdominal ultrasound and CT scan demonstrated multiple congenital extrahepatic porto- systemic shunts with abnormal portal venous and hepatic venous connections
Transferred to Colorado Children’s Hospital for further evaluation and treatment

15. Alloimmunization to ABO Antigens
Usually A and B antigens are weakly expressed on platelets
There is evidence that FNAIT can be caused by anti-A or anti-B if the baby has a high expression of the A or B antigen on his platelets and/or the mother has a high titer of IgG anti-A or anti-B
ABO blood group incompatibility: babies less likely to have severe FNAIT if mother is blood group O compared to blood group A

16. Pathophysiology
It is likely that immunizing antigen is present in maternal blood at weeks gestation: early intrauterine intracranial hemorrhage (ICH) can occur
HPAs are present on fetal platelets at 16 weeks gestation
Fetal platelet exposure may not be sufficient to explain alloimmunization: GPIIIa, which carries HPA-1a/1b and is present on the surface of villous syncytiotrophoblast, may be responsible for alloimmunization
FcRn (neonatal Fc receptor binding IgG to fetal platelets), present on syncytiotrophoblast, transports antibodies into the fetal circulation

17. Pathophysiology
FNAIT can occur in first incompatible pregnancies and there is a high recurrence rate
According to more recent data, most cases of maternal alloimmunization may result from exposure to fetal blood at or soon after birth
More severe FNAIT tends to occur in subsequent pregnancies

18. Differential Diagnosis of Neonatal Thrombocytopenia
Infection (such as toxoplasma, HIV, herpes virus, CMV, gram negative sepsis)
Abnormal clotting (DIC, thrombosis)
Perinatal hypoxic injury
Maternal conditions (such as ITP, maternal medications, diabetes mellitus, placental insufficiency)
Metabolic disease
Trisomy 13, 18 or 21
Prematurity
Vascular malformations (such as Kasabach-Merritt Syndrome)
Bone marrow infiltration (such as leukemia)
Familial thrombocytopenias

19. Differential Diagnosis
NAIT favored over other causes of thrombocytopenia: platelet count < 50,000/mcL during first 24 hours after birth or thrombocytopenia of unknown cause present in a well neonate with a non-thrombocytopenic mother
Neonates with NAIT can respond as well to random platelet transfusions as thrombocytopenic neonates without NAIT

20. Laboratory Diagnosis
Maternal and paternal platelet antigen genotyping on blood samples in order to determine presence of incompatibility
Fetal/neonatal platelet antigen genotyping is indicated if the father is heterozygous
Detection of maternal platelet alloantibodies in blood samples (platelet-specific, class I HLA)
Type paternal and maternal RBCs for ABO antigens

21. Diagnosis: Detection of Platelet Antigens
DNA-based methods are currently used
Allelic discrimination assays: 5’ fluorescently-labeled probes anneal to specific alleles
PCR-sequence-specific primer amplification using electrophoresis and DNA band visualization
PCR-RFLP (restriction fragment length polymorphism-PCR)
Evaluate for the presence of HPA-1 through 6, -9 and -15

22. Detection of Antibodies By Non-specific Tests: Flow Cytometry
Detects platelet-specific, HLA and blood group antibodies
Maternal serum is reacted against washed paternal and maternal platelets and platelets from group O donors with common HPA antigens
Can detect labile and low density antigens
Specific antibody target not identified
Both IgG and IgM can be identified
Sensitivity is high

23. Detection of Antibodies by Specific Solid Phase Assays
Determine the specific glycoprotein to which the maternal alloantibody is directed: purified platelet glycoproteins are immobilized in these tests
- specificity to a particular antigen can be
identified (such as HPA-1a) since serum is
tested against a panel of typed platelets
Types of assays:
- MAIPA
- MACE
- ACE

24. Solid Phase Assays: MAIPA
MAIPA (monoclonal antibody immobilization of platelet antigens) performed in Europe and used to detect antibodies directed against HPA-15a and -15b (using fresh target platelets)
Sensitize target platelets with patient serum
Murine monoclonal antibody (MCA) attaches to target on platelet surface
Platelets washed and solubilized
Supernatant lysate, after centrifugation, is added to wells in a microtiter tray with immobilized goat antibody specific for mouse IgG
Goat antibody attaches to MCA with bound human antibody
Human antibody detected by enzyme labeled goat anti- human immunoglobulin

25. Solid Phase Assays
MACE (modified antigen capture enzyme- linked immunosorbent assay): detects antibodies reactive with antigens on GPIIb/IIIa and GPIa/IIa
ACE (antigen capture ELISA): detects antibodies reactive with antigens on GPIb/IX, the carrier for HPA 2a/b and GPIV, as well as antibodies reactive with class I HLA antigens
PakPlus: an example of an antigen capture ELISA

26. Laboratory Diagnosis: MACE (From McFarland JG
Laboratory Diagnosis: MACE (From McFarland JG. Detection and identification of platelet antibodies in clinical disorders. Transfusion and Apheresis Science 2003;28: )

27. Solid Phase Assays: Fluorescently Labeled Bead-based Assays
Platelet antigens attached to fluorescently labeled beads
Can detect antibodies to low frequency antigens
More sensitive, easier to perform and more expensive than ELISA

28. Solid Phase Assays
Advantages: specific for platelet glycoproteins or Class I HLA antigens
Disadvantages: technically demanding, panels of typed platelets

29. Diagnosis: Interpretation of Test Results
HPA antibody may be present: maternal IgG reacts with paternal and normal panel platelets but not with maternal platelets; no HLA antibodies are detected
Antibody directed against a low frequency HPA antigen or against A1 or B may be present: maternal serum reacts with paternal platelets but not with platelets in the normal panel

30. Diagnosis: Interpretation of Test Results
DNA analysis can be used to identify low frequency antigens on paternal platelets
Testing for alloimmunization due to A1 or B when parents have incompatible blood types:
- identify fathers who are high expressers of A1
or B: test paternal platelets with monoclonal
antibodies directed against A1 or B and compare
reaction strengths with normals
- absorb maternal serum with A1 or B red cells; if
reactivity with paternal platelets is gone, ABO
incompatibility is assumed

31. Laboratory Diagnosis: No Anti-HPA Antibody Detected
Current assays may not detect all alloantibodies directed against HPA-3a and -3b
Low avidity HPA antibodies are not detected by standard assays in which the target antigen is washed
- these low avidity antibodies can be
detected by a technically demanding
technique, surface plasmon resonance
(SPR)
- these low avidity antibodies are pathogenic:
the antibodies destroy human platelets in a
mouse model

32. Laboratory Diagnosis
Parents incompatible for platelet antigens, no maternal anti-platelet antibodies detected:
- FNAIT may still be present if there is clinical
suspicion
- repeat test for maternal anti-platelet
antibodies at 6-9 weeks after delivery

33. Clinical Presentation: Neonate
Typically the first newborn affected with NAIT in a family presents with bleeding and thrombocytopenia or severe unexplained thrombocytopenia at or soon after birth
ICH can occur hours after birth

34. Clinical Presentation
No bleeding
Petechiae
Hematomas
Gastrointestinal bleeding
Hemoptysis
Hematuria
Retinal hemorrhage
Intracranial hemorrhage (ICH)

35. Clinical Presentation: Intracranial Hemorrhage
Neonatal: 15% of neonates with platelet counts less than 50,000/mcL with HPA-1a NAIT develop ICH with an associated mortality of 10%-15%
Antenatal (up to 80% of cases): can occur as early as weeks; 42% occur prior to 30 weeks
79% risk of ICH in a subsequent pregnancy if previous pregnancy had ICH or intrauterine fetal demise
Significant neurologic sequelae of ICH: hydrocephalus, seizures, blindness, brainstem atrophy, poor neurologic development

36. Clinical Presentation: Antibody Specificities and Bleeding
Anti-HPA-5b (compared with anti-HPA-1a)
- milder bleeding
- nadir platelet counts < 30,000/mcL are
less frequent
- bleeding occurs at higher platelet counts
HPA-1a is expressed on endothelial cells and anti-HPA-1a may disrupt intercellular connections with consequent bleeding
Antibodies against GP IIb/IIIa and GP Ia/IIa may cause platelet dysfunction

37. Clinical Presentation: Neonate
Without treatment, thrombocytopenia usually resolves in the first two weeks after delivery
Thrombocytopenia may persist for several months

38. Management of NAIT in Neonates: Transfusion Trigger
No bleeding, platelet count > 50,000/mcL: observe
Transfusion trigger for well term neonate varied among Canadian neonatologists : 20,000 to 50,000/mcL
Other expert opinion is to maintain platelet count as follows:
- well term neonates: >30,000/mcL
- bleeding risk factors: > 50,000/mcL
- ICH/other bleeding: > 100,000/mcL

39. Management of NAIT in Neonates: Platelet Transfusions
If HPA-typed platelets are unavailable, random donor platelets (ABO compatible, volume reduced if needed, irradiated, cytomegalovirus negative) can lead to an increase in platelet counts to > 40,000/mcL and can reduce the risk of bleeding
In one study, transfusion with random donor platelets led to lower mean platelet increments and shorter platelet survival compared with HPA-typed platelets

40. Management of NAIT in Neonates: HPA-compatible Platelet Transfusions
Some blood centers can provide HPA-1b/1b platelets
Mother can provided antigen-negative platelets by apheresis
- remove antibody-containing plasma by
volume reduction and resuspend platelets
in normal saline or wash platelets in
normal saline or AB plasma
- irradiate platelets to prevent TAGVHD

41. Management of NAIT in Neonates: IVIG
British Committee for Standards in Haematology: keep platelet count > 30,000/mcL by transfusion with HPA-compatible platelets (10-20 mL/kg) and add high-dose IVIG
Other expert opinion: use IVIG adjunctively with platelet transfusions to increase platelet survival

42. Management of NAIT in Neonates: IVIG
Platelet count increases > 30,000/mcL occur at rates of 70-80% with the use of IVIG in some studies
Maximal effect of IVIG is reached at hours
Doses of IVIG:
- platelet count < 30,000/mcL:
g/kg/d for 2-5 days
- platelet count > 30,000/mcL and <
50,000/mcL without bleeding: total
dose of 2g/kg over 2-5 days

43. Management of Antenatal FNAIT
Maternal alloantibody previously detected
Determine fetal compatibility:
- determine paternal platelet genotype
- father homozygous for incompatible
antigen: all fetuses incompatible with
maternal alloantibody and at risk for
FNAIT
- father heterozygous for incompatible
antigen: fetus has 50% chance of possessing
incompatible antigen and need to genotype
fetal platelets

44. Managemant of Antenatal FNAIT: Genotyping of Fetal Platelets
Invasive methods:
- Amniotic fluid: weeks
- Chorionic villus tissue: 8-10 wks
Adverse effects of invasive methods:
premature labor, death in utero

45. Management of Antenatal FNAIT: Genotyping of Fetal Platelets
Non-invasive method:
- Cell-free fetal DNA extracted from maternal blood:
two assays based on real-time polymerase chain
reaction and screening for single nucleotide
polymorphisms provide reliable results as early as
15 weeks gestation
- Assays available for HPA-1aa and HPA-1bb women
and are being developed for HPA-5 and HPA-3
Limitations of non-invasive method:
- possible false-negative results due to low quantity of
fetal DNA extracted from maternal blood
- a fetal marker independent of fetal sex is needed

46. Management of Antenatal FNAIT
Approximation of degree of thrombocytopenia in incompatible fetuses helps determine risk of ICH
Invasive approach of PUBS (percutaneous umbilical blood sampling) to determine fetal platelet count and perform in utero platelet transfusions
- fetal loss of 1.3%/procedure and 5-
8%/pregnancy

47. Management of Antenatal FNAIT
Correlation between strength of maternal alloantibody and degree of fetal thrombocytopenia is uncertain:
- some studies identified an approximately inverse
relationship between maternal antibody strength
and neonatal platelet count
- in one study, an anti-HPA-1a antibody level >3.0
IU/mL at 22 or 34 weeks had a positive predictive
value of 54% and a negative predictive value of 95%
for severe thrombocytopenia
Maternal alloantibody levels decrease throughout gestation and highest antibody levels occur up to 6 weeks after delivery

48. Management of Antenatal FNAIT
Antenatal management is controversial
Currently a more conservative approach without invasive procedures is favored: maternal IVIG and/or corticosteroids
Degree of fetal thrombocytopenia and risk of ICH can be reduced by the use of high dose IVIG (with or without corticosteroids)
Studies indicate a tendency to higher neonatal platelet counts with a combination of IVIG and corticosteroids but with no significant decrease in ICH risk

49. Management of Antenatal FNAIT: Cochrane Review 2011 (Raymant R, et al)
Most evidence for antenatal therapy in FNAIT is from observational studies
Objective of review: “determine the optimal antenatal treatment of fetomaternal alloimmune thrombocytopenia to prevent fetal and neonatal haemorrhage and death”
Evaluated randomized clinical trials comparing an intervention with no therapy or comparing two interventions: four studies met criteria with one trial comparing IVIG with corticosteroid and three trials comparing IVIG and corticosteroid with only IVIG

50. Management of Antenatal FNAIT: Cochrane Review (Raymant R, et al)
Conclusion: best antenatal treatment for FNAIT unclear; more studies needed
Stratified treatment based on sibling history appears to be safe
IVIG or prednisone (optimal doses unknown): first- line therapy when pre-treatment fetal platelet count > 20,000/mcL and previously affected sibling had no peripartum hemorrhage
IVIG plus prednisone superior to IVIG alone in raising platelet count when pre-treatment fetal platelet count < 20,000/mcL or sibling had peripartum hemorrhage (optimal doses and timing unclear)

51. Management of Antenatal FNAIT: Treatment Algorithm
FNAIT severity in current pregnancy dependent on presence and time of occurrence of antenatal ICH in previous pregnancy: ICH occurring in early pregnancy predicts severe disease in the next pregnancy
Pacheco et al have developed a treatment algorithm using IVIG and prednisone based on risk (for ICH) stratification with four strata: no fetal blood sampling performed
One study demonstrated that the use of IVIG in subsequent pregnancies reduced the risk of recurrence of ICH from 79% to 11%

52. Management of Antenatal FNAIT Treatment Algorithm: Stratum 1
Thrombocytopenia or ICH of unknown cause in prior fetus/neonate
No HPA antibody identified: paternal incompatibility for HPAs may have been determined
Unknown risk for ICH in current pregnancy
Treatment: serial monitoring for presence of maternal anti-HPA antibodies during gestation; no treatment unless an HPA antibody is found or there is high clinical suspicion for FNAIT without detectable antibody

53. Management of Antenatal FNAIT Treatment Algorithm: Stratum 2
Fetus in current pregnancy positive for incompatible antigen
Serologically confirmed FNAIT in prior fetus/neonate with thrombocytopenia but no ICH
Standard risk for ICH in current pregnancy
Treatment:
- start treatment at 20 weeks with IVIG
1g/kg/week and prednisone 0.5mg/kg/day or
IVIG 2g/kg/week
- at 32 weeks escalate therapy to IVIG
2g/kg/week and prednisone 0.5 mg/kg/day
- deliver by Caesarean section at weeks

54. Management of Antenatal FNAIT Treatment Algorithm: Stratum 3
Fetus in current pregnancy positive for incompatible antigen
Serologically confirmed FNAIT in a prior fetus/neonate with ICH at > 28 weeks gestation
High risk of ICH in current pregnancy
Treatment:
- start treatment at 12 weeks gestation with IVIG
1g/kg/week
-escalate therapy at 20 weeks: IVIG dose
doubled or prednisone 0.5 mg/kg/day added
- escalate therapy at 28 weeks: at this time the
treatment is IVIG 2g/kg/week and prednisone
0.5 mg/kg/day
- deliver by Caesarean section at weeks

55. Management of Antenatal FNAIT Treatment Algorithm: Stratum 4
Fetus in current pregnancy positive for incompatible antigen
Serologically confirmed FNAIT in prior fetus with ICH at < 28 weeks gestation
Very high risk of ICH in current pregnancy
Treatment:
- start treatment at 12 weeks with IVIG
2g/kg/week
- at 20 weeks, prednisone 1 mg/kg/day is added
- delivery by Caesarean section at weeks

56. Management of Antenatal FNAIT: Invasive Procedures
Fetal blood sampling (FBS) is performed to evaluate the fetal platelet count, transfuse platelets and monitor therapy
Intrauterine platelet transfusions for platelet counts < 50,000/mcL can be performed in babies unresponsive to IVIG and steroids

57. Management of Antenatal FNAIT: Invasive Procedures
Adverse effects:
- bleeding
- fetal cardiac arrhythmia
- contamination of amniotic fluid
- premature delivery
- fetal mortality
- maternal sensitization to incompatible antigen
may occur

58. Management of Antenatal FNAIT: Invasive Procedures
Procedures performed under ultrasound guidance
A blood sample from the umbilical vein at the cord insertion site is obtained
Platelet count and mean corpuscular red cell volume (MCV) are determined
MCV > 100 mcL favors fetal red cells rather than maternal red cells

59. Management of Antenatal FNAIT: Platelet Transfusions
Platelets to be transfused should be antigen- negative, irradiated and CMV safe.
HPA-1a-negative platelets can be provided by some blood suppliers
Platelets from the mother, obtained by apheresis hours before transfusion, can be used.
Incompatible platelets can be used in urgent situations.

60. Management of Antenatal FNAIT: Platelet Transfusions
A blood sample is obtained at the end of transfusion in order to evaluate the platelet count.
Platelet transfusions are performed weekly since the platelet life span is 8-10 days.
Delivery at 32 weeks gestation may be best if the baby is undergoing serial transfusions.
Antigen-negative platelets should be available at delivery.

61. Management of Antenatal FNAIT: Maternal Platelets
Infectious disease testing of the mother should occur several days before the platelet donation
Since IVIG may cause falsely positive infectious disease testing results, performing ID testing before initiation of IVIG will help to recognize false positive results
Platelets should be washed to remove antibody.

62. Management of Antenatal FNAIT: Volume of Platelet Transfusion
Volume transfused (mL) =
Fetoplacental volume (mL) x (target final-initial platelet count) x 2
Platelet count of transfused concentrate
Fetoplacental volume = ultrasound fetal weight (g) x 0.14
Factor of 2 in equation: sequestration of platelets in spleen or liver
Target final platelet count: 300, ,000/mcL, which enables a nadir platelet count of 30, ,000/mcL just before the next transfusion

63. Adverse Effects of Prednisone
Hypertension
Fluid retention
Hyperglycemia
Diabetes
Immunosuppression
Mood swings
Acne
Osteoporosis

64. Intravenous Immunoglobulin G (IVIG)
Different products (Gamunex, Privigen, Gammagard, Flebogamma, Octagam)
Usual infusion rate: 1 g/kg over 4-5 hours
Infusion rate of first infusion should be slower
First infusion should be in a hospital setting

65. IVIG
Adverse effects: headache, flushing, myalgias, low back pain, nausea, hypotension, wheezing, fever, chills; rare: aseptic meningitis, kidney injury, thrombosis, hemolytic anemia, stroke
Premedication: corticosteroids, acetaminophen, diphenhydramine; prednisone combined with acetaminophen may also help manage headaches
Hydration with intravenous fluids and slowing the infusion rate also help ameliorate reactions
Contraindications: IgA deficiency; anaphylactic or severe systemic reactions to human immunoglobulin/blood-derived products

66. Screening Programs to Detect HPA-1a Alloimmunization
Identify HPA-1a-alloimmunized women ( %) or women who are HPA-1a negative (>2%), and possibly DRB3*0101 positive (about 0.7% of pregnancies)
Serial screening of women at risk of antibody development during gestation
Disadvantages of screening programs: cost of IVIG, adverse effects of IVIG, adverse effects of prednisone used to treat the side effects of IVIG

67. Prophylactic Anti-HPA-1a Antibody Treatment of FNAIT
About 75% of women are immunized at the time of delivery
Results from a mouse study support the use of anti-HPA-1a given to non-immunized HPA-1a- negative women after delivery of an HPA-1a- positive child in the prevention of HPA-1a alloimmunization and FNAIT

68. Prophylactic Anti-HPA-1a Antibody Treatment of FNAIT: Source
Engineered monoclonal or recombinant antibodies:
- such antibodies may not be effective: efforts to
produce engineered anti-D antibodies to prevent
HDFN have not been successful
Polyclonal antibodies purified from immunized subjects:
- use pooled plasma from HPA-1a immunized
individuals
- FNAIT is rare with few immunized individuals
available: international efforts required

69. Prophylactic Anti-HPA-1a Antibody Treatment of FNAIT: Profnait Project
“Human platelet antigen-1a immunoglobulin” is an orphan drug designated by the European Commission in October, 2011
The drug will be developed by Prophylix Pharma AS
Four stages:
- collect 2000 L of plasma from HPA-1a-immunized
women
- produce drug
- phase I/II trial using healthy HPA-1a-negative
males
- phase III clinical trial treating nonimmunized HPA-
1a-negative women

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