Alloimmune Thrombocytopenia

Sokołowska MałgorzataPomorska Akademia Medyczna

Szczecin

Neonatal alloimmune thrombocytopenia(NAIT)

• This is the platelet equivalent of HDN• Thrombocytopenia is caused by immune destruction of fetal/neonatal platelets• IgG maternal HPA antibodies cross the placenta• Platelet destruction invariably starts before birth• Placental transfer stops at birth, but platelet destruction continues into neonatal life• Not recognised in the antenatal period in women not investigated before

NAT

Fetus inherits platelet antigens from father

Transplacental passage of fetal platelet antigens

Mother forms IgG alloAbs that cross placenta

Maternal alloAb react with fetal platelets

Neonatal Alloimmune Thrombocytopnia

Thrombocytopenia in a fetus or neonate caused by maternal antiplatelet alloantibodies, directed against a fetal platelet alloantigen, inherited from the father.

Definition:

Introduction

Maternalcirculation

Fetalcirculation

Placenta

platelet

IgG

IgG

IgG

platelet

ImmuneSystem

RecognizesAs foreign

1

2

3

Alloimmune thrombocytopenia

HPA alloimmunisation

1. Pregnancy

eg. HPA-1a neg mothercarrying HPA-1a posbaby cc

2. Blood Transfusioneg. HPA-1a neg personreceiving HPA-1a posblood transfusion

Antigen pos platelets enter person’s circulation

Production of platelet antibody (anti-HPA-1a)

Incidence AIT : Platelet count < 150,000ⅹ109/L

(1% of unselecte neonates) Severe : <50,000ⅹ109/L (25% of neonates with

thrombocytopenia) 1:1500 deliveries

NeonatalAlloimmuneThrombocytopenia

Most common cause of severe TCP in infant Most common cause of ICH in term

newborns First pregnancies, without warning Otherwise healthy babies

Pathophysiology

Definition : fetal/neonatal platelet count < 150ⅹ109/L maternal platelet alloantibodies

Manifestations Concentration of maternal IgG Density of the target antigen on the fetal

platelets Phagocytic activity Compensatory ability of the fetal bone marrow

Platelet surface antigen

HLA class I

HPA (human platelet antigen)

ABO antigen

Frequency of HPA-1a

Most common alloantigen in white population : HPA-1a 2nd common alloantigen: HPA-5b

Serologic frequency :

HPA-1a positive : 98%

HPA-1a negative : 2% In Asian : HPA-4b 1,7% (+)

HLA and immune response to HPA-1a

• There is a strong link between HLA-DRB3*0101(DR52a) & HPA-1a alloimmunisation

• In an HPA-1a neg, DRB3*0101 pos woman,

likelihood of anti-HPA-1a formation is 33%

• The chances of anti-HPA-1a developing in a woman negative for DRB3*0101 is < 1%

• This HLA Class II molecule seems to play an

important role in antigen presentation

Listen up!

They say, that the maternal platet count is normal and alloimmunization is not suspected until after the birth of the affected child.Even in the first affected infant , is frequently severe and usually develops before the third trimester. It can thus cause fetal intracranial hemorrhage, even as early as 20 weeks!!!!!!!!!!!!!!!!!!!!!!!!!

Clinical features of NAIT:

Mild disease: asymptomatic only sl. reduction of platelet count Moderate: superficial bleeding e.g.purpura, petechie, ecchymoses etc. Severe:platelet count <30-50x109/l internal bleeding intracranial haemorrhage (ICT)-cysts hydrocephalus & ventriculomegaly Mortality up to 14%

Clinical features

Laboratory Studies

Antiplatelet antibody testing PSIFT (Platelet Suspension

Immunofluorescence Test) MAIPA (Monoclonal Antibody Immobilization of

Platet Antigens)

Platelet antigen typing MAIPA ELISA DNA-based test (PCR-)SPP

Management of NAIT • Treatment is required for symptomatic &

severe cases • Should be started if there is strong clinical

suspicion Treatment of NAIT without waiting for

laboratory diagnosis • HPA compatible platelet transfusions (most

effective) • Intravenous immunoglobulin (IVIg) Steroids (dexamethasone, prednizone) Steroids / immunoglobulin iv • Cranial ultrasound for all severe cases

Management Medical

Iv immunoglobulin / steroids Surgical (favor in Europe)

Uterofetal platelet transfusion

Goal : Prevent antenatal / perinatal ICH ICH : mental retardation, fetal /neonatal death

Pre-natal management of cases with severe NAIT

• Most Fetal Medicine specialists start with

intravenous immunoglobulin (IVIg) injections to

mother from about 12 - 14 wk

• Dose: 1g/kg b.w. every week

• Around 20 - 22 wk, first fetal blood sampling

(FBS) and intrauterine transfusion (IUT) if

thrombocytopenic

• Repeat IUTs as necessary

Antenatal treatment (prevention) IVIg 1g/kg/wk (2g/kg/wk for refractory) IVIg + corticosteroids Intrauterine platelet transfusions Fetal blood sampling (FBS)

Future pregnancies

In a mother who has had an affected baby, thechances of having another affected child is high ifthe implicated Ag is inherited• Severe thrombocytopenia may occur as early as 20- 24 weeks of gestation• Chances of inheriting the paternal antigen dependson the zygosity of the father• Both parents should be counselled• All ‘at risk’ pregnancies should be managed inFMUs

Summary

• NAIT is a serious condition with significant morbidity & mortality (ICH: 11% {34/305}; Deaths : 7.2% {22/305})• Most cases are caused by anti-HPA-1a or anti-HPA-5b or both• In severe cases, treatment should be given ASAP before test results• There must be good communication between FMUs and local hospitals when known cases are referred for delivery• BB staff, Haematologist & Neonatal team must be alerted by the Obstetricians

NAT and HDNNAT HDN

Affected cells

Most common antigen

Affected pregnancy

Timing of sensitization

Affected Infant

Affected fetus

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen

Affected pregnancy

Timing of sensitization

Affected Infant

Affected fetus

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy

Timing of sensitization

Affected Infant

Affected fetus

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization

Affected Infant

Affected fetus

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant

Affected fetus

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant TCP, bleeding Hemolysis, jaundice, kernicterus

Affected fetus

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant TCP, bleeding Hemolysis, jaundice, kernicterus

Affected fetus ICH Hydrops fetalis

Main risk factor

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant TCP, bleeding Hemolysis, jaundice, kernicterus

Affected fetus ICH Hydrops fetalis

Main risk factor Previously affected infant Rh-negative mothers

Treatment

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant TCP, bleeding Hemolysis, jaundice, kernicterus

Affected fetus ICH Hydrops fetalis

Main risk factor Previously affected infant Rh-negative mothers

Treatment Supportive Supportive

Prevention

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant TCP, bleeding Hemolysis, jaundice, kernicterus

Affected fetus ICH Hydrops fetalis

Main risk factor Previously affected infant Rh-negative mothers

Treatment Supportive Supportive

Prevention IVIG Anti-D

Efficacy of prevention

NAT and HDNNAT HDN

Affected cells Platelets Red blood cells

Most common antigen HPA-1a Rh-D

Affected pregnancy First Second +

Timing of sensitization 16 weeks onwards At birth, or during a procedure

Affected Infant TCP, bleeding Hemolysis, jaundice, kernicterus

Affected fetus ICH Hydrops fetalis

Main risk factor Previously affected infant Rh-negative mothers

Treatment Supportive Supportive

Prevention IVIG Anti-D

Efficacy of prevention ? 99%

AIT

The diagnosis can be made on clinical grounds if the mother has normal platelet count and there is no evidence of any immunological disorder , and her infant has thrombocytopenia without evidence of other disease.

Recurs in 70-90 % of subsequent pregnancies,is ofen severe , and usually develops eariel in with each successive pregnancy.

AIT ( Isoimmune thrombocytopenia)

It is caused by maternal isoimmunisation to fetal platet antigens in a manner similar to D-antigen isoimmunization.

Thus , the maternal platet count is normal and alloimmunization is not suspected until after the birth of the affected child.

Even in the first affected infant , is frequentlysevere and usually develops before the third trimester.

It can thus cause fetal intracranial hemorrhage, even as early as 20 weeks

Questions?