Rhesus disease

  • Rh according to Fischer and Race:
    6 antigens: C, D, E, c, d, e
    inheritage with separate genes
    antigen „d” is not detectable in serologic tests – no antibodies exist
  • First blood cells - blood production in yolk sac in 2 weeks old embryo
  • at 35th day of fetal life – liver erythropoesis
  • Bone marrow at 5 weeks.
  • Marrow erythropoesis from 
17 weeks.
  • IgG placental transportation 
by pinocytosis from 18 weeks
  • Immunologic response:
    Primary – Ig M, weak, develops slowly, 8-9 weeks to 6 months after introducing antigen
    Secondary – Ig G, quick, strong expression

Risk of immunisation

Spontaneous miscarriage, Induced miscarriage
Ectopic pregnancy, Molar disease
Fetoreduction, Amniocentesis
Bleeding in 3rd trimester, Term delivery
Blood transfusion (55-80%)

Immunisation mechanisms not related to pregnancy

heterohemotherapy
transfusion of incompatible blood
DRUGS

Prophylaxis

2015 recommendations

  • Anti-RhD immunoglobulin should be given to every Rh-negative woman up to 72 hours after:
    -giving birth to Rh-positive child
    150μg afte normal delivery
    300μg after pathological delivery
    -spontaneous miscarriage, pregnancy termination
    -invasive prenatal diagnosis (amniocentesis, cordocentesis, chorion villus sampling)
    -ectopic pregnancy removal
    -threatening miscarriage or preterm delivery with bleeding,
    -after external version: 50μg up to 20 weeks, 150μg after 20 weeks

2018 recommendations

  • in cases of complete spontaneous miscarriage below 12 weeks (without curettage), without heavy pain, immunoglobulin is not administered, gestational age should be confirmed by ultrasound
  • in recurrent bleeding immunoglobulin administration every 6 weeks should be considered
  • Prenatal prophylaxis:
    300μg of anti-RhD immunoglobulin should be administered at 28-30 weeks to every Rh-negative pregnant woman who has no anti-RhD antibodies

Rhesus disease prophylaxis

  • limited hemotherapy,
  • anti-RhD immunoglobulinę after exposition to risk factors (150-300μg),
  • anti-RhD immunoglobuline at 28-30 weeks (250-300μg).

Diagnosis

  • Assessment of antibodies titer during pregnancy – at the beginning pf pregnancy, if negative, repeated bewteen 2nd and 3rd trimester, if positive, repeated every 4 weeks (>1:16 – every 2 weeks)
  • Ultrasound scan, Fetal blood lab work
  • Amniocentesis, Cordocentesis

ultrasound

Doppler

Severe Rhesus disease

  • Flow speed in cerebral vessels is increased in fetuses with anemia in correlation to severity of anemia.
  • For every pregnancy week median value of Middle Cerebral Artery Peak Systolic Volume is established. MCA PSV >1.5 multiple of median qualifies fetuses to invasive diagnosis.

hepatomegaly, hyperplacentosis
umbilical vein dilatation, mild ascites
hydrothorax, hydropericardium, ascites
skin edema, cardiomegaly

Natural history (the most frequent)

Polyhydramnios

Hyperplacentosis

  • In the 3rd trimester plcental thickness is less than 4.5 cm. Placenta has monoechogenic, granular structure.
  • In pregnancy with fetal anemia placental 2nd and 3rd Gennum stage is not observed.

Splenomegaly

Difficult ultrasound assessment during pregnancy – no gas in fetal bowels

Hepatomegaly

Lower margin is below half of the abdominal cavity (from heart base to the base of urinary bladder)
When urinary bladder is full sometimes it is compressed by the enlarged right lobe

Umbilical vein dilatation

! >10mm in 3rd trimester
! Intrahepatic part measurement

Cardiomegaly

Increased dimensions of both atriums and ventricles
Heart area\thorax area = 1\3

Ascites

Mild – small amount among bowels
Moderate – hypoechogenic echo around liver
Severe – moves diaphragm upwards, freely moving greater omentum

Skin edema

Limbs, Scull skin, Abdominal wall
Don’t measure on the back of the fetus

Hydrothorax

Symmetrical, usually relatively small fluid collections between thoracic wall and lungs

Pericardial effusion

Thin fluid layer around ventricles
Best visibility in transverse section on the level of apex of the heart

Invasive diagnosis

Severe hemolytic disease

  • Severe anemia (MCA PSV >1.5 MoM)
  • Hydrops
  • Positive obstetric history:
    Severe anemia in the neonate
    Exchange transfusions
    Intrauterine fetal therapy
    Fetal/neonatal hydrops
    Intrauterine death
  • Antibodies titer >1:32 (1:16). Antibodies titer correlates with disease severity only during first pregnancy
  • Lower antibodies titer but ultrasound symptoms of fetal hemolytic disease

Cordocentesis, fetal umbilical vein blood tests:

fetal blood group,
antibodies titer,
Ht, Hb, E,
bilirubin,
albumins,
pHmetry

treatment

  • maternal plasmapheresis: (1000-1500 ml/week),
  • gammaglobulin i.v.: (ut to 2 g/kg/set),
  • transfusions:
    intraperitoeal,
    intravenous (therapeutic crodcentesis)