Rhesus Isoimmunisation

Rhesus AlloimunisationRhesus (D) disease

Rhesus incompatibilityRh Haemolytic Disease of the Newborn

Outline

• Terminology• Pathophysiology• Causes/Risk factors• Management

Terminology

• Rhesus – refers to the Rhesus blood group system

• Isoimmunisation/alloimmunisation – production by an individual of antibodies against constituents of the tissues of another individual of the same species

• Erythroblastosis fetalis– Making of immature RBCs in the fetus due to

haemolysis• Hydrops fetalis

– Excessive accumulation of serous fluid in tissues or cavities of the body of the fetus

– Presents as edema in the fetus

ABO System

• Consists of 50 defined blood group antigens.• D, C, c, E, e most important; no d antigen• d refers to absence of D allele• Rh factor, Rh positive, Rh negative refer to D antigen ONLY

Putting both together…

Rh IgG is only present following sensitizing event

Taken from http://bloodcenter.stanford.edu/about_blood/blood_types.html

How sensitization occurs Haemolysis, anemia, and high output cardiac failure

Causes/Risk factors: sensitizing events1. Mismatched transfusion2. Transplacental transfer/FMH

• Child birth (86%)• Antepartum haemorrhage (e.g. threatened miscarriage)• Therapeutic abortion• Abdominal trauma• ECV• Ectopic pregnancy• Invasive antenatal testing (e.g. amniocentesis, CVS,

cordocentesis)• C-section

Management

Primary goal: PREVENTION1. Early detection – screening for Rhesus

grouping at the first bookingi. If mother is Rhesus negative, assess husband’s

Rhesus status + screen for Rh antibodiesii. If both mother and father are Rhesus negative,

there is little problem.iii. If the father is Rhesus positive, close supervision

is required

Management

2 scenarios:• Patients who are nonalloimmunised

(no antibodies)• Patients who are alloimmunised

(antibodies present)

1. Rh –ve, no antibodies• 4 weekly screening until 30 weeks• After that, 2 weekly screening until delivery• Prophylatic anti-D immunoglobulin at 28 and 32

weeks POG.

Anti-D is given ASAP in the following conditions:• Antenatal sensitizing events• After delivery

2. Rh –ve, with antibodies• Maternal serum antibodies dilution titers done

every 2 weeks• Antibodies titer at or below 1:16 unlikely to

cause serious fetal disease• Amniocentesis is indicated if titer more than 1:8

Assess bilirubin level using spectrophotometer. Optical density reflects degree of haemolysis plotted on Liley’s chart

• Fetal ultrasound to detect early ascites, Doppler for blood velocity (middle cerebral artery)

Optical density for bilirubin

Gestation in weeks

mild

moderate

severe

Liley’ chart for classifying the degree of hemolysis

• Mild region, no intervention needed, amniocentesis repeated in 2 weeks.

• Moderate or severe zones, intervention needed:i. Deliver the fetus; following that exchange

transfusion by Paediatricianii. Intrauterine transfusion – intravascular or

intraperitoneal (every 2 weeks up till 34-36 weeks)

iii. Plasma exchange of mothers for antibodies removal

Rho(D) Immune Globulin• Eligibility: Rhesus –ve mothers, no antibodies• Indication: Within 72 hours of any sensitizing event

in the pregnancy• Dosing regiment:

– 250 IU (50ug) for events before 20 weeks– 500 IU (100ug) IM at both 28 & 32 weeks' gestation and

postpartum within 72 hours of delivery * Kleihauer-Betke test on mother’s bld shows >1 fetal cell

per 500 adult red cells (= 4 – 5 ml of packed fetal red cells) Additional 150 IU of anti-D IgG is given for each ml of the transplacental bleed > 4 mls of packed fetal red cells.

MEDICAL DISORDERs IN PREGNANCY

JAUNDICE

Jaundice

• Yellow discolouration of sclera, skin and mucose membrane because of raised serum bilirubin.

• Normal: 3 – 17µmol/L• Detectable clinically

>35µmol/L

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Bilirubin pathway

Approach to jaundice in pregnany

• Similar to the non-pregnant.• Viral hepatitis and gallstones may also cause

jaundice in pregnancy.• History: blood transfusions, IVDU, body

piercing, tattoos, sexual activity, travel abroad, jaundiced contacts, family history, alcohol consumption, drug history

Investigations

• LFT• Coagulation profile• FBC• Renal profile• Viral screen (hepatitis A, B, and C, Epstein Barr and

cytomegalovirus)• Autoimmune screen

– anti-smooth muscle antibody (autoimmune hepatitis)– antimitochondrial antibodies (primary biliary cirrhosis)

• Ultrasound of the hepatobiliary system• UFEME

LFT in pregnancy

• For AST, ALT, GGT and bilirubin, the upper limit of normal throughout pregnancy is 20% lower than the non-pregnant range.

• The increase in ALP in pregnancy is usually placental in origin and so does not normally reflect liver disease.

• In normal pregnancy, LFTs may increase in the first 10 days of the puerperium.

Pregnancy-related causes• Intrahepatic cholestasis of pregnancy• Acute fatty liver of pregnancy• Pre-eclampsia a/w HELLP syndrome• Hyperemesis gravidarum

Non-pregnancy related• Other cause: acute viral hepatitis – most

common

Intrahepatic Cholestasis of Pregnancy

• Slowing or blockage of bile in small ducts of liver• Generally manifests in the 3rd trimester• Multifactorial:

– Genetic mutation in MDR3 gene– Hormonal factor – high estrogen level

• Symptoms: – Generalized pruritus, especially of palms and

soles, worse at night– Jaundice (10-25%), pale stool, dark urine– Others: abdominal pain, steatorrhea

• Investigations: Abnormal LFT. Liver transaminases mildly ↑ (<300 U/L) in 60%. Bilirubin ↑ in 25% (conjugated).

• Symptoms and abnormal LFT resolve after delivery.

• Management:– Measure LFTs weekly until delivery– Ursodeoxycholic acid (UDCA) – improve pruritus

and LFT– Cholestyramine – improve pruritus– If PT prolonged, give Vitamin K 10mg PO BD to the

mother, 1mg IM to the baby at birth– CTG daily– Aim for delivery at 37 weeks

Acute Fatty Liver of Pregnancy

• Rare but grave (incidence: 1:6600 – 13000 deliveries); mortality 90%

• Usually occur at late 3rd trimester (>35 wks)• Unknown aetiology• Risk factors: older maternal age, multiple

pregnancy, pre-eclampsia, male fetus, being underweight, and a history of AFLP

• Symptoms: nausea, vomiting, anorexia, lethargy, abdominal pain, ascites, and progressive jaundice

• Diagnosis: – Liver aminotransferase levels are moderately

elevated (typically 300-500 U/L)– High serum bilirubin – Hypoglycaemia, thrombocytopenia, coagulopathy,

uremia (RBS, FBC, PT/APTT, RFT)– Ultrasound scan of hepatobiliary system– Liver biopsy – diagnostic but rarely performed

• Complications: – Acute renal failure– Hepatic encephalopathy– DIVC– Coma and death– PPH– Neonatal hypoglycemia

• Management:– Continuous fetal monitoring – Supportive treatment for liver & renal failure – Treat hypoglycemia vigorously– Correct clotting disorders– Expedite delivery (epidural & regional anesthesia

are contraindicated)– Monitor postpartum

Pre-eclampsia with HELLP syndrome

• Pre-eclampsia: Increased BP (>140/90 mmHg) with proteinuria (>300mg/24hour)

• H – hemolysis• E – elevated• L – liver enzymes• L – low • P – platelet

• Pathogenesis: – Endothelial injury with fibrin deposit

microangiopathic hemolytic anemia– Endothelial injury platelet activation and

consumption thrombocytopenia, clotting system activation clotting factors consumption DIVC

– Fibrin deposits obstruct hepatic sinusoids hemorrhage liver necrosis

• Symptoms: epigastric pain, nausea and vomiting, malaise, headache, jaundice

• Investigation: (PE profile)– FBC: ↓ platelet (<100 x 109/L), ↓ Hb– LFT: ↑ AST & ALT, ↑elevated bilirubin– RFT:↑ urea, creatinine, uric acid– ↑ LDH (>600 U/L)

• Complications: – DIVC– Renal failure– Abruptio placenta– Liver subcapsular hematoma

• Management: – Definitive treatment: delivery

Maturity of pregnancy

Term (>37 weeks) Preterm (<37 weeks)

If severe disease

MgSO4 and deliveryExpectant management

until term/ delivery

No

Yes

• Maintain BP < 160/110 mmHg by IV hydralazine or labetalol

• IV dexamethasone• PE profile• CTG – fetal monitoring• Any complications – emergency caesarean

section

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Hyperemesis Gravidarum

• Pathological vomiting during pregnancy a/w liver dysfunction & jaundice.

• Liver dysfunction resolves when vomiting subsides.

Acute viral hepatitis

• Most common cause of jaundice in 3rd trimester.

• Clinical features: nausea, vomiting, fever, fatigue and jaundice, epigastric/right hypochondrium pain

• Common aetiology:– Hepatitis A– Hepatitis B

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Hepatitis A• RNA Picornavirus• Spread by fecal-oral route• Incubation period 15-50 days (average 30 days)• Acute symptoms:

– Nausea & Vomiting– Anorexia– Headache– Flu-like illness

• Detected by anti-HAV IgM

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• Self-limiting disease• No chronic infection; lifelong immunity• Practically no maternal-fetal transmission

– anti-HAV immunoglobulin (Ig) G antibodies present during the initial stages of HAV infection cross the placenta and provide protection to the infant after delivery

• No evidence of congenital HAV infection• No intervention needed

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Hepatitis B• DNA Hepadnavirus• Spectrum range from asymptomatic to

fulminant hepatic failure• Transmission:

– Vertical transmission– Through percutaneous or parenteral contact with

infected blood, body fluids & sexual intercourse• HBV does not cross placenta; breaks in

maternal-fetal barrier (e.g. amniocentesis, delivery) permit transmission

• Factors favouring vertical transmission:– Infection in late pregnancy– HBeAg positive (90% likelihood of newborn

becoming infected)– High titers of HBsAg– High HBV DNA

• 2-10% of newborns develop clinical hepatitis• 90% of infected infants will become chronic

carriers

• Investigations:– LFT: ↑AST, ALT– Hepatitis screening

• Prevention:– Antenatal screening– IM HBIG at birth within 12 hours– Vaccination for infant at 0, 1, 6 months– Offer vaccination to all the family

• Breastfeeding is not contraindicated