Lectures in Obstetrics, Gynaecology and Women’s Health

31. Medical Conditions – Cardiac Disease, Thrombophilias, Rhesus Immunisation

Gab Kovacs1 and Paula Briggs2

(1)

Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia

(2)

Sexual and Reproductive Health, Southport and Ormskirk Hospital, Southport, UK

Cardiac Disease

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Rhesus Disease

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Thrombosis in Pregnancy and Thrombophilia

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Thrombophilia and Pregnancy Complications

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Cardiac Disease

Definition

This includes congenital cardiac abnormalities, rheumatic valvular heart disease, ischaemic heart disease, cardiomyopathy and pulmonary hypertension.

Incidence

Congenital heart disease in pregnancy affects less than 1 % of women.

Pregnancy increases the risk of myocardial infarction (MI) three to four fold. The risk of MI in women over 40 years of age is 30 times that of younger women.

The risk of death from ischemic heart disease in pregnancy in the UK is 1 in 130,000.

Aetilogy and Pathogenesis

The normal physiological changes of pregnancy result in additional demands on the heart. These include an increase in blood volume (plasma volume increasing more than red cell mass), peripheral vasodilatation and an increase in cardiac output (up to 40–50 % by 20–28 weeks). These demands increase even further during labour and immediately following delivery.

Patients with pre-existing risk factors include those with hypertension, pre-eclampsia, diabetes, smoking, obesity and hyperlipidaemia.

Clinical Assessment

History

· Chest pain in pregnancy needs to be investigated (consider aortic dissection if severe)

· Shortness of breath (especially postural), should raise suspicion regarding cardiomyopathy

Examination

· Regular assessment of pulse rate and rhythm and blood pressure

· Cardiac auscultation to detect murmurs suggestive of valvular heart disease

Investigations

· ECG

· Chest X ray

· Echocardiogram

· CT scan of chest (to exclude aortic dissection)

· Oxygen saturation in women who are cyanosed

Treatment

Medical

· Joint responsibility (cardiologists and obstetricians)

· Mode and timing of delivery should be planned at the 32–34 week visit

Surgical

· Minor – Minimise cardiovascular stress by eliminating pushing during the second stage with elective assisted vaginal delivery

· Major – Caesarian Section is usually only required for obstetric indications

Complications

Cardiac failure, death

Prognosis

One in thirteen women who have a MI in pregnancy will die

Rhesus Disease

Definition

Rhesus immunisation of a woman who is Rhesus negative in response to blood from a Rhesus positive foetus entering her circulation.

There are also many other antigens on the surface of red blood cells, not as well known as Rhesus, such as Kell, MNS, and Kidd which may also cause iso-immunisation, but Rhesus is the most common and therefore the most relevant clinically.

Incidence

Fifteen percent of women are Rhesus negative and are therefore at risk of Rhesus immunisation by a Rhesus positive foetus.

Aetilogy and Pathogenesis

Everyone carries two genes for Rhesus, so one is either:

Heterozygous for Rhesus (carrying only one gene) or Homozygous (carrying both genes).

There are subsets of Rhesus including the D, Cc and Ee alleles, of which D is most important and determines Rhesus positivity or negativity.

Rhesus negative women carry neither of the genes. If a Rhesus negative woman conceives to a homozygous Rhesus positive partner (DD), all offspring will be Rhesus positive. If the male is heterozygous (only has a single D – and 55 % of men are), only one in two off-spring will be positive. The chance of immunisation is reduced by ABO incompatibility between the parents.

During most of the pregnancy the foetal blood does not cross the placenta. However, in certain circumstances foeto-maternal haemorrhage can take place (antenatal haemorrhage, amniocentesis, External Cephalic Version (ECV), or trauma). This can be confirmed by the Kleihauer test which determines the number of foetal cells in the maternal circulation. If Rhesus positive red cells enter the maternal circulation, anti Rhesus antibodies will be produced. These antibodies are small enough to cross the placenta and attack the foetus’ red cells causing haemolysis. The severity of this haemolysis will depend on the level of maternal antibodies. Consequently the foetus can become anaemic, and due to the raised level of bilirubin, can suffer from kernicterus which can cause hearing loss, permanent brain damage with intellectual disability or death. Hepatomegaly, ascites and polyhydramnios may be present in the mother.

Clinical Assessment

History

Allegedly 20–30 % of pregnancies result from fertilisation by someone other than the woman’s regular partner and therefore the Rhesus status of the partner can be misleading

Examination

There is usually little to be found on examination, but in severe cases hepatomegaly, ascites and polyhydramnios may be present in the mother.

Investigations

All Rhesus negative women should be screened for Rhesus antibodies at the first visit, 28 and 34 weeks and then after delivery

In the presence of anti Rhesus antibodies in the maternal serum, the first sensitised pregnancy can be managed with repeat antibody titers. If the titer rises to 1:64, the foetus needs to be investigated by assessing the bilirubin level in the amniotic fluid. The clinical risk to the foetus is assessed by absorbance of the liquor at 450 nm wavelength, and then calculating from a Liley curve.

Percutaneous umbilical blood sampling can be performed to determine all blood parameters directly.

If the woman has had a previous pregnancy, foetal surveillance should commence 4–8 weeks earlier than the time that problems occurred in the previous pregnancy.

Assessment of blood flow in the middle cerebral artery of the foetus using doppler ultrasound has also been used as a risk assessment tool for severity of haemolytic disease.

Treatment

Medical

Prevention of immunisation is undertaken by administering anti D antibodies within 72 h of the suspected foeto-maternal transfusion, as well as routinely at 28 and 34 weeks in all Rhesus negative un-immunised women, thus “mopping up” the red cells before the maternal immune system is activated to form anti bodies. Standard doses of Anti D (see Chap. 20) are used or the extent of transfusion can be assessed by estimating the number of foetal cells in the maternal circulation and the dose of anti D adjusted accordingly. The absence of antibodies in the maternal circulation should be checked, because once the woman is immunised, anti D is of no benefit.

Occasionally in very severe cases, intravenous immune serum globulin is administered.

Surgical

· Minor – Intrauterine transfusion of an anaemic foetus is sometimes undertaken. Induction of labour can be undertaken if the risk to the foetus is greater in utero than as a result of delivery.

· Major – Elective CS is undertaken if the foetus is judged to be too compromised to risk labour

Complications

The raised bilirubin level in utero can cause kernicterus which manifests as hearing loss, permanent brain damage with intellectual disability or death

Prognosis

Good, with active management following above principles

Thrombosis in Pregnancy and Thrombophilia

Definition

Thrombophilia is an increased tendency to develop blood clots

Incidence

Pulmonary embolism is the leading cause of maternal death in the UK, accounting for 11 % of maternal deaths, or 1–2/1,000,000 births.

The highest risk is during the post partum period.

It is estimated that the risk of VTE post partum is increased 60 fold, compared to a non-pregnant woman.

Aetilogy and Pathogenesis

Risk factors for VTE include a previous venous thromboembolism, or having a thrombophilia. Thrombophilia can be inherited or acquired, and the incidence is shown in Table 31.1. Inherited thrombophilias include: antithrombin deficiency, Protein C or S deficiency, Factor V Leiden deficiency and Prothrombin gene mutation G20210. Acquired thrombophilias include the lupus spectrum, anticardiolipin antibodies, and β2 glycoprotein 1 antibodies.

Table 31.1

Incidence of thrombophilia in the Caucasian population

Inherited thrombophilias

Acquired thrombophilias

Antithrombin deficiency 1:2,000–5,000

Antiphospholipid syndrome- Lupus anticoagulant

Protein C deficiency 1:2,000–5,000

Anticardiolipin antibodies

Protein S deficiency 1:200–5,000

B2 glycoprotein

Factor V Leiden 1:20

Plasma homocysteine

Prothrombin G20210A mutation 1:33

Certain conditions also predispose to VTE. These include:

· Obesity (BMI > 30 kg/m2)

· Smoking

· Multiple pregnancy

· Pre-eclampsia

· Caesarean section

· Prolonged labour

· Operative delivery

· PPH > 1 l

· Ovarian hyperstimulation syndrome after ART

· Immobility

· Dehydration

· Long-distance travel (>4 h).

Clinical Assessment

History

Past or family history of VTE

Examination

In the event of a VTE, a red, hot swollen leg (DVT) or dullness to percussion and reduced air entry (PE)

Investigations

Screening for thrombophilia is only undertaken as a result of a relevant history.

Treatment

Medical

All women with a history of previous VTE should receive postpartum thromboprophylaxis with low molecular weight heparin (LMWH).

Women with recurrent VTE associated with either antithrombin deficiency or the antiphospholipid syndrome are at very high risk and require thromboprophylaxis with LMWH antenatally and for 6 weeks postpartum or until they can be converted back to warfarin following delivery.

Complications

There is a risk of pulmonary embolism and death if DVT occurs.

Prognosis

Appropriate thromboprophylaxis and anticoagulant therapy reduce the danger of VTE. A haematologist will make the decision regarding long term anticoagulation.

Thrombophilia and Pregnancy Complications

Definition

Thrombophilia is the tendency to develop blood clots

Incidence

As in Table 31.1

Aetilogy and Pathogenesis

Pregnancy complications such as pre-eclampsia, placental abruption and small for gestational age and recurrent early pregnancy loss are associated with placental thrombi and infarction. It has therefore been postulated that thrombophilia may be a risk factor for these complications.

Although some case control studies (retrospective comparisons) have shown a slight increase in thrombophilias in women with these factors compared to normal pregnancies, prospective studies have not confirmed this. Whilst biologically plausible, (thrombophilia predisposing to thrombi in the venous circulation, promoting inflammation associated with pre-eclampsia, and placental insufficiency), conclusive evidence is lacking. The best evidence for this association is seen with antiphospholipid syndrome and recurrent early pregnancy loss.

Clinical Assessment

History

Previous VTE

Examination

Nil

Investigations

Thrombophilia screening is controversial. There is no place for population screening

Treatment

Medical

· low dose aspirin (75–100 mg/day) administered from early pregnancy has been shown to be of benefit to women with a history of placenta-mediated pregnancy complications

· Low molecular weight heparin is far more demanding then taking oral aspirin, and there is a lack of evidence that this improves outcome beyond aspirin for women with congenital thrombophilias. For women with recurrent early pregnancy loss, there is some evidence that LWMH improves outcome in acquired thrombophilias.

Complications

Recurrent early pregnancy loss, prematurity, accidental haemorrhage, intrauterine growth restriction and pre-eclampsia.

Prognosis

Management with aspirin, foetal monitoring and appropriate delivery usually results in a good outcome.



If you find an error or have any questions, please email us at admin@doctorlib.org. Thank you!