Amniotic fluid embolism

Why pregnancy is thrombogenic

• Virchow triad: stasis, endothelial injury, hypercoagulability.
• Stasis: progesterone relaxes venous smooth muscle and the uterus compresses the iliac veins and IVC. Most pregnancy DVTs are left-sided and iliofemoral (the right common iliac artery crosses the left iliac vein). Immobility loses the calf muscle pump; immobilisation is the commonest acquired cause of DVT overall.
• Hypercoagulability: oestrogen raises fibrinogen and factors VII, VIII, X and von Willebrand factor; protein S falls.
• Reduced fibrinolysis: the placenta makes plasminogen activator inhibitor-2 (PAI-2), and PAI-1 rises, so fibrinolytic activity falls; it returns to normal within an hour of placental delivery. D-dimer still rises through pregnancy because fibrin turnover increases.
• Injury: delivery, caesarean section, pre-eclampsia, infection.
• Risk is highest per day in the first weeks after delivery, returning to baseline by 6–12 weeks. Thrombophilias (factor V Leiden, antiphospholipid syndrome) add risk.
• Ovarian hyperstimulation syndrome (OHSS): after the hCG trigger, VEGF-driven capillary leak causes ascites and haemoconcentration (haematocrit about 50%), with high oestrogen. Thrombosis can be arterial or venous and characteristically affects upper body veins (internal jugular, subclavian), sometimes weeks later, possibly because ascitic fluid rich in oestrogen drains through the thoracic duct.

Deep vein thrombosis

• DVTs start in valve pockets of calf veins and propagate proximally. Venous thrombi are dark red: red cells trapped in fibrin. The popliteal and femoral veins are classic sites, and most emboli come from the proximal deep veins (femoral, iliac).
• D-dimer is sensitive but not specific, and rises in normal pregnancy, so it has little value; compression duplex ultrasound is first line.
• Complications: pulmonary embolism (the most important acute complication) and the post-thrombotic syndrome (chronic swelling, pain, skin change and ulcer from valve damage).
• Treatment in pregnancy: LMWH throughout pregnancy and for at least 6 weeks postpartum (3 months in total); warfarin is avoided in pregnancy (it crosses the placenta) but can be used after delivery and in breastfeeding.

Pulmonary embolism

• Physiology: an occluded segment is ventilated but not perfused, alveolar dead space (V/Q infinite). In that region alveolar gas approaches inspired air: alveolar PO2 rises and alveolar PCO2 falls. Blood diverted to the rest of the lung creates low V/Q units that cause the hypoxaemia.
• Blood gas: PaCO2 is low, not raised, because hypoxaemia, stimulation of lung J-receptors and anxiety drive hyperventilation. At 30 weeks a PaO2 of 68 mmHg (9 kPa) with PaCO2 25 mmHg (3.3 kPa) is abnormal on both counts, as normal pregnant values are about 100 mmHg and 30 mmHg. A normal PaO2 does not exclude PE.
• Clinical: sudden dyspnoea, pleuritic chest pain, tachycardia, tachypnoea, haemoptysis if infarction.
• ECG: commonest is sinus tachycardia; S1Q3T3, right bundle branch block and right axis reflect acute right ventricular strain.
• Pulmonary hypertension after massive or recurrent emboli: the most specific sign is a loud (palpable) pulmonary component of the second sound, with a right ventricular heave and raised JVP.
• Infarction is uncommon because the lung has a dual supply (bronchial arteries); when it occurs it is wedge-shaped, haemorrhagic and pleural-based. A saddle embolus causes sudden death.
• Imaging in pregnancy: with a normal chest X-ray a perfusion (V/Q) scan is preferred because it gives a much lower radiation dose to the maternal breasts than CTPA; fetal doses from both are very low, so imaging is never withheld.
• Alteplase and heparins do not cross the placenta.
• Autopsy: a postmortem clot is rubbery with currant-jelly and chicken-fat layers; an antemortem thrombus is firm, friable and shows lines of Zahn.

Amniotic fluid embolism

• Sudden collapse, hypoxia, hypotension, seizures and DIC during labour, caesarean section or just after delivery, frequently fatal.
• Fetal material entering the maternal circulation provokes an anaphylactoid immune response rather than simple mechanical blockage.
• Phases: pulmonary vasospasm with acute right ventricular failure, then left ventricular failure and pulmonary oedema, then DIC from tissue factor in amniotic fluid.
• Autopsy shows fetal squames, lanugo and mucin in maternal pulmonary vessels.

• Thromboembolism is by far the commonest type of embolism.

Acute respiratory distress syndrome

• Causes in obstetrics: sepsis (pyelonephritis, septic abortion, chorioamnionitis), acid aspiration, massive transfusion, pre-eclampsia, AFE. Some drugs cause pneumonitis too (methotrexate among DMARDs).
• Mechanism: cytokines recruit and trap neutrophils in lung capillaries; their elastase and oxidants damage the alveolar–capillary membrane, causing protein-rich, non-cardiogenic oedema with a normal wedge pressure (cardiogenic oedema has PAWP over 18 mmHg).

• Type II pneumocytes are the stem cells of the alveolus: they proliferate and differentiate into type I cells. They also make surfactant, so their injury adds to alveolar collapse.
• Neonatal respiratory distress syndrome is a different disease: surfactant deficiency in preterm lungs, also showing hyaline membranes.
• Physiology: flooded alveoli are perfused but not ventilated, a shunt that barely responds to oxygen; lungs are stiff. PEEP reopens alveoli but reduces venous return.
• Berlin definition: onset within a week, bilateral opacities not explained by heart failure, graded by PaO2/FiO2 (mmHg) on PEEP of 5 or more: mild 200–300, moderate 100–200, severe 100 or less.
• Low tidal volume (6 mL/kg predicted weight, plateau under 30 cmH2O) with permissive hypercapnia.
• TRALI: within 6 hours of plasma-rich products, donor anti-HLA or anti-neutrophil antibodies activate recipient neutrophils; TACO (fluid overload) has hypertension and raised BNP.

Remember Thrombosis in pregnancy: progesterone dilates, the uterus compresses, oestrogen coagulates and placental PAI-2 blocks lysis; the riskiest days follow delivery.

Exam trap D-dimer is normally raised in pregnancy; go straight to compression ultrasound.

Exam trap Pulmonary embolism lowers PaCO2 through hyperventilation; a raised PaCO2 is not expected.

How FCPS asks about this

• Most common source of pulmonary emboli: proximal deep leg veins (femoral, popliteal, iliac).
• Blood gas in PE: low PaO2 and low PaCO2 from hyperventilation; in the blocked lung alveolar PO2 rises.
• Why fibrinolysis falls in pregnancy: placental PAI-2, reversed within an hour of placental delivery.
• Why a V/Q scan is preferred in pregnancy with a normal chest X-ray: lower breast radiation dose.
• Cells lining alveoli in organising ARDS: regenerating type II pneumocytes.
• Jugular vein thrombosis after IVF: ovarian hyperstimulation syndrome.
• Most specific sign of pulmonary hypertension: loud pulmonary component of the second heart sound.