Coagulation Defects in Pregnancy

Obstetrics Simplified - Diaa M. EI-Mowafi

Physiological Bases

Factors involved in the arrest of haemorrhage

Haemostasis:
- After injury to any blood vessel haemostasis is achieved by:
  - Vascular responses: obliteration of the injured vessel by;
    - vasoconstrictors released from platelets,
    - external pressure by either haematoma formation, contraction of the surrounding muscles (as in uterine and placental blood vessels) or by artificially applied pressure.
  - Platelets aggregation.
Coagulation:
- Stage I: (few minutes)
  - Intrinsic mechanism: Activation of factors XII, XI and IX respectively by vessel wall damage + Ca++ and factor VIII → activation of factor X.
  - Extrinsic mechanism: Tissue damage leads to release of factor III and VII → activation of factor X.
- Stage II: (10-15 seconds)
  - In which activated factor X (Xa) + factor V+ Ca++ lead to conversion of prothrombin (factor II) → thrombin.
- Stage III: (1-2 seconds)
  - Thrombin converts fibrinogen (factor I) → fibrin monomer → fibrin polymers ® fibrin.

Changes in pregnancy and labour

Coagulation system:
- Fibrinogen (FI): increases from 2-4 gm/L (normal level) to 4-6 gm/L.
- Factors VII, VIII and X: increase by 20-100%.
Fibrinolytic system:
- Although plasminogen increases by about 100%, fibrinolytic activity decreases due to;
  - increase inhibitory activity,
  - high oestrogen and progesterone level reduces fibrinolysis, and
  - placenta contains inhibitors.
Platelets:
- No change.
Uterine vasculature:
- The elastic lamina and smooth muscles of the terminal spiral arteries are replaced by fibrin matrix . This facilitates increase blood flow during pregnancy and closure of the sinuses postpartum by myometrial contraction.

Coagulation Disorders in Pregnancy

Disseminated intravascular coagulation:
Others:
- Inherited:
  - Von Willebrand’s disease: Inability to synthesise factor VIII related antigen.
  - Haemophilia:
  - Haemophilia A = inability to synthesise factor VIII.
  - Haemophilia B = inability to synthesise factor IX.
- Non-inherited:
  - Thrombocytopenia: due to decreased production or increased utilisation.
  - Immunologic (idiopathic) thrombocytopenic purpura.

Disseminated Intravascular Coagulation (DIC)

Pathogenesis

Extensive vessels and tissues damage → release of thromboplastins → utilisation of the fibrinogen and other clotting factors in an aimless coagulation process → fibrin .→ stimulates fibrinolytic system → breaks fibrin and fibrinogen into FDP which have an anticoagulant effect → aggravates haemorrhage and shock → ischaemia → more tissue damage → viscious circle.

N.B. The anticoagulant effect of FDP is due to:

Inhibition of platelet function.
Interference with thrombin/ fibrinogen reaction.
Interference with fibrin polymerisation.
Interference with myometrial contraction.

Predisposing factors

Abruptio placentae.
Amniotic fluid embolism.
Endotoxic shock.
Eclampsia and pre-eclampsia.
Hydatidiform mole.
IUFD and missed abortion.
Intra amniotic hypertonic saline or urea for induction of abortion.
Incompatible blood transfusion or transfusion of massive banked blood which is deficient in factor V and VIII.
Prolonged shock of whatever the cause.
Placenta accreta.
Rupture uterus.

Clinical features

Unexplained spontaneous bleeding from any site e.g.

oozing of blood,
bruising,
epistaxis,
haematuria,
haematoma formation especially at wound and venepuncture site,
postpartum haemorrhage.

Investigations

Bed -side tests:
- Clot observation test:
  - 5-10 C.C. of blood in a test tube will be clotted normally within 10 minutes. In case of DIC no clot will be formed or a clot is formed but it undergoes dissolution within one hour in 37oC.
- Fibrindex test:
  - 0.5 C.C. of fibrindex which contains thrombin is added to 0.5 C.C. of plasma in a test tube. Normally, a visible clot will be formed within 5-10 seconds. In DIC, clot formation is delayed up to 30 seconds (hypofibrinogenaemia) or it will not form at all (afibrinogenaemia).
- Schneider test:
- Thrombin is added to serial dilutions of the patient’s plasma 1:2, 1: 4, 1:8,......1:128.
  - Clot formation in all tubes: Normal.
  - No clot in all tubes: Afibrinogenaemia.
  - No clot in dilutions 1: 16 onwards: Hypofibrinoginaemia.
Laboratory tests:
- Plasma fibrinogen level:
  - During pregnancy the normal level is 4-6 gm/L. Failure of coagulation occurs when its level drops to 1 gm/L.
- Fibrinogen degradation products FDP: increased.
- Platelet count: decreased.

Management

Elimination of the underlying cause.
Fresh blood transfusion: contains clotting factors particularly F II, V and VIII.
Fresh frozen plasma: contains 3 gm fibrinogen/L in addition to FV and VIII.
Fibrinogen: 4-6 gm IV may be given if there is no fresh frozen plasma. However, it is not recommended as it may aggravate the coagulation process (fuel on fire) and cause hepatitis B.
Heparin: to inhibit fibrin production and consumption of the clotting factors but it is contraindicated if there is current bleeding.
Antifibrinolytic agents: as EACA, trasylol or tranexamic acid may be given to suppress the fibrinolytic process. However, this may enhance thrombosis formation.

DEEP VEIN THROMBOSIS (DVT)

Predisposing Factors

Venous stasis,
increased blood coagulability,
venous intimal damage.

These three factors meet with pregnancy and labour due to:

increased clotting factors I, VII, VIII and X.
reduced fibrinolytic activity.
pressure of the gravid uterus on pelvic veins.
antenatal rest, prolonged labour, dehydration, excessive blood loss, pressure on calf muscles during delivery, delay in mobilisation, trauma and pelvic infection.
oestrogen for postpartum suppression of lactation.

Clinical Picture

Superficial Thrombophlebitis:
- Common in varicose veins of the calf, thigh, inguinal region and vulva.
- There is discomfort, localised superficial tenderness, and pain.
- A palpable lump.
- A low grade fever.
Deep Vein Thrombosis:
- Pain and tenderness in calf muscles due to involvement of the posterior tibial vein which may extend to popliteal, femoral and pelvic veins.
- Oedema of the affected leg diagnosed by difference in girth of the limbs of more than 1cm.
- Hotness and cyanosis of the leg.
- Positive Homan’s sign: calf pain on dorsiflexion of the foot but neither its presence nor absence is reliable.
- Fever.

Investigations

Doppler ultrasound:
- The flow of blood as detected by reflection of the waves on RBCs is absent in DVT.
Ascending phlebography:
- 30-40 ml of contrast medium is injected into a vein of the dorsum of the foot after obstructing superficial venous return with a sphygmomanometer cuff at the ankle and thigh. Flow is monitored on a television screen.
Isotope venography:
- using technetium - 99m albumin followed with a gamma camera.
Thermography:
- The rise of temperature of the affected limb is detected by a thermovision infrared camera.

Management

Elastic bandage and elevation of the affected leg to improve the venous return and reduce oedema. This is continued until acute swelling subsides and gradual ambulation is allowed as soon as pain is improved.
Heparin:
- Start with 10.000-15.000 units IV, followed by continuous IV infusion of 10.000 units/ 4-6 hours.
- The aim is to make the blood clotting time or partial thromboplastin time 1.5-2 times their normal values.
- Subcutaneous heparin: can be given instead of IV infusion in a dose of 10.000 units/ 12 hours.
- During labour: Dosage is reduced to 5000 units/ 12 hours.
- Postpartum: 5000 units/ 8 hours is recommended.
- Antidote: Protamine sulphate 1% solution; 10 mg (1ml) for every 1000 units heparin is given by slow IV injection.
- Heparin cannot cross the placenta because of its high molecular weight (16.000-40.000 dalton).
- Oral anticoagulants as coumarin are teratogenic and excreted in breast milk causing foetal haemorrhage and chondrodysplasia punctata (nasal hypoplasia, saddle nose, frontal bossing, short stature, mental retardation, cataract and optic atrophy).
  - Warfarin can be given orally to the postpartum non-lactating woman in an initial dose of 0.75mg/ kg body weight to a maximum of 50 mg. Maintenance dose is 5-13 mg daily controlled by prothrombin time which should be 2-4 times the normal value.
  - Antidote: Vit. K1 10-20 mg slowly IV which can be repeated every 3 hours to a maximum of 40 mg in 24 hours.

PULMONARY EMBOLISM

It may occur with or without preceding deep vein thrombosis.
DVT occurs either during delivery, surgery or in the first 24 hours following them.
Clinical signs of pulmonary embolism appear within 4-14 days after DVT formation.

Diagnosis

Symptoms:
- Range from minimal disturbance to sudden collapse and death depending on the size, number and site of the emboli;
  - Dyspnoea,
  - chest pain,
  - cough,
  - frothy blood stained sputum,
  - haemoptysis,
  - nausea, vomiting and sudden desire to defecate.
Signs:
- Mild pyrexia,
- tachycardia,
- tachypnoea,
- cyanosis,
- raised jugular venous pressure,
- pleural friction rub,
- pleural effusion,
- right ventricular failure.
Investigations:
- ECG: inverted T waves and atrial arrythmia.
- X-ray:
  - triangular radio
  - opaque shadow (infarction),
  - pleural effusion,
  - raised copula of the diaphragm.

Treatment

Prophylaxis:
- Subcutaneous heparin: 5000-7500 units/12 hours in puerperium for women with past history of thrombo-embolism.
- Dextran 70: 500-1000 ml during surgery increases fibrinolysis.
Curative.
- Heparin: start immediate IV therapy as discussed before.
- Defibrinating drugs: as streptokinase 600.000 IU over 30 minutes, followed by 100.000 IU/hour by infusion for 72 hours. They are contraindicated during pregnancy, labour and early puerperium for fear of haemorrhage.
- Oxygen..
- Analgesic: e.g. morphine sulphate 10 mg.
- Digoxin: as an inotropic.
- Aminophylline: 250-500 mg IV to relieve dyspnoea.
- Pulmonary embolectomy; partial or total occlusion of the inferior vena cava by an umbrella filter or iliofemoral thrombectomy are surgical procedures that may be used.

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