Obstetrics and gynecology

DISCUSSION
ON
THROMBO EMBOLIC
DISORDERS

Submitted to:

Mrs. Giggy John

Asst. Professor

Govt. College of Nursing

Thrissur

Submitted by:

Sangeetha Francis

II MSc Nursing student

Govt. College of Nursing

Thrissur

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A. VENOUS THROMBOEMBOLISM (VTE) IN PREGNANCY
Venous thromboembolism is the leading cause of maternal death in many developed countries
and is increasing in prevalence in India as well. Pregnancy increases the risk of
thromboembolism 6 fold and caesarean section another 10-20 fold.

Risk Factors
Why is Pregnancy Itself a Risk Factor?
Virchow proposed a triad of conditions predisposing to venous thrombosis. All these conditions
occur in pregnancy and especially so in the puerperium. The hypercoagulable state in pregnancy
is mainly nature‘s way of preventing excessive bleeding at delivery.
1. Hypercoagulability Increase in clotting factors(fibrinogen, VII], IX and X) Decreased
Fibrinolytic activity Decrease in endogenous anticoagulants like antithrombin III and protein S
2. Venous stasis
3. Trauma to pelvic veins at delivery

Additional Risk Factors

Preexisting

• Previous venous thromboembolism II Congenital thrombophilia

• Acquiredthrombophilia
• Age over 35 years
• Obesity
• Parity> 4
• Sickle cell disease
• Medical disorders like systemic lupus

During Pregnancy

• Operative delivery, especially Caesarean section Immobilisation

• Prolonged labour
• Surgery in pregnancy
• Ovarian hyperstimulation syndrome Hyperemesis
• Severe infections and puerperal sepsis Preeclampsia
• Dehydration
• Haemorrhage and anaemia
• Multifetal gestation

Congenital Thrombophilias

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The likelihood of developing thrombosis in pregnancy is more common in women with cenain
genetic risk factors. The American College of Chest Physicians estimates that about half of the
pregnant women with thrombosis have an identifiable genetic disorder.

• Antithrombin III deficiency

• Protein C deficiency
• Protein S deficiency
• Factor V Leiden mutation
• Prothrombin gene mutation Hyperhomocysteinaemia
Antithrombin is one of the important inhibitors of thrombin in clot formation. It functions as
a natural anticoagulant by inactivating thrombin. Protein C and protein S are also natural
anticoagulants. Activated protein C resistance is usually due to Factor V Leiden mutation.
This is the most common risk factor of the inherited thrombophilias. It is characterised by
resistance of plasma to the anticoagulant effects of activated protein C. Prothrombin G
mutation causes excessive accumulation of prothrombin, which will then be converted to
thrombin. This is extremely rare in non-whites. The most common cause of
hyperhomocysteinaemia is mutation of the enzyme methylene tetrahydrofolate reductase
(MTHFR). The inheritance is autosomal recessive. Increased homocysteine may act by
decreased activation of protein C. It is not clear whether hyperhomocysteinaemia has an
increased risk in pregnancy.

Acquired Thrombophilias
Antiphospholipid syndrome (APLA) is the most common cause of inherited thrombophilia.

DIAGNOSIS
Deep Vein Thrombosis(DV1)
Left sided DVT is more common than right sided. Iliofemoral thrombosis is more common than
popliteofemoral or calf vein thrombosis. The classical features are swelling, redness, pain and
calf muscle tenderness but these are unreliable in pregnancy. Oedema can occur physiologically
in pregnancy. Occasionally, reflex arterial spasm causes a pale, cold extremity with reduced
pulsations. One fourth of untreated cases will have associated pulmonary embolism.
Anticoagulation will reduce this risk to less than 5%. As clinical diagnosis is difficult,
investigations are necessary.

Investigations
Ultrasound and Doppler is the recommended method. It is non invasive and especially
beneficial in diagnosing iliofemoral thrombosis. It is less reliable in diagnosing calf vein
thrombosis, but these are less dangerous as they do not embolise and lead to pulmonary
embolism.

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Venography is considered the gold standard, but if done in pregnancy, abdominal shielding
should be used.

Impedance plethysmography is extremely accurate for the lower iliac, femoral and popliteal
veins. It is based on the observation that alterations in venous return in the calf produced by
inflation and deflation of a pneumatic thigh cuff causes changes in electrical resistance detected
at the skin surface. However, the sensitivity is much less for the small calf veins. Also, there are
increased false positives in pregnancy because of the decreased venous return of the lower
extremities. Hence, it is not much used.
CT and MRI are extremely useful although radiation may be a theoretical risk.

D-dimers widely used outside pregnancy are not helpful in pregnancy as the false positive rate is
high. However, a negative test is reassuring.

Pulmonary Embolism
The clinical diagnosis is unreliable and a high degree of suspicion is essential. The most
characteristic symptoms are sudden onset of dyspnoea, pleuritic chest pain, haemoptysis and
hypotension. Massive embolism may manifest as severe chest pain and sudden collapse. Clinical
signs are tachycardia, tachypnoea and a raised jugular venous pressure.

Investigations

• Chest X-ray to rule out other causes

• ECG may show right axis deviation and T wave Inversion
• Low oxygen saturation with pulse oximetry Arterial blood gas shows hypoxaemia and
hypocapnia
• Lung scan; a ventilation perfusion scan will show ventilation perfusion mismatch in
pulmonary embolism
• Pulmonary angiography in severe cases prior to
• surgery, but is invasive Multidetector spiral CT pulmonary angiography
Multidetector spiral CT is replacing pulmonary angiography as the gold standard for
diagnosis of pulmonary embolism.

MANAGEMENT

• Deep Vein Thrombosis

• Though objective evidence is ideal, treatment should be started on clinical grounds if
confirmatory tests are not available. treatments is with either unfractionated or low
molecular weight heparins. Oral anticoagulants are usually avoided in pregnancy as they
can cross the placenta and cause teratogenesis. The single undisputed use for warfarin in
pregnancy is in women with prosthetic heart valves.

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Unfractionated Heparin
Unfractionated heparin can be given as IV bolus followed by IV infusion to prolong the activated
partial thromboplastin time (AP’I‘T) by 1.5-2 times the control. Doses of heparin as high as
40,000 units in 24 hours may be necessary. IV anticoagulation should be maintained for at least
5-7 days, after which subcutaneous heparin can be given. Monitoring is by APTT and platelet
count weekly, as heparin can cause thrombocytopaenia [heparin induced thrombocytopaenia
(HIT)]. Heparin will not cross the placenta and hence, is safe for the fetus. APTT should be 4-6
hours after the loading dose, 6. hours after any dose change and then, at least daily when in the
therapeutic range. The therapeutic target APTT is usually 1.5-2.5 times the average laboratory
control value.

Low Molecular Weight Heparin

High dose low molecular weight heparin (LMWH) is now being increasingly used. Examples are
enoxaparin or Clexane and dalteparin or Fragmin. The dose of enoxaprin is 1 mg/kg twice daily
and of dalteparin is 100 units/kg twice daily. Anti-Xa levels need not be checked as a routine, but
are recommended in women at extremes of body weight or with other complicating factors. Anti-
Xa activity should be maintained at above 0.1 U/mL. Anti-Xa should be monitored 3.5 hours
after a dose.

The leg should be elevated and a graduated elastic compression stocking applied to reduce
oedema. Mobilisation with graduated elastic compression stockings should be encouraged.
Therapeutic heparin is continued throughout pregnancy and stopped before delivery. LMWH
should be stopped 24 hours before planned delivery. Regional anaesthesia is best avoided due to
the risk of haematoma formation. In women receiving therapeutic doses of LMWH, wound
drains (abdominal and rectus sheath) should be considered at caesarean section and the skin
incision should be closed with staples or interrupted sutures to allow drainage of any haematoma.

Heparin should be restarted about 6-12 hours after delivery (depending upon the type of
delivery), as the puerperium is the time of greatest risk. Warfarin is commenced simultaneously
and thereafter monitoring is by prothrombin time (PT). Once the prothrombin time INR
(international normalisation ratio) is between 2 and 3, heparin can be discontinued. Usually,
warfarin is continued for 6 weeks and is safe for breastfeeding mothers. Postpartum venous
thrombosis is usually managed by starting intravenous heparin and oral warfarin simultaneously.
After delivery, anticoagulation should be continued for a minimum of 6 weeks. At the same time,
a minimum 6 months course should have been given following the initial episode. Hence, if the
venous thrombosis develops postpartum, a minimum of 6 months anticoagulation is essential.

Complications

• Haemorrhage
• Heparin induced thrombocytopaenia
• Heparin induced osteoporosis

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Pulmonary Embolism
Treatment is similar to that of deep vein thrombosis with high doses of IV infusion of heparin. A
loading dose of 80 units/kg followed by an IV infusion of 18 units/kg/hour is usually given.
Other modalities of therapy are vena caval filters, thrombolytic therapy and pulmonary
embolectomy in massive embolism.

Thromboprophylaxis
Thromboprophylaxis in pregnancy is considered for those women at increased risk of
thromboembolism (TE). All women should undergo a risk assessment in early pregnancy

High risk patients need antepartum, intrapartum and postpartum prophylaxis for 6 weeks. Those
with low risk may require intrapartum and postpartum prophylaxis for 6 weeks. Apart from
these, women with additional risk, i.e., combinations of risk factors like obesity, multiparity,
precclampsia, prolonged immobilisation and especially if undergoing caesarean section, may
need heparin prophylaxis during labour and the immediate postnatal period. Use of leg stockings
and early ambulation after caesarean section is also recommended. The thromboprophylactic
dose of conventional heparin is 10,000 units twice daily, enoxaparin 40 mg once daily and
dalteparin 5000 units once daily.

Table 1: Indications for Thrombo prophylaxis

Risk category Risk Factors

High risk • Recurrent factor

• Previous TE with thrombophilia
• Previous TE with family history TE in current pregnancy
Low risk • One episode of previous TE without thrombophilia or family history
• Thrombophilia without previous thrombosis
Additional risk • Caesarean section
• Obesity
• Grand multiparty
• Age above 35 years
• Preeclampsia
• Prolonged immobilisation

TE-thromboembolism

B. CEREBRAL VENOUS THROMBOSIS

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Cerebral venous thrombosis is traditionally associated with the puerperium and is an important
cause of stroke related to pregnancy. Very rarely, it can present in late pregnancy.

Presentation
Cerebral venous thrombosis usually presents in the second week postpartum with severe
headache, drowsiness and convulsions. There may be aphasia,

visual disturbances and focal neurological deficit, hypertension and papilloedma. Usually, the
superficial veins like the lateral or superior sagittal sinus veins are involved. If the deep venous
system is involved, coma is usual. The main differential diagnosis is eclampsia.

Predisposing Factors

• Preeclampsia
• Inherited and acquired thrombophilia
• Sepsis
• Dehydration

Diagnosis and Management

Diagnosis involves a high degree of suspicion. The investigation of choice is MRI with
venography, which will identify the thrombus. It is important to rule out cerebral haemorrhage
before starting treatment. Management includes heparin for anticoagulation, anticonvulsants for
seizure control and antibiotics if septic thrombophlebitis is suspected. Prolonged anticoagulation
with warfarin may be necessary in the puerperium. The overall prognosis is good and the
outcome better than for arterial stroke.

C. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

This was first reported by De Lee in 1901 as ‘The development of temporary haemophilia in a
woman wzth a placental abruption and another with a long dead, macerated fetus.’ This
stimulated interest in obstetnc conditions leading to DIC. It is also termed consumptive
coagulopathy.

Aetiology Obstetric Causes

• HELLP syndrome
• Abruption
• Prolonged retention of a dead fetus Missed abortion
• Amniotic fluid embolism
• Severe preeclampsia and eclampsia
• Sepsis and endotoxic shock .
• Intra amniotic hypertonic saline for mid trimester abortion
• Prolonged bleeding and shock due to any causes

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Medical Causes

• Idiopathic thrombocytopaenic purpura

• Von Willebrand disease
• Drug induced thrombocytopaenia Anticoagulation
• Chronic liver or kidney disease
• Transfusion of stored blood, citrate intoxication and overuse of dextran

Pathogenesis
Pregnancy Hypercoagulability
In pregnancy, there is hypercoagulability with an increase in factor I, VII, VIII, IX and X levels
and this is the underlying cause. Plasminogen levels are also increased.

Pathological Activation of Coagulation

In pathological states, coagulation is activated through the extrinsic pathway by thromboplastin
from tissue destruction and perhaps through the intrinsic pathway when there is loss of
endothelial integrity. The inciting factor in obstetrics may vary. In abruption and intrauterine
death, it is thromboplastin liberated from the placenta and the dead fetus. In septicaemia,
bacterial endotoxins activate the extrinsic clotting system. Amniotic fluid contains abundant
mucin from fetalsquames and this leads to rapid defibrination in amniotic fluid embolism. DIC
should be seen as a complication of some underlying pathological process against which
treatment has to be directed to reverse the process.

First DIC occurs and as a result, fibrin is deposited in all the small vessels, leading to obstruction
of the microcirculation. This consumptive coagulopathy results in consumption of coagulation
factors and platelets. This lack of coagulation factors especially fibrinogen, results in bleeding.
At the same time, in response to the deposition of fibrin, plasminogen is activated and converted
to plasmin. The plasmin lyses fibrinogen, fibrin monomer and fibrin polymer to fibrin
degradation products (FDP), which in turn can increase the bleeding. In addition,
microangiopathic haemolysis may occur due to fibrin deposition.

Diagnosis
Clinical Evidence
Clinically, there may be persistent bleeding from venepuncture sites, bleeding gums and
bloodstained urine.

Bedside Tests
Clot observation test or clotting time is a very useful bedside test. If a clot forms in 10 minutes
and remains firm for another 30 minutes, DIC is unlikely and the fibrinogen level can be
considered >100 mg/dL.

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Clot retraction test is another bedside test, whereby if the clot retracts at the end of one hour,
platelets can be considered adequate.

Clot stability is indicated by a stable clot over 48 hours. A fragile or unstable clot indicates the
presence of FDP.

Coagulation Profile
Fibrinogen assay. In late pregnancy, levels are 300-600 mg/dL. Levels below 100 mg/dL are
indicative of severe hypo flbrinogenaemia. D-dimer test to detect FDP in serum Platelet count ,
Prothrombin time and partial thromboplastin time

Management
Management of the Underlying Cause. In the case of abruption, prolonged retention of a dead
fetus and HELLP syndrome, immediate delivery is indicated.

Fluid Replacement: Fluid replacement with crystalloids and colloids is very important. Dextran
solutions should not be used as they interfere with platelet function and may aggravate bleeding.
Fluid replacement will also prevent renal failure and help to clear elevated levels of fibrin
degradation products from the circulation via the liver.

Blood Component Therapy

Stored blood cells, fresh frozen plasma (FFP), platelet concentrates and cryoprecipitate (if
indicated) are to be given as soon as possible. Human recombinant activated factor VII is also
useful in DIC, but very expensive.

Reference
1. Royal College of Obstetricians and Gynaecologists. The acute management of thrombosis and
embolism in pregnancy and the puerperium. Green top Guideline No. 37b. London: RCOG;2010.

2. American Academy of Pediatrics and American College of Obstetricians and Gynaecologists.

Guidelines for Perinatal Care, 6th ed; 2007.

3. Srivastva SD, Eagleton MJ, et al. Diagnosis of pulmonary embolism with various imaging
modalities. SeminVascSurg 2004;17:173.