PHYSIOLOGICAL CHANGES IN COAGULATION & FIBRINOLOYTICS SYSTEMS IN PREGNANCY

Coagulation system : Increase in levels of coagulation factors,

The result of these changes is hypercoagulable
mainly fibrinogen and factor VII, VIII, IX and X from the
state in pregnancy
beginning of the second trimester.
The benefit of these changes is protection of
Fibrinolytic system : Inhibition of the system, due to increase in
mother from severe haemorrhage after delivery
the levels of plasminogen inhibitors.
The risk of these changes is the increased risk of
Platelet count : No change
thromboembolism
Anticoagulant system : levels of anti-thrombin III, no change in
the levels of protein C & S
DISSEMINATED INTRAVASCULAR COAGULOPATHY
MAIN CAUSES IN
DIAGNOSIS
MANAGEMENT
PREGNANCY
Placental abruption Clinical observation
Insertion of at least 2 large infusion lines
Preeclampsia &
Vaginal bleeding, oozing from
Send at least 20ml of blood for cross-matching
eclampsia
venepuncture sites & surgical incisions.
& coagulation profile, and request at least 6
units of blood & 4 units of FFP.
Endotoxic shock
History of any of the above risk factors.
Correct hypovolaemia by fluids & whole
septic abortion,
Whole blood clotting time prolonged
blood
chorioamnionitis
( Normal 5-10 minutes)
and puerperal
Correct coagulation disorder by FFP
Coagulation profile :
sepsis
NB:- platelet transfusion only indicated in
Platelet count reduced (Normal
Amniotic fluid
presence of active bleeding if platelet count is
150,000 350,000)
embolism
Fibrinogen level reduced ( Normal 2-4 less than 50,000 , and if no active bleeding, if
platelet count less than 20,000.
Prolonged shock
gm/L)
Empty the uterus as rapidly as possible by
Prolonged retention
APTT prolonged (Normal 35-43
delivery or D&C.
of dead fetus
seconds)
NB- DIC is always a 2ry phenomenon to an
missed abortion or
PT prolonged (Normal 10-14 seconds)
underlying stimulus, and is usually self-limiting if
IUFD for >5 weeks
TT prolonged (Normal 10 seconds)
the stimulus producing it is removed therefore
FDPs levels increased
the uterus should be emptied as rapidly as
possible

THROMBOEMBOLISM
RISK FACTORS
Pregnancy hypercoagulate state .
Maternal age > 35 years.
Parity > 4
Obesity > 80 kg.
Caesarean section, particularly
emergency C.S
Previous history of
thromboembolism
*the risk of recurrence of
thromboembolism is 12%, & the
majority occur after delivery .
Prolonged hospital stay.
Family history of thromboembolism.
Thrombophilia ie. Congenital
deficiency of antithrombin III,
protein C or protein S, & presence
of factor V leiden.
Anti cardiolipin syndrome or
presence of lupus inhibitor
Cardiac disease such as valvular
prosthesis or atrial fibrillation.
Sickle cell disease.
Gross varicose veins.
Blood groups other than O
Suppression of lactation with
estrogen

DIAGNOSIS
DVT
PE
1- Sx: Pain & swelling in the leg
*There may be (50%) or may be not
(50%) prior clinical evidence of DVT.
2- Signs: temp of the leg, tender calf
1. Sx: Sudden onset of dyspnoea,
muscles, a difference of >2cm in the
chest pain, cough & haemoptysis,
circumference at identical sites of legs,
and sudden collapse in massive PE
and +ve Homan's sign.
*in 50% of patients there are no clinical 2. Signs: Cyanosis, rapid breathing &
jugular veins distention.
symptoms & signs referable to the
3.
Investigations:
limbs & pulmonary embolism may be
CXR: May be helpful ie.
the 1st indication of thromboembolism
Consolidation, infarction &
.
elevated hemidiaphragm on
*Over 80% of DVT are left-sided.
affected side, but can be totally
3-Investigations :
normal.
I.
Doppler U/S Noninvasive, safe,
ECG: Usually normal except when
accurate in 95%, more accurate if
the embolus is large.
DVT above the knee due to
absence of collaterals than if DVT
Respiratory alkalosis and low
below the knee due to presence of
Pco2 - due to hypoxia
collaterals.
hyperventilation with blowing off
II.
Ascending venography
of CO2 and respiratory alkalosis.
Contraindicated in the 1st
Ventilation & perfusion lung scan
trimester, and maybe indicated
Pulmonary angiography.
after that if Doppler U/S is not
informative.

ANTICOAGULANTS
HMWH HEPARIN
@ High molecular weight heparin
Rarely used ( if LMWH is not
available ).
Given by I.V route. The therapeutic
dose is 10,000 units bolus dose ,
followed by 24,000 units / day,
given via infusion pump.
Monitored therapeutic dose (1mg/kg/day 2x/day) by APTT; should be 2 times
of control.
Monitor maintenance (40mg/ml 1x/day) & prophylactic (20-40mg/ml 1x/day)
dose by plasma heparin level; should be 0.2-0.4 units/ml.
The action of therapeutic heparin is inhibition of thrombin & factors IX, X, XI &
XII.
Heparin DON'T cross the placental barrier & so can be used safely during
pregnancy
The side effect is bleeding.
If bleeding occur, stop the treatment, and in practice this is enough. Rarely if
bleeding not stopped, give specific antidote ie. Protamine sulphate.
The advantages of heparin compared to warfarin - are:1. Does not cross the placenta
2. Small dose prophylaxis- no haemorrhagic hazard
3. Easily and rapidly reversed as heparin disappears from the circulation in 6
hours.
The disadvantages:1. Osteoporosis if given for more than 6 months
2. Thrombocytopenia.
LMWH HEPARIN
Low molecular weight heparin (LMWH)
e.g Enoxaparin sodium (Clexane).
The preferred type used now.
Given by S.C route. The therapeutic
dose is 2 mg/kg/day, given in two
divided doses.

ORAL WARFARIN
The dose is 2.5-5 mg/twice daily
Monitored by International Normalized
Ratio ie. INR (which should be around
2 ) & by PT (which should be 2-2.5
times of control.)
MOA: Inhibition of the synthesis of Vit-K
dependent factors: II, VII, IX & X.
Disadvantages of warfarin are:
1. Bleeding
2. Teratogenic - if given in 1st trimester
during the period of organogenesis coz
warfarin cross the placenta:
chondrodysplasia punctata, cerebral
haemorrhage, calcification &
microcephaly.
3. Fetal & Neonatal cerebral
haemorrhage if given after 36 weeks.
4. Effect not easily or rapidly reversed
as warfarin disappears from the
circulation in 3 days.
In case of bleeding, antidote is FFP.
*Neither heparin nor warfarin are
excreted in breast milk, so that they are
safe to be used during lactation.

MEDICAL TREATMENT OF THROMBOEMBOLISM

ACUTE PHASE
Therapeutic dose of heparin. Either LMWH or HMWH.
LMWHs duration of acute phase therapy 2 3 months.
LMWH (Clexane)
HMWH
The therapeutic dose is 2 mg/kg/day, given in two
The therapeutic dose is 10,000 units bolus dose, followed by
divided doses
24,000 units / day, given via infusion pump.
LONG TERM THERAPY
Either LMWH (S/C) heparin or Oral Warfarin
- If thromboembolism occurs during pregnancy the best after acute phase therapy for 2-3 months, is to give S/C heparin
in the maintenance dose for the rest of pregnancy ( in order to avoid side effects of warfarin during pregnancy) & for 12
weeks postpartum of either S/C heparin or warfarin.
- If thromboembolism occurs after delivery S/C heparin in therapeutic dose for 4 weeks, then either S/C heparin in
maintenance dose or oral warfarin , for 3 months.
HEPARIN
WARFARIN
Given by SC route. The best is LMWH, if not available, HMWH.
Given orally.
Dose of LMWH (Clexane) 40mg/ 1x/day. HMWH 5000IU 2x/day.
Dose is 2.5-5mg 2x/day
Monitored by plasma heparin level; should be between 0.2-0.4 units/ml.
*Monitoring of maintenance or prophylactic dose of SC heparin by APTT is of no value,
coz maintenance & prophylactic dose doesnt level of coagulation factors & so
doesnt cause prolongation of clotting time.

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COUNSELING AFTER AN ATTACK OF THROMBOEMBO DURING PREGNANCY

Explain the risk of recurrence in future pregnancies which is about 12 %
Explain the need for prophylactic anticoagulatnts in future pregnancies
Avoid the use of combined contraceptive pill.
Consider screening for thrombophilia in absence of other risk factors
POLICY OF PROPHYLAXIS

No hx.
Did c-section.
With 1 risk factor.
1 hx of DVT
No risk factor.

Delivery

Delivery
1 hx of DVT.
Other risk factor (e.g.
admitted to hospital)

Admission

Delivery

1wk postpartum

6wk postpartum

6wks postpartum

Hx of 2DVT or 1PE or
anticardiolipin or lupus
inhibitors presence or cardiac Pregnant
Delivery
2months
indication for prophylactic
postpartum
anticoagulants (eg AF,
valvular prosthesis)
*The policy of prophylactic anticoagulant during pregnancy in previous history of pulmonary embolism or DVT or
thrombophilia is by LMWH once daily throughout pregnancy up to 12 hours before delivery .
*The policy of prophylactic anticoagulant during pregnancy in cardiac indication : warfarin in the 1st trimester & up to 36
weeks and then by HMWH, I.V, 6000 units/6hrs up to 12 hours before delivery.
*S/C heparin is not effective in prevention of cardiac thrombosis, and so warfarin given in the 1st trimester in spite of its
known teratogenic effects.