COAGULATION DISORDERS

IN OBSTETRICS

Hassan I. N,
Resident 4 KCMC
 OBJECTIVES
At the end of this session you should be able to:
1. Describe why pregnancy is considered as a risk
factor for venous thromboembolism
2. Describe the physiology of coagulation/clotting
3. Describe the obstetric causes of coagulation
disorders
4. Describe the management of obstetric causes of
coagulation disorders
Background

 Pregnancy and the puerperium present as major challenges

to women's hemostatic system.
 associated with ↑ increased risk of VTE.
 In antepartum period
 VTE is ↑ 5-10 folds
 increased risk in all three trimesters

 In postpartum period
 higher risk
 daily risk 15- to 35-fold
Why pregnancy is considered a risk
factor for VTE
 Pregnancy is a state characterized by Virchow’s triad
 Hypercoagulability
 venous stasis and turbulence
 Endothelial injury & dysfunction

 The risk for each of these increases during normal

pregnancy

 Most evidence suggests that VTE is more common in the

postpartum period compared to during pregnancy
Hypercoagulability

 Pregnancy is a state of hypercoagulability due to

alterations of coagulation proteins.
1. Increase in several coagulation factors
 I, II, VII, VIII, IX, X

2. Decrease in protein S
3. Progressive increase in resistance to activated protein
C.
4. Decreased fibrinolytic system
 Increase in fibrinolytic inhibitors type-1 and type-2

 Plasminogen activator inhibitors (PAI-1 and PAI-2).

Stasis
 Stasis of the lower extremities results from
 compression of pelvic veins and IVC by the
gravid uterus

 Hormonally (progesterone) mediated

increase in deep venous capacitance.
Endothelial Injury
 Distention of the pelvic and lower extremity veins
due to stasis of blood.

 Operative delivery and particularly cesarean

delivery
 C/S is associated with a 9-fold increase in risk
for VTE.
PHYSIOLOGY OF COAGULATION

 The four components of coagulation

that continuously interrelate are:

1. The vasculature (vascular constriction),

2. Platelets (formation of platelet plug),
3. Plasma-Clotting Proteins (Formation of clot),
4. Fibrinolysis (Dissolution of clot)
The Vasculature
 Procoagulants promote coagulation, while
anticoagulants decrease coagulation.
 Factors that prevent blood clotting are
1. Natural anticoagulants
 Antithrombin III,
 Protein C,
 Protein S
2. Normal Blood vessel
Ctd……….
 The normal blood vessels prevent clotting by;
(1) Smoothness of the endothelial cell surface
 prevents contact activation

(2) a layer of glycocalyx on the endothelium

 repels clotting factors and platelets,

(3) a protein bound thrombomodulin-

 activates protein C.
Ctd……….
 When a vessel is ruptured/ traumatised,
 Procoagulants become “activated“ and override the
anticoagulants, then a clot does develop.
 the smooth muscles in the wall contract; instantaneously
reduces the flow of blood from the ruptured vessel.
 The contraction results from
 local myogenic spasm,
 blood platelet activation (Thromboxane A2)
 nervous reflex
Formation of platelet plug
 When platelets come in contact with collagen fibers, immediately
change their own characteristics drastically.
 They swell; they assume irregular forms with numerorous
pseudopds;
 contract forcefully and cause the release of granules
 they become sticky so that they adhere to collagen in the tissues
and to a protein called von Willebrand factor
 they secrete large quantities of ADP; their enzymes form
thromboxane A2.
 This lead to platelet aggregation and eventually formation of a
platelet plug..
Formation of a clot (Coagulation)
 There are three essential steps
1. Complex cascade of chemical reactions involving
more than dozen of coagulation factors leading to
formation of Prothrombin Activator
2. Conversion of Prothrombin to Thrombin
3. Conversion of Fibrinogen into Fibrin (Clot)
Formation of Prothrombin Activator (PA)
 PA is formed by two ways
 Extrinsic pathway- injury to blood
vessel
 Intrinsic pathway- injury to blood
 Extrinsic Pathway
 Activated by the tissue factor - thromboplastin
 This subsequently activates Factor VII when
vascular disruption occurs.
 Prothrombin is converted to thrombin, which
catalyzes the conversion of fibrinogen to fibrin.
 A clot is eventually formed at the site of
vascular injury.
Intrinsic pathway
 Requires injury to the blood itself

 Begins with Factor XII, which is

activated by contact with injured
epithelium.
Common Pathway
Fibrinolysis
 Plasma substrate plasminogen is activated.
 This substrate is converted to the active
enzyme plasmin,
 which lyses fibrin clots
 destroys fibrinogen and Factors XII and VII.
 This is also a protective mechanism against
intravascular thrombosis.
Fibrinolysis

Plasminogen

tPA

Plasmin
Fibrin Fibrin degradation Products (FDP)
Obstetric Causes of Coagulation
Disorders
1. Abruptio placenta
 Decidua is a rich source of tissue factor,
 the primary initiator of coagulation

 Haemorrhage into decidua causes DIC by either

 Release of thromboplastin into the circulation →
activation of extrinsic pathway or
 Intrauterine consumption of fibrinogen and other
coagulation factors
Obstetric Causes of Coagulation
Disorders
2. IUFD
 Release of excess tissue thromboplastin from the
dead fetus into the circulation
Obstetric Causes of Coagulation
Disorders
3. Amniotic fluid embolism
DIC may be caused by:
 Release of tissue thromboplastin into the
circulation → activation of extrinsic pathway
Obstetric Causes of Coagulation
Disorders
4. Sepsis
 Causes: Septic abortion, puerperal sepsis

 Mechanism
 Sepsis leads to release of mediators by inflammations
→ damage the vascular endothelium, platelet
aggregation & consumptive coagulopathy
Obstetric Causes of Coagulation
Disorders
5. Pre-eclampsia and Eclampsia
Cause DIC through the following
mechanisms
a. Release of tissue thromboplastin
b. Thrombocytopenia
 Obstetric Coagulation Disorders cont
6. Other Obstetric Causes
 Saline-induced abortion
 Massive blood transfusion - depleted platelets and clotting
factors
 Dilutional coagulopathy - haemodilution
 Amniotic fluid embolism
 Hepatitis
 Thrombophilia
 Acquired
 Inherited
ACQUIRED THROMBOPHILIA
 Recent major surgery,  Antiphospholipid syndrome
 Presence of a central
venous catheter  Renal disease
 Nephrotic syndrome
 Trauma,
 Renal transplantation
 Immobilization,
 Malignancy,  Cardiovascular risk factors
 Myeloproliferative  Obesity
disorders  Smoking
 Age
 Previous thromboembolism
INHERITED THROMBOPHILIA
 The five most common are
 Antithrombin deficiency

 Protein S deficiency

 Protein C deficiency

 Activated Protein C Resistance -The factor V Leiden

mutation,

 Prothrombin gene mutation,

Common manifestations of VTE in
pregnancy
 Include:
1. Superficial vein thrombosis
2. Deep vein thrombosis (DVT)
3. Pulmonary embolus (PE),
4. Septic pelvic thrombophlebitis (SPT),
5. Ovarian vein thrombosis (OVT)
DVT in Pregnancy
 Venous thromboembolism (VTE) may occur at any
time during gestation
 is much more likely to occur in the left leg
compared with the right leg
 Postulated to be the consequence of May-Thurner
syndrome,
 left iliac vein is compressed by the right iliac artery.
Clinical features of DVT
 pain
 swelling of the lower extremity
 Warmth
 Calf pain on dorsiflexion of the foot (Homans sign)
 A palpable, indurated, cordlike, tender
subcutaneous venous segment
 Variable discoloration of the lower extremity
Investigations for DVT in pregnancy
 D-dimers (Fibrin degradation products)
 Elevated in most cases
 compression ultrasound (CUS) of the lower extremity
veins
 Current initial test of choice
 not as accurate for diagnosis of pelvic DVT as for
extremity DVT
 MRI
 If CUS not conclusive
 Venography- Invasive contrast venography
Ctd….
 Bedside clotting time
 Used to assess F II, VII and X
 Normal 5 – 10 minutes
 Bleeding time
 Time required for haemostasis after skin
puncture ↑ in DIC
 Seen in thrombocytopenia
Ctd………
 Prothrombin time (PT)
 Measures the time required for clotting by extrinsic and
the final common pathways.
 Elevated in DIC

 Partial prothrombin time (aPTT)

 Measures the function of the intrinsic and the final
common pathways.
PULMONARY EMBOLISM
 Clinical Presentation
 dyspnea
 chest pain
 cough
 syncope
 hemoptysis
 tachypnea,
 apprehension,
 tachycardia.
 accentuated pulmonic closure sound,
 rales, and/or friction rub
Investigations ctd……
 ECG:
 Right axis deviation
 T-wave inversion
 chest radiography
 Normal about half
 atelectasis
 an infiltrate, or an effusion
 loss of vascular markings in the lung region supplied by
the obstructed artery
Diagnosis of PE:
 a high index of suspicion
Treatment
1. Primary goal:
 Correct the underlying cause
 Termination of pregnancy,
 Empty the uterus - evacuation
Special conditions
 Hypercoagulability states as in DVT
 Anticoagulants
 Indirect thrombin inhibitors
 Direct thrombin inhibitors
 Vitamin K antagonist

 Thrombolytic therapy
 Streptokinase (SK),
 recombinant tissue type plasminogen activator and
 recombinant human urokinase (UK)
Anticoagulants
1. Indirect thrombin inhibitor
 unfractionated heparin
 low molecular weight heparins (eg, enoxaparin),
 synthetic heparin pentasaccharides (eg, fondaparinux)
 Factor Xa inhibitors (eg, rivaroxaban).
2. Direct thrombin inhibitors
 Argatroban, lepirudin, and bivalirudin.
3. Vitamin K antagonist eg warfarin..
NOTE:
 Thrombolytic therapy
 associated with more rapid and complete
lysis of DVT and less postphlebitic
syndrome.

 seldom used in patients with DVT

Treatment of PE
 support blood pressure with vasopressors.
 Oxygen treatment
 endotracheal intubation
 mechanical ventilation
 thrombolysis
 filter placement
 embolectomy
Monitoring of treatment
 Unfractionated heparin
 aPTT

 For treatment of thrombosis

 target aPTT is 1.5-2.5 within the first 24hrs of
treatment.

 Heparin doses used for prophylaxis do not require

monitoring as do not lead to prolongation of aPTT
Ctd………..
Monitoring of Warfarin therapy.
 By the Prothrombin time(PT)-
 achieve an international normalized ratio (INR) of 2 to 3
Warfarin and Pregnancy.
 It freely crosses the placenta barrier.
 Teratogenic effect
 In first trimester may cause limb and facial defects
(warfarin embryopathy)
 In the last few wks of pregnancy may cause fetal
bleeding at delivery.
 Can be used from 12 to 36wks.
Labour and Delivery
 Heparin is discontinued during labour
 If aPTT is abnormal and there is a risk of bleeding
incremental doses of protamine .
 Planned elective induction of labour or LSCS at
least
 12 hours after prophylactic dose LMWH or UFH
 24 hours after therapeutic dose LMWH or UFH
STOPPING TREATMENT
 At least 6-12 weeks post partum or until at least
three months of therapy have been completed.

 Assess for the presence of ongoing risk factors for a

VTE prior to making the decision to stop
anticoagulation therapy.
 Complications of DIC
1. Complications of severe haemorrhage
2. Widespread fibrin deposition → multiple
organ failures including:
 Liver failure,
 Renal tubular necrosis,
 Lungs (hypoxaemia).
Sequelae of VTE
 pulmonary hypertension,
 venous insufficiency
 post-thrombotic syndrome,
 not well defined;
 symptoms (pain, cramps, heaviness, pruritus, and paresthesia)
 signs (edema, skin induration, hyperpigmentation, venous
ectasia, redness, pain during calf compression, and in more
severe forms, venous stasis ulcer) in the extremity affected by
DVT.