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1. DR LAICHENA

2. Outline
 Definition
 Pathophysiology
 History
 Predisposing factors
 Examination findings
 Differentials
 Investigations
 Treatment
 Complications
 Prognosis
 Prophylaxis
 Conclusion

3. DEFINITION
It is the formation of a blood clot or clots within the venous vascular cavity.
Incidence
Exact incidence isn’t known because most studies are limited by the inherent
inaccuracy of clinical diagnoses.
1 in 1000 pregnancies.
Pregnancy is a hypercoagulable state
A pregnant woman has a fivefold risk of DVT compared to general population.
Caesarean section increases the incidence by 1-2%
Mortality
Death from DVT is attributable to massive pulmonary embolism.

4. Epidemiology
 Pregnancy and puerperium are well-established risk
factors for venous thromboembolism (VTE)
 The age-adjusted incidence ranges from 5 to 50 times
higher in pregnant versus non-pregnant women

5. Epidemiology
 Complicates 1 in 500-2000 pregnancies
 More common post partum
 Antepartum risk is equally distributed across
trimesters
 Twice as higher after a caesarean section than vaginal
delivery

6. Hemostasis
 Formation of clots in the walls of damaged blood
vessels
 Prevention of blood loss
 Maintaining blood in a fluid state within the vascular
system

7. Hemostasis
 Components of hemostasis
 Vascular spasm
 Initiation and formation of platelet plug
 Propagation of coagulation cascade
 Termination of antithrombotic control mechanisms
 Removal of clot by fibrinolysis

8. Clotting cascade

9. Hemostasis
 Control mechanisms and termination of clotting
 Antithrombin, heparin and glucosaminoglycan heparan
sulfate
 Activated protein C and S
 Tissue factor pathway inhibitor
 Prostacyclin and thromboxane
 Nitric oxide

10. Clot elimination and
fibrinolysis

11. Anatomical changes in
pregnancy and peuperium
 Venous Stasis
 Gravid uterus
 Low capacitance vessels
 Immobilisation
 Endothelial injury
 vascular injury and changes at the uteroplacental surface
during delivery
 instrumental, or surgical delivery

12. Coagulation changes in
pregnancy
 Increase in levels of Fibrinogen by 50% (450mg/dl
cf. 300mg/dl)
 Other factors increased: Factor VII, VIII, IX, X
 Factor II (prothrombin) increased slightly
 Factors XI, XII & protein S reduced
 Resistance to activated protein C.
 Decreased platelet per unit volume

13. Pathophysiology
Vascular clotting develops mainly due to circulating stasis, infection, vascular
damage, or increased coagulabiltiy of blood
All elements of Virchow’s triad; circulatory stasis, vascular damage and
hypercoagulability of blood are present during pregnancy and puerperium.
Virchow’s triad is more in pregnancy due to:-
i. Increased clotting factors VII, VIII and X
ii. Increase in caliber of capacitance vessels produces vascular stasis.
iii. Reduced fibrinolytic activity
iv. Pressure of the gravid uterus on pelvic veins reduces venous return
v. Antenatal rest, prolonged labour, dehydration, excessive blood loss, pressure
on the calf muscles during delivery, delay in mobilization, trauma and pelvic
infection.
vi. Vascular injury after delivery
Sites
 Posterior tibial and popliteal veins of the calf muscle and extend proximally as
far as the femoral or iliac veins or rarely even in into the IVC(Inferior Vena
Cava).
 Pelvic veins due to diminished blood flow in the hyper-trophied uterine veins
extending into the iliac veins

14. HISTORY
The symptoms and signs of Deep Venous thrombosis(DVT) are related to
the degree of obstruction to venous outflow and inflammation of the
vessel wall. Clinical diagnoses of DVT is neither specific or sensitive
with the false positive rate as high as 50%. Many patients are
asymptomatic however the history may include the classical features
which are;-
o Edema/Leg swelling of affected site of the legs
o Leg pain (50% of patients) and pain on dorsiflexion of the
leg(Homan’s sign)
o Tenderness(75% of patients)
o Local cyanosis
o Fever
o Warmth and erythema of the skin can be present over area of
thrombosis

15. Risk factors
 Immobilization
 Surgery
 Obesity
 Prior history of VTE
 Trauma
 Thrombophilias
 Prior use of oral
contraceptives
 Pregnancy or
postpartum status
 Stroke
 Malignancy

16. PREDISPOSING FACTORS
 Thrombophilia
Inherited thrombophilias are conditions that increase
the risk of thromboembolic disease.
During pregnancy, the thrombogenic potential of
these disorders is enhanced because of pregnancy-
associated changes in several coagulation factors.
 There are two types of thrombophlias:
Acquired thrombompilias.
Inherited thrombompilias

17. Acquired Thrombophilias
 Also called antiphospholipid syndrome.
 Presence in the serum of at least one type of
autoantibody known as an antiphospholipid antibody
(aPL).
Lupus anticoagulant antibodies
Anticardiolipin antibody antibodies
 Their presence predispose to risk of thromboembolism
and other obstetric morbidities( recurrent abortions,
preeclampsia, stillbirths)

18. Inherited Thrombophilias
 Are genetic conditions that increase the risk of
thromboembolic disease. And other obstetric
morbidities( abortions, Preeclamsia, IUGR,stillbirths)
Factor V Leiden, the most common cause of activated
protein C resistance
Prothrombin gene mutation (PGM)
Antithrombin (AT) deficiency
Protein C deficiency
Protein S deficiency

19. Clinical presentation
 DVT is more common in the left than the right leg.
 WHY

20. Reason
 Increased venous stasis in the left leg due to
compression of the left iliac vein by the right iliac
artery,
 Compression of the inferior vena cava by the gravid
uterus itself

21. EXAMINATION FINDINGS/SIGNS
1) Edema of affected limb usually unilateral.Commoner on the left as the
left common iliac vein is crossed by the right common iliac & left
internal iliac arteries thus increasing resistance to flow. A
circumference of 2-3cm greater in the affected limb than in the normal
limb 10 cm from the tibial tuberosity and 20cm from ASIS(Anterior
Superior Iliac Spine)
2) Pain and tenderness usually confined to the calf muscles or acting along
the course of the deep veins in the medial thigh.
3) Fever usually low grade.
4) Homan’s sign i.e. discomfort in the calf muscles on forced dorsiflexion of
the foot with the knee straight. (1/3 of patients with DVT)
5) Cyanosis of the affected limb
6) Warmth on the affected limb

22. DIFFERENTIAL DIAGNOSES
o Cellulitis (may coexist)
o Ruptured Baker's cyst (both may coexist) - especially in individuals with pre-
existing rheumatoid disease of the knee
o Spontaneous/post-traumatic calf haematoma
o Osteomyelitis
o Pyomyositis
o Pulmonary embolism
o Thrombophlebitis superficial or septic
o Lymphangitis
o Varicose veins
o Lymphedema
o Achilles tendonitis
o Arterial insufficiency
o Asymptomatic peripheral edema secondary to CHF, Liver failure, renal failure
or nephrotic syndrome.

23. INVESTIGATIONS
1) Imaging Studies
a) Doppler U/S - Gold standard
The flow of blood as detected by reflection of waves on rbcs is absent in DVT.
b) Impedance Plethysmography
Is based on recording changes in blood volume of an extremity, which are directly
related to venous outflow. Standardized graphs are used to discriminate
normal IPG study results from abnormal results.
c) IV contrast Venography
Is most definitive mtd of dx venous thrombosis bt 1-2% of patients develop
phlebitis following procedure
d) MRI
Reserved for specific occasions which ultra-sound findings are equivocal or
negative ultra-sound findings but strong clininical suspicion.
e) CT-SCAN
Requires contrast agents and ionizing radiation. DXT exposure to the foetus is
negligible unless pelvic veins are imaged.

24. 2) Lab Studies
D-dimer Blood test
Are fibrin degradation products (FDP)
D-dimer fibrin fragments are present in fresh fibrin clot and in fibrin degradation
products or cross-linked fibrin.Monoclonal abs specific for the D-dimer
fragment are used to differentiate fibirn-specific clot form non-cross linked
fibrin and from fibrinogen. Thus has high sensitivity for venous
thromboembolism.
Low sensitivity

25. Treatment
 Rationale
 Prevent further clot extension
 Prevention of acute pulmonary Embolism(PE) cos
association with high mortality > 60%.
 Reducing the risk of recurrent thrombosis
 Limiting development of late complications e.g.
postphlebitic syndrome, chronic venous insufficiency.

26. TREATMENT
Consists of anti-coagulation, bed rest and analgesia.
1) Supportive management
Consists of elevating the affected limb(s), serial measurements, elastic stockings and
analgesia. Thus will alleviate the oedema and improve venous return & promote
early ambulation.
2) Definitive management i.e. Anti-coagulation
a) Heparin
used in the Acute phase
Can use either Unfractionated Heparin(UFH) or Low molecular weight
heparin(LMWT)
i)Using UFH, start with 10,000-15,000IU IV followed by contionous IV infusion of
10,000IU/ 4-6hrly. Aim is to make the APTT/KCCT 1.5-2X the control values
UFH can also be used s.c @ 10,000-15,000IU tds. Heparin cannot cross the placenta due
to its high molecular weight (16000-40000 daltons)
Pharmacodynamics
Anti-thrombin (an endogenous inhibitor of coagulation) inhibits clotting factor
proteases by forming equimolar stable complexes with them. Heparin catalyzes the
anti-thrombin-protease reaction without being consumed. Anti thrombin inhibits
the intrinsic pathway{Factor IIa (Thrombin), Factor IXa (Christmas factor), Factor
Xa (Stuart-Prower factor)}
Heparin enhances Anti-Thrombin activity.

27. Pharmacokinetics of UFH
Onset of action - 30mins
T1
/2 - 1.5hrs
Duration of action - 8hrs
Adverse effects
o Thrombocytopenia- is immune mediated and develops 6-10 days presenting
with artertial thrombosis-White Clot syndrome. It results from irreversible
aggregration of platelets induced by heparin
o Osteoporosis-prolonged use
o Hyper K+- inhibits aldosterone secretion
o Hypersensitivity
o Alopecia (rare)
Antidote;
Protamine sulphate 1mg/100U heparin IVI given within 15mins; Max dose; 50mg
(if exceeded may itself have anticoagulant effect).

28. ii) LMWT heparin (enoxaparin (clexane®), dalteparin)
o Inhibit FXa but have less effect on anti-thrombin & on coagulation in general
o Convenient to use - SC OD/BD
o Longer duration of action
o Does not require monitoring
o Reduce dose in renal insufficiency
o Disadvantage is their high cost.
b) Oral anticoagulation
Warfarin- Coumarin derivative
Is started once the acute phase is over and the APTT/KCCT IS 1.5-2X the control.
Warfarin is continued for 3-4 days while on Heparin s.c. unitl the INR IS 2-3X
the control then Heparin can be discontinued.
Initial dose is 5mg od and is titrated to get an INR OF 2-3X the control
Pharmacodynamics
Blocks the γ-carboxylation of several glutamate residues in extrinsic pathway
(Vitamin K dependent) factors II, VII, IX, & X as well as the endogenous
anticoagulant protein C & S. The blockade results in incomplete molecules that
are biologically inactive in coagulation.

29.  Warfarin is use in pregnancy:
 Controversial cos associated teratogenicity.
 Use after first trimester, convert patient back to Heparin at 36 weeks in
preparation for labor to avoid bleeding- neonate and mother.
 Instituted after delivery till end of puerperium.
o Lifelong in recurrent DVT, proximal DVT
Pharmacokinetics
Onset of action - 48-72hrs
T1
/2 - 36hrs
Adverse effects
o Hypercoagulability within the first few days of administration due to the rapid
degradation of Protein C & S which have a short half life in plasma (2.5-3hrs)
thus heparin is administered together with Warfarin for first 3-4 days.

30. Warfarin Antidote
o Stop the drug and administer large doses of vitamin K1 (phytonadione) 10mg -
takes 6-8hrs to take effect (disadvantage) & FFP or factor IX concentrates or
cryoprecipitates
o In emergencies, use fresh frozen plasma(FFP) or fresh blood.

31. warfarin embryopathy
 Warfarin crosses placenta and has teratogenic
potential.
 There is convincing evidence that warfarin
administration between the sixth and ninth weeks of
gestation is potentially teratogenic
 The most common developmental abnormalities affect
bone and cartilage; causing chondromalacia punctata,
with stippled epiphyses and nasal and limb hypoplasia

32. warfarin embryopathy
 central nervous system (CNS) abnormalities
(including optic atrophy, microcephaly, mental
retardation, spasticity, and hypotonia)
 Fetal or neonatal hemorrhage is a concern when
warfarin is administered in the third trimesters.
 So avoided in pregnancy when Heparin admnistration
possible.
 Avoid before week 14-16, convert to Heparin injection
at 36 weeks as you await labor.

33. c) Other treatment modalities are;
Venous thrombectomy still has a role in the management of patients with
extensive iliofemoral disease in which limb loss is imminent
IVC filters may be used in;
o Active bleeding
o When anti-coagulants fail
o To minimize risk of PE during venous thrombectomy
PROPHYLAXIS
o Heparin 5000IU s.c. bd
o Junior Aspirin 1 tablet od
o Claxane (LMWT Heparin) 40 mg od s.c.
PROGNOSIS
All patients with proximal vein DVT are at long term risk of chronic venous
innsufficiency.
Approximately 20% of untreated proximal(above the calf) DVTs progress to
pulmonary emboli, and 10-20% of these are fatal. With anti-coagulation
therapy the mortality is decreased 5- to 10- fold.

34. COMPLICATIONS
o Acute Pulmonary embolism
o Systemic embolism
o Chronic venous insufficiency
o Post- phlebitic syndrome( i.e. pain and edema in the affected limb without new
clot formation)
o Soft tissue ischaemia associated with massive clot and very high venous
pressures phlegmasia cerulea dolens
PREVENTION
o Avoid prolonged bed rest
o Early ambulation following Surgery
CONCLUSION
DVT is a clinical condition which needs early diagnoses so as to reduce the
incidence of pulmonary embolism and death.

35. Subsequent Pregnancies
 Prophylactic anticoagulation.

36. THANK YOU