Basic info's about virchows traid,risk factors for TE during pregnancy,hypercoagulabiltiy states,APAS,factor V Leiden, protein C,and Antithrombin iii deficiency

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Pathophysiology
of Thromboembolism

2. is associated with:
• 2x fibrinogen
• 20 -1,000% factors VII, VIII, IX, X & XII
• vWF by 400 % at term
• Prothrombin and factor V remain unchanged
• Modest factor XIII and XI
• 40% protein S
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Why is pregnancy at risk?

3. • Parity
• Postpartum endomyometritis
• Operative vaginal delivery
• Cesarean delivery 9x in the risk of
thromboembolism compared with vaginal delivery
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Risk factors for TE

4.  Compression of the inferior vena cava, and
 Pelvic veins by the enlarging uterus
 Hormone-mediated in DVC 2° to:
 Estrogen
 Local production of prostacyclin and
 NO
Note:
Left leg veins thrombosis > right leg thrombosis
2° lower flow velocities
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5. • Age >35 years
• Obesity
• Trauma
• Immobility
• Infection
• Smoking
• Nephrotic syndrome
• Cancer
• Surgery
• Prior history of DVT or PE
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6. Introduction
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7. Endothelial injury
THROMBOSIS
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8. 1. Endothelial Injury
• Dysfunction or mechanical trauma
• Contribute thrombus formation
• Heart
• Arterial circulation
• Major consequence of endothelial cell injury:
• Vasculitis
• Endocardial injury

9. Abnormal Blood Flow
Turbulence
• Cause arterial and cardiac thrombosis by
• Endothelial injury or dysfunction
• Disrupt laminar flow
• Forming countercurrents and local pockets of stasis
Stasis
• Major contributor in the venous thrombi
• Prevent dilution of activated clotting factors

10. 3.
• Definition:
• Alteration of the coagulation pathways that
predisposes to thrombosis
• Also called thrombophilia
• Divided into:
1. Primary (genetic)
2. Secondary (acquired) disorders

11. TABLE: Hypercoagulable States
Common
• Factor V mutation (G1691A mutation; factor V Leiden)
• Prothrombin mutation (G20210A variant)
• 5,10-Methylenetetrahydrofolate reductase (homozygous
C677T mutation)
• Increased levels of factors VIII, IX, XI, or fibrinogen
Rare
• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency

12. Very Rare
• Fibrinolysis defects
• Homozygous homocystinuria (deficiency of cystathione β-
synthetase)

13. 2. SECONDARY (ACQUIRED)
High Risk for Thrombosis
• Antiphospholipid antibody syndrome
• Heparin-induced thrombocytopenia
• Prolonged bedrest or immobilization
• Myocardial infarction
• Atrial fibrillation
• Tissue injury (surgery, fracture, burn)
• Cancer
• Prosthetic cardiac valves
• Disseminated intravascular coagulation

14. Lower Risk for Thrombosis
• Cardiomyopathy
• Nephrotic syndrome
• Hyperestrogenic states (pregnancy and postpartum)
• Oral contraceptive use
• Sickle cell anemia
• Smoking

15. Antiphospholipid Antibody Syndrome
(APAS)
Definition:
• Xized by arterial or venous thrombosis or specific
pregnancy complications
• in women with laboratory evidences of (APAs) to
proteins bound to anionic phospholipids
 Previously called Lupus anticoagulant syndrome
 Antiphospholipid Antibodies (APAs)
• Self-recognition Igs
• Directed against proteins bound to phospholipids

16. clinical manifestations
 Recurrent thromboses
 Repeated miscarriages
• Inhibit throphoblastic invasion
• placental vessels thrombosis
 Cardiac valve vegetations
 Thrombocytopenia
 Pulmonary embolism
 Pulmonary hypertension
 Stroke
 Bowel infarction
 Renal failure
• Renal Microangiopathy

17. Two forms of APAS :
I. Primary APAS
• Patients exhibit only a hypercoagulable state
• Lack evidence of autoimmune disorders
• Occasionally with certain drugs or infections
II. Secondary APAS
• Well-defined autoimmune disease like SLE

18. Diagnosis
The diagnosis of APAS requires
1. The presence of prior or current vascular
thrombosis, or characteristic obstetric complications
2. At least one laboratory criterion (e.g.,
anticardiolipin antibodies or lupus
anticoagulant

19. Factor V Leiden Mutation
 Activated Protein C Resistance
 Most prevalent thrombophilic syndromes
 Characterized by resistance of plasma
 To the anticoagulant effects of activated
protein C
• Heterozygous mutation 20 to 40 % of nonpregnants
with thromboembolic disease
• Homozygous inheritance 100-fold

20. Protein C Deficiency
• With protein S inactivating factors Va and VIIIa
• Protein C levels are unchanged during normal
pregnancy
 Predisposes to coagulation
• Prevalence is 2 to 5 per 1000
• Inheritance is autosomal dominant
• Risk of thromboembolism in pregnant women is
3-20 %
 Most episodes occur during the puerperium

21. Antithrombin Deficiency
• One of the most important inhibitors of thrombin
in clot formation
• The most thrombogenic of the heritable
coagulopathies
 Homozygous antithrombin deficiency is lethal !!!
 Although antithrombin deficiency is rare,
 Affect 1 in 5000 individuals,
 Lifetime risk of thrombosis is 50-90 %
 50- 60 % during pregnancy , and
 33 % during the puerperium