2. HEMOSTASIS:
Is a physiological process designed to limit
and stop the bleeding.
Hemostasis involves:
-vasoconstriction of blood vessels
- platelet plug formation
- fibrin clot formation
- Clot dissolution
3.
4. (platelet adhesion )
Platelet attachment to
vascular end byVWF
(platelet activation)
By collagen ,thrombin and
thrombexan A2
Release of alpha and dens granules leading to more
aggregation and recruitment And expression of
surface glycoproteins receptors for fibrinogens and
formation of platelet plug
5. It is series of sequential events (coagulation
cascade) leading to formation of stabilized
cross linked fibrin .
How?
6. Tissue factor(III)
Activation of factor VII
This pathway is
down regulated
Activation factor X by tissue factor
pathway
inhibitor
Protrhrombin thrombin
7. Intrinsic pathway
Activated
factor XII
Activated factor XI
Activation of factor IX
Activation of factor X
Protrhrombin thrombin fibrin monemer XIII stabilized fibrin
8. At the same time +ve feed back is mediated
by thrombin itself
Activated
thrombin
activation of intrinsic
pathway
leading to continous
formation of thrombin
fibrin monemer XIII stabilized fibrin
13. Fibrinolytic
pathway
Endothelial cell This Is Regulated
Thrombin which bind
derived tissue By Ptn ALPHA 2
to thrombomodulin
plasminogen
to endothelial cell ANTIPALSMIN
activator
AND
PLASMINOGEN
ACTIVATOR
INHIBITOR
Activation of protein C Plasminogen to
which is natural anti plasmin
coagulant
Inactivation of factor V Formation and production
and VIII of FDPs
14. to prepare the expectant mother to the
haemostatic challenge of delivery
-Increased factor V,VII,VIII,IX ,X
,XII , fibrinogen and VWF.
-Increased resistance to protein C and
decrease in protein S
-Mild increase in platelets.
15. -Fibrinolytic system is reduced by
plasminogen activator inhibitor type I&II
- D-Dimer is also increased
All these changes return to normal 6-8
weeks post- partum
17. itself is a risk factor for
venous thromboembolism and is
associated with 10 fold increase compared
with the risk of non pregnant women.
18. A group of acquired or inherited conditions
predisposed to thrombosis.
Thrombosis includes :
-Venous thrombosis e.g. upper and lower extremities
with or without pulmonary embolism (most common
type)
- Arterial thrombosis e.g. MI and stroke
-Both arterial and venous
19. Most inherited conditions are associated
with increase in the risk of venous
thromboembolism
Acquired conditions are associated with both
arterial and venous thromboembolism
20. Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Factor V Leiden (activated protein C resistance)
Prothrombin G20210A mutation
Hyperhomocysteinemia ((Inherited &acquired)
Antiphospholipid syndrome(Inherited &acquired)
(Alpha macroglobulin deficiency-hyperfibrinogenemea-
plasminogen deficiency- thrombomodulin deficiency -factor
VII ,VIII, XI excess)
21. Its vit K dependent protein with its cofactor
protein S
I t leads to activation of factor V &VII
its deficiency is autosomal dominant
Thrombosis occurs in 25% of pregnancies
without anticoagulant
22. Its vit K dependent protein and is a cofactor to
protein C
Its level is decreased during prgnancy
Its prevelance is not known
23. It is natural anticoagulant which inactivate
factors IX,X,XI and XII
Autosomal dominant
1:5000
Risk of thrombosis 70%
24. Causes :-mutation of the gene for clotting
factor V ( factor V leiden)
- increase factor VIII
- antiphospholipid antibodies
Prevalence :2:15 % in caucasian
Most common inherited thrombophilia
It increases the risk of thromboembolism by 20 folds
25. Prevalence :2%
It increases plasma prothrombin level
It increases the risk of VTE by five times
causes : -genetics
-acquired (vit B6 ,B12 deficiency and
anti folic medications)
Its associated with both arterial and venous thrombosis
26. Either : 1ry
2ndry- autoimmune e.g. SLE
- drugs e.g. procainamide
- viral e.g. hepatitis, HIV &syphilis
Clinically presented by increases in the risk of
both arterial and venous thrombosis.
27. Prevalence
Is present in 15 % of westren population
And about 50 % of those with previous
history of VTE
Symptoms and signs
There is no specific symptoms or signs but the
most common clinical manifestation of
underlying hypercoagulable state is lower limb
DVT with or without pulmonary embolism
28. Thrombophilia And Pregnancy Outcome
A systemic review reported the thrombophilic
associations with adverse pregnancy
outcome including:
Recurrent miscarriage
IUGR
IUFD
PREECLAMPSIA
Placental abruption
N.B :This occurs mainly with APS
29. Diagnosis
Performed only in selected patients when the
result affect the management
Select testing should be considered mainly in the
following
circumstances:
-Idiopathic VTE -VTE at young age (<45 years)
-Recurrent VTE -VTE in unusual sites.
-VTE in the setting of a strong family history of VTE
-Recurrent pregnancy loss (more than three consecutive
first-trimester pregnancy losses without an
intercurrent term pregnancy)
30. Careful timing of investigation and
interpretation are required as some tests of
heritable thrombophilia are affected by
pregnancy and post thrombotic state
Ideally, testing should be performed in the
outpatient setting at least 4 to 6 weeks
after any acute thrombotic event.
31. Activated APTT
PT
Thrombin clotting time
functional essay to asses antithrombin III
level of protein C
Antiphospholipid antibodies
Immonoreactive assay for protein S antigens
The modified APC:SR test
PCR based test for PGM and FVL
32. PREVIOUS TYPE OF THROMBOPHILIA RISK OF VTE IN ANTENATAL POSTNATAL
VTE PREGNANCY PROPHYLAXIS PROPHYLAXIS
YES ANY +VE TEST -- YES LMWH YES LMWH
NO Anti thrombin III deficiency 40-70% YES LMWH YES LMWH
NO Protein c def. 0-22% YES LMWH YES LMWH
NO Homozygous factor V 10% YES LMWH YES LMWH
NO Homozygous PMG ???? YES LMWH YES LMWH
NO PMG +FVL ???? YES LMWH YES LMWH
NO Protein S def. ???? ???CONSIDER
NO CONSIDER
ASPIRIN
NO Heterozygous FVL 3% NO CONSIDER ???CONSIDER
ASPIRIN
NO Heterozygous PMG 1-4% NO CONSIDER ???CONSIDER
ASPIRIN
YES ANY OTHER 30% YES LMWH YES LMWH
DEFECT
33. Risk factor for VTE
PREVIOUS VTE THROMBOPHILIA SURGICAL OHSS
PROCEDURE
Antithrombin III Protein C &S hyperemesis Severe infection
FVL Nephrotic synd. Severe dehydration Immotility >4 days
PGM Inflammatory Excessive blood loss preeclampsia
disorders
IBD
APS(Inherted Sickle cell disease Long haul travel Prolonged labor
&acquired type
Age>35 Gross varicose veins Midcavity C.S
instrumental
delivery
BMI>30 Myeloplorifertative Immobility HIT
disorders
Parity >4 Hyperhomocysteinaem Malignancy
ia(Inherted,acquired
type)
34. Women with three or more risk factors (table 2)
Should be considered for antenatal and
postparum LMWH for 3-5 days
Women with two risk factors (table 2)
Should be considered for postparum LMWH for 3-
5 days after vaginal delivery.