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
(platelet adhesion ) Platelet attachment to vascular end byVWF (platelet activation) By collagen ,thrombin and thrombexan A2Release of alpha and dens granules leading to more aggregation and recruitment And expression ofsurface glycoproteins receptors for fibrinogens and formation of platelet plug
It is series of sequential events (coagulation cascade) leading to formation of stabilized cross linked fibrin . How?
Tissue factor(III) Activation of factor VII This pathway is down regulated Activation factor X by tissue factor pathway inhibitor Protrhrombin thrombin
Intrinsic pathway Activated factor XII Activated factor XI Activation of factor IX Activation of factor XProtrhrombin thrombin fibrin monemer XIII stabilized fibrin
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
FIBRINOLYTIC SYSTEMIMPORTANCE: Localize thrombus formation to the side of the injury Limit thrombus size How ???????
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 INHIBITORActivation of protein C Plasminogen to which is natural anti plasmin coagulantInactivation of factor V Formation and production and VIII of FDPs
to prepare the expectant mother to thehaemostatic challenge of delivery-Increased factor V,VII,VIII,IX ,X ,XII , fibrinogen and VWF.-Increased resistance to protein C anddecrease in protein S-Mild increase in platelets.
-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
itself is a risk factor for venous thromboembolism and is associated with 10 fold increase compared with the risk of non pregnant women.
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
Most inherited conditions are associated with increase in the risk of venous thromboembolism Acquired conditions are associated with both arterial and venous thromboembolism
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)
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
Its vit K dependent protein and is a cofactor to protein C Its level is decreased during prgnancy Its prevelance is not known
It is natural anticoagulant which inactivate factors IX,X,XI and XII Autosomal dominant 1:5000 Risk of thrombosis 70%
Causes :-mutation of the gene for clotting factor V ( factor V leiden) - increase factor VIII - antiphospholipid antibodiesPrevalence :2:15 % in caucasianMost common inherited thrombophiliaIt increases the risk of thromboembolism by 20 folds
Prevalence :2% It increases plasma prothrombin level It increases the risk of VTE by five timescauses : -genetics -acquired (vit B6 ,B12 deficiency and anti folic medications)Its associated with both arterial and venous thrombosis
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.
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
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
Diagnosis Performed only in selected patients when the result affect the managementSelect testing should be considered mainly in the followingcircumstances:-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)
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.
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
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
Risk factor for VTEPREVIOUS VTE THROMBOPHILIA SURGICAL OHSS PROCEDUREAntithrombin 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)
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.