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ANESTHESIA & ANALGESIA, 2012
ThrombophiliaInherited or acquired abnormality of hemostasis
predisposing to thrombosis
• Prevalence and Relative Risk• Thrombophilia Testing Recommendation• Management Guidelines
• Among patients with unprovoked (DVT), up to 50% have an underlying thrombophilic defect
• One third of patients with unprovoked VTE will have a reoccurrence over the next 10 years
J Thromb Haemost.2006
• Thrombophilia must be considered in the context of other risk factors
• The therapy for acute thrombosis is no different for those with than for those without a recognized thrombophilia.
Prevalence of thrombophilia and relative risk estimates for various clinical manifestations
Br j Haematology, 2008
Thrombophilias
• Consistently associated with a first episode of VTE, with relative risk increases of 2 to 10
• Modestly increase the risk of recurrent episodes of VTE• Arterial thrombosis Is not consistent• Pregnancy complications Is not consistent
Thrombophilia: clinical manifestations
• Purpura Fulminans
• Superficial or deep vein thrombosis, pulmonary embolism
• Thrombosis of “unusual” venous circulations
(e.g., cerebral, hepatic, mesenteric, and renal veins; possibly arm, portal, and ovarian veins)
• Warfarin‐induced skin necrosis
• Possibly arterial thrombosis (e.g., stroke, acute MI)
• Recurrent fetal loss
• Possibly complications of pregnancy
(e.g., intrauterine growth restriction, stillbirth, severe pre‐eclampsia, abruptio placentae)
• Prevalence and Relative Risk• Thrombophilia Testing Recommendation• Management Guidelines
Thrombophilia Testing RecommendationGuidelines from the College of American Pathologists (CAP) and the American
College of Medical Genetics (ACMG) :
• First venous thromboembolism (VTE) <50 years of age• Recurrent VTE• VTE at any age with a strong family history of thrombotic disease
(i.e., several affected relatives or relatives with VTE<50 years of age)• VTE in an unusual site at any age
(such as the hepatic, mesenteric, portal, and cerebral veins)• women suffering VTE in association with pregnancy, the immediate
post‐partum period, or oral contraceptive use.
• It is less clear whether testing should be offered in cases of VTE in the setting of post‐menopausal hormone (oestrogen) therapy or unprovoked VTE for patients >50 years of age
FAVALORO et al. Pathology (2011)
To avoid testing:
False identification of congenital defects carries many adverse consequences (stress , psychological distress, potential for being placed on extended anticoagulation therapy)
(1) Just post thrombotic events Due to possible ‘consumption’ of the test parameter under investigation and thus leading to a possible false positive diagnostic event (e.g., low AT)
(2) Whilst individuals are on anticoagulant therapy e.g., heparin and (VKA) therapy may affect various test parameters such as APCR, AT, PC and PS
• With the obvious exceptions of genetic testing
FAVALORO et al. Pathology (2011)
Most commonly tested Inherited Thrombophilias
• Deficiencies of o Antithrombin
o Protein C Functional Assayo Protein S
• Mutations factor V Leiden and prothrombin G20210A• APS
o Lupus anticoagulanto Anticardiolipin antibodieso Anti–2‐glycoprotein 1 antibodies
• Measurment of fasting total Plasma Homocysteine
• Prevalence and Relative Risk• Thrombophilia Testing Recommendation• Management Guidelines
Thrombophilic individuals with VTE
Clinical/Laboratory EvalulationDuration Of Therapy
VTE and transient risk factor(i.e. trauma ,surgery ,immobility ,travel ) 3‐6 months
Idiopathic VTE(no identifiable transient risk factor is present) VTE in patient with heterozygous FVL, PG
mutation in the absence of other ongoing risk factors for VTE ? Factor VIII level
6‐12 months ,(may consider indefinite)
VTE in the presence of:More than one allelic abnormality (e.g FVL+PG)Heterozygosity for : AT, ?PC, ?PS deficiencyA life threatening VTE(e.g massive PE, cerebral, mesenteric VTE)Recurrent VTE, especially if idiopathicActive cancerAPS
Indefinite
Semin Respir Crit CareMed 2008
Recommended Prophylaxis during Pregnancy
RecommendationRisk group
Surveillance + GC StockingNo VTE / Thrombophilia
Surveillance + GC Stocking Or Heparin prophylaxis + 6weeks PP
History of single VTE / No Thrombophilia
Heparin prophylaxis + 6weeks PPHistory of single VTE / Thrombophilia
Heparin Treatment + Warfarin PPHistory of multiple VTE
Heparin prophylaxisRecurrent pregnancy loss/Thrombophilia
Heparin prophylaxis + low dose AspirinAntiphospholipid Antibodies
Conclusions
• Testing for thrombophilia serves only a limited purpose and should not be performed on a routine basis
• Thrombophilia testing in asymptomatic relatives may be useful in
• Families with antithrombin, protein C,or protein S deficiency,• Siblings of patients who are homozygous for factor V Leiden• Limited to women who intend to become pregnant or who would like to use oral contraceptives
• Testing for such defects to prolong anticoagulant therapy can not be justified
• ASH 2011
ASH, Hematology 2007
ASH, Hematology 2007
Semin Respir Crit CareMed 2008
Br J Haematol. 2008;143(3)