Are there still any valid indications for thrombophilia screening in DVT?

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1 Carotid artery stenosis and risk of stroke Are there still any valid indications for thrombophilia screening in DVT? Armando Mansilha MD, PhD, FEBVS Faculty of Medicine of University of Porto Munich, 2016

2 Risk Factors for Thrombosis Hereditary thrombophilia Atherosclerosis Acquired thrombophilia Immobility Thrombosis Surgery trauma Inflammation Malignancy Estrogens

3 Circulation. 2008;118:

4 Acquired Thrombophilia Auto-immune diseases Antiphospholipid syndrome Bechet s disease Rheumatoid arthritis Malignancy Myeloproliferative disorders Essential thrombocythemia Polycythemia vera Hemolytic anemias PNH Inflammatory bowel disease Crohn disease Ulcerous colitis Acquired AT deficiency Liver disease Nephrotic syndrome

5 Antiphospholipid Syndrome - APLS Clinical criteria Vascular thrombosis Venous thrombosis 50% Arterial thrombosis CNS (AIS) 50% Cardiac 25% Eye, kidney, peripheral thrombosis 25% Embolism 4% Pregnancy morbidity Laboratory criteria Lupus anticoagulant Clotting test, dependent on PLs Anti-aCL antibodies ELISA - IgG and/or IgM, titers >40 GPL /MPL Anti- b 2 - GPI antibodies ELISA - IgG and/or IgM, titers >20 GPL/MPL

6 Inherited Thrombophilia - Presentation VTE before years of age Unprovoked thrombosis at any age Recurrent thrombosis at any age Thrombosis at unusual or multiple sites Strong family history of VTE

7 Inherited Thrombophilia - Presentation Venous thromboembolism DVT Pulmonary embolism VT at unusual sites Cerebral venous sinus Splanchnic veins Upper limb Retinal vein occlusion Purpura fulminans Neonatal Warfarin-induced skin necrosis Obstetric problems Recurrent miscarriage Prematurity Low-weight newborns HELLP syndrome Arterial thrombosis Peripheral arterial occlusion Acute myocardial infarction Ischemic stroke

8 Inherited Thrombophilia Natural coagulation inhibitors deficiencies Antithrombin Protein C Protein S Raise of levels / function of clotting factors Factor V Leiden (FVR506Q or apcr) Prothrombin G20210A FVIII, IX and XI Dysfibrinogenaemia Impared fibrinolysis

9 Prevalence and Clinical Significance of Hereditary Trombophilias Preval. N (%) Preval VTE (%) RR for 1ºVTE RR - recurrence Def. AT Def. PC Def. PS FV Leiden Heter. FV Leiden Homoz G20210A K.Cohoon et al. Circulation,2014,129:

10 Thrombophilia Evaluation Key Points Why? Who? Clinic usefulness Which tests? When? Family studies Results Anticoagulant therapy

11 Why should be tested Clinical usefulness To establish the pathogenesis and etiology of thrombosis To influence duration of therapy - Risk of recurrence To offer prophylaxis to high-risk patients during periods of potentially increased stimulus To alert patient s kindred to the presence of high-risk thrombophilia Prophylaxis in high risk circumstances Avoid oral contraceptives or HRT

12 Who should be tested Unprovoked VTE and < 50 years Recurrent VTE and < 50 years VTE + family history of unprovoked/recurrent thrombosis Pregnant women with a previous unprovoked VTE Cerebral vein thrombosis and <50 years Asymptomatic relatives of patients with thrombophilias AT, PC and PS deficiencies, FV Leiden homozygotes, Combined thrombophilias (FVLeiden + G20210A)

13 Do not test Unselected patients presenting with a first episode of VTE To assess the thrombotic risk in patients admitted to hospital Asymptomatic relatives of those with low-risk thrombophilia Central venous catheter-related VTE

14 What should be tested Functional assay of antithrombin Functional assay of protein C Functional assay of protein S Repeat tests for identification of deficiencies APCR detection Genetic assays FV Leiden mutation Prothrombin G20210A mutation Clotting test for lupus anticoagulant/elisa for cardiolipin and b 2 GPI antibodies Measurement of fasting total plasma homocysteine

15 When should be tested Do not test for thrombophilia at the time of acute VTE Treatment not influenced by test results Reduction of natural anticoagulants Higher FVIII Do not test under anticoagulation therapy Heparin reduce AT AVKs reduce PC, PS; interferes with LA determination

16 How should be tested Patient permission and counselling is needed before testing Psycological impact Socio-economic impact Experienced laboratory staff and internal and external laboratory quality controls Results interpretation by an experienced clinician The incidence of thrombosis in thrombophiliac individuals is variable Failure to identify a thrombophilic defect on laboratory testing does not prove that no thrombophilia exists. Clinicians may overestimate the risk of thrombosis and underestimate the risks of anticoagulation.

17 PORTO 2017

18 Carotid artery stenosis and risk of stroke Are there still any valid indications for thrombophilia screening in DVT? Armando Mansilha MD, PhD, FEBVS Faculty of Medicine of University of Porto Munich, 2016

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