VTE: Dx / Mnt / Complications / Controversies

Content of this page Ischemic Limb: How to approach Thrombophilia Acquired  Hereditory  VTE prevention VTE prophylaxis in hospital In hereditory thrombophilia  PE  Special cirfumstances Cancer associated VTE  Pregnancy and VTE  Superficial thrombosis  VTE of unusual site  Treatment  First 5 days 5 days - 30 days Past 30 days  Apixaban in VTE  Complications Due to VTE Due to treatment  Controversies in management of VTE : ACP 2016  Extending VTE prophylaxis  Outpatient treatment of VTE  Ischemic LImb With no pulses (thrombosis or thromboembolism of limb arteries) Please see https://sites.google.com/site/medicinereference/cardiology/pad-and-chronic-venous-insufficiency-1 for details  With Pulse (thrombosis of limb microcirculation including small venules due to DIC leading to loss of natural anti-coagulant mechanism) 2 main syndromes if ALI with pulse DIC with DVT (Venous Limb Gangrene)  HIT, APLA, Metastatic Adenocarcinoma PEARL:  When using Coumadin for DVT, Thrombocytopenia is typically associated with INR > 4. Here, Supratherapeutic INR is a proxy of reduced Protein C  Cancer Patient, Platelet drop after use Heparin Bridge is Over due to consumption coagulopathy, and in association with INR > 4 Platelet count increases on restarting Heparin, and consumptive use of platelet will be decreased.  DIC without DVT  Symmetrical Peripheral Gangrene   Purpura Fulminans Septic Shock, Cardiogenic Shock PEARL: Thrombocytopenia, INR >2, Symmetrical Gangrene, Shock at some point  Other DDx Frostbite Ergotism Vasospasm (Idipathic or Scleroderma associated Raynaud's) Calciphylaxis Post-operative TTP  Myeloproliferative or Lymphoproliferative Disorders including Monoclonal gammopathies Certain Rheumatolgoical or Immunological Diseases APLA AOSD Uncontrolled Proinflammatory diseases UC  Reference: Ischemic Limb Gangrene with Pulses NEJM 2015 Supplement to: Ischemic limb gangrene with pulses. NEJM 2015 Thrombophilia Acquired Thrombophilia  Cancer Drugs (estrogen) APLA Hereditary Thrombophilia Mechanism of Thrombophilia  Loss of anti-coagulants Gain of Pro-coagulants  Approximate relative risks and prevalences within UK population for different heritable thrombophilias Factor V Leiden (most common),  heterozygous 3-5 , 4 homozygous 10, 0.05 Rare in Asian, and AA  Prothrombin gene mutation, heterozygous 2-4, 1.5 (2nd most common) Double heterozygosity for factor V Leiden and prothrombin gene mutation  Antithrombin deficiency (type 1) 5, 0.05 Protein C deficiency 10-20, 0.02 Protein S deficiency Uncertain, 0.1  Note: Except for PT Gene mutation, all hypercoaguable state are due to loss of anti-coagulant activity than due to actual procuaguable state.  Ref:  BMJ 2014  Severe vs Less Severe Thrombophilias  NEJM 2013  Less Severe: Heterozygous Factor V, Heterozygous PT Gene Mutation G2210A Severe: Everything other than less severe i.e Protein C, Protein S, Homozygous Factor V, Antithrombin Deficiency, APLA, homozygous PT Gene mutation, compound heterozygous of Factor V and PT gene mutation  Tests or Thrombophilia Screen Prothrombin time Prolonged in disseminated intravascular coagulation, liver disease, and warfarin treatment Activated partial thromboplastin time Prolonged in disseminated intravascular coagulation, liver disease, lupus anticoagulant and heparin treatment Antithrombin activity Low levels in disseminated intravascular coagulation, liver disease, and nephrotic syndrome, or heparin or L-asparaginase treatment Protein C activity (chromogenic) Low levels in disseminated intravascular coagulation, liver disease, and warfarin treatment Free protein S antigen Low levels in disseminated intravascular coagulation, liver disease, with acute phase reaction, pregnancy, and warfarin or hormones containing oestrogen treatment Factor V Leiden genotype Unaffected by clinical condition or drugs Prothrombin gene mutation Unaffected by clinical condition or drugs  Reference: Diagnosis and management of heritable thrombophilias BMJ 2014  VTE prevention  In hospitalized patient  PADUA: has not been prospectively validated VTE Prophylaxis in Hospital Venous Thromboembolism Prophylaxis in Hospitalized Patients: ACP Guideline Annals 2011 How I manage venous thromboembolism risk in hospitalized medical patients Blood 2012 Antithrombotic Therapy and Prevention of VTE, 9th ed: ACCP Clinical Practice Guidelines  2012 In thrombotic disorder (ALIWAPAS) RCT: In patients with aPL-positive with SLE and/or obstetric criteria for APS, adding warfarin to low-dose aspirin did not reduce risk for thrombosis. Rheumatology 2013 VTE prvention in a patient with ICH  http://stroke.ahajournals.org/content/41/9/2108.full.pdf Pulmonary Embolism Evaluation of Patients With Suspected Acute PE: Best Practice Advice From the Clinical Guidelines Committee of ACP Annals 2015 Evaluation of Patients With Suspected Acute PE: Best Practice Advice From the Clinical Guidelines Committee of ACP Annals 2015 Evaluation of Patients With Suspected Acute PE: Best Practice Advice From the Clinical Guidelines Committee of ACP Annals 2015 Evaluation of Patients With Suspected Acute PE: Best Practice Advice From the Clinical Guidelines Committee of ACP Annals 2015 Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla NEJM Editorial (PEITHO Trial) 2014 Diagnosis and management of pulmonary embolism BMJ 2013 How I diagnose acute pulmonary embolism Blood 2013 Acute Pulmonary Embolism NEJM 2010 Acute Pulmonary Embolism NEJM 2008 Chronic Thromboembolic Pulmonary Hypertension NEJM 2011 VTE in special circumstance  Cancer Associated VTE Treatment of cancer-associated thrombosis Blood 2013 Myeloproliferative neoplasms and thrombosis Blood 2013 Preganancy and VTE Venous Thromboembolic Disease and Pregnancy NEJM 2008 Pregnancy Complicated by Venous Thrombosis NEJM 2015 Superficial Throbosis Treatment of Lower Extremity Superficial Thrombophlebitis JAMA 2014 How I treat superficial venous thrombosis Blood 2011 VTE of unusal sites How I treat splanchnic vein thrombosis Blood 2014 Deep-Vein Thrombosis of the Upper Extremities NEJM 2011 Deep-Vein Thrombosis of the Upper Extremities NEJM 2010 Retinal-Vein Occlusion NEJM 2010 Thrombosis of the Cerebral Veins and Sinuses NEJM 2005 VTE Treatment First 5-6 days  Paradox, and Enoxapan are not used. They were bridged with parententeral agent for first few day Xarelto, Apixaban can be used from the beginning.  5-6 days to 3 month Pradoxa and Enoxapan can be used in this patient population After 3 month How I treat isolated distal deep vein thrombosis (IDDVT) Blood 2014 New Oral Anticoagulants for Acute Venous Thromboembolism JAMA 2014 Treatment of Venous Thromboembolism JAMA 2014 Apixaban in VTE  Oral Apixaban for the Treatment of Acute Venous Thromboembolism NEJM 2013 Apixaban for Extended Treatment of Venous Thromboembolism NEJM 2013 PE: treatment:   PEITHO Trial NEJM 2014 Complications related to VTE or its treatment  VTE complications VTE Recurrence Post-thrombotic syndrome  Upto 50 % of patients with acute DVT Upto 2 yrs after diagnosis of DVT  How I treat postthrombotic syndrome Blood 2009 Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. (With proximal DVT, elastic compression stockings no better than placebo stockings) Lancet 2013 CTEPH CV events  Anti-coag complications :  Please use this link: Management-of-an-anticoagulated-patient and complications Controversies in management of VTE : ACP 2016  VTE prophylaxis in high risk medical patient upon discharge  EXCLAIM study : Annals 2012  Enoxaparin extended by 30 days.  Most of the events were asymptomatic clots. NNT: 46 to avoid one event NNH: 220 patients to have one major bleeding.  Not a standard of care yet ADOPT Trial (DOAC / NOAC) Apixaban 2.5 mg BID for 30 days vs (???) enoxaparin 40 g / day for 10-14 days No significant outcome.  Slight increased risk of bleeding with apixaban Rivaroxaban Increased risk of bleeding  MEINWE CA MAFLLN Summary: Not approved for out of hospital prophylaxis  Outpatient treatment of PE Small PE  Absence of cardiac stress or strain (BNP, Troponin, ECHO) Study HESTIA study  ACCP guidelines 2016 VTE without cancer: DOAC is preferred over warfarin (2B) VTE and Cancer: LMWH over warfarin (2C) VTE treated with anticoagulation. Recommend against IVC filter (1B) Recurrent VTE on oral anti-coagulation: Switch to LMWH at least temporarily (2C) DOAC in pregnancy associated VTE or postpartum (if beast feeding) Massive PE or DVT (Phlegmesia cerulean dolmens): Role of thrombolysis? Very obese or frail patients: DOAC?? Renal dysfunction (Cr < 30) and role of DOAC?? Patients with altered GI anatomy (gastric bypass procedures) and DOAC? Are they really absorbing the medication? Caution of DOAC use in "difficult" or highly prothombotic patients? Recurrent VTE Active Cancer patient  APLS  HIT  Non-compliant patient: Probably Warfarin is better.