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  • VenousThromboEmbolism (VTE) Deep Vein Thrombosis – DVT Pulmonary Embolism – PE

    Dr. Mudi Misgav

    The National Hemophilia & Thrombosis center

    http://newsnetwork.mayoclinic.org/files/2014/01/DVT.jpg

  • Topics

    Treatment options

    Treatment duration

    Cancer associated VTE (CAT)

    Medical patients

  • VTE treatment

    AC Thrombolysis PMCDT

    Pharmaco-mechanical catheter directed thrombolysis

    AC – Anticoagulation

  • תיאור מקרה בריא , 25בן

    כאב שמתחיל בסובך שמאל

    . והרגל מתנפחת לכל אורכהמתגבר ימים הכאב 5במהלך של

    -פנייה לחדר מיון

    Fem-Pop DVT

  • The probability of DVT (DVT in 3months FU)

    ≥ 3 High (49%)

    1 / 2 Intermediate (14.3%)

    ≤ 0 low (3.2%)

    Modified Well’s criteria

    Wells, Anderson et al . Lancet 1997 Anderson DR , et al . Arch Intern Med . 1999

    Previously documented DVT 1

    The probability of DVT ≥ 2 DVT likely

    ≤ 1 DVT Unlikely

  • Recurrent VTE

    NEJM 1992

    Chart1

    AC

    UFH+AC

    20

    6.7

    Sheet1

    AC UFH+AC

    20 6.7

  • Chest 2010

  • Chest 2010

  • Anti-coagulation

    LMWH vitK antagonist DOAC

    “Traditional” treatment

  • Prothrombin

    Fibrinogen Fibrin

    Va

    TF

    Extrinsic pathway

    Intrinsic pathway

    Xa

    VIIa

    Oral DXa Inhibitor

    Rivaroxaban (Xarelto)

    Apixaban (Eliquis)

    Thrombin (IIa)

    Oral DTI Dabigatran (Pradaxa)

  • Acute VTE treatment studies

    RE-COVER (I+II) (dabigatran)

    • DVT-PE (2009+2013)

    EINSTEIN (rivaroxaban)

    • DVT (2010) • PE (2012)

    AMPLIFY (apixaban)

    • DVT-PE (2013)

    HOKUSAI VTE (edoxaban)

    • DVT-PE (2013)

    27,023 patients

  • DOAC

    Pradaxa (Dabigatran)

    Re-Cover UFH/LMWH for ~10d

    Pradaxa 150mg B.I.D

    Xarelto (rivaroxaban)

    Einstein Dosing: 15mg B.I.D

    for 21d follow by 20mg O.D

    Eliquis (Apixaban

    Amplify Dosing: 10mg B.I.D for 7 days follow by

    5mg B.I.D

    * The comparator warfarin

  • Events DOAC ENX-VKA

    Rec VTE 2.04 % 2.26%

    MB+CRNMB 7.34% 9.77%

    Main outcomes

  • Odds ratio meta-analysis plot [fixed effects]

    0.2 0.5 1 2

    HOKUSAI 0.82 (0.58, 1.16)

    AMPLIFY 0.83 (0.58, 1.20)

    EINSTEIN PE 1.14 (0.74, 1.75)

    EINSTEIN DVT 0.69 (0.44, 1.09)

    RECOVER II 1.08 (0.62, 1.89)

    RECOVER I 1.06 (0.63, 1.78)

    combined [fixed] 0.90 (0.76, 1.06)

    odds ratio (95% confidence interval)

    Rec. Symptomatic adjudicated VTE OR = 0.89 (0.76 – 1.06) FIXED MODEL

    = Non-inferiorityיעילות זהה

  • MB+CRNMB OR = 0.70 (0.54 – 0.90) RANDOM MODEL

    Odds ratio meta-analysis plot [random effects]

    0.2 0.5 1 2

    HOKUSAI 0.80 (0.69, 0.93)

    AMPLIFY 0.42 (0.33, 0.53)

    EINSTEIN PE 0.90 (0.74, 1.08)

    EINSTEIN DVT 1.00 (0.78, 1.29)

    RECOVER II 0.61 (0.44, 0.86)

    RECOVER I 0.61 (0.44, 0.85)

    combined [random] 0.70 (0.54, 0.90)

    odds ratio (95% confidence interval)

    בטיחות עדיפה

  • VTE - Treatment

    Vitamin K antagonist

    UFH or LMWH

    Initial (0 to ~7days)

    Extended (~3 months to indefinite)

    Long-term (~7 days to ~3 months)

    Phases of anticoagulation

    LMWH, Dabigatran, Rivaroxaban, Apixaban, Edoxaban

    Rivaroxaban / Apixaban

    Kearon C et al. Chest 2012

  • VTE - Treatment

    AHJ 2018

  • VTE - Treatment

    AHJ 2018

  • תיאור מקרה כאב שמתחיל בסובך שמאל ותוך יומיים והרגל מתנפחת , 28בת

    -לחדר מיון פנייה . לכל אורכה

    Ilio-Fem DVT

  • Treatment

    AC PMCDT

    Pharmaco-mechanical catheter directed thrombolysis

  • Thrombolysis for Deep vein Thrombosis

     Not to decrease mortality

     Not to prevent recurrence

     To prevent Post-thrombotic syndrome

  • Post Thrombotic Syndrome

  •  209 pt randomly assigned to control 108 or CDT 101

     iliofemoral DVT within 21 days.

     FU for 24 months >>

    Lancet 2012

  • NNT = 8.7 NNH = 11.2

    Events CDT Standard Rx P

    Ilio-femoral V. (6m) 65.9% 47.4% 0.012

    PTS - 6m 30.3% 32.2% 0.77

    PTS – 24m 41.1% 55.6% 0.047

    Bleeding M+CRNM 8.9% 0%

    CaVenT 5 years follow-up  37 CDT Vs 63 of control had PTS (P

  • Thrombolysis for acute deep vein thrombosis -

    Cochrane Database Nov-16

    The rationale for the use of thrombolysis for DVT is

    to prevent long-term complications related to poor

    venus function including PTS and ulceration

  • Thrombolysis for acute deep vein thrombosis -

    Cochrane Database Nov-16

    Main results > Seventeen RCTs with 1103 Pt. > There was no significant effect on mortality > Systemic thrombolysis and CDT had similar effectiveness.

  • Thrombolysis for acute deep vein thrombosis -

    Cochrane Database Nov-16

    Main results (long term 6m-5y)

    > PTS significantly less (RR 0.66, P < 0.0001, NNT-4)

    > Complete clot lysis (RR 2.44; P = 0.002)

    > Bleeding complications (RR 2.23; P = 0.0006).

  • IVC-ilio-Fem deep vein thrombosis 10.4.18

    Mostly occluded

  • IVC-ilio-Fem deep vein thrombosis 10.4.18

    More than 50% patency

  • 692 pts with acute prox. DVT

    PCDT N= 337

    SOC N=355

    • Pharmaco-mechanic catheter directed thrombolysis • Standard of care

    ATTRACT study

     Inclusion criteria DVT symptom duration < 14d

    NEJM 2017

  • Events PCDT Standard Rx P PTS all types 46.7% 48.2% 0.56 Severe PTS 17.9% 23.7% 0.035 Recurrent VTE 12.5% 8.5% 0.09

    All bleeding 4.5% 1.70% 0.049 Major bleeding 1.7% 0.3% 0.049

    Primary outcome – PTS (6-24m)

  • March 2017

  • Events PCDT Standard Rx P

    Severe PTS 17.9% 23.7% 0.035

    - Ileo-femoral DVT 18.4% 28.2%

    - femoro-popliteal DVT 17.1% 18.1%

    Results Summary

  • * Compared with MB rates

    Events NNT NNH

    Severe PTS 17.2 71.4

    - Ileo-femoral DVT 10.2 71.4

    - femoro-popliteal DVT 100 71.4

    Risk-Benefit ratio

    High NNT - The average number of patients who need to be treated to prevent one bad outcome

  • Plegmasia cerulea Dolens Painful Blue edema

    Venous gangrena

    Thrombolysis ?  65

  • תיאור מקרה

    שלושה חודשים לאחר התחלת גלולות , 29בת

    מתארת כאב פליאוריטי וקוצר נשימה

    BP - 120 / 85

    HR - 125/min

    RR - 34 / min

    Temp. - 37c°

    Arterial O2 - 96%

  • Diagnosis of PE Modified Well’s criteria for Pulmonary Embolism (PE)

    ≤ 4 PE Unlikely > 4 PE likely

    T&H 2000

  • Fibrinolysis

  • Positive predictive value 40-80% Elevated D-dimer levels are not specific for VTE • Hospitalized patients

    • Elderly

    • Malignancy

    • Recent surgery

    • Renal insufficiency

    • Inflammation

    • Second and third trimester of a normal pregnancy

    D-dimer test

    dDimer negative predictive value of > 95 %

  • Suspected PE – Hemodynamically stable patients

    ≤ 4 PE Unlikely > 4 PE likely

  • Treatment ?

  • VTE treatment

    AC PMCDT

    Pharmaco-mechanical catheter directed thrombolysis

    AC – Anticoagulation

  • Low risk: Class I < 66, class II 66-85 >> 30d mortality 1-2%

    High risk: Class III 86-105, IV 106 -125 , V 125 >> 30d mortality 3-15%

  • Anti-coagulation

    LMWH vitK antagonist DOAC

    “Traditional” treatment

    Or

  • תיאור מקרה

    שבוע לאחר טיסה מיפן, 50בן

    גוש בריאה אובחן לפני כחודש נמצא בבירור: רקע רפואי

    קוצר נשימה חולשה , מתאר כאב פליאוריטי BP - 95 / 65

    HR - 125/min

    RR - 34/min

    Temp. - 37c°

    Arterial O2 - 93%

  • Suspected PE with shock or Hypotension

  • Suspected PE with shock or Hypotension

  • Echocardiogra