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Prevention and Treatment of DVT and PE (VTE) L. Bernardo Menajovsky, MD, MS. Associate Professor of Medicine Director, Anticoagulation Clinics Texas A&M Health Sciences Center College of Medicine Scott & White Memorial Hospital and Clinic Temple, Texas, USA

Prevention and Treatment of DVT and PE (VTE) · Prevention and Treatment of DVT and PE (VTE) ... Case Study #1 27-year-old woman ... • History of Hypertension and DM type 2

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  • Prevention and Treatment of DVT and PE (VTE)

    L. Bernardo Menajovsky, MD, MS. Associate Professor of Medicine Director, Anticoagulation Clinics

    Texas A&M Health Sciences Center College of Medicine Scott & White Memorial Hospital and Clinic

    Temple, Texas, USA

  • Need for recommendations - guidelines

    Most practitioners need to identify the useful and pertinent information for practice

  • When it comes to anticoagulation management

    ACCP guidelines 2012 AT9

    However

    There are several others

  • Grade

    Meaning (1,2)

    Evidence (A,B,C)

    1 A Strong

    recommendation

    High quality

    1 B Strong

    recommendation

    Moderate quality

    1 C Strong

    recommendation

    Low or very low quality

    2 A Weak

    recommendation

    High quality

    2 B Weak

    recommendation

    Moderate quality

    2 C Weak

    recommendation

    Low or very low quality

  • Strong recommendation: 1 Benefits clearly outweigh risk and burdens or vice versa (we recommend)

    Methodology grades of recommendation

    Weak recommendation: 2 Benefits closely balanced with risks and burden (we suggest)

    9th ACCP, Chest. 2012 Feb;141(2 Suppl):53S-70S.

  • AT9 has many weak recommendations (grade 2) replacing the strong recommendations (grade 1) of AT8...

    Main differences from AT8

    resulting in many 1A recommendations turning into 2A or, more commonly, 2B

    No New Studies Published

  • Methodology for AT9 More rigorous evaluation of studies with standardized

    methodology, reviewing the risk of bias, imprecision and inconsistency of results of a RCT

    Attempt to exclusion of financial and intellectual conflicts of interest Authors involved:

    Editor: Methodologists Clinicians with few experience on the subject Panelists: the experts (no voting)

    Caution in interpretation of single studies and recommendations

    9th ACCP, Chest. 2012 Feb;141(2 Suppl):53S-70S.

  • Decrease in 1 A recommendations

    2004 123 540 2008 182 901 2012 29 801

    1A Pages

    Hirsh J, Guyatt G, Lewis SZ. Chest. 2008 Jun;133(6):1293-5. PMID: 18574282 Guyatt GH. Chest. 2012 Feb;141(2 Suppl):48S-52S. PMID: 22315255

  • Apply recommendations to particular clinical scenarios

    and check whether these recommendations fit them

    It is always useful to read the small prints!

    Recommendations AT9

  • Big Change

    Hard Outcomes = Clinically significant VTE Soft Outcomes = Venographic or US VTE

    12

  • Facts

    50% clinically significant DVT Asymptomatic

    60-70% of Fatal PE Asymptomatic DVT

    Heit JA, et al. Arch Intern Med. 1999;159:445.

  • Application of Guidelines

    Real Life Cases

  • Case Study #1

    27-year-old woman, who began having left leg pain 6 days ago, woke up in the morning with the pain. Since the pain did not go away, she then went to the ED. The patient states that she has felt otherwise well. She denies any swelling of the leg or warmth, but she does complain of tenderness to palpation.

  • Case Study #1 (cont)

    PMH: Non-contributory. FH: Father prostate cancer. No clotting disorders PSH: Repair of septated uterus in 2003. SH: No smoking. Occ alcohol. No illicit drug use. ALLERGIES: allergic to penicillin. ROS: Just back from a non-stop 10 hr. car trip. MEDS: OCPs since age 17.

    16

  • Case Study #1 (PE)

    VS: BP 123/83, HR 88, RR 18, O2 sat on RA 97%. Temp 101.0.

    GEN: moderate distress (pain). HEENT; NECK; CV; LUNGS; ABD; all normal. EXTREMITIES: Mod tenderness to palp in left

    calf. Leg is warm, 1+ edema and erythema, positive Hommans sign. 2+ pedal pulses.

    The patient did not ambulate, but states that she has been walking with a limp because of the pain.

    17

  • Case Study #1 (Labs)

    CBC: WBC 10.3, Hgb 13.1, Hct 38.4, plat 153. CMP, and LFTs within normal limits. INR 1.2. Serum pregnancy test is pending.

    18

  • Q1: What is your diagnosis?

    1. DVT vs. Cellulitis. 2. Cellulitis vs. DVT. 3. Other

    19

    DVTvs.Cellulitis.

    Cellulitisvs.D

    VT.

    Other

    33%33%33%

    :10

  • Q2: What is your next step?

    1. Doppler US lower extremity veins.

    2. High sensitivity D- dimer.

    3. Start treatment immediately.

    4. Hypercoagulable panel.

    5. 2 and 4

    20

    DopplerUSlowerextremi..

    HighsensitivityDdimer.

    Starttreatm

    entim

    media...

    Hypercoagulablepanel.

    2and4

    20% 20%20%20%20%

    :15

  • Q3: Potential contributing factors for this patients condition are (except)?

    1. Use of OCPs 2. Long dist travel. 3. 1 and 2. 4. Age 5. None: All are

    contributing factors.

    23

    UseofOCPs

    Longdisttravel.

    1and2. Ag

    e

    None:Allarecontributin...

    20% 20%20%20%20%

    :10

  • Epidemiology Incidence 24

    Zller, Circulation 2011

    Higher risk in females aged 15-35 years Estrogen containing birth control pill Pregnancy

  • Epidemiology of VTE and HT

    99% of cases occur during the first 2 years 90% within the first 6 months.

    Zller, Circulation 2011

  • Long distance travel and VTE

    Evidence is poor Events are unusual The majority of patients have other major risk

    factors Only air travel longer than 6 hours in economy

    class has been studied Not a single study on land travel.

  • Case 1 (cont)

    All tests you order are pending and you decide to start systemic anticoagulation.

    27

  • Q4: In addition you order the following:

    1. Stop OCPs (particularly estrogen based) immediately and never use them again.

    2. Avoid traveling for at least one year.

    3. Graduated compression stockings, 40 mmHg at level of ankle

    4. Bed rest for at least one week.

    5. 1 and 2

    28

    StopO

    CPs(particularly...

    Avoidtravelingforatlea..

    Graduatedcompression...

    Bedrestforatleastone...

    1and2

    0% 0%0%0%0%

    :20

  • Estrogen-related VTE Management

    Attitude towards contraception Stop the estrogen-containing pill

    - No rush (anticoagulant therapy) - Refer to the physician in charge of her contraception - Estrogens should be stopped ideally 6 weeks prior to

    anticoagulant discontinuation

    Which contraception after a VTE? - Mechanical - Progestin-only pill or levonorgestrel-releasing intra-uterine

    device (Mirena) appear inoffensive, although no RCT is available to support this attitude. Avoid injectable progesterone

    - Never resume an estrogen-containing contraceptive

    29

    Conard, Contraception 2004

  • Estrogen-related VTE - Prevention

    Avoid their use in women with other VTE risk factors Age > 35 years Obese Family hx of VTE, particularly if first degree relatives

    with hormone-related thrombosis Known thrombophilia (but no evidence to support

    prior testing) Current smokers Hx of diabetes, hypertension, dyslipidemia

    30

  • Case 2 42 y/o white man comes to the ED with a 1 day

    h/o pain and swelling of the left upper extremity. The patient states that he was helping his

    brother-in-law moving to his brand new 2nd story apartment over the weekend.

    PMH: unremarkable. PSH: Appendectomy as a child. FHx: Parents alive and well; one sister (32) in

    good health except for trouble getting pregnant. SHx: Accountant; smokes and drinks

    occasionally; works out 5 times a week.

  • Case 2 (PE)

    Alert, moderate distress from pain on left arm. HEENT; Neck; CV; Lungs; Abdomen all normal. Left arm swollen and tender with prominence of

    superficial venous circulation. Pulses and sensation normal.

    32

  • Case 2 (Dx tests)

    Labs: All normal.

    Doppler US LUE: Occlusive thrombus on axillary, brachial and basilic veins.

    33

  • Q1: What is your next step?

    1. Start anticoag immediately with a LMWH and Warfarin the same day.

    2. Hypercoagulable panel. 3. No anticoagulation; arm

    elevation and warm compresses + NSAIDs

    4. Consult IR for venography and thrombolysis.

    34

    Startanticoagimm

    ediat...

    Hypercoagulablepanel.

    Noanticoagulation;arm...

    ConsultIRforvenograp..

    0% 0%0%0%

    :20

  • Anatomy of Upper Extremity

  • Types of UEDVT

    Primary Unprovoked or without thrombophilia-idiopathic Effort related Paget-Schrtter syndrome Thoracic outlet syndrome (TOS) Incidence

    - 2 per 100,000 person years - 30% of all UEDVTs

    Flinterman LE. J Thromb Haemost. 2008;6:1262-1266

  • Paget-Schrtter Syndrome Effort induced thrombosis

    Rapid onset of DVT after strenuous activity Intimal microtrauma to vessel wall after exertion Activation of coagulation system

    Occurs in young, healthy adults; males more often than female

    Should be treated as an emergency Considered venous manifestation of TOS

    Flinterman LE. J Thromb Haemost. 2008;6:1262-1266

  • Thoracic Outlet Syndrome

    3-10% of TOS cases related to vasculature; venous or arterial

    Compression of thoracic outlet veins by clavicle and first rib Rapid occlusion of vein Typically subclavian vein

    60% of patients with primary UEDVT have the TOS

    Watson HG. J Thromb Haemost. 2008;6:1267-1268

  • Treatment Recommendations- Paget-Schrtter Syndrome

    Course of action Venography Thrombolysis Anticoagulation Surgery

    Flinterman LE. J Thromb Haemost. 2008;6:1262-1266

  • Treatment Recommendations- Paget-Schrtter Syndrome

    Surgery Lysis of adhesions around subclavian vein Resection of part of clavicle and/or first rib Scalene muscle resection Subclavian vein patching Bypass procedures

    Flinterman LE. J Thromb Haemost. 2008;6:1262-1266

  • Case 3

    52 y/o white man with h/o COPD admitted for exacerbation and IV antibiotics. Right upper extremity PICC placed due to poor IV access.

    On hospital day # 3, RUE swollen, red and tender.

    PE: VS normal; Pox 96% on RA ; Lungs with decrease breath sounds, no wheezing.

    Right arm is slightly swollen and tender. No erythema, good pulses.

    Doppler US: Occlusive clot on Axillary, brachial, basilic, and cephalic veins.

    41

  • Q1: What is your next step? 1. Start anticoagulation

    immediately with a LMWH and Warfarin the same day. Leave PICC in place.

    2. Request a hypercoagulable panel.

    3. Remove PICC. No anticoagulation; arm elevation and warm compresses

    4. Consult IR for venography and thrombolysis

    42

    Startanticoagulationi...

    Requestahypercoagulab..

    RemovePICC.Noanticoa...

    ConsultIRforvenograph...

    25% 25%25%25%

    :20

  • Types of UEDVT

    Secondary Provoked by central venous catheters Pacemakers Cancer IV drug abuse Coagulation abnormalities

    - Protein C/S deficiency - Factor V Leiden gene mutation - Hyperhomocysteinemia - Antiphospholipid antibody syndrome

    Flinterman LE. J Thromb Haemost. 2008;6:1262-1266

  • Malignancy

    Related to placement of CVCs 18 fold increase risk of developing UEDVT compared

    to patients without active malignancy.

    Hypercoagulability of malignancy Tumor mass compression Comprises 24% of UEDVT cases Types

    Lymphoma Lung cancer

    Flinterman LE. J Thromb Haemost. 2008;6:1262-1266

  • Diagnosis

    Doppler Ultrasound Disadvantages

    - False negative - Clavicle may shadow segment of subclavian vein

    Use venography if Doppler is negative and strong clinical suspicion of UEDVT

    Gaffar M. Hospital Physician. 2005:29-34

  • Diagnosis

    Venography Gold standard Contrast dye injected into basilic vein Defects in intraluminal filling indicate thrombus Limited use due to complications and invasive nature

    Gaffar M. Hospital Physician. 2005:29-34

  • Diagnosis

    Magnetic Resonance Angiography Higher resolution imaging of thoracic veins compared

    to Doppler Blood flow information and collateral vessel

    visualization better Strong correlation to results of venography

    - Is noninvasive and accurate - May use if venography is contraindicated

    Gaffar M. Hospital Physician. 2005:29-34

  • Differential Diagnosis

    Hematomas Muscle contusions or tears Cellulitis Lymphedema Gangrene All may present with pain and swelling in upper

    extremity

    Gaffar M. Hospital Physician. 2005:29-34

  • Complications

    Pulmonary embolism Occurs in up to 30% of patients Occurs more frequently if CVC in place Less common than in patients with LEDVT

    Gaffar M. Hospital Physician. 2005:29-34

  • Complications

    Post thrombotic syndrome Occurs in up to 40% of patients Results from chronic venous insufficiency from clot Characteristics

    - Edema - Pain - Venous ulcers - Skin pigmentation changes

    Treatment/prevention

    Gaffar M. Hospital Physician. 2005:29-34

  • Treatment Recommendations

    Dependent upon anatomic distribution of thrombus Subclavian vein

    involvement - Mid-subclavian line and

    lateral-conservative treatment

    - Mid-subclavian line and medial-pharmacological management

  • Treatment Recommendations-Lateral to Mid-Subclavian Line

    Catheter related UEDVT Removal of line Conservative

    treatment - Bed rest - Local heat - Limb elevation - Compression arm

    sleeve Venogram demonstrating completely thrombosed right axillary-subclavian vein

  • Treatment Recommendations-Lateral to Mid-Subclavian Line

    Catheter related UEDVT Removal of line not possible

    - Anticoagulate patient for duration of line involvement - Repeat imaging after line removed

  • Treatment Recommendations-Medial to Mid-Subclavian Line

    Catheter Related UEDVT Removal of line if possible

    - Anticoagulate for total of 12 weeks Removal of line not possible

    - Anticoagulate patient for duration of line involvement - Begin 12 weeks of anticoagulation once line is removed

  • Case 4

    73 year old man scheduled for elective right total knee replacement surgery

    History of Hypertension and DM type 2 Creatinine clearance: 35 ml/min BMI 35 Med: metoprolol 50mg, HCTZ 12.5 mg, Lantus 10

    55

  • Q1: What VTE prophylaxis would you recommend?

    1. LMWH S/Q 2. Heparin (UFH): 5,000 U

    S/Q Q8hs 3. Heparin (UFH): 5,000 U

    S/Q Q12 4. Fondaparinux 2.5 mg. S/

    Q daily. 5. Dabigatran 75 mg PO

    every 12 hs 6. Rivaroxaban 10 mg PO

    daily 7. ASA 325 mg. PO daily

    56

    LMWH

    S/Q

    Heparin(UFH):5,000US..

    Heparin(UFH):5,000US..

    Fondaparinux2.5mg.S/...

    Dabigatran75mgPOeve..

    Rivaroxaban10m

    gPOdaily

    ASA325mg.POdaily

    14% 14% 14%14%14%14%14%

    :25

  • Q8hr dosing schedule 0700 1500 2300

  • Methods Compare:

    Patients that were prescribed Enoxaparin once daily to Patients that were prescribed with UFH twice daily or three times daily.

    Patients enrolled were required to have a hospitalization period > 4 days. Followed patients for the duration of their hospitalization. Adherence = Number of Doses Administered Number of doses Scheduled for Administration We identified all doses that were omitted or late. We measure the time interval between:

    Successive administered doses Time interval between scheduled administration time and dose administration

    time.

    Fanikos, J. et.al AmJMed Volume 123, Issue 6 , Pages 536-541, June 2010

  • Results

    Outcomes/Compliance

    LMWH Once Daily

    N=125 UFH BID

    N=28 UFH TID

    N=97 P-Value Number of scheduled doses 648 204 1195

    Number of doses administered 615 177 1049

    Number of doses omitted 33 27 146

    Adherence 94.9% 86.8% 87.8%

  • Prevention of VTE in surgical patients Whats new in the 2012 9th ACCP guidelines?

  • 9th ACCP recommendations on prophylaxis after major orthopedic surgery

    For THR and TKR: LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, UFH, VKA, aspirin (1B) or IPC (1C) for at least 10-14 days

    In patients undergoing MOS suggest the use of LMWH in preference to other agents (2B) except VKA or aspirin (2C)

    For MOS suggest extending thromboprophylaxis for up to 35 days rather than only 10-14 days (2B)

    In patients undergoing MOS who decline injections, we recommend using apixaban or dabigatran (alternatively rivaroxaban or VKA) (1B)

    In MOS patients at increased risk of bleeding: IPC or no prophylaxis rather than pharmacological treatment. (2C)

    Falck-Ytter Y, et al. Chest. 2012; 141 (2) (Suppl): e278s-e325s

  • Remarks: If started preoperatively, we suggest administering LMWH 12 h before surgery. Patients who place a high value on avoiding the inconvenience of daily injections with LMWH and a low value on the limitations of alternative agents are likely to choose an alternative agent. Limitations of alternative agents include the possibility of increased bleeding (which may occur with fondaparinux, rivaroxaban, and VKA), possible decreased efficacy (LDUH, VKA, aspirin, and IPCD alone), and lack of long-term safety data (apixaban, dabigatran, and rivaroxaban).

    Major Orthopedic Surgery: Total Hip Arthroplasty (THA), Total Knee Arthroplasty (TKA), Hip Fracture Surgery

    (HFS)

  • Bleeding and anti-coagulation: to what extent?

  • The decision to prophylax: The balance of benefits and harms

    Major orthopedic surgery patients are at high-risk for post-operative venous thromboembolism (VTE)1

    Risk of major bleeding associated with pharmacological prophylaxis is a concern for orthopedic surgeons2,3

    1. Geerts WH, et al. Chest 2008;133:381-453. 2. Schulman S, et al. Chest. 2008;133:257S-298S.

    3. Ng JH, Crowther MA. Semin Hematol. 2006;43:S77-S83.

    Symptomatic thromboembolic

    events

    Bleeding

  • More VTE events

    Less VTE events

    More bleeding events

    Less bleeding events

    Agent is non-approvable Necessary to assess

    LHH

    No brainer Is it relevant to assess LHH?

    When to assess benefits versus harms ratio (LHH)?

    ?

    ?

  • A quantitative assessment of the benefits and harms

    Clinical benefit = number of patients needed to be treated (NNT)

    Clinical harm = number of patients needed to be harmed (NNH)

    LHH >1 patients have more benefits than harms related to study treatment

    Battaggia and Vaona, Rivista the quality and the qualities in general practice 2006;11: 2-4; www.rivistaqq.it.

    Overall balance of benefits and harms = LikeliHood of Helping vs Harming (LHH)

    LHH = (1/NNT)/(1/NNH)

  • A quantitative assessment of the benefits and harms

    Clinical benefit = number of patients needed to be treated (NNT) Clinical harm = number of patients needed to be harmed (NNH)

    LHH

  • Estimation of benefits versus harms ratio (LHH) for fondaparinux

    PEGASUS1

    PENTATHLON2

    EPHESUS3

    PENTAMAKS4

    NNH

    97

    125

    Heterogeneity p=0.262

    52

    ARR (%)

    - 1.03

    - 0.80

    - 1.30 77

    - 1.94

    Favors LMWHcomparator Favors fondaparinux

    1. Agnelli G, et al. Br J Surg 2005;92:1212-20. 2. Turpie AG, et al. Lancet. 2002;359:1721-6. 3. Lassen MR, et al. Lancet. 2002;359:1715-20. 4. Bauer KA, et al. N Engl J Med. 2001;345:1305-10.

    Major bleeding including surgical site

    0.01 1 84.89

    Benefits versus harms ratio favors LMWH comparator

    (NNT)

    (1429)

    (125)

    129

    (588)

    0.07

    1

    0.40

    0.13

    LHH

  • Estimation of clinical benefits for rivaroxaban

    RECORD 11

    RECORD 32

    RECORD 43

    NNT

    435

    77

    213

    Symptomatic VTE

    Favors rivaroxaban

    Favors rivaroxaban Favors LMWH comparator

    Heterogeneity p=0.553

    1 Eriksson BI, et al. N Engl J Med. 2008;358:2765-2775. 2 Lassen MR, et al. N Engl J Med. 2008;358:2776-2786. 3 Turpie A, et al. Lancet. 2009;373:673-80.

    ARR (%)

    0.23

    1.30

    0.47

    1 2 0.05

  • Estimation of benefits versus harms ratio (LHH) for rivaroxaban

    0.1 1.9 3.9 1

    RECORD 11

    RECORD 32

    RECORD 43

    ARR (%)

    - 0.18

    - 0.09

    - 0.39

    NNH

    556

    256

    1111

    Heterogeneity p=0.536

    Major bleeding excluding surgical site

    Favors LMWH comparator Favors rivaroxaban

    1 Eriksson BI, et al. N Engl J Med. 2008;358:2765-2775. 2 Lassen MR, et al. N Engl J Med. 2008;358:2776-2786. 3 Turpie A et al. Lancet. 2009;373:673-80.

    Benefits versus harms ratio favors the study treatment

    (NNT)

    (435)

    (77)

    (213)

    LHH

    1.278

    1.202

    14.43

  • 0.1 1.9 3.9 1

    RECORD 11

    RECORD 31

    RECORD 41

    Major bleeding including surgical site

    Favors LMWH comparator Favors rivaroxaban

    Estimation of benefits versus harms ratio (LHH) for rivaroxaban

    1. FDA regulatory document.

    ARR (%)

    - 0.33

    - 0.35

    - 0.70

    NNH

    Heterogeneity p=0.709

    303

    286

    143

    (NNT)

    (435)

    (77)

    (213)

    LHH

    0.697

    3.714

    0.671

  • LMWH (489)

    Rivaroxaban (559)

    P

    Return to operating room with wound complications

    9 (1.8%) 22 (3.94%) P = 0.04

    Rate of deep infection 5 (1%) 14 (2.5%) P = 0.10

    Mean time from surgery to reoperation (days, range)

    17.2 (8-25)

    16.8 (6-30)

    P = 0.89

    Indication: wound hematoma

    0 9 (1.6%) P = 0.03

    Return to the OR following THR and TKR, before and after the introduction of rivaroxaban

    Jensen CD et al. JBJS (Br) 2011; 93-B: 91-95

    We have discontinued the use of rivaroxaban in our hospital until robust evidence for independent trials become available.

  • 1. Ansell J et al. Chest. 2004;126:204S-233S. 2. Hirsh J et al. J Am Coll Cardiol. 2003;41:1633-1652. 3. Rothberg MB et al. Ann Intern Med. 2005;143:241-250.

    Balancing Risks and Benefits of Prophylactic Anticoagulation Therapy

  • Q2: For how long?

    1. Until discharge from hospital

    2. 10 14 days. 3. 28 35 days. 4. Until ambulation is

    achieved.

    75

    Untildischargefrom

    hosp...

    1014days.

    2835days.

    Untilambulationisachi...

    25% 25%25%25%

    :20

  • Duration of the risk of postoperative VTE Million-woman study

    Sweetland S, et al. Br Med J. 2009;339:b4583.

    Rel

    ativ

    e ris

    k, (9

    5% C

    I)

    1 2 3 4 5 6 7 0 8 9 10

    40

    80

    120

    160

    200

    11 12

    Weeks since in-patient surgery

    PE DVT

    Relative risk for time without surgery = 1

    Women having surgery were 70 times more likely to be readmitted with VTE up to 12 weeks post-operatively

  • Time course and clinical presentation of post-operative VTE in RIETE

    Arcelus JI, et al. Thromb Haemost. 2008;99:546-51.

    19%

    77%

    53% of VTEs were diagnosed after prophylaxis was

    discontinued

    PE Distal DVT Proximal DVT

    24 hours 48 hours 7 days 15 days 30 days 60 days Clinically overt PE, % 22 (2.8) 41 (5.2) 149 (19) 376 (48) 608 (77) 787

    Distal DVT, % 2 (1.1) 5 (2.8) 34 (19) 98 (54) 145 (80) 182

    Proximal DVT, % 9 (1.4) 21 (3.3) 91 (14) 248 (39) 432 (68) 633

    Days

    Cum

    ulat

    ive

    inci

    denc

    e

    5 10 15 20 25 30 35 40 0

    45 50 55 60 0

    100

    200

    300

    400

    500

    600

    700

    800

  • For patients undergoing major orthopedic surgery, we suggest extending thromboprophylaxis in the outpatient period for up to 35 days from the day of surgery rather than for only 10 to 14 days (Grade 2B)

    Major Orthopedic Surgery: Total Hip Arthroplasty (THA), Total Knee Arthroplasty (TKA), Hip Fracture Surgery

    (HFS)

  • Back to the Basics

    79

  • Treatment DVT LMWH Vs UFH Meta-analyses

    Authors Leizorovicz et al 94 Lensing et al 95 Siragusa et al 96 Gould et al 99 Dolovich et al 00 van den Belt 00

    Outcomes More or as effective < Major bleeding < Thrombocytopenia

  • Concerns With LMWH Use

    Obesity Renal insufficiency Pregnancy Adverse effects

    osteoporosis HIT

    HIT = heparin-induced thrombocytopenia

  • UFH

    Therapeutic levels -- First 24 hours. Otherwise, risk of recurrent VTE -- 15 X

    Hull, et al. NEJM 1986; 315, 1109-13 Brandjes DPM et al. NEJM 1992; 327, 1485-90

  • Treat for at least 5 days with UFH or LMWH, overlapping

    oral anticoagulation

  • Duration of Treatment

  • General Aspects

    Short-term treatment associated with 15-50% frequency of extension of thrombus or recurrent disease.

    Minimum duration 3 months. Treatment with VKA is the preferred approach

    for long-term treatment.

  • WHY?

    I Know I Dont Know

    Can I fix it?

    Yes No

    Idiopathic

    4 months Indefinite

    6 12 months vs.

    Indefinite

    Menajovsky L.B. Am J Med in press

  • Conclusions

    Treat acutely with Heparin or LMWH Advantages of LMWH Either way: Treat for at least 5 days,

    overlapping oral anticoagulation Thrombolytic therapy and

    Thrombectomy for selected patients Careful discharge planning

  • Consequences of VTE

    Recurrent VTE Post-thrombotic syndrome (PTS)1

    Presence of leg symptoms (pain, cramps, heaviness, pruritus, and paresthesia) and signs (pretibial edema, skin induration, hyperpigmentation, new venous ectasia, redness and pain during calf compression)

    Mortality2

    1. Prandoni P et al. Haematologica. 1997;82:423-428. 2. Pengo V et al. N Engl J Med. 2004;350:2257-2264.

  • Thank you!