Venous Thromboembolism in Rehabilitation Medicine: “the Last Frontier” Dr. Bill Geerts...

Venous

Thromboembolism in

Rehabilitation Medicine:

“the Last Frontier”Dr. Bill GeertsSunnybrook & Women’s College HSC

University of Toronto

March 1, 2002

Medical College of Virginia

OBJECTIVES

1. Risks of venous thromboembolism in various

patient groups who undergo rehabilitation.

2. Current thromboprophylaxis recommendations

for each of these groups in acute care.

3. Published studies of VTE in rehabilitation settings.

4. Thromboprophylaxis strategies in rehabilitation.

5. Current treatment of acute VTE.

Risk of DVT in Hospitalized Patients

Patient group DVT prevalence

Medical patients 10-20 %

Major gyne/urol/gen surgery 15-40 %

Neurosurgery 15-40 %

Stroke 20-50 %

Critical care patients 15-80 %

Hip/knee surgery 40-60 %

Major trauma 40-80 %

Spinal cord injury 60-80 %

Rehabilitation low-high

6th American College of Chest Physicians Consensus Conference

on Antithrombotic Therapy

Prevention of Venous

ThromboembolismChest January 2001 Supplement

Mechanical Prophylaxis

• Graduated compression stockings

• Intermittent pneumatic compression

• Venous foot pump


ADVANTAGES DISADVANTAGES

• no bleeding• efficacious in moderate risk patients


ADVANTAGES DISADVANTAGES

• no bleeding• efficacious in moderate risk patients

• limited efficacy data• no data related to routine use• cumbersome• poor compliance• may mobilization • no long-term use data• no mortality data• cost

Pharmacologic Prophylaxis• Low dose heparin

• Adjusted-dose heparin

• Low molecular weight heparin

• Danaparoid

• Hirudin

• Pentasaccharide

• Oral thrombin inhibitors: ximelagatran

• Warfarin

Pharmacologic Prophylaxis

ADVANTAGES DISADVANTAGES• proven efficacy (RRR 60-80%)• broad spectrum of pts• N > 100,000• multiple agents• ease of use• high compliance• no monitoring (except OAC)• demonstrated cost-effectiveness• mortality reduction

Pharmacologic Prophylaxis

ADVANTAGES DISADVANTAGES• proven efficacy (RRR 60-80%)• broad spectrum of pts• N > 100,000• multiple agents• ease of use• high compliance• no monitoring (except OAC)• demonstrated cost-effectiveness• mortality reduction

• bleeding - GS 0.1% - ortho 1%• cost (low high)

Orthopedic

SurgeryHip arthroplasty

Knee arthroplasty

Hip fracture surgery

HIP ARTHROPLASTY - PROPHYLAXIS

No. of No. of Risk Regimen Trials Patients DVT Red’nControl/placeboGrad comp stockings AspirinLow dose heparinWarfarinInt pneum compressLMW heparinHirudin

ACCP CONSENSUS GUIDELINES - CHEST (2001)

• prospective trials with mandatory venography

1246

11 13

730

3

626290473

1016 1828

42362161172

54 %42 %40 %30 %22 %20 %16 %16 %

---23 %26 %45 %59 % 63 %70 %70 %

Elective hip replacementRecommended: LMWH started 12 hr before surgery, 1A 12-24 hr after surgery, or 4-6 hr after surgery at half the usual high dose or Warfarin (INR 2-3) 1A

Alternative: adjusted-dose heparin to aPTT > ULN 2A

Not recommended: aspirin, LDH, IPC alone

6th ACCP Consensus Conference on Antithrombotic Therapy

KNEE ARTHROPLASTY - PROPHYLAXIS

No. of No. of Risk Regimen Trials Patients DVT Red’n

Placebo

Aspirin

Warfarin

Low dose heparin

LMW heparin

Int pneum compress

6

6

9

2

13

4

199

443

1294

236

1740

110

64 %

56 %

47 %

43 %

31 %

28 %

---

13 %

27 %

33 %

52 %

56 %



Recommended: LMWH 1A or Warfarin (INR 2-3) 1A

Alternative: optimal use of IPC 1B

Not recommended: aspirin, LDH 1C+


Elective knee replacement

HIP FRACTURE - PROPHYLAXIS

No. of No. of Risk Regimen Studies Patients DVT Red’n

Control/placebo

Aspirin

Low dose heparin

LMW heparin

Warfarin

9

3

2

5

5

381

171

59

437

239

48 %

34 %

27 %

27 %

24 %

---

29 %

44 %

44 %

48 %



Recommended: LMWH 1B or Warfarin (INR 2-3) 1B

Alternative: Low dose heparin 2B

Not recommended: aspirin 2A



NEED FOR POST-DISCHARGE PROPHYLAXIS

THR RLMWH

placebo

LMWH

dischargeday 6-14

venogramday 30-35

(or warfarin)

In-hosp

In-hosp + 3-4 weeks post-discharge

In-hospital vs Post-discharge LMWH After THR

Author, yearBergqvist, 1996

Planes, 1996

Dahl, 1997

Spiro, 1997

Lassen, 1998

Hull, 2000*

COMBINED

Patients 223

173

218

435

215

533

1797

Placebo 37 %

19 %

32 %

23 %

12 %

37 %

27 %

LMWH 18 %

7 %

19 %

8 %

4 %

20 %

14 %

Placebo 24 %

8 %

13 %

13 %

5 %

9 %

12 %

LMWH 7 %

6 %

9 %

3 %

1 %

3 %

4 %

* In-hospital prophylaxis with warfarin.

DVT Proximal DVT


Eikelboom - Lancet (2001)

Extended Duration Prophylaxis: Symptomatic

VTE

Trauma

MAJOR TRAUMA PATIENTS ARE

THE HIGHEST RISK GROUP

FOR THROMBOSIS

Sunnybrook VTE in Trauma Study - 1

• ISS > 9; no prophylaxis given• Prospective; routine bilateral venography• N = 443; mean age 39; ISS 27

All patients 58 % 16 %

Major injuries: Face/ chest / abdomen 50 % 15 %

Head 54 % 20 %

Spine 62 % 27 %

L.E. Ortho 69 % 24 %Geerts - NEJM (1994)

DVT PROX DVT

Major TraumaRecommended: Prophylaxis should be used if possible LMWH as soon as considered safe 1AWith high bleeding risk: initial mechanical prophylaxis (IPC, 1C ES) until LMWH safeHigh TE risk + suboptimal prophylaxis: consider screen with DUS 1CIVC Filter: not for prophylaxis 1C


Spinal Cord Injury

ACUTE SPINAL CORD INJURY: LDH + EPC vs LMWH

• Randomized trial in 27 acute spinal cord units• C2-T12 SCI ASIA A, B, or C (motor nonfunctional)

Heparin + IPC Heparin 5000 U Q8H5000 U Q8H

Enoxaparin Enoxaparin 40 mg once daily30 mg Q12H

2 weeksbilateral venography

+ DUS

8 weeks DUS

VTER

No VTE

No VTE

Acute Phase Rehab Phase

SCI Multicenter Trial:Rehabilitation Phase (Weeks 2-8)

• Patients who completed Acute Phase without VTE

• Routine DUS at start of Rehab Phase + 6 weeks later

Heparin Enoxaparin5000 Q8H 40 mg QD

No. 60 59

New VTE 22% 8%

DVT 18% 7%

PE 3%* 2%

Major bleeding 1 0 * 1 fatal


Acute Spinal Cord InjuryRecommended: LMWH 1B

If anticoagulants C/I early after injury: IPC and ES LMWH 2B

Possible alternative: IPC/ES + LMWH/LDH 2B

Not recommended: LDH, ES, IPC alone 1C

Rehabilitation phase: continue LMWH or warfarin (INR2-3) 1C

Stroke

Ischemic Stroke

Recommended:

LDH, LWMH, danaparoid 1A

If anticoagulants contraindicated:

ES or IPC 1C+


Studies of VTE in

Rehabilitation

VTE IN REHABILITATION: PROBLEMS1. Scanty, poor quality data - ??? risk

2. Huge patient variability: underlying conditions, time

in acute care, pre-rehab prophylaxis, duration of rehab

3. Some patients have DVT on admission

4. Symptoms/signs: nonspecific, reduced communication

5. Risk often prolonged

6. Often no diagnostic testing on site

7. ? Higher threshold for Dx larger thrombi/emboli

8. Resource utilization: transportation, diagnostic tests,

two hosp beds, interrupts/prolongs rehab, drug costs

GENERAL REHABILITATION

Author, year

Prophylaxisprior to rehab

Method of Dx

When screened No. DVT

Prox DVT

Halvorsen, 1985a

Katz, 1995

NS

70 %(various)

FgLS veno

IPG DUS

NS

on adm(< 6 mos)

150

301

18%

---

NS

1%

STROKE REHABILITATION

Author, yr


Method of Dx


Prox DVT

Cope, 73

Miyamoto, 80

Sioson, 88

Desmukh, 91

Oczkowski, 92

Pambianco, 95

Harvey, 96

NS

NS

21%

NS

35 %

NS

some

veno

FgLS

IPG

DUS

IPG

DUS

DUS

on adm

10-14 d

45 d

21 d

81 d

on adm

25 d

42

141

98

123

93

421

105

40 %

28 %

---

18 %

---

14 %

13 %

NS

NS

33 %

NS

12 %

NS

NS

TRAUMATIC BRAIN INJURY REHABILITATION

Author, year


Method of Dx


Prox DVT

Cifu, 1996

Meythaler, 1996

All (LDH or

IPC)none

DUS

DUS

On adm(4-29 d)

On adm(< 4 mos)

82

116

18%

NS

14 %

8 %

SPINAL CORD INJURY REHAB

Author, year


Method of Dx


Prox DVT

Jarrell, 1983Yelnik, 1991

Gunduz, 1993

LDH

91%

allnone

FgLS + IPGveno

venoveno

NS

on adm(45 d)80 d27 d

209

127

87 30

65 %

23 %

14 %53 %

NS

NS

NS28 %

VTE in Rehabilitation

The best strategy is

optimal prophylaxis

in the acute care setting

PROPHYLAXIS OPTIONS IN REHAB

1. Mobilization

2. Physiotherapy

3. Low dose heparin

4. Low molecular weight heparins

5. Warfarin

PREVENTING VTE in REHAB: PRINCIPLES

• Appropriate prophylaxis MUST start in acute care

• Written policy (care pathway)

• Simple, universal

• Routine prophylaxis for high risk patients (SCI,

hip and knee surgery, orthopedic trauma)

• No prophylaxis (or individual decision) for lower

risk patients (stroke, head injury, amputation, burn)

• No routine screening for DVT

Strategies to facilitate effective, safe, efficient, and cost-effective

thromboprophylaxis in rehab settings

• Written, “approved” and used protocols

• Pharmacy involvement

• Point of care INR testing

• Greater use of LMWH if LOS < 2 weeks

• “Education” of referring centers

REHAB PROPHYLAXIS SUMMARY

Patient Group

Spinal cord injury

LE orthop trauma

THR

TKR

Hip fracture

Others

Method

Warfarin (INR 2-3)

Warfarin (INR 2-3)• LMWH• Warfarin

(INR 2-3)

• None• Individualize

Duration

Until discharge

Until discharge

2-4 wks postop

(~ til discharge)

? Post-rehab Prophylaxis

Almost never

Treatment of VTE in

Rehabilitation

Treatment of Venous Thromboembolism:S/C Low Molecular Weight Heparin

is Preferred over IV Heparin

1. At least as efficacious

2. Safer: bleeding

HIT

3. Reduced all-cause mortality

4. Cheaper

5. No lab monitoring

6. Most can be treated as out-patients

Treatment of DVT/PE

LMWH S/C

Oral Anticoagulation (INR 2.0 - 3.0)

5-7 d 3 mos-indefinite

• Subcutaneous LMWH:

dalteparin (Fragmin) 100 U/kg BID or 200 U/kg QD

enoxaparin (Lovenox) 1 mg/kg BID or 1.5 mg/kg QD

nadroparin (Fraxiparine) 86 U/kg BID

tinzaparin (Innohep) 175 U/kg QD

• No lab monitoring or dosage adjustment

INDICATIONS FOR PROLONGED LMWH THERAPY

1. Pregnancy2. Uncontrolled malignancy3. High risk of bleeding4. Warfarin failure5. Major chemotherapy6. INR monitoring difficult

- poor venous access

- geographic inaccessibility- unstable values

7. Need for recurrent invasive procedures8. PATIENT PREFERENCE

Indications for an IVC Filter

Recent PROXIMAL DVT PLUS:

1. Absolute C/I to full anticoagulation

2. Untreatable, major bleeding on anticoag

NOT for: PE without proximal DVT

Minor bleeding

Minor/moderate surgery

Primary prophylaxis

“Recurrent” VTE/failure of Rx

Vitamin K: Routes & Doses

IM NEVER

SC RARELY (only if NPO)

IV 1 mg for MINOR bleeding 10 mg for MAJOR bleeding

PO ROUTE OF CHOICE INR < 9 1 mg

INR > 9 2.5-5 mg

FFP Only if major bleeding, surgery imminent

Duration of Anticoagulation

1. RISK FACTOR RESOLUTION

2. NUMBER OF EPISODES OF VTE

3. THROMBOEMBOLISM RESOLUTION

4. BLEEDING RISK

5. PATIENT PREFERENCE

INDIVIDUALIZE

Discussion

Questions

6th ACCP Consensus Conference on Antithrombotic TherapyChest Supplement January 2001

Prevention of Venous Thromboembolism

Bill Geerts, chair

John Heit

Patrick Clagett

Graham Pineo

Cliff Colwell

Fred Anderson

Brownell Wheeler

ACCP CONSENSUS CONFERENCES ON ANTITHROMBOTIC

THERAPY

Chest 1986, 1989, 1992,

1995, 1998, 2001, 2003

Pulmonary Embolism in UK Hospitals

• 0.9 % of pts admitted to hospital DIE from PE

• < 1/2 of high risk pts had any prophylaxis

• 400 deaths/yr could be saved by prophylaxis

• £ 33-82 million/yr COST SAVINGS with more

appropriate use of prophylaxis

Office of Health Economics (1996)

Making Health Care Safer: A Critical

Analysis of Patient Safety Practices

• UCSF-Stanford Evidence-Based Practice Center report for

Agency for Healthcare Research and Quality, US DOHHR• systematic review of practices to improve patient safety • rank practices according to strength of evidence supporting

more widespread implementation

No. 1 = “Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk”

Shojania (2001)

Rationale for Prophylaxis

• high incidence of VTE

• associated mortality and morbidity

• cost of diagnosis and treatment

• treatment-related complications

OPPORTUNITY TO: 1. Improve patient outcomes, AND 2. Reduce costs

VTE Prevalence after THR or TKR Surgery, or Surgery for Hip Fracture

* DVT rates among control/placebo groups in RCTs using routine venography

Procedure

THR

TKR


Deep Vein Thrombosis*

Total, % Proximal, %

45-57 23-36

40-84 9-20

36-60 17-36

Pulmonary Embolism Total, % Fatal, %

0.7-30 0.1-0.4

1.8-7 0.2-0.7

4.3-24 3.6-12.9


HIP ARTHROPLASTY

1000 patients undergoing THA

Without Prophylaxis:

500 develop DVT

166 have symptomatic DVT

100 develop symptomatic nonfatal PE

20 die due to PE

Paiement - Am J Surg (1991)

DVT after THR

• 289 patients prophylaxed with GCS + SCD• Ipsilateral duplex ultrasound 5 days postop

Proximal DVT

OverallAnesthetic - general - regionalAge > 75 < 75Age > 75 + GA

6 %11 % 4 %16 % 3 %26 %

Woolson - JBJS (1996)

Warfarin vs Dalteparin in THR

Francis - JBJS (1997)

• 580 patients; bilateral contrast venography

PatientsDVTProximal DVTMajor bleedingOp site bleedingTransfused - OR day - D 1 - 8

190 26 % 8 % 1 % 1 % 65 % 44 %

192 15 % 5 % 2 % 4 % 69 % 68 %

Warfarin Dalteparin P INR 2.5 5000 U daily

0.006 NS NS0.03 NS0.004

Prevention of DVT After THR Surgery*

Prophylaxis Regimen

Control/placebo

Elastic stockings

Aspirin

Low dose heparin

Adjusted-dose warfarin

IPC

LMWH

Recombinant hirudin

Adjusted-dose heparin

No. ofTrials

12

4

6

11

13

7

30

3

4

Combined

Enrollment

626

290

473

1016

1828

423

6216

1172

293

Total DVTPrevalence RRR

54 % ---

42 % 23 %

40 % 26 %

30 % 45 %

22 % 59 %

20 % 63 %

16 % 70 %

16 % 70 %

14 % 74 %

* Pooled DVT rates using routine contrast venography.

Proximal DVTPrevalence RRR

27 % --

26 % 4 %

11 % 57 %

19 % 27 %

5 % 80 %

14 % 48 % 6 % 78 %

4 % 85 %

10 % 62 %


Prevention of DVT After TKR Surgery*

Prophylaxis Regimen

Control/placebo

Elastic stockings

Aspirin

Warfarin

Low dose heparin

Venous foot pump

LMWH

Int. Pneum. Compr.

No. ofTrials

6

2

6

9

2

4

13

4

Combined Enrollment

199

145

443

1294

236

172

1740

110

Total DVTPrevalence RRR

64 % ---

61 % 6 %

56 % 13 %

47 % 27 %

43 % 33 %

41 % 37 %

31 % 52 %

28 % 56 %

* Pooled DVT rates using routine contrast venography.

Proximal DVTPrevalence RRR

15 % --

17 % --

9 % 42 %

10 % 35 %

11 % 25 %

2 % 85 % 6 % 63 %

7 % 52 %


Prevention of DVT After Surgery for Hip Fracture*

Prophylaxis Regimen

Control/placebo

Aspirin

Low dose heparin

LMWH/heparinoid

Warfarin

No. ofTrials

9

3

2

5

5

Combined

Enrollment

381

171

59

437

239

DVT

48 %

34 %

27 %

27 %

24 %

(95 % CI)

(43-53)

(27-42)

(16-40)

(23-31)

(19-30)

Relative RiskReduction

- -

29 %

44 %

44 %

48 %

* Pooled total DVT rates in RCTs using routine contrast venography.


This concept has been challenged by 4 prospective studies based on symptomatic

VTE after in-hospital prophylaxis for THR or TKR

02.0%7.3LMTHRHeit 2000

0.1%3.7%7.0WTHR 1999

0.1%3.6%7.5LMTHRColwell

0.4%3.9%9.0LMTKR 1998

04.3%9.0LMTHRLeclerc

00.6%9.8WTKR 1997

9.8 W

588

1494

1516

842

1142

257

249THRRobinson

SymptDVT Fatal

PE

nDuration,

dProcedure Therapy

W, warfarin; LM, low molecular weight heparin ACCP - Chest (2001)

1.2% 0


Extended Duration Prophylaxis:Venography

Expt Ctrl Peto OR Weight Peto OR Study n/N n/N (95% CI Fixed) % (95% CI Fixed)

Bergqvist 2/191 10/131 19.7 0.26 (0.08, 0.79)

Dahl 4/117 6/110 16.6 0.62 (0.17, 2.18)

Helt 7/607 10/588 26.6 0.66 (0.26, 1.78)

Hull 4/291 9/133 10.2 0.58 (0.12, 2.91)

Lassen 2/140 9/141 8.5 0.57 (0.11,6.92)

Planes 3/90 7/88 16.9 0.49 (0.12, 1.52)

Total (95% CI) 22/1370 39/1192 100.0 0.50 (0.30, 0.83)

Risk reduction of clinical VTE

1051.2.1

Favours treatment Favours control

Cohen - Thromb Haemost (2001)


Orthopedic Surgery - Other Issues

Duration of Prophylaxis:

Uncertain, but at least 7-10 days

Extended, out-of-hospital LMWH may reduce

clinically-important VTE and is recommended

at least for high-risk patients

Pre-discharge Screening:

Routine DUS not recommended

1A

1A

1A

Symptomatic VTE After In-hospital Prophylaxis

Author, yearRobinson, 1997

Leclerc, 1998

Colwell, 1999

Heit, 2000

OperationTHR

TKR

THR

TKR

THR

THR

THR/TKR

No. 506

518

1,142

842

1,516

1,495

588

Prophylaxis warfarin

warfarin

LMWH

LMWH

LMWH

warfarin

LMWH

Duration ofProphylaxis 9.8 d

9.8 d

9.0 d

9.0 d

7.5 d

7.0 d

7.3 d

Sympt.VTE, (%) 6 (1.2)

3 (0.6)

49 (4.3)

33 (3.9)

55 (3.6)

56 (3.7)

11 (1.9)

Fatal PE, (%) 0

1 (0.2)

0

3 (0.4)

2 (0.1)

2 (0.1)

3 (0.5)

6th Consensus Conference on Antithrombotic Therapy

Clinical Outcomes After THA

• Patients: elective, unilateral, primary THA• Design: 156 centers, unblinded RCT• Interventions: enoxaparin 30 mg BID postop warfarin INR 2-3 pre- or postop

in hospital(x = 7.3 d)}

No.Symptomatic VTE (OR ---> 3 mos)

In-hospitalDischarge ---> 3 mos

Fatal PEBleeding - all - major

Warfarin* Enoxaparin1495 1516 3.7 % 3.6 % 1.1 % 0.3 % p=0.008 2.6 % 3.4 % 2 2 7.4 % 10.0 % p=0.01 0.5 % 1.2 % p=0.06

* only 35 % had INR >2 by day 7 Colwell - JBJS (1999)

• Extended duration of prophylaxis for 30 – 42 days reduced symptomatic VTE:

1.3 % vs 3.3 %, OR: 0.38, 95% CI: 0.24 – 0.61, NNT = 50

• Asymptomatic venographic DVT also significantly reduced:9.6 % vs 19.6 %, OR: 0.49,

95% CI: 0.36 – 0.63, NNT = 10

• Major bleeding: similar in extended prophylaxis as in placebo and untreated groups

• Routine use of extended-duration prophylaxis will prevent 20 sympt.

VTE/1000 elective THR or TKR

• Assuming 5% case-fatality rate, this is equivalent to preventing 1 additional death for every 1000 patients

• Outpatient costs is US $24 – 28


• There is good evidence that prolonged prophylaxis reduces asymptomatic DVT

• Also good evidence that prolonged prophylaxis reduces symptomatic VTE

• Unable to identify the patients at risk for late VTE

• A 2 % rate for (preventable) symptomatic VTE is excessive in view of the high frequency of major orthopedic surgery

Conclusions

Duration of Prophylaxis after Major Orthopedic Surgery

Optimal duration after THR/TKR uncertain

Recommendations: at least 7-10 days 1A extended out-of-hospital prophylaxis 2A may reduce clinically important VTE and is recommended at least for high- risk patients6th ACCP Consensus Conference on Antithrombotic Therapy

Incidence of DVT in Trauma Patients (No Prophylaxis)

Freeark, 1967

Hjelmstedt, 1968

Nylander, 1972

Kudsk, 1989

Geerts, 1994

Abelseth, 1996

LE Prox Author, yr Patients No . Fracture DVT DVT

Injuries bedrest > 3 weeks

Tibial fractures

Tibial fractures

Multisystem trauma, bedrest > 10 d

Major trauma, ISS > 9

Isolated LE # Rx’d surgically

42

76

14

38

349

102

33 %

100 %

100 %

55 %

52 %

100 %

29 %

45 %

57 %

63 %

58 %

28 %

NS

8 %

NS

32 %

18 %

4 %


Randomized Studies of DVT Prevention after Acute SCI

Regimen Author, yr Endpoints DVT, No. (%)

Low-dose heparin Green, 1988 Green, 1990 Geerts, 1996

IPC Green, 1982

Adjusted-dose heparin Green, 1988

LMWH Green, 1990 Geerts, 1996

Combinations Green, 1982(IPC, ASA, dipyridamole)

IPGIPG, DUSVenography

FgLS/IPG

IPG

IPG, DUSVenography

FgLS/IPG

9/29 (31) 5/19 (26)10/15 (67)

6/15 (40)

2/29 ( 7)

0/16 ( 0) 4/8 (50)

3/12 (25)


DVT in Patients with Acute SCI - No Prophylaxis

Author, year

Brach, 1977

Rossi, 1980

Myllynen, 1985

Merli, 1988

Petaja, 1989

Geerts, 1994

Endpoint

FgLS/IPG

FgLS

FgLS

FgLS/IPG

FgLS

Venography

DVT

90 %

72 %

100 %

48 %

67 %

81 %

Proximal DVT

NS

17 %

NS

NS

NS

35 %

No. of

Patients

10

18

9

8

9

26


SCI Multicenter Trial:Acute Treatment Phase (Weeks 0-2)

• Routine venography and DUS day 14 + 3; blinded interpretation

Heparin 5000 Q8H Enoxaparin + IPC 30 mg BID

No. rand/completed 246/48 230/58

VTE 63% 66%

DVT 46% 60%

Proximal DVT 7% 9%

PE 10% 3%

Major VTE (pDVT+PE) 16% 12%

Major bleeding 5% 3%

1 2 3 4 5 6 weeks

1 2 years

RISK

B

CA

RISK OF SYMPTOMATIC VTE AFTER SCI

A. age-matched controlsB. no prophylaxisC. prophylaxis

Cost-effectiveness of Prophylaxis

• 1000 patients undergoing THA

Paiement - Am J Surg (1991)

Strategy

Observation only

Warfarin

Warfarin + duplex scan

Warfarin X 12 wks

Fatal PE

20.0

4.0

0.3

0.15

Charges (US $)

$ 774,000

394,000

616,000

595,000

VTE in Stroke• Prospective studies• No prophylaxis• Routine screening for DVT (17/18 used FgLS)

Studies 18

Patients 749

DVT 49 %

Prox DVT 11 % (17/152)

PE 6 % (10/174)

Fatal PE 4 % (12/270)

Prevention of DVT in Ischemic Stroke

Trials Patients DVT RRR

Control

Low dose heparin

LMWH

Danaparoid

8

5

3

4

346

364

158

203

55 %

24 %

23 %

10 %

---

56 %

58 %

82 %

Geerts (6th ACCP) - Chest (2001)

Risk Factors for VTE in Stroke

UNKNOWN

NO

YES Degree of paralysisAge

Level of consciousness

Improvement in weaknessPrevious VTEVaricose veinsObesity

DVT Treatment: UFH or LMWH?

• meta-analysis of RCTs• adjusted UFH vs fixed-dose S/C LMWH• 11 studies, 3674 patients

Recurrent VTE

All cause mortality

Major bleeding

UFH

5.4 %

6.8 %

1.9 %

LMWH

4.6 %

5.0 %

1.1 %

RRR

15 %

27 %

42 %

P

> 0.2

0.02

0.47

NNT

114

61

164

Gould - AIM (1999)

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Venous Thromboembolism in Rehabilitation Medicine: “the Last Frontier” Dr. Bill Geerts...

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