IN THE NAME OF GOD

Prevention of Venous

Thromboembolism

Dr.Shirali

The prevention of VTE is the number one strategy to improve patient safety in hospitals according to the Agency for Health Care Research and Quality.Effective and safe prophylactic measures are now available for most high risk patients and numerous evidence-based guidelines have been published for the prevention of VTE.

In spite of the availability of these guidelines and the availability of safe and effective prophylactic agents, numerous audits have demonstrated that appropriate thromboprophylaxis is not being offered to large numbers of surgical patients:examples

Prophylaxis against DVT therefore should be used in an effort to decrease the incidence of PE. Each patient should be assessed for thromboembolic risk.

Every hospital should develop a formal active strategy for the prevention of VTE in medical and surgical patients.This should be in the form of a written institution-wide thromboprophylaxis policy endorsed by department heads.

There are two approaches to the prevention of

fatal PE :

Primary prophylaxis : Primary prophylaxis is carried

out using either drugs or physical methods that are

effective for preventing DVT.

Secondary prevention : Secondary prevention involves

the early detection and treatment of subclinical venous

thrombosis by screening postoperative patients with

objective tests that are sensitive for the presence of DVT.

However, no single screening method (eg, contrast

venography, ultrasonography, MRI venography) has

found universal acceptance for secondary prevention.

Accordingly, primary prophylaxis is preferred in

most clinical circumstances; it is more cost effective

than treatment of complications once they occur .

Secondary prevention with screening is reserved

for patients in whom primary prophylaxis is either

contraindicated or shown to be ineffective.

Surgical risk groups: The risk of post-

operative VTE depends upon a number of

factors related to the surgical procedure

itself (degree of invasiveness, type and

duration of anaesthesia, requirement for

immobilization) , as well as a number of

patient-related adverse risk factors.

RISK FACTORS: VIRCHOW’S TRIADStasisImmobilityCongestive heart failureInjurySurgery (especially major orthopedic and pelvic)TraumaThrombophiliaCancerOral contraceptivesHereditary states

RISK FACTORS FOR VTE — There are numerous risk

factors for the development of VTE in surgical patients, including

• the type and extent of surgery or trauma

• duration of hospital stay,

•immobility

• recent sepsis

•presence of a central venous access device

• pregnancy or the postpartum period

•Increasing age

•Prior VTE in patient or family members

•Presence of malignancy or obesity

•Presence of an inherited or acquired

hypercoagulable state

•One or more significant medical

comorbidities (eg, heart disease, infection,

inflammatory conditions, recent stroke)

2008 ACCP Guidelines have divided

patients undergoing surgical procedures

into :

1. low risk

2. moderate risk

3. high risk groups .

Low risk patients : 1. under the age of 40 +

2. no adverse patient-related or surgery-

related risk factors +

3. general anaesthesia for less than 30

minutes.

Without prophylaxis their risk of DVTis

less than 1 percent and the risk of fatal PE

is less than 0.01 percent.

Moderate risk patients :1- Include those undergoing minor surgery

who have additional risk factors. or

2- those age 40 to 60 who will require general

anaesthesia for more than 30 minutes and

have no additional adverse patient- or

surgery-related risk factors.

Without prophylaxis their risk of DVT is 2 to 4

percent and their risk of fatal PEis 0.1 to 0.4 percen.

High risk patients :

The high risk surgical group includes those

>60 years of age undergoing major surgical

procedures as well as those ages 40 to 60

with additional patient- or surgery-related

risk factors .

Without prophylaxis the risk of DVTand

fatal PE in this group has been estimated to

be 4 to 8 percent and 0.4 to 1.0 percent,

respectively.

BASELINE RISK OF VTE

CASE SCENARIO50-year-old woman scheduled to

undergo elective laparoscopic cholecystectomyPMH notable for moderate COPDNo personal or family history of VTEMedications: Spiriva®, albuterolStopped smoking 1 year ago

What should we recommend for perioperative VTE prophylaxis in this patient?

BASELINE RISK OF VTE

4

ACCP GRADING SYSTEM

Reflects system adopted for all ACCP guidelines

The strength of any recommendation depends on two factors:The trade-off between benefits, risks, costs, and level of confidence in estimates of those benefits and risksThe quality of the evidence upon which the recommendations are based

If benefits do outweigh risks, and costs, a strong (Grade 1) recommendation is used.

If there is less certainty about magnitude of benefits and risks, burdens, and costs, a weak (Grade 2) recommendation is used.

Support for recommendations may come from high-quality, moderate-quality, or low-quality evidence, labeled, respectively, A, B, and C.

The phrase “we recommend” is used for strong recommendations (Grade 1A, 1B, 1C) and “we suggest” for weak recommendations (Grade 2A, 2B, 2C).

VTE PREVENTIONTargets one or two legs of Virchow’s triad:

Mechanical prophylaxis (stasis)Elastic compression stockingsIntermittent pneumatic compression devices

Pharmacological prophylaxis (hypercoagulability)Unfractionated heparinLow-molecular-weight heparinsFondaparinux

. Aspirin)?(

VTE PREVENTION

Targets one or two legs of Virchow’s triad:Mechanical prophylaxis (stasis)Elastic compression stockingsIntermittent pneumatic compression devices

Perioperative Management of Antithrombotic Therapy in Nonorthopedic Surgical

Patients-----

Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest

Physicians Evidence-Based Clinical Practice Guidelines

Copyright: American College of Chest Physicians 2012©

1- For general and abdominal-pelvic

surgery patients at very low risk for

VTE (0.5%;Rogers score,7; Caprini

score, 0), we recommend that no

specific pharmacologic (Grade 1B) or

mechanical (Grade 2C) prophylaxis be

used other than early ambulation.

2. For general and abdominal-pelvic sur-

gery patients at low risk for VTE

( 1.5%; Rogers score, 7-10; Caprini

score, 1-2), we suggest mechanical

prophylaxis, preferably with inter-

mittent pneumatic compression (IPC),

over no prophylaxis (Grade 2C) .

3. For general and abdominal-pelvic sur-gery

patients at moderate risk for VTE ( 3.0%;

Rogers score, . 10; Caprini score, 3-4) who are

not at high risk for major bleeding complica-

tions, we suggest LMWH (Grade 2B ), LDUH

(Grade 2B) , or mechanical prophylaxis, prefer-

ably with IPC (Grade 2C) , over no prophylaxis.

4. For general and abdominal-pelvic sur-

gery patients at moderate risk for VTE

(3.0%;Rogers score, 10; Caprini score, 3-4)

who are at high risk for major bleeding

complications or those in whom the

consequences of bleeding are thought to be

particularly severe, we suggest mechanical

prophylaxis, preferably with IPC, over no

prophylaxis (Grade 2C) .

5. For general and abdominal-pelvic surgery patients

at high risk for VTE ( 6.0%;Caprini score, 5) who

are not at high risk for major bleeding

complications, we recommend pharmacologic

prophylaxis with LMWH (Grade 1B) or LDUH

(Grade 1B) over no prophylaxis.

We suggest that mechanical prophylaxis with elastic

stockings or IPC should be added to pharmacologic

prophylaxis (Grade 2C) .

6. For high-VTE-risk patients undergoing

abdominal or pelvic surgery for cancer who

are not otherwise at high risk for major bleed-

ing complications, we recommend extended-

duration pharmacologic prophylaxis (4

weeks) with LMWH over limited-duration

prophylaxis (Grade 1B)

7. For high-VTE-risk general and abdominal-

pelvic surgery patients who are at high risk for

major bleeding complications or those in

whom the consequences of bleeding are

thought to be particularly severe, we suggest

use of mechanical prophylaxis, preferably

with IPC, over no prophylaxis until the risk of

bleeding diminishes and pharmacologic

prophylaxis may be initiated (Grade 2C) .

8. For general and abdominal-pelvic surgery

patients at high risk for VTE (6%; Caprini

score, 5) in whom both LMWH and unfrac-

tionated heparin are contraindicated or

unavailable and who are not at high risk for

major bleeding complications, we suggest low-

dose aspirin (Grade 2C) , fondaparinux (Grade

2C) , or mechanical prophylaxis, preferably

with IPC (Grade 2C) , over no prophylaxis.

9. For general and abdominal-pelvic surgery

patients, we suggest that an inferior vena cava

(IVC) filter should not be used for primary VTE

prevention (Grade 2C) .

10. For general and abdominal-pelvic surgery

patients, we suggest that periodic surveillance

with venous compression ultrasound (VCU)

should not be performed (Grade 2C) .

Timing of commencement of prophylaxis :

Prophylaxis is ideally started either before or shortly

after surgery and continued at least until the patient

is fully ambulatory . The administration of

thromboprophylaxis in close proximity to surgery

has been shown to enhance its efficacy in a

systematic review that compared prophylaxis with

LMW heparin versus warfarin .

In general, LMW heparin has been shown to be superior to

UFH or warfarin but inferior to fondaparinux in terms of

efficacy, with similar bleeding rates in patients undergoing

total hip or total knee replacement surgery.

The use of the enoxaparin differs between regions :

In North America, enoxaparin is commonly used in the dose of

30 mg twice daily starting 12 to 24 hours postoperatively.

In Europe, enoxaparin at a dose of 40 mg is started 12 hours

preoperatively and is then given once daily.

Other LMW Heparin preparations have usually been given in

a once daily dosage, starting postoperatively.

Extended prophylaxis : As the result of

shortened hospital length of stay, many patients will

require out-of-hospital prophylaxis. This is

particularly true after total hip replacement, where

the evidence is that patients require 28 to 35 days of

prophylaxis with LMW heparin, rather than 7 to 10

days . Although warfarin is effective in extended

prophylaxis, the incidence of major bleeding was

higher than that seen with LMW heparin .

Patients undergoing cancer

surgery or major abdominal

surgery also benefit from

extended prophylaxis.

A meta-analysis in patients undergoing cancer

surgery concluded that there was no difference

between LMW heparin and UFH in terms of

efficacy, DVT location, or bleeding

complications .

Low dose unfractionated heparin : Low

dose subcutaneous unfractionated heparin

(UFH) for prophylaxis of VTE is usually

given in a dose of 5000 units two hours

preoperatively and then every 8 to 12

hours postoperatively (ie, either twice or

three times daily).

In addition to its relatively low side effect

profile, low dose UFH has the advantage that

it is relatively inexpensive, easily

administered, and anticoagulant monitoring is

not required.

However, the platelet count should be

monitored regularly in all patients receiving

low dose UFH to detect the development of

heparin-induced thrombocytopenia .

Low molecular weight heparin : A number of

low molecular weight heparin (LMW Heparin)

preparations are available. These drugs have

the advantage that they can be given

subcutaneously once or twice daily at a

constant dose without laboratory monitoring.

In addition, there is a lower incidence of

heparin-induced thrombocytopenia than with

UFH.

Fondaparinux has been evaluated in the prevention of VTE in

patients undergoing orthopedic surgery, general surgery, and in

hospitalized medical patients. Fondaparinux 2.5 mg once/day by

subcutaneous injection has been compared with the enoxaparin 40

mg once daily starting 12 hours preoperatively in patients

undergoing total hip or total knee replacement, with enoxaparin 30

mg twice daily in patients undergoing total hip replacement, and

with enoxaparin 40 mg daily in patients suffering hip fracture .In a

2002 meta-analysis of four available trials, it was concluded that the

efficacy of fondaparinux was superior to that of enoxaparin .

In these studies, major bleeding occurred more

frequently in fondaparinux-treated subjects, but there

was not an increase in bleeding leading to death or re-

operation or bleeding into a critical organ with

fondaparinux compared with enoxaparin.

Most of the patients who bled had their initial

fondaparinux injection less than eight hours

postoperatively.

Oral anticoagulation : Oral anticoagulation with

vitamin K antagonists (VKA) such as warfarin can be

commenced preoperatively, at the time of surgery, or

postoperatively for the prevention of VTE .

However, therapy started at the time of surgery or in

the early postoperative period may not prevent small

venous thrombi from forming because the

anticoagulant effect of the VKAs is not achieved until

the third or fourth day of treatment .

Nonetheless, warfarin appears to effectively inhibit

extension of such thrombi if present, thereby

preventing clinically important VTE. Because of its

delayed onset of action along with bleeding rates

similar to those seen with LMW heparin, warfarin has

been favored as a thromboprophylactic agent by

orthopedic surgeons in the United States.

Venous Thromboembolism

(VTE) in Patients with

Cancer

The risk of VTE including (DVT) and (PE) is increased several-fold in patients with cancer. Hospitalized patients with cancer and those receiving active therapy seem to be at thegreatest risk for development of VTE. In a population-based study, cancer was associated with a 4.1-fold greater risk of thrombosis, whereas the use of chemotherapy increased the risk 6.5-fold.

Risk Factors for VTE in Patients With Malignant Disease

Patient-related factorsOlder ageRace (higher in African Americans; lower in Asian-Pacific Islanders)Comorbid conditions (obesity, infection, renal disease, pulmonary disease, arterial thromboembolism)Prior history of VTEElevated prechemotherapy platelet countHeritable prothrombotic mutations

Cancer-related factorsPrimary site of cancer (GI, brain, lung, gynecologic, renal, hematologic)Initial 3-6 months after diagnosisCurrent metastatic diseaseTreatment-related factorsRecent major surgeryCurrent hospitalizationActive chemotherapyActive hormonal therapyCurrent or recent antiangiogenic therapy (thalidomide, lenalidomide, bevacizumab)Current erythropoiesis-stimulating agentsPresence of central venous catheters

SHOULD HOSPITALIZED PATIENTS WITHCANCER RECEIVE ANTICOAGULATION FORVTE PROPHYLAXIS ?

1. Hospitalized patients who have active malignancy with acute

medical illness or reduced mobility should receive pharmacologic

thromboprophylaxis in the absence of bleeding or other

contraindications.

2. Hospitalized patients who have active malignancy without

additional risk factors may be considered for pharmacologic

thromboprophylaxis in the absence of bleeding or other

contraindications.

3. Data are inadequate to support routine thromboprophylaxis in

patients admitted for minor procedures or short chemotherapy

infusion, or in patients undergoing stem cell/ bone marrow

transplantation.

Pharmacologic Prophylaxis in

Hospitalized medical patients

Unfractionated heparin 5,000 U q8h

Dalteparin 5,000 U qd

Enoxaparin40 mg qd

Fondaparinux 2.5 mg qd

Duration for medical patients is for the length of hospital stay

or is fully ambulatory.

Unfractionated heparin 5,000 U every 12 hours has also been

used but appears to be less effective;

SHOULD AMBULATORY PATIENTS WITH CANCERRECEIVE ANTICOAGULATION FOR VTE PROPHYLAXIS DURING SYSTEMIC CHEMOTHERAPY?

1. Routine pharmacologic prophylaxis is not

recommended in cancer outpatients.

2. Based on limited RCT data, clinicians may consider LMWH

prophylaxis on a case-by-case basis in highly selected outpatients with

solid tumors receiving chemotherapy. Consideration of such therapy

should be accompanied by a discussion with the patient about the

uncertainty concerning benefits and harms, as well as dose and duration

of prophylaxis in this setting.

3. Patients with multiple myeloma receiving thalidomide- or

lenalidomide-based regimens with chemotherapy and/or

dexamethasone should receive pharmacologic thromboprophylaxis with

either aspirin or LMWH for lower-risk patients and LMWH for higher-

risk patients

SHOULD PATIENTS WITH CANCER UNDERGOING SURGERY RECEIVE PERIOPERATIVEVTE PROPHYLAXIS?

1. All patients with malignant disease undergoing major surgical

intervention should be considered for pharmacologic

thromboprophylaxis with either UFH or LMWH unless

contraindicated because of active bleeding or a high bleeding risk.

2. Prophylaxis should be commenced preoperatively.

3. Mechanical methods may be added to pharmacologic

thromboprophylaxis, but should not be used as monotherapy for

VTE prevention unless pharmacologic methods are

contraindicated because of active bleeding or high bleeding risk.

4. A combined regimen of pharmacologic and mechanical prophylaxis

may improve efficacy, especially in the highest-risk patients.

5. Pharmacologic thromboprophylaxis for patients undergoing major

surgery for cancer should be continued for at least 7-10 days.

Extended prophylaxis with LMWH for up to 4 weeks

postoperatively should be considered for patients undergoing

major abdominal or pelvic surgery for cancer who have high-risk

features such as restricted mobility, obesity, history of VTE, or

with additional risk factors .In lower risk surgical settings, the

decision on appropriate duration of thromboprophylaxis should be

made on a case-by-case basis considering the individual patient.

Surgical patientsUnfractionated heparin 5,000 U 2-4 h pre-op and q8h

thereafter or 5,000 U 10-12 h preop and 5,000 U qd

thereafter

Dalteparin 2,500 U 2-4 h pre-op and 5,000 U qd

thereafter or 5,000 U 10-12 h pre-op and 5,000 U qd

thereafter

Enoxaparin 20 mg 2-4h pre-op and 40 mg qd thereafter

or 40 mg 10-12 hr pre-op and 40 mg qd thereafter

Fondaparinux 2.5 mg qd beginning 6-8h post-op

All doses are given as subcutaneous injections except as

indicated, When neuraxial anesthesia or analgesia is

planned, prophylactic doses of once-daily LMWH should

NOT be given within 10 – 12 h prior to the

procedure/instrumentation (including epidural catheter

removal). After the surgery, the first dose of LMWH can

be given 6 – 8 h postoperatively. After catheter removal,

the first dose of LMWH can be given no earlier than 2

h afterwards. Clinicians should refer to their institutional

and the American Society of Regional Anesthesia

Guidelines for more information.

for surgical patients, prophylaxis should be continued for at least 7-10 days. Extended prophylaxis for up to 4 weeks should be considered for high-risk patients.

THANKS FOR YOUR

ATTENTION