DEEP VEIN THROMBOSIS

PRESENTED BY:
SIM SUI THENG
HOSPITAL MIRI
 OUTLINE
2

Introduction
Epidemiology
Risk Factors
Clinical Assessment
Prophylaxis
Treatment
Pharmacology
Conclusion
References
 INTRODUCTION
3

Thrombus – a solid mass formed along the endothelium

from blood constituents
Venous thrombosis – process of clot (thrombus) formation
within the veins
Deep Vein Thrombosis (DVT)

Venous thrombi develop

Endogenous Accumulation of fibrin & within deep vein
fibrinolysis platelets at direction of
blood flow

DVT
Residual thrombus will
Narrowing of lumen +
organize, vein
valvular incompetency
incompletely recanalize
 INTRODUCTION
4

3 main factors predispose to thrombus formation

Endothelial Venous
Injury Stasis
Virchow’s Triad

-Mechanical -Prolonged immobility

-Chemical -Obesity
-CHF
-Varicose vein
-Inherited lack of Hypercoagul -Shock
natural ability
anticoagulants
-Pregnancy
-OCP etc
 INTRODUCTION
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DVT can occur spontaneously or in patients admitted to

hospital either for surgical or medical problem
Most common site: vessels of the legs
No local symptoms may be produced; warmth, aching &
swelling of the calf/thigh may develop together with
erythema (‘palpable cord’)
If untreated, 50% of proximal DVT will embolize to the
lungs resulting in pulmonary embolism (PE)  fatal!
 EPIDEMIOLOGY
6

Venous thromboembolism affects 1 – 2 per 1000

people in general population each year
Reported incidence of DVT in hospitalized patients
varies from 0.45-30%
Types of patients vs incidence of DVT in hospitals
Types of patients Incidence of DVT (%)
General surgical* 2.2-15.3 2-5
Gynaecological* 2.4 6
Orthopaedic* 4.0-62.5 7-8
Medical (CHF, COAD) # 16 9

ICU 25-32 10-12

*Post-operative patients
Post-stroke 11-53 13-15
#Absence of prophylaxis
 RISK FACTORS
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Table 1: Risk Factors for Thromboembolism from Thromboembolic Risk
Factors (THRIFT) Consensus Group, 1992 1
 CLINICAL ASSESSMENT
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Table 2: Clinical Model for Predicting Pretest Probability of Lower Limb DVT16
 MANAGEMENT
9

Generally there are two approaches:

 Prophylaxis
 Mechanical method (graduated elastic compression stocking &
intermittent pneumatic compression devices)
 Pharmacological approaches (UFH, LMWH, oral anticoagulants &
new agents)
 Treatment
 Mechanical method (stents & filters)
 Pharmacological approaches (supportive therapy +
anticoagulation)
 PROPHYLAXIS
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Recommended for hospital patients at moderate-high risk of VTE

Two types of prophylaxis:
 Primary prophylaxis – Prevent occurrence via drugs/devices
 Secondary prevention – Early detection & treatment via screening post-operative
patients using a reliable test
Primary prophylaxis is preferred because safer, easier to
administer and more cost-effective
Should be started before surgery & continue until patient is fully
mobile
Duration of prophylaxis:
 Low-moderate risk: At least 5 days or until hospital discharge
 High risk: Until illness & immobility have resolved or until hospital discharge
 Continue prophylaxis for weeks for pts with continuing risk factors
 PROPHYLAXIS
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Mechanical Method
 Graduated elastic compression stocking & intermittent
pneumatic compression devices
 Reduce incidence of DVT
 Enhance protection afforded by low dose heparin
 Advantages:
 Maybe an option for ppl C/I to anticoagulant drugs (risk of
bleeding)
 Disadvantages:
 Cannot effectively wear these stockings due to unusual limb size &
shape
 Not much clinical trials support effectiveness to reduce fatal PE
 PROPHYLAXIS
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Pharmacological approach
 Low dose unfractionated heparin
 s/c 5000U q12h post-surgery
 In ortho surgery, s/c 3500U q8h, starting 2 days pre-surgery &
adjusting the APTT ratio in upper normal range
 Low molecular weight heparin (LMWH)
 Givens/c as once daily dosing
 Generally more effective therapy compared to UFH
 Oral anticoagulant
 Used when heparin is C/I
 Warfarin is used & maintain INR at 2.0-2.5 or 2.0-3.0 (ortho)
 The pentasaccharide fondaparinux sodium
 Dose: 2.5mg od, target to ortho surgery, starting 6H post-
operation, 2.5mg od for 5-9 days
 PROPHYLAXIS
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Table 3: Risk Stratification & Prevention Strategies in Medical & Surgical Patients17-18
 PROPHYLAXIS
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Table 4: Prevention strategy for deep vein thrombosis vs medical condition 1

Medical condition
Intracranial neurosurgery
Knee replacement
Hip replacement
Hip fracture
Multiple trauma
Prevention Strategy
IPC, may add LMWH 48h post-operatively
Either LMWH, fondaparinux or adjusted dose oral
anticoagulants (target INR 2.0-3.0), continue for 7-
10 days
Either LMWH, fondaparinux or adjusted dose oral
anticoagulants (target INR 2.0-3.0), continue for at
least 10 days
Warfarin (target INR 2.0-3.0), fondaparinux or fixed
dose LMWH started pre-operatively, may combine
graduated compression stockings
LMWH, may add IPC

*IPC- Intermittent Pneumatic Compression

 PROPHYLAXIS
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Medical condition Prevention Strategy

Acute Stroke with paralysis of LMWH, may add graduated compression stockings
lower limb with or without IPC
Pregnancy (for high risk S/C low dose UFH or LMWH
women only)
Extended travel (>6 hours & Single dose LMWH or graduated compression
additional risk factors) stockings
 TREATMENT
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Objectives:
 Relieve symptoms
 Reduce the risk of PE to the systemic circulation
 Prevent post-thrombotic syndrome
 Prevent recurrence
 TREATMENT
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Anticoagulation
1) Low dose unfractionated heparin
Check baseline APTT, PT,
RF, LFT, FBC, thrombophilia Overlapped warfarin with
screen (if necessary) heparin, start 5mg on 1st 2
days, then adjust daily dose
according INR
Check APTT at 6, 12, 24
hours (must achieved target
1.5-2.5 within 24 hours) Discontinue heparin* once
target INR achieved w/i 2
consecutive days
Check platelet count from D3
until end of 2nd week

*Usual duration of heparin regimen: 5-7 days

 TREATMENT
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To standardize management of IV UFH, a weight-

based normogram is used
Table 5: Management of IV UFH using weight-based normogram 1
APTT ratio Dose
Initial dose 80IU/kg bolus, then 18IU/kg/hr
APTT < 35s (<1.2x control) 80IU/kg bolus, then increase infusion rate
by 4IU/kg/hr
APTT 35-45s (1.2-1.5x control) 40IU/kg bolus, then increase infusion rate
by 2IU/kg/hr
APTT 46-70s (1.5-2.3x control) No change
APTT 71-90s (2.3-3x control) Decrease infusion rate by 2IU/kg/hr
APTT > 90s (>3x control) Hold infusion for 1 hour, then decrease
infusion rate by 3IU/kg/hr
 TREATMENT
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Anticoagulation (con’t)
2)Low Molecular Weight Heparin (LMWH)
Table 6: LMWHs & Its Recommended Dosage in Treatment of DVT 1,19
LMWH recommended Dose
Enoxaparin (Clexane®) 1.5 mg/kg od OR 1 mg/kg bd
Dalteparin (Fragmin®) 200 IU/kg od OR 120IU/kg bd
Nadroparin (Fraxiparine®) 0.1 ml/kg bd
Nadroparin (Fraxiparine® Forte) 0.1 ml/kg od
Tinzaparin (Innohep®) 175 IU/kg od

*Warfarin will be started on D1 of LMWH and overlapped for 5 days

*Monitoring of LMWH with anti-Xa level is generally not necessary except in
renal failure, extreme obesity & late pregnancy
*Target therapeutic range: 0.6-1.0 units/ml
 TREATMENT
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Anticoagulation
3) Heparinoids 19
o Used in patients with history of heparin-induced thrombocytopenia
o Danaparoid sodium: IV 2500 units followed by 400 units/hr for 2
hours, then 300 units/hr for 2 hours, then 200 units/hr for 5 days
3) Hirudins 19
o Used in patients with history of heparin-induced thrombocytopenia
o Lepirudin: IV 400mcg/kg followed by 150mcg/kg/hr (adjusted
according to APTT) for 2-10 days
3) Fondaparinux sodium 19
o Targeted to orthopedic surgery patients
o S/C 5 mg od (<50kg), 7.5 mg od (50-100kg), 10 mg od (>100kg) for at
least 5 days
 TREATMENT
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Table 7: Duration of Therapy 1

Time Therapy
3 to 6 months 1st event with reversible or time-
limited risk factors (Eg. surgery,
trauma, immobility, estrogen use)
6 months Idiopathic VTE, 1st event
12 months to life time Persistent risk factors (Eg.
- 1st event with cancer until resolved antithrombin deficiency, recurrent
event)

- Following discharge, patients should be followed up within a week with a repeat INR
- If INR remains within therapeutic range, the same dose is maintained & next follow-
up will be 2 weeks later
- If INR still within therapeutic range, then monthly follow-up with INR is advised
- Frequent visits are required if therapeutic INR is not achieved
 TREATMENT
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Supportive treatment
 Adequate analgesia (Non-aspirin analgesics)
 Legs are elevated above heart
 Graduated elastic compression stockings applied as soon as
patient can tolerate
 Encourage mobilisation
 PHARMACOLOGY
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Unfractionated Heparin
 MOA: Potentiates the action of antithrombin III and thereby
inactivates thrombin (as well as activated coagulation factors IX,
X, XI, XII and plasmin) and prevents the conversion of fibrinogen
to fibrin 13
 Onset: Immediate (IV); ~20-30mins (S/C); not IM (hematoma)
 Does not cross placenta & not excreted in breast milk
 Renal & hepatic clearance, affected by obesity, renal function,
hepatic function, malignancy, presence of PE & infections
 Anticoagulant response is nonlinear
 Main side effects: Bleeding, thrombocytopenia, osteoporosis
(long term therapy), hyperkalemia
 PHARMACOLOGY
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Unfractionated Heparin (Con’t)

 Drug Interactions: Cephalosporins ( bleeding risk), drugs that
affect platelet function (aspirin, NSAIDS, dipyridamole,
ticlopidine, clopidogrel etc), IV nitroglycerine ( anticoagulation
effect), penicillins, warfarin, tetracycline, quinine, digoxin
 Monitoring parameters:
 Platelet
counts
 FBC & signs of bleeding
 APTT (measured 6 hours after IV administration)
 PHARMACOLOGY
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Low Molecular Weight Heparin (Enoxaparin)

 MOA: Similar to UFH except it strongly inhibits factor Xa more than
UFH
 Onset: Peak effect (2-4 hours)
 Anti-Xa activity to a fixed dose of LMWH is highly correlated with
patient’s body weight  can be given S/C od or bd w/o need for lab
monitoring of APTT
 Can be used in pregnancy (risk B) & breastfeeding
 Not need dose adjustment (except in pregnancy, morbid obesity,
renal failure)
 Side effects: bleeding (13%), injection site hematoma (9%), fever
(8%)
 PHARMACOLOGY
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Low Molecular Weight Heparin (Con’t)

 Drug interactions: drugs which affect platelet function
(Aspirin, NSAIDS, dipyridamole, ticlopidine, clopidogrel etc),
thrombolytic agents, warfarin
 Monitoring parameters:
 Platelet counts
 Occult blood
 Anti-Xa activity
 PHARMACOLOGY
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Table 8: Comparison of Unfractionated Heparin & Low Molecular Weight Heparin

Heparin Unfractionated Heparin Low Molecular Weight
Heparin
MOA Anti-XIIa, XIa, IXa, VIIa, Mostly anti-Xa
antithrombin
Route of administration S/C & IV S/C
Bioavailability S/C – 10-30% at low doses, > 90%
90% at higher doses
IV – 100% (theoretically)

Effective half life S/C – 1.5 hours 4 hours

IV – 30 mins
Between & within individual Extensive Minimal
variation
Monitoring APTT Not required (Anti-Xa)
Elimination Liver and kidney Kidney
Cost $ $$$
 PHARMACOLOGY
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Warfarin
 MOA: Inhibits Vitamin K epoxide reductase in the liver, an enzyme required
for the activation of factors II, VII, IX, X
 Onset: 36-72 hours, full therapeutic effect: 5-7 days
 Oral absorption is rapid & complete (F~100%)
 Hepatic metabolism via CYP2C9, minor include CYP2C19, 1A2, 3A4
 Crosses placenta & cause embryopathy (nasal hypoplasia, stippled epiphyses)
in 1st trimester, CNS abnormalities & fetal hemorrhage  C/I in pregnancy!
 Can be used in breastfeeding (does not enter breast milk)
 Side effects: bleeding, angina, purple toes syndrome, skin necrosis
 PHARMACOLOGY
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Warfarin (Con’t)
 Factors influencing INR:
 Dietary Vitamin K intake
 Alcohol consumption
 Underlying diseases: diarrhea, prolonged fever, CHF, liver disease,
hepatic congestion, hyper- and hypothyroidism
 Concurrent drug administered

 Monitoring parameters:
 PT
 INR
 Signs& symptoms of bleeding (gum bleeding, dark stool,
hematuria, skin petechiae etc)
 PHARMACOLOGY
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Warfarin (Con’t)
Table 9: Clinically Significant Warfarin Drug Interactions

Antibiotics

Oral contraceptives

Omeprazole/Ranitidine

Antiepileptics

Antifungals

Statins

Antiplatelets/anticoagulants

Thyroid drugs

NSAIDS
 CONCLUSION
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DVT is a potentially fatal disease because it can progress to PE if not

being managed carefully
Prophylaxis should be initiated according to risk factors either
pharmacologically or mechanically
After confirm on a diagnosis of DVT, decide on treatment regimen
(UFH/LMWH +/- warfarin), duration & monitor patient closely
Upon discharge, on going anticoagulation is essential to prevent
recurrence
COMPLIANCE, COMPLIANCE, COMPLIANCE…
 REFERENCES
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THANK YOU!