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PRESENTED BY:
SIM SUI THENG
HOSPITAL MIRI
DEEP VEIN THROMBOSIS
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OUTLINE
Introduction
Epidemiology
Risk Factors
Clinical AssessmentProphylaxis
Treatment
Pharmacology
Conclusion
References
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INTRODUCTION
Thrombus a solid mass formed along the endotheliumfrom blood constituents
Venous thrombosis process of clot (thrombus) formationwithin the veins
Deep Vein Thrombosis (DVT)
Venous thrombi develop
within deep veinAccumulation of fibrin &platelets at direction of
blood flow
Endogenousfibrinolysis
Residual thrombus willorganize, vein
incompletely recanalize
Narrowing of lumen +valvular incompetency
DVT
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INTRODUCTION
3 main factors predispose to thrombus formation
Endothelial
InjuryVenous
Stasis
Hypercoagulability
Virchows Triad
-Mechanical-Chemical
-Prolonged immobility-Obesity-CHF
-Varicose vein-Shock-Inherited lack ofnaturalanticoagulants-Pregnancy-OCP etc
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INTRODUCTION
DVT can occur spontaneously or in patients admitted tohospital 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 witherythema (palpable cord)
If untreated, 50% of proximal DVT will embolize to thelungs resulting in pulmonary embolism (PE)fatal!
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EPIDEMIOLOGY
Venous thromboembolism affects 1 2 per 1000people 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* 2.46
Orthopaedic* 4.0-62.5 7-8
Medical (CHF, COAD) # 16 9
ICU 25-32 10-12
Post-stroke 11-53 13-15*Post-operative patients#Absence of prophylaxis
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RISK FACTORS
Table 1: Risk Factors for Thromboembolism from Thromboembolic RiskFactors (THRIFT) Consensus Group, 1992 1
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CLINICAL ASSESSMENT
Table 2: Clinical Model for Predicting Pretest Probability of Lower Limb DVT16
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MANAGEMENT
Generally there are two approaches: Prophylaxis
Mechanical method (graduated elastic compression stocking &intermittent pneumatic compression devices)
Pharmacological approaches (UFH, LMWH, oral anticoagulants &new agents)
TreatmentMechanical method (stents & filters)
Pharmacological approaches (supportive therapy +anticoagulation)
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PROPHYLAXIS
Recommended for hospital patients at moderate-high risk of VTETwo 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 toadminister and more cost-effectiveShould be started before surgery & continue until patient is fully
mobileDuration 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
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PROPHYLAXIS
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
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PROPHYLAXIS
Pharmacological approach Low dose unfractionated heparins/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)Given s/c as once daily dosingGenerally more effective therapy compared to UFH
Oral anticoagulant
Used when heparin is C/IWarfarin is used & maintain INR at 2.0-2.5 or 2.0-3.0 (ortho)
The pentasaccharide fondaparinux sodiumDose: 2.5mg od, target to ortho surgery, starting 6H post-
operation, 2.5mg od for 5-9 days
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PROPHYLAXIS
Table 3: Risk Stratification & Prevention Strategies in Medical & Surgical Patients17-18
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PROPHYLAXIS
Medical condition Prevention Strategy
Intracranial neurosurgery IPC, may add LMWH 48h post-operatively
Knee replacement Either LMWH, fondaparinux or adjusted dose oralanticoagulants (target INR 2.0-3.0), continue for 7-
10 days
Hip replacement Either LMWH, fondaparinux or adjusted dose oralanticoagulants (target INR 2.0-3.0), continue for atleast 10 days
Hip fracture Warfarin (target INR 2.0-3.0), fondaparinux or fixed
dose LMWH started pre-operatively, may combinegraduated compression stockings
Multiple trauma LMWH, may add IPC
Table 4: Prevention strategy for deep vein thrombosis vs medical condition 1
*IPC- Intermittent Pneumatic Compression
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PROPHYLAXIS
Medical condition Prevention Strategy
Acute Stroke with paralysis oflower limb
LMWH, may add graduated compression stockingswith or without IPC
Pregnancy (for high riskwomen only)
S/C low dose UFH or LMWH
Extended travel (>6 hours &additional risk factors)
Single dose LMWH or graduated compressionstockings
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TREATMENT
Objectives: Relieve symptoms
Reduce the risk of PE to the systemic circulation
Prevent post-thrombotic syndrome
Prevent recurrence
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TREATMENT
Anticoagulation
1)Low dose unfractionated heparin
Check baseline APTT, PT,
RF, LFT, FBC, thrombophiliascreen (if necessary)
Check APTT at 6, 12, 24hours (must achieved target
1.5-2.5 within 24 hours)
Check platelet count from D3until end of 2nd week
Overlapped warfarin with
heparin, start 5mg on 1st 2days, then adjust daily doseaccording INR
Discontinue heparin* oncetarget INR achieved w/i 2consecutive days
*Usual duration of heparin regimen: 5-7 days
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TREATMENT
To standardize management of IV UFH, a weight-based normogram is used
APTT ratio Dose
Initial dose 80IU/kg bolus, then 18IU/kg/hr
APTT < 35s ( 90s (>3x control) Hold infusion for 1 hour, then decreaseinfusion rate by 3IU/kg/hr
Table 5: Management of IV UFH using weight-based normogram 1
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TREATMENT
Anticoagulation (cont)
2)Low Molecular Weight Heparin (LMWH)
LMWH recommended Dose
Enoxaparin (Clexane) 1.5 mg/kg od OR1 mg/kg bd
Dalteparin (Fragmin) 200 IU/kg od OR120IU/kg bd
Nadroparin (Fraxiparine) 0.1 ml/kg bd
Nadroparin (Fraxiparine Forte) 0.1 ml/kg od
Tinzaparin (Innohep) 175 IU/kg od
Table 6: LMWHs & Its Recommended Dosage in Treatment of DVT 1,19
*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
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TREATMENT
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 days3)Fondaparinux sodium 19
o Targeted to orthopedic surgery patients
o S/C 5 mg od (100kg) for atleast 5 days
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TREATMENT
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- 1st event with cancer until resolved
Persistent risk factors (Eg.antithrombin deficiency, recurrentevent)
Table 7: Duration of Therapy1
- 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
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TREATMENT
Supportive treatmentAdequate analgesia (Non-aspirin analgesics)
Legs are elevated above heart
Graduated elastic compression stockings applied as soon as
patient can tolerateEncourage mobilisation
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PHARMACOLOGY
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
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PHARMACOLOGY
Unfractionated Heparin (Cont) 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)
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PHARMACOLOGY
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 highlycorrelated with
patients body weight can be given S/C od or bd w/o need for labmonitoring 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%)
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PHARMACOLOGY
Low Molecular Weight Heparin (Cont) Drug interactions: drugs which affect platelet function
(Aspirin, NSAIDS, dipyridamole, ticlopidine, clopidogrel etc),thrombolytic agents,warfarin
Monitoring parameters: Platelet countsOccult blood
Anti-Xa activity
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PHARMACOLOGY
Heparin Unfractionated Heparin Low Molecular WeightHeparin
MOA Anti-XIIa, XIa, IXa, VIIa,antithrombin
Mostly anti-Xa
Route of administration S/C & IV S/CBioavailability S/C 10-30% at low doses,
90% at higher dosesIV 100% (theoretically)
> 90%
Effective half life S/C 1.5 hours
IV 30 mins
4 hours
Between & within individualvariation
Extensive Minimal
Monitoring APTT Not required (Anti-Xa)
Elimination Liver and kidney Kidney
Cost $ $$$
Table 8: Comparison of Unfractionated Heparin & Low Molecular Weight Heparin
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PHARMACOLOGY
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
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PHARMACOLOGY
Warfarin (Cont) 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)
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PHARMACOLOGY
Warfarin (Cont)Table 9: Clinically Significant Warfarin Drug Interactions
Antibiotics
Oral contraceptives
Omeprazole/Ranitidine
Antiepileptics
Antifungals
Statins
Antiplatelets/anticoagulants
Thyroid drugs
NSAIDS
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CONCLUSION
DVT is a potentially fatal disease because it can progress to PE if notbeing managed carefully
Prophylaxis should be initiated according to risk factors eitherpharmacologically 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 preventrecurrence
COMPLIANCE, COMPLIANCE, COMPLIANCE
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REFERENCES
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THANK YOU!