deep vein thrombosis_2003

8/14/2019 Deep Vein Thrombosis_2003

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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

1) Management of venous thromboembolism. MOH Clinical Practice Guidelines. Retrieved from:http://www.acadmed.org.my/cpg/Management_of_Venous_Thromboembolism.pdf[31 January 2009]2) Cunningham IGE, Yong NK. The incidence of post-operative deep vein thrombosis in Malaysia. Br J Surg 1974; 61:482-483.3) Nandi P, Wong KP, Wei WI, Ngan H, Ong GB. Incidence of deep vein thrombosis in Hong Kong Chinese. Br J Surg 1980;

67:251-253.4) Inada K, Shirai N, Hayashi M, Matsumoto K, Hirose M. Postoperative deep vein thrombosis in Japan: incidence and

prophylaxis.Am J Surg 1983;145:775-779.5) Tun M, Shuaib IL, Muhamad M, Mat Sain AH & Ressang AS. Incidence of post-operative deep vein thrombosis in general

surgical patients of Hospital Universiti Sains Malaysia. Malaysian J Med Sciences 2001; 8: 67.6) Chumnijarakij T, Poshyachinda V. Postoperative thrombosis in Thai women. Lancet 1975; 1:1357-1358.

7) Mok CK, Hoaglund FT, Rogoff SM, Chow SP, Ma A, Yau ACMC. The incidence of deep vein thrombosis in Hong Kong Chineseafter hip surgery for fracture of the proximal femur. Br J Surg 1979; 66: 640-642.8) Kim YH, Suh JS. Low incidence of deep vein thrombosis after cementless total hip replacement. J Bone Joint Surg (Am) 1988;

70-A: 878-882.9) Hirsh, J., Warketin, T.E., Shaughnessy, S.G., Anand, S.S., Halperin, J.L., Raschke, R., Granger, C., Ohman, E.M., and Dalen,

J.E., (2001), Heparin and Low Molecular Weight Heparin Mechanisms of Action, Pharmacokietics, Dosing, Monitoring,Efficacy, and Safety, CHEST 2001, p.119:64S-94S.

10) Hirsh DR, Ingenito EP, Goldhaber SZ: Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA1995; 274: 335337

11) Cade JF. High risk of the critically ill for VTE. Crit Care med 1982; 10:448-45012) Fraisse F, Holzapfel L, Couland J-M. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD.

Am J Respir Crit Care Med 2000; 161:1109-1114

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REFERENCES

13) Hirsh DR, Ingenito EP, Goldhaber SZ: Prevalence of deep venous thrombosisamong patients in medical intensive care. JAMA 1995; 274: 335337

14) Cade JF. High risk of the critically ill for VTE. Crit Care med 1982; 10:448-45015) Fraisse F, Holzapfel L, Couland J-M. Nadroparin in the prevention of deep vein

thrombosis in acute decompensated COPD. Am J Respir Crit Care Med 2000;161:1109-1114

16) Wells, Hirsch J, Anderson DR, et al. Accuracy of clinical assessments of deep-vein

thrombosis. Lancet 1995;354:1275-129717) Gallus AS, Salzman EW, Hirsh J. Prevention of VTE: In: Colman RW, Hirsh J,

Marder VJ, eal, eds. Haemostasis and thrombosis: basic principles and clinicalpractice. 3rd ed. Philadelphia, PA: JB Lippincott, 1994: 1331-1345.

18) Nicholaides AN, Bergqvist D, Hull R, et al. Prevention of VTE: internationalconsensus statement ( guidelines according to scientific evidence). Int Angiol1997; 16: 3-38.

19) British National Formulary 55, March 2008. British Medical Association.20) UpToDate21) Lexi-Comps Drug Information Handbook, 13th Edition.

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deep vein thrombosis_2003

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