venous thromboembolism

VENOUS THROMBOEMBOLISM

Ubaidur Rahaman

Senior Resident, CCM, SGPGIMS

Lucknow, India

Virchow’striad

stasis

Coagulationactivation

Vascular injury

•>90% of PE- thrombi arise from deep veins of leg

• clinically important PE- thrombi arise from popliteal or more proximal deep veins of leg

•Clinical manifestation of PEsize, site and number of thrombi + cardiorespiratory reserve of patient

•Recurrence of VTE is more with ileofemoral vein thrombosisthan popliteal vein thrombosis

diagnosisClinical presentation

9%11%Cyanosis

17%7%Fever (>38C)

10%15%Signs of DVT

23%26%Tachycardia( >100/min)

68%70%Tachypnoea(>20/min)

Signs

11%19%Syncope

7%11%Hemoptysis

25%20%Cough

8%12%Chest pain- substernal

43%52%Chest pain-pleuritic

59%80%Dyspnoea

Symptoms

PE excludedPE confirmed

CXR• plate like atelectasis

•Elevation of hemidiaphram•Pleural effusion

ABG- ↓PaO2, ↑A-aO2

EKG- signs of RV strain , RBBB

•Non specific•Helpful in exclusion of other causes

•Usually found in massive PE

•Can be caused by other causes

Normal in upto 20% patients

D- dimer

degradation product of cross linked fibrin

Elevated in presence of acute clot formationsimultaneous activation of coagulation and fibrinolysis

But fibrin is also produced in inflammation, necrosis, malignancy, dissection of aorta, aging

high negative predictive value, low positive predictive value

DVT

Detection of DVT in proven PEvenography – 70%

compression USG – 50%

Compression USG•Sensitivity-90%, specificity-95% for proximal DVT

•Not sensitive for isolated calf vein thrombosis•Negative result-Should be repeated after 1 week

COMPRESSION USG **•back up procedure to avoid false positive results with SDCT

•Patients with contraindication to dye or irradiation

**GUIDELINES ON THE DIAGNOSIS AND MANAGEMENT OF ACUTE PULMONARY EMBOLISM- EHJ 2008

Objectively documented DVT50% suffer PE, many are asymptomatic

Angiographically documented PE50-70% have detectable DVT

clinically suspected PE>50%-diagnosis not confirmed by investigation

Objective test for diagnosis of PE

•V/Q scan•Pulmonary angiography•Spiral CT- chest•MR angiography

•costly •Invasive•Radiation •Mobilization of patient

•2 D echocardiography

•≥40% of vascular bed obtstructionto produce detectable features of RV overload

•TEE more valuable than TTE•Coexistent cardiorespiratory disease•Not useful in hemodaynamically stable patients

•Clinical signs, symptoms and routine investigation do not help in confirmation or exclusion of PE

•Help in increasing the index of suspicion

Suspected PEwhich patient should be mobilized for costly, invasive/ radiation exposure investigation

Clinical probability of PELow- 9% prevalence of PE

Intermediate-30% prevalence of PEHigh-68% prevalence of PE

Clinical prediction rule Based on history, sign and symptoms

CLINICAL PREDICTION RULEWELLS score

3nAlternate clinical diagnosis less likely than VTE

1nhemoptysis

1.5nHR >100

3nClinical signs and symptoms of DVT

Clinical sign/ symptoms:

1nActive cancer- receiving treatment or treated in last 6 months or palliative care

1.5nRecent immobilization ≥ 3 days or major surgery in last 4 weeks

1.5nPrevious documented DVT or PE

predisposing factors:

2 level> 4- -------- likely PE0-4-------- unlikely PE

3 level0-1--------------- low2-6---- intermediate≥7--------------- high

CLINICAL PROBABILITY

WELLS SCOREclinical prediction rule

More than10,000 patients studied

<1% develop VTE within 90 days of evaluation

Prevalence of PE- 20%

• Clinical probability- PE unlikely• D-dimer- negative• No treatment with anticoagulants

•Clinical probability- PE likely •Clinical probability- PE unlikely but D- dimer- positive

Risk stratification according to expected PE related early mortality riskGUIDELINES ON THE DIAGNOSIS AND MANAGEMENT OF ACUTE PULMONARY EMBOLISM- EHJ 2008

Early discharge

or

Home treatment---LOW

<1%

+--

-+-Hospital

admission

++-INTERMEDIATE

3-15%NON-HIGH

Thrombolysis

or

Embolectomy+a+a+HIGH

> 15%

Myocardial

injuryRV dysfunction

Shock

or

hypotension

POTENTIAL TREATMENT

IMPLICATIONS

RISK MARKERS

MORTALITY RISK

a in the presence of shock or hypotension it is not necessary to confirm presence of RV dysfunction/ myocardial injury to classify as high risk PE related mortality risk.

Principle markers use for risk stratification

Elevated Trop T, Trop IMarkers of

myocardial injury

ECHO- RV dialatation, hypokinesia or pressure overloadSPIRAL CT- RV dialatation

PA catheter- increased pressures

Biochemical- elevated BNP, pro BNP

Markers of RV dysfunction

Shock or hypotensionaClinical markers

a SBP<90 or drop of ≥ 40 from baseline for >15 min, if not caused by new onset arrhythmia, hypovolemia or sepsis

GUIDELINES ON THE DIAGNOSIS AND MANAGEMENT OF ACUTE PULMONARY EMBOLISM- EHJ 2008

Diagnostic algorithm for suspected HIGH RISK PE

CT Immediately available

ECHORV overload

MD-CTPA

NO orpatient unstable to be transported

YES

NO YES

No other test availableor patient unstable

Consider thrombolysis orembolectomy

Search for other causes


NEGATIVEPOSITIVE

CT available orPatient stabilizes


Surgical embolectomy- where thrombolysis is contraindicated or failedPercutaneous catheter embolectomy or fragmentation- alternate to surgical embolectomy

Diagnostic algorithm for suspected non-HIGH RISK PE

ASSESS CLINICAL PROBABILITYClinical prediction rule score

D-dimer MD-CTPA

Low/ intermediate probabilityor PE unlikely

High probabilityor PE likely

Negative positive

No treatmentor investigate further

Treatmentantithrombosis


positivenegative

MD-CTPA

negativePositive

Treatmentantithrombosis

No treatment


Compression

USG

anticoagulation

Start without delay, awaiting definitive diagnostic confirmation

DrugsUnfractionated heparin, LMWH, anti Xa- fondaparinux, vit K antagonist

High risk PE- unfractionated heparinLMWH was not included in study for safety

Non high risk PE- LMWH, fondaparinuxexcept when

renal failure- CLcr<30 or high risk of bleeding- unfractionated heparin

Vit K antagonist- warfarinstart simultaneouly with heparin,

stop heparin only after INR is 2-3 for 2 consecutive days

HEPARINUNFRACTIONATED

•Efficacy depends on achieving therapeutic level within first 24 hours•Failure associated with 23.3% recurrent VTE

•Dose- 80 U/kg iv stat, then 18 U/kg/hr•Dose titrated according to normogram

•aPTT Q4h- modify dose accordingly- achieve target within 24 hour•Once target achieved – aPTT Q24h

Heparin Normogram

Stop infusion for 1 hr, then ↓ infusion rate by 3 U/kg/hr>90 ( > 3 times control)

↓ infusion rate by 2 U/kg/hr71-90 ( 2.3- 3.0 times control)

No change46-70 ( 1.5-2.3 times control)

40 U/kg bolus, ↑ infusion rate by 2 U/kg/hr35-45 ( 1.2-1.5 times control)

80 U/kg bolus, ↑ infusion rate by 4 U/kg/hr<35 ( < 1.2 times control)

Dose modificationaPTT ( sec)

Vit K antagonistWARFARIN

Inhibits vit K dependent gamma corboxylation of factors Clotting facors- II, VII, IX, X

Anticoagulant factors- protein C, protein S

Decreased levels of protein C, protein S – procoagulant activityCombined with heparin for first 5 days

Factor VII has shortest T1/2- 6 hoursAnticoagulant activity starts in 6 hours, but full effect takes 36-72 hours

Target INR- 2-3Start simultaneously with heparin

5 mg PO OD – titrate according to INRStop Heparin once INR is 2-3 for 2 consecutive days

Vit K antagonistWARFARIN

vit K bioavailabity• Diet

• Drugs1. Antimicrobials- gut flora producing vit K

2. Interaction with warfarinProtein binding

Metabolism

3. Increase potency for causing bleeding- antiplatelets

WARFARIN OVERANTICOAGULATION

•INR 3-5 -------- hold dose of that day•INR ≥5 – 7.5-- hold dose of that day + vit K 1 mg ivi stat•INR ≥7.5-10----hold dose of that day + vit K 2 mg ivi stat•INR ≥10 --------hold dose of that day + vit K 3 mg ivi stat

•If active bleeding – fresh frozen plasma- 10-15ml/kg bw

demonstrable reduction in INR- 6-8 hourscorrection on INR-----------------12-24 hours

Half life of vit K < warfarin– repeat dose may be required

Antagonist- vit K

Hemodynamic support

Volume challenge•modest and cautious

Ionotropes and vasodialators•Iv- isoprenaline- added advantage of pulmonary vasodialatation

•Iv- Dobutamine, noradrenaline, adrenaline•Iv- Levosimenden- ionodialator

•Oral/ iv- Sildenafil

•Inhaled- NO, PGI2

Respiratory support

Mechanical ventilationhigh ITP may further aggravate RV afterload and failure

Low PEEPLung protective ventilation

Not everything that counts can be counted. And not everything that can be counted counts.

--Albert Einstein

venous thromboembolism

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