PE and DVT

Pathogenesis of VT Virchow’s triad: Damage to vessel wall Venous stasis Hypercoagulability

Source Most PE’s originate from thrombi in the deep venous system of the legs, although they may also originate in the pelvic, renal or upper extremity veins. HOWEVER, less than 30% of pts will have symptoms in their legs at the time of diagnosis of PE 20% of calf vein thrombi propagate above the popliteal fossa. 20% of lower extremity venous emboli begin in the proximal veins without prior calf involvement.

Acquired Risk Factors Age Previous thrombosis Immobilization Major surgery – especially Ortho Estrogen – OCP, HRT, SERMs Antiphospholipid Ab syndrome Malignancy Nephrotic syndrome Inflammatory bowel disease Myeloproliferative d/o – esp p. vera and ET PNH Long distance air travel HIT

Inherited Risk Factors Factor V Leiden mutation G20210A prothrombin gene mutation Antithrombin deficiency Protein C or S deficiency Dysfibrinogenemia Hyperhomocysteinemia

Presentation Dyspnea Pleuritic chest pain Cough +/- hemoptysis On exam may have Tachypnea Tachycardia S4 Loud P2 May have fever – rarely >102 In massive PE can have hypotension and shock Look at legs for swelling and Homan’s sign – but only helpful if positive.

Homan’s Sign Passive dorsiflexion of the foot with the knee straight may give pain in the calf and back of the knee when there is a deep venous thrombosis. Some concern that vigorous dorsiflexion of the foot can expel clot from the veins and so this test may have its dangers. The sign is not specific for DVT

DDX swollen calf DVT Bakers Cyst Cellulitis Gout – if really bad it can sometimes look like a cellulitis If bilateral think about CHF, Nephrotic syndrome, liver failure, venous insufficiency, pregnancy or pelvic mass, vasodilators esp nifedipine

ABG Usually shows hypoxia, hypocapnia, respiratory alkalosis A-a gradient: Normal 7-14 depending on age Increases with age, FiO2 and supine posture Estimate of normal for age: Age/4 +4 A-a gradient = (FiO2 x713 – pCO2/0.8) – PaO2 If A-a gradient normal, PaO2 <80, Pa CO2 >45 then hypoventilation accounts for hypoxia Increased A-a gradient occurs in V/Q mismatch, shunting and any kind of barrier to diffusion (e.g. pulmonary edema) BUT can be normal and still have PE!

Labs Troponin, LDH, AST and BNP may all be elevated Check baseline CBC, PT/PTT/INR, Cr D-dimer Normal D-dimer excludes PE, but positive D-Dimer is not helpful (as it can be positive in many conditions including sepsis, immobility, post Sx and CAP)

EKG May have non specific ST and T wave changes “Typical” SI, QIII, TIII - rare. Sinus tachycardia T wave inversions in right to mid chest leads Poor R wave progression (acute RV dilation) P pulmonale RV conduction delays Right axis shift

CXR May have area of atelectasis May have wedge shaped infarct peripherally Pleural effusion occurs in about 40%

DVT – D-Dimer Fibrin degradation product elevated in active thrombosis Negative test can help exclude VTE Preferred test Quantitative Rapid ELISA – sensitivity 96/95% for DVT/PE Other methods include latex agglutination and RBC agglutination (SimpliRED) Less helpful in malignancy and recent surgery. Rapid RBC agglutination (SimpliRED) – sensitivity 87/78% for DVT/PE 1st generation ELISA accurate but slow Latex agglutination only useful if quantitative Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Int Med. 2004;140(8):589-602

DVT – D-Dimer In 283 patients with suspected DVT, low-moderate Wells DVT score and negative d-dimer only 1 (NPV 99.6%) had DVT over next 3 months 556 consecutive patients with suspected DVT, 283 (51%) had low-mod prob and neg d-dimer Used a quantitative latex agglutination test (sens 97.1% in this study; method sens 85%/89% for DVT/PE in Stien SR) Sensitive d-dimer testing can rule out DVT in low-moderate risk patients Bates SM, Kearon C, Crowther M, et al. Ann Intern Med. 2003;138:787-94

Doppler US of lower extremities If high clinical suspicion should be repeated 7-10 days after initial scan as below knee DVT can propagate Also remember that some pt develop DVT’s elsewhere – so you may not find a DVT in their legs if the source was their arm!

PE – Assigning Pretest Probability Single most important step in the diagnosis of pulmonary embolism May be done based on clinical judgment or aided by a clinical scoring system Modified Wells Criteria is the most widely used and studied Reliably stratifies patients by likelihood of PE to allow selection of safe (<2% VTE risk if no anticoagulation) management strategy Low(57%) 1.3%; Moderate(36%) 16.2% and High(7%) 37.5%

DVT – Wells Score The following were assigned a point value of 1 if present: Cancer Paralysis or plaster immobilization Bedrest > 3d or surgery in past 4 wks Localized tenderness Entire leg swollen Calf > 3cm larger than unaffected leg Pitting edema greater than unaffected leg Collateral superficial veins Alternative diagnosis more likely than DVT = - 2 points Probability High (≥ 3), Moderate (1-2) or Low (0 or less) DVT risk: High – 75%, Moderate – 17%, Low – 3% Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350:1795-8

PE – Imaging Studies PIOPED study quantified the value of V/Q scans in diagnosing PE Normal/near-normal scans exclude PE in low-moderate risk patients High probability scans confirm PE in moderate-high risk patients Drawbacks: more difficult test and 73% patients had indeterminate scans LE compression US showing DVT helps diagnostically, but a negative study insufficient to exclude VTE PIOPED Study. JAMA. 1990;263(20):2753-59

Clinical Models to Assess PE Risk PIOPED Criteria – Correlates well with incidence of PE Based entirely of clinician impression, not clinical risk factors Pretest Clinical Gestalt of PE Probability Actual PE Rate on PA Angiogram Low (“<20%” should have PE) 9% Intermediate (“20-79%” should have PE) 30% High (“80-100%” should have PE) 68% PIOPED Investigators. JAMA 1990; 263: 2753-2759.

PE – Helical CT (CTA) Eng performed a systematic review (SR) of all studies & SRs on CTA prior to 2003 Only 1/6 SRs and 3/8 primary studies found CTA >90% sensitive for PE In a similar SR in 2005 Roy concluded Negative CTA could safely exclude PE in low risk patients Negative LE US plus negative CTA could exclude PE in moderate risk patients At the time of those SRs no studies of faster multidetector CTA (MDCT) were available Faster scanning times and 50% thinner cuts presumably would result in increased sensitivity for smaller PEs Eng J, Krishnan JA, Segal JB, et al. AJR 2004;183(6):1819-27. Roy PM, Colombet I, Durieux P, et al. BMJ 2005;331(7511):259.

PE – PIOPED II Published June 2006 in NEJM Findings 1090 consecutive patients with suspected PE All given Modified Wells Score MDCT - mostly 4 slice Gold standard – composite - V/Q, angiogram & LE US Findings MDCT: sens 83% & spec 96% for PE Positive predictive value >90% in moderate/high risk Negative predictive value 96% in low risk patients but only 89% in moderate risk patients Findings generally consistent with Roy’s SR Concordant findings helpful - Need neg LE US to exclude in moderate risk patients Discordant findings – low pretest – pos CT or high pretest – neg CT need more testing.

V/Q scanning Look for evidence of ventilation perfusion mismatch Can only really be done if pt has normal CXR Normal scan virtually excludes PE even if pretest clinical probability was felt to be high. If a patient with intermediate clinical probability of PE has an intermediate scan then need further testing

A 60-year-old man with asthma is evaluated in the emergency department because of the acute onset of chest pain while lifting a heavy object. The pain is sharp and accentuated by deep breathing and by movement of the upper extremities. It is located over the left precordium. The physical examination and chest x-ray are normal. A ventilation-perfusion lung scan shows matched areas of perfusion and ventilation. Which one of the following is the correct interpretation of the ventilation-perfusion lung scan? ( A ) Normal ( B ) Low probability ( C ) Indeterminate ( D ) High probability

Correct Answer = A The lung scan is normal, with matched perfusion and ventilation. This lung scan rules out a pulmonary embolism, and another source for the chest pain should be sought. Often asthma does complicate the interpretation of the lung scan, but the problem relates to matched defects in which the airway obstruction decreases the ventilation to an area of the lung. The consequent hypoxia in that area leads to reduction in blood flow in the same area. These areas are rarely segmental.

Spiral CT/CT angiogram Used if CXR not normal Picks up large central emboli but is less sensitive for the smaller peripheral emboli. True pulmonary angiography rarely used now, though can do direct thrombolysis in massive PE.

Echo More than 80% of pts with PE will have abnormalities of RV size or function, or TR. McConnells sign – regional wall motion abnormalities that spare the R ventricular apex are very suggestive of PE BUT echo is only really used for Dx of massive lifethreatening PE’s when rapid diagnosis is needed to determine whether thrombolysis should be given.

Treatment Identify any contraindications to anticoagulations – if yes then IVC filter Inquire about h/o HIT If yes, then use direct thrombin inhibitor Assess need for hospitalization Extensive iliofemoral DVT with circ compromise Increased risk of bleeding Limited cardioresp reserve Poor compliance CI to LMW heparin

Treatment Administer LMW heparin or unfractionated heparin Goal 1.5-2.5 x PTT in first 24 hours Check platelet count on day 3-5 Treat at least five days and until patient’s INR is >2 on coumadin for two consecutive days Start coumadin on day 1

Treatment Duration 3-6 months in most patients Indefinite treatment: >1 spontaneous event One spontaneous life threatening event Antiphospholipid syndrome Antithrombin deficiency >1 genetic allelic abnormality Homozygote for Factor V Leiden or prothrombin gene mutation Heterozygote for both Protein C/S deficiency Continuing RF especially active advanced CA

Contraindications to Anticoagulation Absolute Active bleeding Severe bleeding diathesis Platelet count <20 Neurosurgery, ocular surgery or intracranial bleeding within the past 10 days

Contraindications to Anticoagulation Relative Mild/moderate bleeding diathesis or thrombocytopenia Brain mets Major abdominal surgery within 2 days GI or GU bleeding within 14 days Endocarditis Severe HTN (SBP >200, DBP > 120)

Inferior Vena Cava Filter Reduce risk of PE but carry increased risk of DVT Use in pts with DVT who cannot take anticoagulation e.g. due to bleeding risk Also used with or without anticoagulation in patients with high risk of death should further PE occur.

Hypercoagulation Workup Test all patients for unprovoked VT for antiphospholipid ab syndrome and hyperhomocysteinemia

Hypercoagulation Workup Test for Factor V Leiden, prothrombin gene mutation and deficiencies of antithrombin, protein C/S in the following patients: Family h/o VT VT before the age of 50 Recurrent VT Thrombosis in an unusual site (mesenteric, renal, cerebral, hepatic) Heparin resistance (antithrombin deficiency) Warfarin induced skin necrosis (protein C/S def) Neonatal purpura fulminans

Hypercoagulation Workup Wait to check for deficiency in antithrombin, protein C or S until 2 weeks after anticoagulation rx is completed

VTE – Prevention Underutilized DVT-FREE prospective registry of 5,451 patients at 183 US hospitals Only 32% of medical patients with DVT received DVT prophylaxis

VTE – Prophylaxis in Medical Patients Indications CHF or severe respiratory disease Bedrest with additional risk factor Cancer Prior VTE Most ICU patients Options Low dose unfractionated heparin or LMWH Sequential compression devices Graduated compression stockings Acute neurologic disease Inflammatory bowel disease