Venous Thromboembolism (PE and DVT) Management in the ED

Transcription

1 Venous Thromboembolism (PE and DVT) Management in the ED Haldun Akoglu, Assoc. Prof., MD Marmara University Department of Emergency Medicine December, 2014 What is Venous Thromboembolism (VTE)? VTE forms as a result of excessive fibrin production from the action of thrombin on fibrinogen. Factors that enhance fibrinogen synthesis and promote its catalysis to fibrin include Systemic inflammation, Traumatic or immune-related vascular trauma, Inherited thrombophilias and hemoglobinopathies, Cancer, Pregnancy, and Sluggish blood flow. 1

2 What is Venous Thromboembolism (VTE)? Cardinal inciting mechanisms for VTE Venous injury, Slow blood flow, and Hypercoagulability, Most clinical decision rules for VTE incorporate these factors. In addition, each year of life independently increases the likelihood of imbalanced clot formation Deep Vein Thrombosis 2

3 DVT Disease spectrum Minimally symptomatic isolated calf vein thrombosis A limb-threatening iliofemoral venous obstruction. True incidence unknown in the ED population Approx. 600,000 hospital admissions per year Anatomy The venous anatomy of the lower extremity deep system anterior tibial, posterior tibial, peroneal, collectively called the calf veins. popliteal femoral sometimes called superficial femoral. A clot in the superficial femoral is a DVT and should be tx. (superficial) femoral + deep femoral = common femoral External iliac superficial systems greater saphenous short saphenous perforating. Proximal DVT = clot in the popliteal vein or higher, Distal DVT = clot isolated to calf veins. 3

4 Clinical Presentation Can be as subtle and nonspecific as a mild cramping sensation or sense of fullness in the calf, w/o objective swelling, and may be difficult to differentiate clinically from myriad other, unrelated disorders. Many patients use the term charley horse to describe the sensation of an early DVT (painful spasms and cramps in the leg muscles). It is precisely at this early stage, however, that DVT can be treated most effectively to minimize the potential morbidity and mortality associated with VTE. 4

5 Clinical Presentation Because the left iliac vein is vulnerable to compression by the left iliac artery, leg DVT occurs with a slightly higher frequency in the left leg Bilateral leg DVT < 10% of ED patients diagnosed with DVT. Clinical Presentation Clinical signs of DVT unilateral swelling, edema, erythema, warmth; tenderness to palpation along the distribution of the deep venous system; dilation of superficial collateral veins; palpable venous cord. 5

6 Clinical Presentation Homan s sign pain felt in the calf or posterior aspect of the knee on passive dorsiflexion of the foot while the knee is extended is insensitive and nonspecific for DVT has no role in clinical assessment of the patient. Clinical Presentation Upper extremity DVT thrombosis in the axillary vein causes arm swelling on the same side as an indwelling catheter or recent intravenous infusion site. In the absence of a catheter, the most frequent location of arm DVT is on the dominant hand side. Patients frequently note that their rings become tight as an early sign of DVT 6

7 Diagnosis Diagnosis of DVT and PE starts with an estimation of the pretest probability (PTP). This estimation may be accomplished either by the clinical gestalt of an experienced practitioner or in conjunction with a clinical decision tool, such as that derived and validated by Wells and colleagues Patients with a low PTP can have DVT excluded with a normal quantitative D-dimer Lab D-dimer protein derived from enzymatic breakdown of crosslinked fibrin, an elevated plasma concentration indicates the presence of a clot formed somewhere in the body within the previous 72 hours. concentration is proportionate to the size of the clot and decreases as the clot matures, so the test is less sensitive with small or chronic clots 7

8 Lab D-dimer concentration may be elevated with any condition that causes fibrin deposition, malignancy, pregnancy, advanced age, prolonged bed rest, recent surgery, infection, inflammation, new indwelling catheters, stroke, myocardial infarction. D-Dimer Assays The D-dimer protein can be measured in plasma with several techniques, and the differences in D-dimer assay methodology greatly affect diagnostic accuracy. 75 different d-dimer assays approved by FDA 2 major types: Qualitative Quantitative ELISA Immunoturbidimetric 8

9 D-Dimer Assays For many assays, less than 500 ng/ml (or 1000 fibrinogen equivalent units ([FEUs]) is a negative test result carries an 88 to 97% diagnostic sensitivity for symptomatic proximal DVT 83 to 94% sensitivity for calf DVT or asymptomatic proximal DVT. A negative quantitative D-dimer assayed by the ELISA or immunoturbidimetric technique is sensitive enough to exclude the diagnosis of DVT in patients at low or moderate risk without further evaluation. 9

10 Radiographic Evaluation DVT evaluation is by a combination of D-dimer testing Duplex venous USG by an expert. 3-point sequence (common and superficial femoral veins and popliteal vein, excluding the calf and saphenous veins) USG Sens & Spec 95% for proximal DVT The diagnostic test of choice in most centers. Dx Sens of a SINGLE venous USG for the exclusion of a clot at risk of progressing to a proximal DVT is increased significantly by including the calf and saphenous veins Radiographic Evaluation Low risk (PTP) pt + Neg 3-point USG = R/O DVT Any risk (PTP) pt + single normal whole-leg USG (including normal calf and saphenous veins) = R/O DVT Any risk (PTP) pt + Neg 3-point USG + Neg quant. D-dimer = R/O DVT Higher than low risk (PTP) pt + Neg 3-point USG = inadequate as a sole method to exclude DVT High risk (PTP) pt + High/No D-Dimer + Neg 3-point USG = repeat USG in 2 to 7 days, if negative R/O PE. Pos 3-point USG = DVT 10

11 Radiographic Evaluation Indirect CT venography (CTV) is not a primary imaging modality for DVT May be performed in conjunction with CT pulmonary angiography (CTPA) of the chest during the evaluation of suggested PE. CTV + CTPA: incremental increase in the Sens for VTE, identifying DVT in approximately 2% of patients in whom the CTPA is read as negative for PE but at the expense of significant additional radiation exposure to the pelvis and lower extremities. Routine use of CTV is not necessary when CTPA is performed Treatment When the diagnosis of DVT has been established, anticoagulation should be initiated, unless contraindicated, with a low-molecular-weight heparin (e.g., enoxaparin 1 mg/kg subcutaneously [SQ] every 12 hours), fondaparinux (5-10 mg SQ once daily, depending on patient weight), or unfractionated heparin (70-80 units/kg IV bolus followed by units/kg/hr infusion), assuming normal renal function The treatments work equally well and are safe in the absence of contraindications to anticoagulation. 11

12 Treatment Treatment requires transition to oral anticoagulation with warfarin for at least 3 months. Patients should be encouraged to ambulate after anticoagulation for DVT. Bed rest promotes DVT extension, increases the risk of embolization, and ultimately predisposes the patient to the postphlebitic syndrome. Patients who cannot be given anticoagulants or who have a recurrence of VTE despite anticoagulation therapy should be considered for vena caval intervention. Tx - Superficial Leg Thrombophlebitis Clot in the greater saphenous vein that extends above the knee are at risk for progression to DVT = anticoagulation. Saphenous vein thrombophlebitis tx NSAIDs, heat, graded compression stockings (fitted to exert mm Hg of pressure at the ankle) a mandatory repeat USG in 2 to 5 days. If the clot is extending, then anticoagulation is indicated. full-dose LMWH or fondaparinux for 10 days followed by repeat USG. 12

13 Tx - Isolated Calf Vein Thrombosis Tibial or peroneal vein thrombosis in an otherwise healthy, ambulatory pt with no other indication for anticoagulation Aspirin (325 mg of enteric-coated per day) Close follow-up with repeat USG at 2 to 5 days 25% of isolated calf vein thromboses propagate proximally = Tx w anticoagulation as for proximal DVT. Tx - Phlegmasia Cerulea Dolens (Painful Blue Leg) Massive iliofemoral occlusion results in swelling of the entire leg with extensive vascular congestion and associated venous ischemia, producing a painful, cyanotic extremity. There may be an associated arterial spasm resulting in phlegmasia alba dolens (painful white leg or milk leg), which may mimic an acute arterial occlusion. Consultation with a vascular surgeon for emergent thrombectomy evaluation. If timely consultation is not possible, early thrombolytic therapy in the absence of contraindications. Alteplase (1 mg/min to a total dose of 50 mg) via a peripheral IV catheter distal to the thrombus 13

14 Tx - Upper Extremity Venous Thromboses Etio use of indwelling venous catheters (50%) wires for electronic cardiac devices Upper extremity DVT can cause PE, and all patients with DVT above the elbow require definitive treatment Dx & R/O w venous USG. Value of D-dimer?? Tx - Upper Extremity Venous Thromboses UE DVT(+) + NO pain or infection Does NOT automatically warrant catheter removal if the catheter serves a current, vital purpose. Give anticoagulation if they do not have contraindications. Anticoagulate for at least 3 months after catheter removal 14

15 Complications Most feared complication of DVT is fatal PE DVT damages venous valves, causing venous insufficiency. painless varicosities to severe postphlebitic syndrome unremitting pain and swelling, varicose veins, skin changes, and nonhealing ulcers. 15

16 Q & Pulmonary Embolism 16

17 Pulmonary Embolism Clot that formed hours, days, or weeks earlier in the deep veins and dislodged, traveled through the venous system, and traversed the RV into the pulmonary vasculature. Symptoms vary from no symptom to CV collapse. About 8% of ED patients with PE die within 30 days, even when PE is promptly diagnosed and treated Pathophysiology of Pulmonary Vascular Occlusion Young persons w/o CV disease tolerate at least 30% obstruction, often with minimal symptoms or signs. Clot lodged deeply in a segmental artery (1/16 of all) can obstruct blood flow to a sufficient degree to cause tissue necrosis. Focal, sharp, pleuritic pain Over several days the infarcted segment becomes consolidated on CXR and exudes a pleural effusion, Chest pain from noninfarcting PE can be highly variable and vague. About 30% of patients with definite PE have no perception of chest pain. 17

18 Pathophysiology of Pulmonary Vascular Occlusion 90% of pts w non-infarcting emboli have sensation of dyspnea. Dyspnea may be constant and oppressive or may be intermittent and perceived only with exertion. Pathophysiology of Pulmonary Vascular Occlusion 15% of pts w PE have a normal A-a gradient of oxygen normal defined as age in years/4 + 4 A-a gradient is abnormally high in most pts who are evaluated for PE but ultimately found to not have PE. Presence of hypoxemia (pulse oximetry <95%, breathing room air) that cannot be explained by a known disease process increases the probability of PE. A normal oxygen saturation can NOT R/O PE. 18

19 Pathophysiology of Pulmonary Vascular Occlusion 50% patients with PE have HR > 100 beats/min. In one study, the probability of PE was not reduced in patients who normalized any vital sign while in the ED. Arterial hypotension: ominous hemodynamic consequence of PE; it occurs in only about 10% of patients but signifies a fourfold increase in risk of death Pulseless electrical activity (PEA) is the most common electrocardiogram (ECG) result from obstructive PE. The survival rate for cardiac arrest from PE is abysmally low, even if the arrest is witnessed and heroic treatment is initiated Clinical Presentation Variables that increase the probability of PE in epidemiologic studies are not useful for individual ED patients with signs and symptoms suggesting PE. From an epidemiologic standpoint, people who smoke are at a significantly higher risk for venous clots than are people who do not smoke. However, in the ED, smoking by a given patient does not seem to increase that person s risk for PE over that of a nonsmoker with an otherwise identical clinical presentation. 50% of patients diagnosed with PE have no apparent clinical risk factors for VTE. 19

20 Clinical Presentation Any ED visit rel d to weakness, SoB, dizziness or syncope, pain, extremity discomfort, or nonspecific malaise or functional deterioration could represent a potential PE. This does not mean that every pt w one of these sx should be worked up for PE. Consider Sx in the context of the entire clinical picture. A typical patient with PE Presents with 2 to 3 days of SoB, now worsened. Chest pain is vaguely described. A few pts have focal pleuritic chest pain, Many say that their chest hurts with breathing on lateral. Purely substernal chest pain is rare and suggests cardiac The presence or absence of sudden onset of symptoms neither increases nor decreases the probability of PE. 20

21 Clinical Presentation From antemortem histories of patients who die suddenly and unexpectedly from PE most have complained of nagging symptoms for weeks before collapse, 40% already had seen a physician for care. PE with lung infarction Clinical picture similar to lobar pneumonia, (focal chest pain, fever, and unilateral rales on auscultation). Temperature greater than 38,6 C suggests infection In pulmonary infarction onset of pain and blood-red hemoptysis are on the same day, In lobar pneumonia productive cough is present for a few days before rust-tinged sputum Clinical Presentation PExam Unilateral leg asymmetry (DVT) Jugular venous distention in a pt w severe dyspnea and clear lung fields on auscultation = pure RV failure. Wheezing suggests bronchospasm, which is not common in PE and makes the diagnosis less likely (but does not exclude it). Bilateral rales suggest LV failure, although localized rales often are heard over infarcted lung tissue. 21

22 Diagnosis CXR: Suggest alternative Dx (Pnem, CHF, PTX) Unilat basilar atelectasis prob of PE Hampton s Hump Apex-cental, pleure-based, wedge-shaped infiltrate Westermark s sign Unilateral lung oligemia very rare and only in large PE Diagnosis EKG Alternative Dx (pericarditis, AMI) PE EKG findings are due to scute or subacute pulm HTN Tachycardia Symm T-inversion V1-4 McGinn-White S1Q3T3 pattern Incomplete/Complete RBBB Each doubles prob of PE in Sx ic Pts 22

23 Approach to the Dx Strategy of PE 50% of patients diagnosed with PE have no identifiable classic risk factors Currently EPs evaluate 1-2% of all patients for PE Each year more than 16 million patients come to the ED with chest pain or dyspnea. Although numerous cases of PE are probably still missed, overtesting for PE can also be harmful. There is a risk of false-positive interpretation of CTPA, which may occur in as many as 10% of scans read as positive for PE So, there should be a rational, reproducible strategy to guide the decision-making and diagnostic processes 23

24 Approach to the Dx Strategy of PE This strategy should begin with estimation of PTP. Methods for estimating PTP can be implicit (meaning the clinician s best guess) or explicit (meaning use of a scoring system or flow algorithm to categorize the probability) Approach to the Dx Strategy of PE One approach to the workup for PE is to compare the PTP with the test threshold for PE. The test threshold represents the point above which some type of workup should be initiated and below which the clinician can justify not starting the workup. For PE the test threshold is 1 to 2.5%. Patients with a PTP less than 2.5% are more likely to be harmed than benefited by a workup and vice versa for patients with a PTP greater than 2.5% The question becomes how to quantify the PTP accurately. 24

25 Approach to the Dx Strategy of PE Clinical judgment alone is subject to cognitive error inherent to medical diagnosis, framing heuristic conditions in the ED at the time (e.g., is one less likely to pursue a relatively low-likelihood diagnosis when the department is very busy), conditions of the clinician (e.g., fatigue, dysphoria, subjective feelings about the patient), availability of diagnostic studies (e.g., daytime vs. nighttime, weekday vs. weekend). In addition, there is variability among clinicians who may not agree that a 19-year-old with cough and pleuritic chest pain, a normal CXR, and no other risk factors has less than a 2% probability of PE Decision rules help to deal with these problems because they are structured and more transparent. 25

26 Approach to the Dx Strategy of PE Although gestalt reasoning and clinical decision rules may provide adequate stratification to guide the workup (i.e., D-dimer vs. pulmonary vascular imaging), they have not been able to reproducibly identify the very low-risk population whose PTP lies below the 2% test threshold To identify the very low-risk group in whom PE could be safely excluded at the bedside with no diagnostic testing, the PE rule-out criteria (the PERC rule) were derived When the physician s unstructured clinical suspicion for PE is low and each of the eight elements of the rule is satisfied, the PERC rule identifies a very low-risk population among whom no patient has a PTP for PE of greater than 2%. In the large validation series, the rule excluded PE at the bedside in 20% of cases and yielded a false-negative rate of 1% (95% confidence interval [CI] %). Patients with risk factors but w/o any sx/signs of PE (e.g., no chest pain, SoB, dyspnea on exertion, normal vitas, no syncope) DO NOT warrant workup for PE unless there is some compelling clinical indication. 26

27 Algorithm w CTA For a patient for whom suspicion is implicit or with explicit score suggesting a PTP over 40%, clinicians should skip the D- dimer, order pulmonary vascular imaging, and strongly consider initiating anticoagulation in the absence of contraindications. Because the half-life of circulating D-dimer is less than 8 hours, the sensitivity of the D-dimer may decrease if the patient s symptoms have been present for longer than 3 days. False-negative D-dimer measurements may also be seen with ongoing warfarin therapy and in the subset of patients with pulmonary infarction. Algorithm w V/Q * May require patient admission. Additional testing Option 1: Crossover to perform scanning or CT for algorithms A and B. Option 2: Perform lower extremity venous USG, and if initial venous USG is negative, repeat in 1 week. Option 3: Perform formal pulmonary angiography. 27

28 Subsegmental Embolism in CTPA It is reasonable that if the patient has no evidence of DVT, no signs of cardiopulmonary stress, no ongoing major risk for thrombosis (e.g., active malignancy), isolated subsegmental findings are the equivalent of no findings, and anticoagulation is not indicated. 28

29 Management - Anticoagulation Unfractionated heparin (80 units/kg intravenous bolus, followed by 18 units/kg/hr intravenous infusion), Fractionated LMWH (e.g., enoxaparin, 1 mg/kg SQ or intravenously [IV] every 12 hours), pentasaccharide factor Xa inhibitor fondaparinux (5-10 mg, depending on body mass) can be used for treatment of most patients with PE. Side Effects of LMWH << UFH But, reversal agent Protamine Sulfate reverses UFH 100%, LMWH 50%, fondaparinux 0% Fact All patients with A high PTP, No contraindication to anticoagulation, evidence of hemodynamic instability, recent syncope, hypotension, hypoxemia, clinical evidence of RV heart strain (more severe moderate PE or high-risk PE) should receive immediate empirical heparin. 29

30 Fact For a patient diagnosed with PE in the presence of a major contraindication to anticoagulation, (recent cerebral hemorrhage or large cerebral infarction) consultant should be contacted for urgent placement of an inferior vena cava filter. If vena caval interruption cannot be performed within 12 hours, perform a baseline head CT scan, then start UFH infusion at 18 units/kg/hr (without a bolus) admit the patient to the ICU for close neurologic monitoring and frequent PTT. The rationale for use of UFH is that it can be reversed more reliably (by discontinuing the heparin drip and administering protamine, 1 mg/kg IV) Thrombolytics Thrombolytic therapy in PE is controversial. Alteplase results in more rapid symptomatic improvement than standard antithrombotic therapy alone and causes more rapid and complete normalization of RV function. Alteplase also increases the risk of hemorrhage, especially minor hemorrhage It is not known with certainty how many patient lives would be saved, or definitively improved, by the addition of thrombolytic treatment to heparin therapy versus the number of patients who would experience a fatal or lifethreatening bleeding event as a result of thrombolytic treatment. Benefit-risk analysis suggests that fibrinolysis is of greatest value in the subset of patients with proven, massive PE. 30

31 Thrombolytics and Massive PE Massive PE is defined as, hypotension with a SBP < 90 mm Hg for more than 15 min In patients with preexisting HT, SBP < 100 mm Hg or a reduction in the baseline SBP > 60 mm Hg. In the absence of contraindications, patients with proven massive PE probably benefit from fibrinolysis. There is insufficient evidence to recommend initiation of empirical fibrinolysis in the absence of confirmatory pulmonary vascular imaging or the presence of otherwise unexplained shock in a patient with known DVT and high clinical suspicion for PE. Thrombolytics and Submassive PE A subset of patients with submassive PE may benefit from fibrinolysis, those with moderate-to-severe respiratory distress and hypoxia (oxygen saturation less than 95%) and, those with Echo evidence of RV dysfunction. If Echo not available laboratory markers of RV dysfunction may be useful, elevated TnI level or BNP > 90 pg/ml. 31

32 Unique Questions That Commonly Arise in the Emergency Department I cannot get imaging at night. Is it reasonable to treat the patient with heparin until morning? The short answer to this question is yes, if the patient has no contraindications. Many smaller hospitals routinely use this method and use a single dose of enoxaparin. 32

33 How do I manage the patient who is being treated for pulmonary embolism who returns to the ED for chest pain? If the patient has a therapeutic INR ( ) and returns with symptoms only (e.g., chest pain, dyspnea) and without syncope, appears relatively comfortable, has normal vital signs, and has no new changes suggesting Pulm HTN on ECG (in particular, no S1Q3T3 pattern and no T wave inversion in leads V1 through V4), follow-up imaging is probably not needed. Other causes of chest pain (esp ACS) should be considered How can I rule out pulmonary embolism in a pregnant patient without use of ionizing radiation? One clinical conundrum is the fact the pregnancy is accompanied by both an increased risk of PE and a predictable elevation in D-dimer, even in the absence of PE. Given that PE is the most common nontraumatic cause of death in pregnant women, clinicians are justified in adopting a liberal rule-out PE approach to all pregnant women with dyspnea. 33

34 How can I rule out pulmonary embolism in a pregnant patient without use of ionizing radiation? First, assess the PERC rule criteria and apply a modified version of the PERC rule with a slightly elevated top limit for the pulse rate (normal up to 104 beats/min instead of 99 beats/min). If the result of this modified PERC rule is negative, then order a quantitative D-dimer. Use thresholds to define a normal D-dimer that is elevated on the basis of trimester (first trimester, 1.5 ; second trimester, 2 ; and third trimester, 2.5 standard threshold). If the result of the modified PERC rule is positive or the D- dimer is above the adjusted threshold, then order bilateral lower extremity ultrasound; if this is positive for DVT, then treat for PE. If the bilateral ultrasound is negative, proceed to pulmonary vascular imaging. How can I rule out pulmonary embolism in a pregnant patient without use of ionizing radiation? The issue of the optimal imaging procedure in pregnancy remains controversial. A 2003 survey of radiologists indicated an almost equal split (53% in favor of CTPA, 47% in favor of V/Q scanning) in their choice for imaging for PE in pregnancy. A plain film CXR be taken first, and if CXR shows no air space disease, that Q scan can be considered only the perfusion phase, the radiation dose is halved. Give prehydration, place a Foley catheter to accelerate removal of radiolabel in the bladder. If the CXR has evidence of airspace disease, CTPA should be performed and abdomen should be shielded. If Q scan negative = R/O PE N CXR perfusion defects = PE = UFH If Q scan non-diagnostic = CTPA 34

35 How do I evaluate the patient with possible pulmonary embolism who is too obese to fit in a CT scanner? Duplex USG of the lower extremities to R/O DVT. If positive = PE Another option is to anticoagulate empirically based on a moderate-to-high pretest probability and a D- dimer concentration that exceeds 1000 ng/ml. The adequate regimen for anticoagulation is uncertain, but many experts recommend SC enoxaparin, 1 mg/kg of actual body weight up to a maximum of 200 µg/kg. Q & haldun.akoglu@marmara.edu.tr 35