Venous Thromboembolism - Management (1 of 21) DEEP VEIN 1 THROMBOSIS Patient presents w/ symptoms suggestive of DVT DVT 2 DIAGNOSIS What is the clinical pretest probability? Low (unlikely) clinical pretest probability Moderate or high (likely) clinical pretest probability Is Is duplex D-dimer1,2 venous Positive 2 Positive positive or ultrasonography (US) negative? positive or negative? A MANAGEMENT Negative Non-pharmacological therapy Negative Patient education Low (unlikely) clinical • pretest probability Bed rest & leg elevation • Graduated elastic compression stockings (GECS) B Parenteral anticoagulants ALTERNATIVE • DIAGNOSIS Low-molecular-weight Heparin (LMWH), or Moderate or high (likely) (Exclude DVT) • clinical pretest probability Unfractionated Heparin (UFH) • Fondaparinux C Oral anticoagulants • Non-vitamin K oral anticoagulants (NOACs) • Warfarin rombolytic therapy • FOLLOWUP STUDIES G Only in massive DVT • Repeat US in 1 week Invasive procedures Negative • Venography (magnetic Positive • rombectomy resonance venography if • Inferior vena cava (IVC) fi lters available) when appropriate D Follow-up © MIMS• Oral anticoagulant 1D-dimer may be used for excluding DVT in a moderate or intermediate pretest probability population if prevalence is approximately ≤15% 2Interim therapeutic anticoagulation may be given while awaiting test result; use an anticoagulant that can be continued if DVT is confi rmed Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B205 © MIMS 2020 Venous Thromboembolism - Management (2 of 21) VENOUS THROMBOEMBOLISM (VTE) • Most commonly manifested as pulmonary embolism (PE) & deep venous thrombosis (DVT), & is associated w/ signifi cant morbidity & mortality - ⅓ of patients present w/ symptoms of DVT & ⅔ w/ PE - Also manifests as superfi cial vein thrombosis (SVT), a less severe form of DVT • One of the most common life-threatening cardiovascular diseases in the US & w/ increasing incidence & mortality rates in Asia VTE - MANAGEMENT • All patients admitted for major trauma, surgery or acute medical illness should be assessed for risk of VTE & bleeding before starting prophylaxis of VTE - Studies show that appropriate VTE prophylaxis should be given to surgical patients in Asia who are at risk for VTE Pathogenesis • Virchow’s triad theorizes 3 factors contributing to the development of VTE: Hypercoagulability, endothelial damage, & stasis • Hypercoagulability has been associated w/ factor V Leiden mutation & prothrombin gene mutation - Cancer also produces a hypercoagulable state due to the procoagulant activity produced by malignant cells & also secondary to eff ects of chemotherapeutic agents • Major contributing risk factors include history of trauma, surgical procedures, spinal cord injury, long bone fractures, & previous VTE Risk Factors Transient or Reversible Provoking • Surgery within the past 4 weeks (eg hip or knee replacement) • Major trauma • Immobilization for at least 3 days • Bedridden for >3 days • Estrogen therapy • Pregnancy/postpartum • Lengthy travel, eg airline fl ight >8 hours Persistent Provoking • Active cancer • Active autoimmune disease • Antiphospholipid antibody syndrome • Chronic infl ammatory states, eg infl ammatory bowel disease Other Risk Factors • Increasing age • Past medical history or family history of VTE • Spinal cord injury • Lower limb fracture • Myocardial infarction or hospitalization for atrial fl utter/fi brillation or heart failure within the past 3 months • Congestive heart failure or respiratory failure • Obesity • Varicose veins • Blood transfusion & erythropoiesis-stimulating agents 1 DEEP VEIN THROMBOSIS (DVT) • A frequent manifestation of VTE in which there is a blood clot blocking a deep vein • Patients are generally asymptomatic w/ a calf DVT but becomes symptomatic w/ proximal extension of the DVT & venous outfl ow obstruction Signs & Symptoms Suggestive of DVT • Localized tenderness along the distribution of the deep venous system • Unilateral or entire leg is swollen • Calf swelling >3 cm compared to asymptomatic leg (measured 10 cm below tibial tuberosity) • Pitting edema is greater in the symptomatic leg • Collateral superfi cial veins (non-varicose) • Erythema • Warmth • Superfi cial© thrombophlebitis w/ a palpableMIMS cord over a superfi cial vein • Phlegmasia cerulea dolens (blue leg) - deoxygenated hemoglobin in the stagnant veins causes a cyanotic hue in the leg • Phlegmasia alba dolens (pale leg) - pallor in the edematous legs because the interstitial tissue pressure has exceeded capillary perfusion pressure B206 © MIMS 2020 Venous Thromboembolism - Management (3 of 21) 2 DIAGNOSIS Clinical fi ndings are important to the diagnosis of DVT but are poor predictors of the presence or severity of thrombosis • Pretest probability is needed to guide the diagnostic process WELLS SCALE OF CLINICAL PRETEST PROBABILITY FOR DVT Pretest Total VTE - MANAGEMENT Clinical Features Points Probability Points Entire leg swollen 1.0 High risk ≥3 Calf swollen by >3 cm compared to the asymptomatic side (measured 1.0 Moderate risk 1-2 10 cm below tibial tuberosity) Low risk ≤0 Localized tenderness along the deep venous system distribution 1.0 Pitting edema (greater in the symptomatic leg) 1.0 If both legs are symptomatic, score Collateral superfi cial veins (non-varicose) 1.0 the more severe side Immobilization for ≥3 days or major surgery within 12 weeks 1.0 Paralysis, paresis, recent plaster immobilization of lower extremity 1.0 Previously documented DVT 1.0 Simplifi ed version*: Active cancer (ongoing treatment within the last 6 months or 1.0 Likely ≥2 current palliative therapy) Unlikely <2 Alternative diagnosis as likely or greater than that of DVT -2.0 Modifi ed from: Institute for Clinical Systems Improvement. Health care guideline: venous thromboembolism diagnosis and treatment. 13th ed. January 2013. *National Institute for Health and Care Excellence (NICE). Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. https://www.nice.org.uk/guidance/ng158. 26 Mar 2020. Diff erential Diagnosis • Since pain & swelling are common presenting complaints, DVT must be diff erentiated from other causes including the following: - Muscle strain, rupture or tear - Leg swelling in paralyzed leg - Lymphangitis, lymphedema - Cellulitis - Ruptured popliteal cyst (Baker’s cyst) - Venous insuffi ciency - Superfi cial thrombophlebitis Diagnostic Tests • Baseline blood tests when initiating anticoagulation treatment includes a complete blood count (CBC), renal & hepatic function assessment, prothrombin time (PT) & activated partial thromboplastin time (aPTT) D-dimer Level by ELISA Assay • A highly sensitive but nonspecifi c screening test for the presence of VTE - D-dimer levels may also be elevated in patients w/ MI, sepsis, cancer, infl ammation, infection, necrosis, trauma, pregnancy, etc - erefore, high concentration of D-dimer has a poor positive predictive value for DVT & cannot be used to rule in the disease • Normal D-dimer level by ELISA assay (<500 ng/mL) has a high negative predictive value & is useful to rule out VTE thus reducing the need for imaging when used in conjunction w/ clinical probability, plethysmography, or US - Patients w/ a low clinical pretest probability of DVT & a negative D-dimer assay are considered to have no DVT or have a very low risk of subsequent DVT & can be followed up clinically without further testing unless new or progressive symptoms develop • is is most useful in ED patients, in ambulatory care settings & in patients w/ recent onset of symptoms who are not currently taking anticoagulants - Can be used after a negative duplex US to determine the need for further radiologic evaluation - In elderly or inpatients, the D-dimer retains a high negative predictive value but is normal in <10% of patients & therefore is not useful in these patients Duplex Venous Ultrasonography (DUS) • B-mode, (eg 2D) imaging & pulse-wave Doppler interrogation • Primary radiologic device for the evaluation of proximal DVT - Most often used non-invasive test to diagnose DVT in patients w/ moderate or high clinical pretest probability - Has a very high sensitivity & specifi city for diagnosing proximal DVT in symptomatic patients, but less favorable results for calf vein & asymptomatic DVT - e primary© diagnostic criteria to establishMIMS the presence of DVT by US is incomplete vein compressibility - Proximal & distal compression ultrasound for DVT has 90.3% sensitivity & 97.8% specifi city • Combined use of clinical pretest probability & duplex US (w/ compression) is eff ective in confi rming or excluding the diagnosis of DVT - In patients w/ clinical suspicion of DVT, positive D-dimer & negative US, consider repeat US for suspected calf thrombosis or venography for suspected proximal thrombosis in 3-7 days B207 © MIMS 2020 Venous Thromboembolism - Management (4 of 21) 2 DIAGNOSIS (CONT’D) Duplex Venous Ultrasonography (DUS) (Cont’d) • In patients w/ negative computed tomographic pulmonary angiography (CTPA) results & positive D-dimer & a PE likely clinical probability, further evaluation w/ DUS should be used to improve clinical likelihood of diagnosing disease & avoid more invasive testing - A positive result confi rms the diagnosis of DVT & requires treatment regardless of the presence or absence of PE VTE - MANAGEMENT - For a negative result, incorporation of clinical pretest probability (CPTP) can improve diagnostic accuracy & potentially avoid unnecessary