VTE refers to deep vein thrombosis and pulmonary embolism, which share common risk factors and pathophysiology. Risk factors include immobilization, recent surgery or trauma, inherited or acquired hypercoagulable states, and certain medical conditions. Signs and symptoms of DVT include leg pain and swelling, while PE presents with dyspnea, chest pain, and potentially hemodynamic instability in severe cases. Diagnosis involves clinical assessment, imaging like ultrasound or CT, and blood tests like D-dimer and Wells criteria. Treatment consists of anticoagulation with heparins or warfarin to prevent clot extension and recurrence.

2. Presented by Sherif Mohamed Abd Elsamad

3. Definition of VTE VTE is a term that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). They share common risk factors, patho-physiologies and management.

4. Risk factors for VTE Three main factors contribute to the development of VTE: Stasis: mainly caused by heart failure, prolonged immobility Endothelial injury: mainly caused by either direct trauma (severed vein) or local irritation (by chemotherapy, past DVT, phlebitis) Hypercoagulability: inherited (AT III deficiency, protein C or S deficiency) or acquired (malignancy, pregnancy, AT III deficiency, protein C or S deficiency as in nephritic syndrome, disseminated intra-vascular coagulopathy (DIC) and liver failure. These represent the Virchow triad

5. Risk factors for VTE (cont’d) Immobilization Surgery within the last 3 months Stroke History of venous thromboembolism Malignancy Preexisting respiratory disease Chronic Heart Disease Age >60 Surgery requiring >30mins of anesthesia Behçet’s disease Recent travel (past 2weeks, >4 hours) Varicose veins Superficial vein thrombosis Central venous catheter/port/pacemaker Additional risk factors in women: Obesity BMI ≥ 29 Heavy smoking (>25cigs/day) Hypertension Pregnancy OCP’s

6. Well’s risk score for VTE Variables Points Clinical Signs and Symptoms of DVT? (Calf tenderness, swelling >3cm, erythema, pitting edema affected leg only) +3 PE is the 1 ry Diagnosis, or equally likely +3 Heart Rate > 100 +1.5 Immobilization at least 3 days, or Surgery in the Previous 4 weeks +1.5 Previous, objectively diagnosed PE or DVT? +1.5 Hemoptysis +1 Malignancy with Rx within 6 mo, or palliative? +1

7. Well’s risk score for VTE (cont’d) Score Risk >6 High 2 to 6 Moderate <2 Low

8. Pathogenesis The thrombus usually originates in the soleal venous sinuses or valvular sinuses (the calf vein is the usual site). It may also originate in the iliac or femoral vein (pelvic veins). Other sites also include the renal veins, upper limb veins, the right side of the heart and in-situ thrombosis in the pulmonary circulation.

9. Symptoms & signs Symptoms of DVT: Dull pain, heaviness, oedema and warm limb With extensive DVT : massive oedema, cyanosis, dilated superficial collateral veins and low grade fever. With ilio-femoral DVT : Phlegmasia cerulea dolens (cyanosed limb due to obstructed vein) Phlegmasia alba dolens (pale, pulseless cold limb due to concurrent arterial spasm) The last two entities are limb-threatening conditions and considered vascular emergencies.

10. Symptoms & signs (cont’d) Symptoms of PE: Dyspnea: Acute onset of exertional dyspnea, usually not associated with orthopnea Palpitation: Usually rapid and regular but may be irregular if atrial fibrillation (AF) or multi-focal atrial tachycardia (MAT) develop Pleuritic chest pain Cough: Dry, irritant in nature Hemoptysis: either blood-tinged or blood-streaked sputum or fresh blood

11. Symptoms & signs (cont’d) Signs of DVT: Increased girth of the affected limb Hotness, cyanosis and oedema (non-pitting): usually unilateral Homan’s sign (tenderness during passive dorsiflexion of foot): it is contraindicated because of it’s role in thrombus detachment and thus emobilization Moses sign (tenderness on touching the calf muscle)

12. Symptoms & signs (cont’d) Signs of PE: Tachypnea Tachycardia Right-sided S 4 gallop Accentuated pulmonic component of S 2 (A 2 ) Fever: Temperature < 39°C Massive PE: Hemodynamic instability SBP <90mmHg or ≥ 40mmHg drop in baseline SBP, elevated jugular venous pressure, right-sided S 3 , and para-sternal lift.

13. Investigations Lab: CBC: For abnormalities in Hb%, WBC’s or platelets Bleeding and coagulation profile: May show prolongation of PT and aPTT (consumption) D-dimer: Unspecific but excellent negative predictive value Troponin: High in moderate to large PE Arterial blood gases (ABG): May show hypoxemia, hypocapnea, respiratory alkalosis or respiratory failure in cases of massive PE

14. Investigations (Cont’d) ECG: Sinus tachycardia (most common presentation) Non-specific ST-T changes Right atrial abnormality Right ventricular strain and hypertrophy Right axis deviation Right bundle branch block (RBBB) AF or MAT S I Q III T III : Deep S-waves in lead I with pathological Q-waves and inverted T-waves in lead III

15. Investigations (Cont’d) Imaging Chest X-ray: Normal, atelectasis and/or pulmonary parenchymal abnormality, pleural effusion or cardiomegaly. A wedge-shaped, pleural-based opacity (Hampton’s hump) or central oligemia (Westermark’s sign) Duplex U/S: Sensitivity and specificity >95%, Include both B-mode and Doppler studies. Able to detect other pathology like Baker’s cyst. Highly operator-dependant. Ventilation/perfusion (V/Q) scan: Rarely used. Results are low, intermediate or high probability

16. Investigations (Cont’d) Imaging (cont’d) Multi-slice CT (MSCT) pulmonary angiography: Increased availability and use nowadays. Useful in triple rule-out of patients with chest pain. Echocardiography: May show right ventricular enlargement, right atrial enlargement or tricuspid regurgitation. Regional right ventricular wall-motion abnormality sparing the RV apex (McConnell’s sign) or RV/RVOT thrombus may rarely be seen. Other rarely used: Phlebography, magnetic resonance venography and invasive pulmonary angiography.

17. Hypercoagulability work-up No consensus on who to test Increased likelihood if: Age <50 years without immediate identifiable risk factors (idiopathic or unprovoked) Family history Recurrent clots If clot is in an unusual site (portal, hepatic, mesenteric, cerebral) Unprovoked upper extremity clot (no catheter, no surgeries) Patients with warfarin-induced skin necrosis (they may have protein C deficiency)

18. Hypercoagulability work-up (cont’d) Protein C or S deficiency Factor V leiden deficiency Anti-thrombin III deficiency Prothrombin gene mutation Antiphospholipid antibody High Homocysteine The most common cause of congenital hyper-coagulability is protein C resistance due to factor V Leiden mutation

19. Differential diagnosis Unilateral limb involvement: Muscular strain, tendon rupture, cellulitis, lymphodema or retroperitoneal fibrosis pressing over the vein. Bilateral limb involvement: Liver, heart or renal failure or IVC obstruction PE: Other causes of acute chest pain mainly acute coronary syndromes, aortic dissection and diffuse oesophageal spasm

20. Complications of VTE Recurrent VTE Varicose veins Chronic venous insufficiency (CVI) Post-phlebitic syndrome (pain, edema, ulceration and pigmentation) Chronic pulmonary hypertension and vascular cor-pulmonale Death due to massive or sub-massive PE

21. Management of VTE Prophylaxis Mechanical Pharmacological IVC filter (2 ry ) Treatment Anti-coagulation Thrombolysis Embolectomy

22. Prophylaxis of VTE Mechanical: Leg elevation Graded compression stocking Early ambulation Pneumatic compression boot

23. Prophylaxis of VTE (cont’d) Pharmacological Un-fractionated heparin (UFH): given every 8 hours SC Low-molecular weight heparin: Enoxaparin 30-40mg SC every 24 hours Fondaparinux: 2.5mg SC every 24 hours Desirudin: A recombinant direct thrombin inhibitor. Dose: 15mg SC every 12 hours Rivaroxaban: A novel oral anti-Xa agent. Dose: 10mg every 24 hours

24. Prophylaxis of VTE (cont’d) Inferior vena cava (IVC) filter Considered as secondary prophylaxis or secondary prevention against PE but not DVT. IVC filter is indicated in patients with high risk of recurrence when other methods are contra-indicated (Class IIb, LOE B). The routine use of IVC filters is not recommended (Class III, LOE B).

25. Treatment of VTE Anti-coagulation UFH: Given as a bolus 5000 Units IV followed by continuous IV infusion at a rate of 1000 Units/h. The dose is adjusted to keep the aPTT 1.5-2.5 times normal which should be evaluated every 6h. LMWH: Enoxaparin is used in a dose of 1mg/Kg every 12h. Fondaparinux: The dose is adjusted to the body weight given SC every 24h (<50Kg- 5mg, 50-100Kg- 7.5mg, >100Kg- 10mg)

26. Treatment of VTE (cont’d) Anticoagulation (cont’d) Warfarin: Started as early as possible to achieve a target INR of 2-3. Duration of treatment depends on several factors. Event Duration First Time event of reversible cause (surgery/trauma) At least 3 months First episode of idiopathic VTE At least 6 months Recurrent idiopathic VTE or continuing risk factor At least 12 months Symptomatic isolated calf-vein thrombosis 6 to 12 weeks

27. Treatment of VTE (cont’d) Thrombolysis Thrombolytic therapy is indicated in the following: Persistent arterial hypotension Cardiogenic shock Right ventricular dysfunction Large perfusion defects on V/Q scan Severe hypoxemia Intermediate-risk patients may also be considered candidates for thrombolytic therapy.

28. Treatment of VTE (cont’d) Thrombolysis Approved thrombolytic regimens for PE Agent Dose Streptokinase 250,000 IU as loading dose over 30 min, followed by 100,000 IU/h over 12 to 24 h 1,500,000 IU over 2 h Urokinase 4,400 IU/Kg as a loading dose over 10 min, followed by 4,400 IU/Kg/h over 12-24 h 3 million IU over 2 h Reteplase (rtPA) 100mg over 2 h 0.6mg/Kg over 15 min (max. 50mg)

29. Treatment of VTE (cont’d) Embolectomy Either surgical or catheter-based Surgical pulmonary embolectomy is indicated in patients in whom thrombolysis is absolutely contra-indicated or has failed (Class I, LOE C) Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contra-indicated or has failed (Class IIb, LOE C)