the pvd. org venous thromboembolism (vte) deep vein thrombosis (dvt) & pulmonary embolism (pe)...

The PVD. org Venous Thromboembolism (VTE) Deep Vein Thrombosis (DVT) & Pulmonary Embolism (PE) Evaldas Giedrimas, MD Duane Pinto, MD

The PVD. org Overview Etiology and Risk Factors of VTE Etiology and Risk Factors of VTE Symptoms of DVT and PE Symptoms of DVT and PE Evaluation and Pretest Probability Evaluation and Pretest Probability Diagnostic Modalities Diagnostic Modalities Treatment and Prevention Overview Treatment and Prevention Overview FDA Approved Therapies FDA Approved Therapies Length of Treatment Length of Treatment Unusual Site DVTs Unusual Site DVTs

The PVD. org Etiology of VTE Virchows Triad: Virchows Triad: Vascular injury Stasis Hypercoagulable state 1/1000 or 400,000 per year 1/1000 or 400,000 per year increased incidence after age 60 increased incidence after age 60 30 day mortality is 30% (20% due to PE) 30 day mortality is 30% (20% due to PE) Subsequent risk of recurrent DVT 30 % within 10 years Subsequent risk of recurrent DVT 30 % within 10 years

The PVD. org Etiology of VTE: PE 4th leading cause of death 4th leading cause of death 3rd cardiovascular cause of death behind MI and CVA 3rd cardiovascular cause of death behind MI and CVA 30-50% from ileo-femoral DVTs and 10-20% from upper extremity DVTs 30-50% from ileo-femoral DVTs and 10-20% from upper extremity DVTs

The PVD. org Risk Factors of VTE Majority of VTEs occur in non-surgical patients Majority of VTEs occur in non-surgical patients Initial VTE event contributes to recurrence Initial VTE event contributes to recurrence Non-surgical Non-surgical hospital or nursing home confinement, malignancy, central venous catheter or pacemaker, superficial venous thrombosis, and neurological disease with extremity paresis IBD IBD Nephrotic syndrome Nephrotic syndrome Renal vein involved in 35% of VTEs with nephrotic syndrome Urinary excretion of anti-thrombin III, platelet hyperactivity, elevated plasma viscosity Travel Travel Increased risk when travel exceeds 10 hours Malignancy Malignancy Incidence of VTE ~ 11%, after resection can increase to 40% Pancreas, GI tumors, ovary, prostate, lung are thombogenicPancreas, GI tumors, ovary, prostate, lung are thombogenic Trousseau's syndrome migratory thrombophlebitisTrousseau's syndrome migratory thrombophlebitis

The PVD. org Risk Factors of VTE in Hospitalized Patients Usually have more than one risk factor Usually have more than one risk factor NYHA Class III/IV Heart Failure COPD exacerbation Sepsis Advanced age History of prior VTE Cancer Stroke with limb paresis Bed rest

The PVD. org Risk Factors of VTE in Surgical Patients Orthopedic surgery, hip/knee replacement, hip fracture surgery, trauma surgeries with spinal cord injuries Orthopedic surgery, hip/knee replacement, hip fracture surgery, trauma surgeries with spinal cord injuries Cancer, congenital thrombophilia, prior history of VTE, obesity, increasing age >60 years Cancer, congenital thrombophilia, prior history of VTE, obesity, increasing age >60 years

The PVD. org Estrogen Associated Risk Factors for VTE During Pregnancy Increases risk by 3-6x especially with increasing age Increases risk by 3-6x especially with increasing age Incidence is even across 3 trimesters Incidence is even across 3 trimesters Especially high during 6 weeks after delivery Especially high during 6 weeks after delivery Immobility and Obesity Prior VTE High estrogen Venous stasis Pelvic trauma with delivery Acquired hypercoagulability: elevated fibrinogen, von Wilebrand factor, and factor VIII, and decreased natural anticoagulants (Protein S) Left leg > Right leg ( left iliac compression by the right iliac artery) Left leg > Right leg ( left iliac compression by the right iliac artery)

The PVD. org Estrogen Associated Risk Factors for VTE: OCP Use Among women in 20-30s 3-6 x greater risk Among women in 20-30s 3-6 x greater risk Higher in Factor V Leiden or prothrombin mutation carriers Higher in Factor V Leiden or prothrombin mutation carriers Greatest risk 6-12 month after onset Greatest risk 6-12 month after onset Proportional to the estrogen dose Proportional to the estrogen dose Trans-dermal preparation carry less risk Trans-dermal preparation carry less risk

The PVD. org Symptoms of VTE Deep Vein Thrombosis (DVT) Deep Vein Thrombosis (DVT) Sudden onset of pain, swelling, in one limb Pain usually in the calf, crampy, bursting, worse with ambulation, precedes swelling Bilateral presentation usually due to underlying malignancy or hypercoagulable disorder Pulmonary Embolism (PE) Pulmonary Embolism (PE) Abrupt onset of dyspnea, cough, syncope Pleuritic chest pain

The PVD. org DVT Evaluation and Pretest Probability Active cancer - 1 pt Active cancer - 1 pt Paralysis or recent limb casting 1 pt Paralysis or recent limb casting 1 pt Recent immobility > 3 days 1 pt Recent immobility > 3 days 1 pt Local vein tenderness 1 pt Local vein tenderness 1 pt Limb swelling 1 pt Limb swelling 1 pt Unilateral calf swelling > 3 days 1 pt Unilateral calf swelling > 3 days 1 pt Collateral superficial vein 1 point Collateral superficial vein 1 point Alternative diagnosis likely subtract 2 points Alternative diagnosis likely subtract 2 points High probability = 3+High probability = 3+ Moderate = 1-2Moderate = 1-2 Low =

The PVD. org PE Evaluation and Pretest Probability Clinical symptoms of DVT 3 pts Clinical symptoms of DVT 3 pts Alternate explanation less likely than PE 3 pts Alternate explanation less likely than PE 3 pts Heart Rate > 100 1.5 pts Heart Rate > 100 1.5 pts Immobilization or surgery within 4 weeks 1.5 Immobilization or surgery within 4 weeks 1.5 Prior VTE 1.5 pts Prior VTE 1.5 pts Hemoptysis 1 pt Hemoptysis 1 pt Malignancy 1 pt Malignancy 1 pt High probability >6 High probability >6 Moderate = 2-6 Moderate = 2-6 Low

The PVD. org Treatment FDA approved therapy Heparin/Unfractionated Heparin (cont.) Resistance Resistance 25% of individuals who require > 35,000 units per day Non-specific binding, high factor VIII and fibrinogen levels, antithrombin III deficiency, increased heparin clearance, aprotinin and NTG use Heparin Induced Thrombocytopenia (HIT) Heparin Induced Thrombocytopenia (HIT) 50% drop in platelets or < 100,000 platelet count 5-7% of patients, 5-10 days after initiation 50% pro-thrombotic event rate lasting 30 days after discontinuation

The PVD. org Treatment FDA approved therapy Warfarin Inhibits vitamin K dependent pro-coagulation factors (II, VII, IX and X) Inhibits vitamin K dependent pro-coagulation factors (II, VII, IX and X) Also inhibits protein C and S synthesis which is associated with pro-coagulability and reason for overlap with heparin therapy Also inhibits protein C and S synthesis which is associated with pro-coagulability and reason for overlap with heparin therapy 24 hour decrease in Factor VIII, Protein C 24 hour decrease in Factor VIII, Protein C Followed by Factor IX on day 2, Factor X on day 3.5, Factor II on day 5 Followed by Factor IX on day 2, Factor X on day 3.5, Factor II on day 5

The PVD. org Treatment FDA approved therapy LMWH Small heparin fragments (4000-6000 kD) still causes conformational change Small heparin fragments (4000-6000 kD) still causes conformational change Higher affinity for factor Xa than thrombin by anti-thrombin enzyme Higher affinity for factor Xa than thrombin by anti-thrombin enzyme Safe in a daily or BID dose based on weight Safe in a daily or BID dose based on weight Similar and/or improved mortality, morbidity, recurrence and side effect profile Similar and/or improved mortality, morbidity, recurrence and side effect profile Effective for PE treatment but needs initial inpatient monitoring Effective for PE treatment but needs initial inpatient monitoring

The PVD. org Treatment FDA approved therapy LMWH (cont.) HIT HIT less than 1% Monitoring Monitoring Suggested in obese, pregnant patients, prolonged therapy, especially with renal insufficiency Anti-factor Xa level - 4 hours after last LMW heparin dose (goal 0.5-1.0 IU/ml BID & 1.0-2.0 for QD dose)

The PVD. org Treatment FDA approved therapy Fondaparinux Ultra-low molecular weight heparin Ultra-low molecular weight heparin Synthetic pentasaccharide analog for ATIII activation Synthetic pentasaccharide analog for ATIII activation Given SQ, renal excretion (not for pts with CrCl

The PVD. org Unusual Site DVT Ovarian Vein Thrombosis Rare, but often post-partum Rare, but often post-partum Etiology Etiology R>L, due to tortuosity and multiple valves Suppurative pelvic thrombophlebitis Presentation and Complications Presentation and Complications Fever unresponsive to antibiotics PE, thrombus extension into L renal vein or IVC Ureteral obstruction Low rate of recurrent thrombosis and thromboembolism

The PVD. org Unusual Site DVT Ovarian Vein Thrombosis (cont.) Diagnosis often incidental Diagnosis often incidental Clinical diagnosis during postpartum period or laparotomy CT is preferred, with MRI, Ultrasound also used Therapy Therapy 7-10 day course of heparin and antibiotics for post- partum OVT Excellent long-term survival

The PVD. org Unusual Site DVT Budd-Chiari Syndrome Rare Rare Etiology Etiology of hepatic venous drainage most commonly due to hepatic vein thrombosis Tumor (hepatocellular Ca, renal cell Ca, Wilms tumor), primary veno-occlusive disease, congenital obstruction, myeloproliferative disease, paroxysmal nocturnal hemoglobinuria, pregnancy, OCP Presentation Presentation Can be slow insidious to rampant progression of acute hepatic failure Type 1 IVC is occluded +/- hepatic veno-obstruction Type 2 occlusion of major hepatic veins Type 3 fibrous obliteration of small centrilobular intra-hepatic venules often during BMT

The PVD. org Unusual Site DVT Budd-Chiari Syndrome (cont.) Symptoms Symptoms Sinusoidal congestion, venous HTN, stasis, hypoxia, hepatocyte necrosis, hemorrhage, parenchymal damage. Diagnosis Diagnosis Doppler ultrasound, MRI, CT Therapy Therapy Decompression, functional restoration, prevention of thrombus propagation and recurrence Fibrinolytics: hemodynamic instability after PE, catheter-directed lytic therapy has not been proven in RCThemodynamic instability after PE, catheter-directed lytic therapy has not been proven in RCT Anticoagulation is controversial Surgical shunts can be helpful

The PVD. org Unusual Site DVT Cerebral Venous Sinus Thrombosis Young-to-middle aged womenYoung-to-middle aged women Etiology Etiology Heterogeneous age group with heterogeneous risk factors 70% - Occur in superior sagittal and lateral sinuses Idiopathic, hormone therapy, malignancy, venous malformation, post-operative, infectious, dehydration, pregnancy, IBS, thrombophilia Presentation Presentation Headache, focal neurological deficits, seizures, or altered consciousness

The PVD. org Unusual Site DVT Cerebral Venous Sinus Thrombosis (cont.) Diagnosis Diagnosis CT- ~ 80% sensitivity and specificity ; MRI more accurate yet still often incorrect Cerebral angiography definitive diagnosis Therapy Therapy Heparin use but little evidence for support of use, duration and dose

The PVD. org Unusual Site DVT Retinal Venous Thrombosis Atherosclerosis risk factors rather than VTE Atherosclerosis risk factors rather than VTE Etiology Etiology Associated with HTN, DM, CAD, connective tissue disease, malignancy, OCP use, IBS Presentation Presentation Retinal arterial HTN, atherosclerosis, causing retinal venous compression and stasis Visual loss 2 nd to diabetic retinopathy Retinal hypertension, macular edema, vitreous hemorrhage and glaucoma Therapy Therapy surgery, topical steroids, cyclocryotherapy, photocoagulation

the pvd. org venous thromboembolism (vte) deep vein thrombosis (dvt) & pulmonary embolism (pe)...

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