Management Of Venous Thromboembolism Khaled O. Hadeli, MD Pulmonary and critical care 12/16/99

Introduction l Complex vascular syndrome l Multifactorial pathogenesis l Wide spectrum l 1 in 1,000 people affected l 50,000 deaths/year in the USA Nordstrom et.al, J.IM:232;

Predisposing Factors l Race, age, genetics l Thrombophilia l Immobility l Surgery l Trauma l Pregnancy and child birth l Carcinoma Clagett,et.al, 1995 Chest 108:312s-334s

Case l 68 yo male with acute chest pain l R/O (AMI), & R/I PE by spiral CT l sent home on Warfarin l 1 months later came back with GI bleed » Htc 45 to 28 l Review of the spiral CT, new CT and leg US NEGATIVE

Cases l 62 yo male with acute SOB and chest pain R/O PE by spirat CT l 6 weeks later some SOB and no chest pain l Review of CT again show large PE

Diagnosis DVT l 1 / 4 PEOPLE l DDx » Cellulitis » CHF with edema » Ruptured Baker’s cyst » Chronic venous insufficiency

Ginsberg. NEJM 1996

Pulmonary Embolism l Dyspnea, Pleuritic CP, Hemoptysis l Hemodynamic instability & Syncope l mimic indolent Pneumonia, CHF, COPD

Ginsberg. NEJM 1996

5 Reasons why CT is replacing VQ Scan 1. Dr Stern wants to be the next Faculty to own a “Porsche” 2. VQ Scan “Sucks” 3. CT Scan is more available 4. CT Scan is more reliable 5. CT Scan is cheaper

Major PE at Autopsy with Antetmortem diagnosis l Stein et.al % l Goldhaber et.al % l Rubenstein 31%

CT Vs. VQ scan Mayo, Radiology 1997

l N=164 patients wit Indeterminate VQ and negative leg US l If CT is negative NO Angio, NO Rx l 3 month F/U show 2.8% recurrence, and 1 patient died of PE Ferretti, Radiology 1997

Spiral CT Scan

Case l 58 yo male R/I PE by spiral CT l 2 months later came back with acute SOB l INR = 2 l VQ scan show high probability for PE

Treatment

l Unfractionated heparin l Low-molecular-weight heparin l Warfarin l Thrombolytics » streptokinase, urokinase, tPA l IVC filter l Surgical intervention

Unfractionated Heparin l Start heparin before testing l High starting dose l U/ml protamine titration assay l Sub therapeutic levels lead to 15X risk of recurrence

Heparin Resistance l High dose of heparin >40,000U/day l High levels of heparin binding proteins l High levels of factor Vlll l APTT/plasma heparin dissociation l measure plasma heparin levels or change to LMWH

Low Molecular Weight Heparin l Fractionated from the parent molecule l Molecular weight kd l Longer effective plasma half life l Predictable dose response l Low incidence of HIT l Low incidence of heparin resistance l Low incidence of osteopenia

Koopman,et.al. NEJM, 1996;334:682-7

Oral Anticoagulants l Warfarin l 1st - 3rd day of therapy l 5mg q day l INR l Teratogenic l Drug interaction: » medications, diet, alcohol, and illness

Lead article in the NEJM 3/25/99 “Patients with a first episode of idiopathic VTE should be treated with anticoagulant agent for longer than 3 months”

Case l 38 yo Female on Warfarin for DVT l Acute chest pain and SOB l +ve Urine pregnancy test

VTE In Pregnancy l Increased risk; late pregnancy and early post partum l Leg studies are not reliable l VQ scan is safe l Pulmonary angio can be done l Warfarin is contraindicated

Thrombophilia l Inherited recurrent VTE » Hyperhomocysteinemia » Protein C deficiency » Protein S deficiency » Antithrombin deficiency » Activated protein C resistance

Case l 63 yo male with acute respiratory distress. l Failed out patient Rx l PCO l Hemodynamically unstable….Death l Autopsy ( massive PE)

Massive PE l PE that leads to acute right ventricular failure l Death within 1st 2 hrs l Occlusion of 75% of the pulmonary bed l Echo findings: Rt Vent dysfunction and enlargement, TR, increase pulmonary artery size, Rt sided thrombus (18%)

Management of massive PE Hemodynamics l Oxygen l Mechanical ventilation l Fluid resuscitation; very cautiously l Vasoactive agents l Thrombolytics l IVC filter & Surgery

Thrombolytics

Alpert et.al Arch.1997:157,

IVC Filter l Surgical » slit like channel, serrated miles, Adam and De Weese device l Percutaneous » Greenfield » Vena -Tech » Bird’s nest » Simon - Nitinol

l No difference in 2 year survival l Indications » contraindication to anticoagulation » failure of anticoagulation » compromised pulmonary vascular bed l Complication » filter migration, erosion, or obstruction Backer, et.al Arch. 1992: 152:

Heparin Induced Thrombocytopenia l Thrombocytopenia leading to thrombosis l 3 - 4% of pt on regular heparin l days of treatment l Difficult to diagnose drop of platelet to 100,000 or 50% l DDx “HAT”

Heparin Induced Osteoporosis l Associated with prolonged use l Partially reversible l Dexa scan l Calcium and vitamin D questionable efficacy

Warfarin Induced Skin Necrosis l Uncommon l Protein C & S deficiency l Large loading dose l Associated with malignancy and “HIT” l Treatment unfractionated heparin or LMWH

VTE in Malignancy l Increased risk l Idiopathic recurrent VTE may be due to occult malignancy l Do not respond to Warfarin, need to use heparin LMWH

Thrombosis and Pulmonary Embolism are today no longer dreaded either by patients or by physicians, although only few years ago we where still completely powerless to combat them. Harry Zilliacus 1946