Management Of Venous Thromboembolism

Khaled O. Hadeli, MD

Pulmonary and critical care

12/16/99

Introduction

Complex vascular syndrome Multifactorial pathogenesis Wide spectrum 1 in 1,000 people affected 50,000 deaths/year in the USA

Nordstrom et.al, J.IM:232;155-160

Predisposing Factors

Race, age, genetics Thrombophilia Immobility Surgery Trauma Pregnancy and child birth Carcinoma

Clagett,et.al, 1995 Chest 108:312s-334s

30% POST T HROM BOTIC SYNDROM

M ASSIVE PE CLINICALY SEGNIFICANT

30% SYM PT OM ATIC PE

CHRONIC PEPHT N

COR PULM

30% ASYM PTOM ATIC PE 40% NO PE

20% PROXIM AL DVT 80% RESOLVE

CALF VEINS

VTE

Case

68 yo male with acute chest pain R/O (AMI), & R/I PE by spiral CT sent home on Warfarin 1 months later came back with GI bleed

» Htc 45 to 28 Review of the spiral CT, new CT and

leg US NEGATIVE

Cases

62 yo male with acute SOB and chest pain R/O PE by spirat CT

6 weeks later some SOB and no chest pain

Review of CT again show large PE

Diagnosis DVT

1 / 4 PEOPLE DDx

» Cellulitis» CHF with edema» Ruptured Baker’s

cyst» Chronic venous

insufficiency

Ginsberg. NEJM 1996

Pulmonary Embolism

Dyspnea, Pleuritic CP, Hemoptysis

Hemodynamic instability & Syncope

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

Stein et.al. 1996 27%

Goldhaber et.al 1966 30%

Rubenstein 31%

CT Vs. VQ scan

CT PE NO PE

Pos. 40 2

Indet. 1 3

Neg 5 88

Mayo, Radiology 1997

N=164 patients wit Indeterminate VQ and negative leg US

If CT is negative NO Angio, NO Rx 3 month F/U show 2.8% recurrence, and

1 patient died of PE

Ferretti, Radiology 1997

Spiral CT Scan

Case

58 yo male R/I PE by spiral CT 2 months later came back with acute

SOB INR = 2 VQ scan show high probability for PE

Treatment

C alf ve in s D V T P roxim a l D V Tan d P E

M ass ive P E

V en ou s Th rom b oem b o lism

Treatment

Unfractionated heparin Low-molecular-weight heparin Warfarin Thrombolytics

» streptokinase, urokinase, tPA IVC filter Surgical intervention

Unfractionated Heparin

Start heparin before testing High starting dose 0.2 - 0.4 U/ml protamine titration assay Sub therapeutic levels lead to 15X risk

of recurrence

Heparin Resistance

High dose of heparin >40,000U/day High levels of heparin binding proteins High levels of factor Vlll APTT/plasma heparin dissociation

measure plasma heparin levels or change to LMWH

Low Molecular Weight Heparin

Fractionated from the parent molecule Molecular weight 3 - 7 kd Longer effective plasma half life Predictable dose response Low incidence of HIT Low incidence of heparin resistance Low incidence of osteopenia

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

Oral Anticoagulants

Warfarin 1st - 3rd day of therapy 5mg q day INR 2.5 - 3.5 Teratogenic 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

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

VTE In Pregnancy

Increased risk; late pregnancy and early post partum

Leg studies are not reliable VQ scan is safe Pulmonary angio can be done Warfarin is contraindicated

Thrombophilia

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

Case

63 yo male with acute respiratory distress.

Failed out patient Rx PCO2 60..75..88..99 Hemodynamically unstable….Death Autopsy ( massive PE)

Massive PE

PE that leads to acute right ventricular failure

Death within 1st 2 hrs Occlusion of 75% of the pulmonary bed Echo findings: Rt Vent dysfunction and

enlargement, TR, increase pulmonary artery size, Rt sided thrombus (18%)

Management of massive PE

Hemodynamics Oxygen Mechanical ventilation Fluid resuscitation; very cautiously Vasoactive agents Thrombolytics IVC filter & Surgery

Thrombolytics

Alpert et.al Arch.1997:157,2550-56

Alpert et.al Arch.1997:157,2550-56

IVC Filter

Surgical» slit like channel, serrated miles, Adam

and De Weese device Percutaneous

» Greenfield» Vena -Tech» Bird’s nest » Simon - Nitinol

No difference in 2 year survival Indications

» contraindication to anticoagulation» failure of anticoagulation» compromised pulmonary vascular bed

Complication» filter migration, erosion, or obstruction

Backer, et.al Arch. 1992: 152:1985-94

Heparin Induced Thrombocytopenia

Thrombocytopenia leading to thrombosis

3 - 4% of pt on regular heparin 5 - 15 days of treatment Difficult to diagnose

drop of platelet to 100,000 or 50% DDx “HAT”

Heparin Induced Osteoporosis

Associated with prolonged use Partially reversible Dexa scan Calcium and vitamin D questionable

efficacy

Warfarin Induced Skin Necrosis

Uncommon Protein C & S deficiency Large loading dose Associated with malignancy and “HIT”

Treatment unfractionated heparin or LMWH

VTE in Malignancy

Increased risk Idiopathic recurrent VTE may be due to

occult malignancy 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