Ven ous T h romboemboli sm Risk in Medical Patients

Venous Thromboembolism Risk in Medical Patients

Dr. H. Gül ÖNGEN

İstanbul University

Cerrahpaşa Medical Faculty

Pulmonology Department

• Epidemiology of VTE – In the general population– Different countries

• Recent studies – (VITEA, IMPROVE, ENDORSE)

• Medical VTE risks– Gender and sex– Medical risk factors and their relative weight

VTE is a multifactorial disease

THROMBOSISA multifactorial accident

Hypertension

Diabetes

Smoking

Age

Pregnancy

Cancer

Antiphospholipids

Congenital thrombophilia

HIT

Acute infections

Hyperlipidaemia Others

DVT and PE as one disease !

• Symptomatic DVT is often associated with asymptomatic PE.

• Symptomatic PE is often associated with asymptomatic DVT

Major PE remain undiagnosed untill autopy !

• 1964-1977– Coon1 : % 84– Goldhaber2 : % 70 Mean: % 77

‘PE is most comman preventable cause of death among hospitalized medical patients.’

‘PE is often a cause of unexpected death’1Coon WW.Arch Surg. 1976;111:398-402

2Goldhaber SZ.etal Am J Med.1982;73:822-6

Epidemiology of VTE

• Mortality Symptomatic PE– initial presentation is death in ¼ of patients1

– Risk of early death among patients with symptomatic PE is 18-fold high compared to patients with DVT alone2

– Risk of death is high among elderly patients

1Heit JA J Thromb Thorombolysis. 2006:21:23-9

2Heit JA.et al.Arch Intern Med. 1999:159:445-53

Fatal PE among hospitalised patients

Death: (1991-2000)

n=16 104

PE: n=265 (erişkinlerin

%5.2)

Medical patients

n=212 (%80.8)

Acute medical disease n=110 (%51.4)

R Alikhan.et al J Clin Pathol. 2004;57:1254-7

Autopsy:

n=6833 (% 42.4)

Acute infections n=26

(%24)

Sandler DA, et al. J R Soc Med. 1989;82:203-5.

75%

25%

Medical patients

Surgical patients

VTE: Mortality PE kills 3 times more medical patients than surgical patients.

VTE is a disease having long term complications and risk of

recurrence.

• % 30 VTE:– Recurrence within 10 years.– Venous stasis syndrome occurs within 20

years.

Heit JA J Thromb Thorombolysis. 2006:21:23-9

Frequency of VTE• General population• Hospitalized patients (sugical, medical, ICU..)

• Medical outpatients• In special group of patients

– Women taking oral contraseption or HRT– Pregnent women ( pregnancy and the puerperium)– Patients with cancer– Patients with thrombophilia (congenital, acquired)

Epidemiology of VTE in the general population

Different countries Gender and sex In special groups Recent studies (VITEA, IMPROVE,

ENDORSE) Risk factors and their relative weight

Annual VTE incidence in the USA

Death

Pulmonery Hypertension

Pulmonery Embolism

Post-thrombotic syndrome

Symptomatic DVT

Asymptomatic DVT

60 0001

30 0002

600 0001

800 0003,4

2 million 1

1.Hirsh J. Circulation,19962Pengo V. NEJM, 2004

3 Brandjes DP. Lancet 19974KahnSR. J Gen Intern Med 2000

• 250 000 incident VTE cases occur annually among US whites

–incidence is similar or higher among African-Americans

–and lower among Asian and native- Americans

•VTE is one of the main cause of maternal death in the western wolrd.

Epidemiology of VTE in the USA

•Each year > 25 000 people die from VTE acquired in hospital.

•Fatal PE is the cause of 10% of deaths duiring hospitalization

•Mortality of VTE is higher than the mortality of AIDS, brest cancer and car accident

www.parliament.uk (2005)

Epidemiology of VTE in UK

http://www.parliament.uk/

EPI-GETBO Study:

•in the Brest district

•Annual incidence: 1.83/1,000

Oger E Thromb Haemost. 2000

Epidemiology of VTE in France

DVT PE ± (DVT)

EPI-GETBO Study: Charecteristics of patients with VTE (n=674) and clinical settings at the time of diagnosis


Age (years) 66 ±17 77 ± 15

% females % 57 % 61

Clinical settings

•Home % 68 %52

•Medical unit % 8 %34

•Surgical unit % 11 % 5

•Nursing home % 11 % 7

•Others % 2 % 2Geçirilmiş VTE % 27 % 23


Epidemiology of VTE in France

An

nu

al in

cid

enc

e / 1

00

000

0

600

1200

0-14

Gender, Age and VTE

Arch Intern Med, 1998;158:585-93

1000

800

400

200

15-19

20-24 30-34 40-44 50-54 60-64 70-74 80-84

25-29 35-39 45-49 55-59 65-69 75-79 >85

age

malefemale

Pe

r 1

0 0

00

EPI-GETBO Study

Incidence of VTE, including patients diagnosed and managed outside the hospital

0

10

20

30

40

50

60

70

80

0-19 20-39 40-59 60-74 > 74

DVT,maleDVT,femalePE±DVT,malePE±DVT,female

Total of all events:

•1.52 /1 000 / year in male

•2.03 / 1 000 / year in female

Oger E Thromb Haemost. 2000; 83: 657-60.

Gender and age

0

2

4

6

8

10

12

14

0-19 20-39 40-59 60-74 > 74

femalemale

Oger E Thromb Haemost. 2000; 83: 657-60.

years

inci

den

ce o

f V

TE

per

100

0 p

er a

nn

um

Age ≤ 80 years ≥ 80 years

(n=10 121) (n=2 890)

Fatal PE (%) 1.1 3.7

Fatal bleeding (%) 0.4 0.8

Major bleeding (%) 212 (2.1) 99 (3.4)

Lopez-Jimetez. Haematologica. 2006; 91: 1046-51.

VTE in the elderly patients: findings from a prospective

registry (RIETE)• 2 890 patients > 80 years old (out of 13 011 patients )

VITAE Study( VTE Impact Assessment Group in Europe)

•Total annual VTE events and mortality from 25 EU countries

→ DVT+ PE : 1.5 million

→VTE mortality: 543.000

→DVT : 684.000

A T Cohen, et al, 2007 (in press)

First large study to evaluate the burden of VTE in 25 European countries.


•Results in France

→General population: 60.424.000

→VTE-related deaths: 71.196

→Non-fatal VTE events: 140.000

→Cost (million Euros): 452 (316-621)



•Results:

→ VTE is a major public health problem in EU.

→Given the availibilty of VTE prophlaxis, many of these events and deaths could be prevented


ENDORSE ( multinational, cross sectional,

multicentric, observational survey)•Aim→To identify patients at risk of VTE among medical and surgical patients hospitalized in representative hospitals globally and locally throuhout the world.

→To determine the propotion of at risk hospitalpatients who receive effective types of VTE prophylaxis based on consensus guidelines.

ICTH Congress, 6-12 July 2007

35 ENDORSE Ülkesi

ENDORSE Countries

• Algeria Algeria • Australia/NZAustralia/NZ• BangladeshBangladesh• BrazilBrazil• BulgariaBulgaria• ColombiaColombia• Czech RepublicCzech Republic• EgyptEgypt• GreeceGreece• Gulf StatesGulf States

• Saudi ArabiaSaudi Arabia• SlovakiaSlovakia• SwitzerlandSwitzerland• Thailand Thailand • TunisiaTunisia• TurkeyTurkey• VenezuelaVenezuela

• Hungary Hungary • India India • IrelandIreland• Israel Israel • MexicoMexico• PakistanPakistan• PolandPoland• PortugalPortugal• RomaniaRomania• RussiaRussia

ENDORSE: Global data analysis flow

• 35 countries• 165.831 beds in participating hospitals• 99.664 beds in eligible wards• 84.637 patients in eligible wards • 77.738 evaluable patients in eligible wards

• 54.812 patients for VTE risk analysis

Study Population - TURKEY• 5161 beds in participating hospitals

• 3119 beds in eligible wards

• 2363 patients in eligible wards

• 2066 evaluable patients in eligible wards

• 1809 patients enrolled in eligiable wards

1503 patients for VTE risk analysis

Turkey (11 sites)

Istanbul (4)

Kocaeli

GaziantepIzmir (2)

Samsun

Kayseri

Antakya-Hatay

ENDORSE: Selected centers

• Eşrefpaşa Hospital (Izmir)

• Erciyes University, Oncology

Hospital

• Gaziantep University Hospital

• Göztepe Education Hospital

• Vezirköprü State Hospital

(Samsun)

•Anadolu Çınar Hospital(Ist)

•Kocaeli University Hospital

•Şişli Etfal Hospital (Ist)

•Süreyyapaşa Hospital (İst)

•Dr. Suat Seren Hospital

(Izmir)

•Hatay (Private) Hospital

ENDORSE: Study population - TURKEY

Study population (n=1503) VTE risk analysis patients population

medical (1204) 80%

surgical (299) 20% surgical

medical

SIRIUS Study:

VTE risk factors in medical patients

Samama, Arch Inter Med. 2000; 160:3415-3420.

• Pregnancy 11.41 (1.40-93.29)• Deterioration of general state 5.75 (2.20-15.01)• Immobilisation 5.61 (2.30-13.67)• Long-duration travel (>5-6hr) 2.35 (1.45-3.80)• Infectious disease* 1.95 (1.31-2.92)

Worsening Factors

• History of DVT/PE * 15.6 (6.77-35.89)

• Venous insufficiency 4.45 (3.10-6.38)

• Chronic heart failure 2.93 (1.55-5.56)

• Obesity ( BMI> 30 kg/m2 ) 2.49 (1.88-3.87)

• > 3 months pregnancy

• Prolonged standing ( > 6 hours /day)

Intrinsic Factors

Risk OD CI

IMPROVE Study: International Medical Prevention Registry on

Venous Thromboembolism

J Thromb Haemost 2003;(suppl)

0

10

20

30

40

50

cardiac n=254)

Pulmonery ( n=348)

Neurological ( n=208)

Cancer ( n=104)

50 %19 45

%13

46%22

24%23

Pa

tie

nts

in p

rop

hy

lax

sis

(%)

Primary reason of admission

70 % of medical patients with

acute diseases do not receive

any prophylaxis

Goldhaber SZ, et al. Chest. 2000;118:1680-4.

43%

16%10%

9%

8%14% Medical

General surgery

Medical oncology

Orthopedi

Thoracic surgery

Others

VTE: According to the wards

MAJOR MEDICAL RISK FACTORS?

Major VTE risk factors

age

Immobiliztion

Cancer

Pregnancy/postpartum

Oral contraception

Hormone RT

Antiphospholipid sendr.

Myeloporoliferative

sndr.

Hyperhomocysteinemia

Increased levels of:

•Factor VII

•Fibrinogen

•Factor XI

•Factor IX

Franco RT, Hum Genet. 2001;109:369-84.

Deficiency in AT

Deficiency in ProteinC

Deficiency in Protein S

Factor V Leiden

Protrombin gene mut.

Deficiency in

Fibrinogen, Plasminojen

Inherited Acquired Inher./Acquir.

The range of risk of VTE according to clinical situation

Risk Factors Risk*

Recent operation 3-21.7

Non-surgical hospitalization /immobilization 5.7-11.1

Congestive heart failure 1.4-9.6

Venous insufficiency 0.9-4.2

Cancer and chemotherapy 6.5

Myocardial infarction 5.9

Ischaemic stroke 2.0-3.0

Malignancy 2.4-5.6 Venous catheter 5.6-6.0

Samama MM,et al. Heamatologica,2003;88

• *Risk includes odds ratio, relative risk, ralative hazard, and hazard ratio

Range of VTE Risk

Risk Factors Risk*

Age 1.8-14.8

Hyperhomocystenaemia 7.1

Obesity 1.0-4.5

Oral contraception 1.7-4.7

Personel history of VTE 5.9

Secondery antiphospholipid syndrome 4.3


*Risk, odd ratio, relatif risk, ralatif hazard, ve hazard ratio’yu kapsar

Risk Factors Risk*

Smoking 1.0-3.3

Hormone replacement therapy 2.1-2.7

Black ethnicity 1.4

Male 0.6-1.4

Family history of VTE 3.3-3.4


Range of VTE Risk

Combination of Risk Factors

•Combination of hereditary and/ or acquired risk factors

•Multiplication effct of combination of risk factors

•Mathematical models are very rare.

Risk assessment in medical patients?

Risk assessment in medical patients?

Lutz L, et al. Med Welt, 2002

No risk dehydratation > 60 age Thrombophlia polisitemia pregnancy history ofVTE varikosis nephrotic synd. Active cancer family his. VTE myoloprolipheratiph s. or obesity kateg.1 >2 risk Kateg. 1 > 3r

Kateg. 2 >2r

Predisposing risks

0 1 2 3

•Ischaemic stroke •COPD, acute repr. Failu. + ventilation support•Myocardial infarction

•Heart failure•COPD, acute repr. Failu. + no ventilation support•Sepsis•Infection/acute inflam.disease:confined to bed•Infection/acute inflam.disease:not confined to bed•Venous catheter•No risk

Exposed risks(acute risks)

3

2

1

0

0

1

2

3

0 1 2 3

High Risk

Low Risk

x

Risk assessment in medical patients

• Stroke• Congestive

h. failure• Acute respir.

failure• Infections• Acute MI

• Immobilization• Malignanacy • Chemoterapy

• History of VTE

• Advabced age > 65

• Obesity• Coagulation

disorders

At least 1 At least 2At least 1+ 1 minor risk

Major Risks Minor Risks Additional Risks

Nicolaides AN et al. International Consensus Statement. Int Angiol 2006; 25: 101-61.

Ven ous T h romboemboli sm Risk in Medical Patients

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