Venous Thromboembolism Risk in Medical Patients

1
Venous Thromboembolism Risk in Medical Patients

• Dr. H. Gül ÖNGEN
• Istanbul University
• Cerrahpasa Medical Faculty
• Pulmonology Department

2

• 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

3
VTE is a multifactorial disease
Acute infections
Cancer
Pregnancy
Congenital thrombophilia
Age
THROMBOSIS A multifactorial accident
Smoking
HIT
Diabetes
Antiphospholipids
Hypertension
Hyperlipidaemia
Others
4
DVT and PE as one disease !

• Symptomatic DVT is often associated with
  asymptomatic PE.

• Symptomatic PE is often associated with
  asymptomatic DVT

5
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. 1976111398-402 2Goldhaber
SZ.etal Am J Med.198273822-6
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.
20062123-9 2Heit JA.et al.Arch Intern Med.
1999159445-53
7
Fatal PE among hospitalised patients
Death (1991-2000) n16 104
Autopsy n6833 ( 42.4)
PE n265 (eriskinlerin 5.2)
Medical patients n212
(80.8)
Acute medical disease n110 (51.4)
Acute infections n26 (24)
R Alikhan.et al J Clin Pathol. 2004571254-7
8
VTE Mortality
PE kills 3 times more medical patients than
surgical patients.
Sandler DA, et al. J R Soc Med. 198982203-5.
9
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. 20062123-9
10
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)

11
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

12
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

13
Annual VTE incidence in the USA
60 0001
Death
30 0002
Pulmonery Hypertension
600 0001
Pulmonery Embolism
800 0003,4
Post-thrombotic syndrome
Symptomatic DVT
2 million 1
Asymptomatic DVT
1.Hirsh J. Circulation,1996 2Pengo V. NEJM,
2004 3 Brandjes DP. Lancet 1997 4KahnSR. J Gen
Intern Med 2000
14
Epidemiology of VTE in the USA

• 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.

15
Epidemiology of VTE in UK

• Each year gt 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)
16
Epidemiology of VTE in France

• EPI-GETBO Study
• in the Brest district
• Annual incidence 1.83/1,000

Oger E Thromb Haemost. 2000
17
Epidemiology of VTE in France
EPI-GETBO Study Charecteristics of patients with
VTE (n674) and clinical settings at the time of
diagnosis
DVT PE (DVT)
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 2

Oger E Thromb Haemost. 2000
Geçirilmis VTE 27 23
Oger E Thromb Haemost. 2000
18
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

19
Gender, Age and VTE
1200
male
female
1000
800
Annual incidence / 100 000
600
400
200
0
0-14
20-24
30-34
40-44
50-54
60-64
70-74
80-84
15-19
25-29
35-39
45-49
55-59
65-69
75-79
gt85
age
Arch Intern Med, 1998158585-93
20
Incidence of VTE, including patients diagnosed
and managed outside the hospital
EPI-GETBO Study
Per 10 000

• 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.
21
Gender and age
incidence of VTE per 1000 per annum
years
Oger E Thromb Haemost. 2000 83 657-60.
22
VTE in the elderly patients findings from a
prospective registry (RIETE)

• Age 80 years 80 years
• (n10 121) (n2 890)
• Fatal PE () 1.1 3.7
• Fatal bleeding () 0.4 0.8
• Major bleeding () 212 (2.1) 99 (3.4)

• 2 890 patients gt 80 years old (out of 13 011
  patients )

Lopez-Jimetez. Haematologica. 2006 91 1046-51.
23
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

24
VITAE Study( VTE Impact Assessment Group in
Europe)
First large study to evaluate the burden of VTE
in 25 European countries.

• 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)
25
VITAE Study( VTE Impact Assessment Group in
Europe)

• 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)

A T Cohen, et al, 2006 (in press)
26
VITAE Study( VTE Impact Assessment Group in
Europe)

• 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

A T Cohen, et al, 2007 (in press)
27
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
28
35 ENDORSE Ülkesi
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ENDORSE Countries

• Algeria
• Australia/NZ
• Bangladesh
• Brazil
• Bulgaria
• Colombia
• Czech Republic
• Egypt
• Greece
• Gulf States

• Saudi Arabia
• Slovakia
• Switzerland
• Thailand
• Tunisia
• Turkey
• Venezuela

• Hungary
• India
• Ireland
• Israel
• Mexico
• Pakistan
• Poland
• Portugal
• Romania
• Russia

30
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

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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

32
Turkey (11 sites)
33
ENDORSE Selected centers

• Anadolu Çinar Hospital(Ist)
• Kocaeli University Hospital
• Sisli Etfal Hospital (Ist)
• Süreyyapasa Hospital (Ist)
• Dr. Suat Seren Hospital (Izmir)
• Hatay (Private) Hospital

• Esrefpasa Hospital (Izmir)
• Erciyes University, Oncology Hospital
• Gaziantep University Hospital
• Göztepe Education Hospital
• Vezirköprü State Hospital (Samsun)

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ENDORSE Study population - TURKEY
35
SIRIUS Study VTE risk factors in medical patients
CI
OD
Risk
Samama, Arch Inter Med. 2000 1603415-3420.
36
IMPROVE Study International
Medical Prevention Registry on Venous
Thromboembolism
Patients in prophylaxsis()
cardiac n254)
Pulmonery ( n348)
Cancer ( n104)
Neurological ( n208)
Primary reason of admission
J Thromb Haemost 2003(suppl)
37
VTE According to the wards
Goldhaber SZ, et al. Chest. 20001181680-4.
38
MAJOR MEDICAL RISK FACTORS?
39
Major VTE risk factors
Inherited
Acquired
Inher./Acquir.
age Immobiliztion
Cancer
Pregnancy/postpartum Oral contraception Hormone
RT Antiphospholipid sendr. Myeloporoliferative
sndr.

• Hyperhomocysteinemia
• Increased levels of
• Factor VII
• Fibrinogen
• Factor XI
• Factor IX

Deficiency in AT Deficiency in ProteinC
Deficiency in Protein S
Factor V Leiden Protrombin
gene mut. Deficiency in Fibrinogen, Plasminojen
Franco RT, Hum Genet. 2001109369-84.
40
The range of risk of VTE according to clinical
situation
Risk Factors Risk
Recent operation 3-21.7
Non-surgical hospitalization /immobilization 5.7-1
1.1
Congestive heart failure 1.4-9.6
Cancer and chemotherapy 6.5
Myocardial infarction 5.9
Venous insufficiency 0.9-4.2
Ischaemic stroke 2.0-3.0
Malignancy 2.4-5.6
Venous catheter 5.6-6.0

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

Samama MM,et al. Heamatologica,200388
41
Range of VTE Risk
Risk Factors Risk
Age 1.8-14.8
Hyperhomocystenaemia 7.1
Oral contraception 1.7-4.7
Personel history of VTE 5.9
Obesity 1.0-4.5
Secondery antiphospholipid syndrome 4.3
Risk, odd ratio, relatif risk, ralatif hazard,
ve hazard ratioyu kapsar
Samama MM,et al. Heamatologica,200388
42
Range of VTE Risk
Risk Factors Risk
Family history of VTE 3.3-3.4
Smoking 1.0-3.3
Hormone replacement therapy 2.1-2.7
Black ethnicity 1.4
Male 0.6-1.4
Samama MM,et al. Heamatologica,200388
43
Combination of Risk Factors

• Combination of hereditary and/ or acquired risk
  factors
• Multiplication effct of combination of risk
  factors
• Mathematical models are very rare.

44
Risk assessment in medical patients?
45
Risk assessment in medical patients? Lutz L, et
al. Med Welt, 2002
46
Risk assessment in medical patients
Major Risks
Minor Risks
Additional Risks

• Stroke
• Congestive h. failure
• Acute respir. failure
• Infections
• Acute MI

• Immobilization
• Malignanacy
• Chemoterapy

• History of VTE
• Advabced age gt 65
• Obesity
• Coagulation disorders

At least 1 1 minor risk
At least 1
At least 2
Nicolaides AN et al. International Consensus
Statement. Int Angiol 2006 25 101-61.