Post on 14-Jan-2016
description
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
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
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
Oger E Thromb Haemost. 2000
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
Oger E Thromb Haemost. 2000
Epidemiology of VTE in France
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
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 )
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
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.
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)
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)
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
Samama MM,et al. Heamatologica,2003;88
*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
Samama MM,et al. Heamatologica,2003;88
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.