Prof. Rosanna Abbate
Univ.di Firenze
Incidence of VTE:
The third most common vascular disease
Annual incidence (US data)
Deep vein thrombosis
(DVT) only1,2
Pulmonary embolism
(PE) with or without
DVT3
Up to 145/100,000
Up to 69/100,000
1. Gillum RF. Am Heart J 1987;114:1262–4
2. Anderson FA Jr, et al. Arch Intern Med 1991;151: 933–8
3. Silverstein MD, et al. Arch Intern Med 1998;158:585–93
Diagnosi
Il TEV spesso non viene diagnosticato
se non quando è troppo tardi
Oltre il 70% delle EP fatali
viene scoperto post mortem1,3
1. Stein PD, et al. Chest 1995; 108(4): 978–81
2. Lethen H, et al. Am J Cardiol 1997; 80(8): 1066–9
3. Sandler DA, et al. J R Soc Med 1989; 82(4): 203–5
Circa l’80%
delle TVP è
clinicamente
silente2,3
VTE:
Heavy burden of long-term complications
Long-term outcomes after a first DVT in symptomatic patients
Cumulative incidence
Recurrent DVT Post-thrombotic
syndrome
Survival
rate
2 years
17%
25%
80%
5 years
24%
30%
74%
8 years
30%
30%
69%
Prandoni P, et al. Haematologica 1997; 82:423–428
Economic Burden of VTE
Direct inpatient costs
of a VTE event are comparable
with MI or stroke1,2
PE1
Additional long-term
healthcare costs
of a DVT: 75%
of the initial cost3
$12,795
DVT1
$9,337
MI2
$9,643
Stroke2
$6,367
0
2500
5000
7500
10000
Average cost per admission
12500 in the US ($)
1. Bick RL. Clin Appl Thromb Hemost 1999;5:2–9
2. Medicare & DRG. 1996. [http://www.hcfa.gov]
3. Bergqvist D, et al. Ann Intern Med 1997;126:454–7
Annual incidence of TE disease in
the U.S.A.
600
males
females
500
400
300
200
100
0
0-9 9-19
20-29
Worchester study 1991
30-39
40-49
Age (years)
50-59 60-69 70-79
>80
Clin Med Cardiol FI
Fattori di rischio di TEV: Età
• < 40 a.
•
•
soggetti/a.
40-60 a.
soggetti/a.
> 75 a.
= 1 TEV su 10.000
= 1 TEV su 1000
= 1 TEV su 100 soggetti/a.
VTE: A large population at risk
Prevalence of VTE risk in a typical hospital population:
Percentage of patients with at least three VTE risk factors
19% of hospitalized
patients have at least
three risk factors
All hospitalized
All major surgery
Abdominal surgery
Vascular surgery
This can be
up to 70%
in some wards
Neurosurgery
Urology
Cardiac surgery
0
10
20
30
40
50
60
70
80
Patients with at least three risk factors (%)
Anderson FA, et al. Arch Intern Med 1992;152:1660–4
Tromboembolia venosa
Triade di Virchow dei fattori di rischio (1)
Ipercoagulabilità
Ereditaria
Acquisita
Stasi
Acquisita
Trombosi
venosa
Lesione vascolare
Acquisita
Virchow R. In Gesammelte Abhandlugen zur Wissenschaftlichen Medizin, 1856;
Frankfurt: Staatsdruckerei
Rosendaal FR. Lancet 1999; 353:1167–1173
Risk factors observed in 1231 consecutive
patients treated for acute DVT and/or PE
Risk Factor
Patients
(%)
Age ≥40 years
Obesity
History for venous thromboembolism
Cancer
Bed rest ≥5 days
Major surgery
Congestive heart failure
Varicose veins
Fracture (hip or leg)
Estrogen treatment
Stroke
Multiple trauma
Childbirth
Myocardial infarction
88.5
37.8
26.0
22.3
12.0
11.2
8.2
5.8
3.7
2.0
1.8
1.1
1.1
0.7
1 or more risks
2 or more risks
3 or more risks
96.3
76.0
39.0
Clin Med Card –FI
Anderson and Spencer, Circulation 2003
Risk Factors for VTE
Strong risk factors
(odds ratio >10)
Fracture (hip or leg)
Hip or knee replacement
Major general surgery
Major trauma
Spinal cord injury
Clin Med Card –FI
Anderson and Spencer, Circulation 2003
Risk Factors for VTE
Moderate risk factors
(odds ratio 2-9)
Arthroscopic knee surgery
Central venous lines
Chemotherapy
Congestive heart /respiratory failure
Hormone replacement therapy
Malignancy
Oral contraceptive therapy
Paralytic stroke
Pregnancy/, post-partum
Previous venous thromboembolism
Thrombophilia
Anderson and Spencer, Circulation 2003
Risk Factors for VTE
Weak risk factors
(odds ratio <2)
Bed rest >3 days
Immobility due to sitting
(e.g. prolonged car or air travel)
Increasing age
Laparoscopic surgery
(e.g. cholecystectomy)
Obesity
Pregnancy/, ante-partum
Varicose veins
Anderson and Spencer, Circulation 2003
The incidence of newly diagnosed malignancies
during first year in unselected cohorts of pts with
confirmed VTE
Gore, 1992
8.8 %
3.7 %
Goldberg, 1987
3.5 %
Griffin, 1987
8.5 %
Monreal, 1988
4.8 %
Nordstrom, 1994
1.5 %
Ahmed, 1996
4.0 %
Hettiarachchi, 1997
6.0 %
Prandoni, 1992
9.1 %
Bastounis, 1996
10.6 %
Monreal, 1991
Ranft, 1991
Prins et al, 1997
11.5 %
0
5
10
15
Incidence of newly diagnosed malignancies (%)
Clin Med Cardiol FI
Risk factors for DVT:
Cancer
Cancer
RR for VTE: 7
Cancer is responsible for 10-15%
of all VTE in general population
Goldberg et al, 1987
Clin Med Cardiol FI
Extensive screening for occult
malignantdisease in idiopathic TE
A prospective randomized clinical trial
(stopped prematurely)
N=201
Extensive screening
US abdomen/pelvis
CT scanning abdomen/pelvis
Gastroscopy , Flexible sigmoidoscopy
CEA, alphaFP,CA 125 Hemoccult
Sputum cytology
Gynecol exam.+PAP smear
Mammography
Transabd. US of prostate
PSA
Piccioli et al J Thromb Haemost 2004
Extensive screening for occult
Malignant disease in idiopathic TE-2 yrs f-up
A prospective randomized clinical trial
(stopped prematurely)
N=201
Neoplasia identified in 13.1% pts extensively
screened vs 0 in routine clinical examination
Sensitivity of extensive screening :
93%
Mean delay 1 month vs 11 months
Mortality 2% vs 3.9 %
Piccioli et al J Thromb Haemost 2004
Symptomatic venous thromboembolism
in cancer patients treated
with chemotherapy
An underestimated phenomenon
Annual incidence of VTE: 10.9%
Clin Med Card –FI
Hans-Martin MB Otten et al., Arch Intern Med 2004
Fattori di rischio di TVP:
IMMOBILIZZAZIONE
• Rischio relativo = 11 volte
(Leiden Thrombophilia Study)
• Rischio attribuibile per tutte le TVP =
15%
Risk of DVT in long-haul flights (>8h
in economic class passengers
No stockings passengers:
DVT: 12/116 (10%)
Stockings passengers:
DVT: 0/115 (0%)
The Lancet 2001
Odds ratios on the risk of travel and thrombosis
for different duration categories of travelling
in patients with suspected
venous thromboembolism
Duration of travelling
Patients with
venous
thromboembolism
Patients without
venous
thromboembolism
Pooled odds ratio
(95% CI)
Number of patients
477
1470
Any travel (%)
32* (7%)
105** (7%)
0.9 (0.6-1.4)
Duration 3-5 hours
9
44
0.7 (0.3-1.3)
Duration 6-10 hours
10
34
0.9 (0.4-1.8)
Duration 11-15 hours
8
10
2.5
(1.0-6.2)
Duration >16 hours
3
8
1.3
(0.4-4.3)
* for two patients duration of travel is missing
** for nine patients duration of travel is missing
Clin Med Card –FI
Ten Walde, Thromb Haemostas 2003
Acute MI
We recommend that most patients with acute MI
receive prophylactic or therapeutic anticoagulant
therapy with sc LDUH or iv heparin (GRADE 1A)
Ischemic Stroke
1. For patients with ischemic stroke and impaired mobility, we
recommend the routine use of LDUH, LMWH, or the
heparinoid, danaparoid (all GRADE A)
2. If anticoagulant prophylaxis is controindicated we recommend
mechanical prophylaxis with ES or IPC (GRADE 1C+)
Other Medical Conditions
In general medical patients with risk factors for VTE
(including cancer, bedrest, heart failure, severe lung
disease), we recommend LDUH or LMWH (GRADE 1A)
Sixth ACCP Consensus Conference 2001
Clin Med Cardio, Fi
Risk factors for VTE-Medical patients
Inflammatory bowel disease
Renal Transplantation
Nephrotic syndrome
Sepsis
Hyperviscosity syndrome
Myeloproliferative disease
Paroxysmal nocturnal hemoglobinuria
Modified by G.F.Gensini et al, 1997
Seminars in Thrombosis and Hemostasis
Clin Med Cardiol FI
Protein
aPL
PAI
APC
TF
PGI2
s
Thrombin Protein C
THROMBOMODULIN
EC
CRITERI CLINICI
• Trombosi vascolari : uno o più episodi di
trombosi arteriose, venose o dei piccoli vasi, in
qualsiasi organo o tessuto, confermate da
tecniche
di
imaging,
doppler
o
dall’istopatologia
• Mortalità in gravidanza:
a. Una o più morti fetali oltre la 10° settimana;
b. Uno o più parti prematuri prima della 34°
settimana, accompagnati da preeclampsia o
severa insufficienza placentare;
c. Tre o più aborti spontanei in assenza di
anomalie ormonali o cromosomiche prima
della 10° settimana.
CRITERI PER LA DIAGNOSI
DEL LUPUS ANTICOAGULANT
PROPOSTI DAI SSC
(Brandt J.T.,Thromb.Haemost 1995;74: 1185-90)
• Prolungamento di 2 o più test di screening PL
dipendenti (aPTT, KCT, dRVVT, dPT o TTI)
• Studi di mixing (1:1) per dimostrare la presenza
di un inibitore ed escludere eventuali carenze di
fattori
• Test di conferma per dimostrare che l’inibitore è
diretto contro i PL
• Esclusione di altre coagulopatie (es. inibitore del
fattore VIII o presenza di eparina)
RICERCA DEGLI ANTICORPI
ANTIFOSFOLIPIDI NELLA
PRATICA CLINICA
• Lupus anticoagulant
• Anticorpi anticardiolipina
• Anticorpi antibeta 2 glicoproteina
• NECESSARIO ESCLUDERE CONDIZIONI
INFIAMMATORIE E INFETTIVE e
• E’ OBBLIGATORIO CONFERMA DOPO
6 SETTIMANE
• Interferenza terapia anticoagulante
Long-term Anticoagulation
Sixth ACCP Consensus Conference on
Anti thrombotic Therapy 2001
For patients with recurrent idiopathic VTE
or a continuing risk factor such as …….or
………….
anticardiolipin antibody syndrome,
we recommend treatment for 12 months or
longer (grade 1C)
A comparison of two intensities of
warfarin
for
the
prevention
of
recurrent thrombosis in patients with
the antiphospholipid antibody syndrome
Moderate intensity: INR 2.0-3.0
High intensity: INR 3.1-4.0
No differences in recurrencies and bleeding were found
between the two INR
NEJM 2002
Rischio relativo medio per TEV dell’uso di
EP
(rispetto al non uso di EP)
EP di 2° generazione
(levonorgestrel)
4.2
EP di 3° generazione
(Desogestrel,Gestodene)
9.2
Risk factors for DVT:
Pregnancy and post-partum
Pregnancy: RR 5-10
DVT incidence during pregnancy: 0.5-1/1000
Post-partum:RR 10-15
The risk for DVT is potentiated by additional risk
factors:
immobilization
cesarean delivery
instrumental procedures
NHI Consensu Conference, 1986
Clin Med Cardiol FI
Hormone Replacement Therapy Risks
Venous TE and HRT use
3.5
Daly et al., Lancet 1996
Venous TE and HRT use
3.3
Jick et al., Lancet 1996
Pulmonary Embolism and HRT use
2.1
0
1
Clin Med Card FI
Grodstein et al., Lancet 1996
2
3
4
5
RELATIVE RISK
Thromb Haemost 2001 86: 452-63
Relative risk of non-fatal venous
Thromboembolism in subjects of the
VITA project( cross-sectional study,n= 15055)
Odds ratio
(95% CI)
Corrected odds ratio
(95% CI)
Previous SVT
4.9
(3.0-7.8)
6.8
(3.9-12.0)
Oral contraceptives use*
3.9
(1.9-8.0)
4.7
(2.0-10.8)
Positive family history
3.5
(2.0-6.1)
4.5
(2.4-8.5)
Smoking
1.6
(1.1-2.3)
1.7
(1.0-2.7)
Body mass index**
Lower-tertile
Upper-tertile
0.7
1.7
(0.4-1.2)
(1.1-2.6)
0.5
2.9
(0.3-0.9)
(1.4-6.2)
SVT, superficial vein thrombophlebitis; VTE, venous thromboembolism
*Use of oral contraceptives at time of VTE or at time of investigation; percentages are referred to the femal population
**The mid-tertile was taken as the baseline for risk estimation
Clin Med Card –FI
Tosetto et al., J Thromb Haemostas 2003
Thrombosis can be caused by
interacting genetic and acquired risk
factors
Risk Factors
Risk Factors
Genetic+Genetic
Genetic+Acquired
Thromboembolism
Lane, 1996
Clin Med Cardio, Fi
Frequency (%) of inherited thrombophilic
Syndromes in the general population and
In patients with venous thrombosis
Syndrome
General
Population
Unselected patients
with venous thrombosis
AT deficiency
0.02-0.17
1.1
0.5-4.9
PC deficiency
0.14-0.5
3.2
1.4-8.6
2.2
1.4-7.5
PS deficiency
-
APC resistance
3.6-6.0
21.0
Prothrombin
G20210A
1.7-3.0
6.2
selected patients
with venous thrombosis*
10-64
18
* Age 45 years and/or recurrent thrombosis. Adapted from De Stefano V, Finazzi G, Mannucci PM
Clin Med Card –FI
Anderson and Spencer, Circulation 2003
Via intrinseca
Superficie di
contatto
XII
XIIa
XI
XIa
Membrana delle
piastrine
APCR
Via estrinseca
lesione
IX
TF
+
VIIa
IXa
+
VIII
Complesso
protrombinasico
X
Membrana delle
piastrine
Xa
+ PS
+ PS
Va
Leiden
Proteina C
Attivata
Protrombina
Trombina
Va
Estimated population incidence of first DVT in
women aged 15-49, according to presence of
Factor V Leiden mutation and use of OC
Patients Person- Incidence/
yrs
10000/yrs
OR
Factor V Leiden neg
Non OC use
36
Current OC use
84
437870
275858
0.8
3.0
1
3.75
Factor V Leiden pos
Non OC use
10
Current OC use
25
17515
8757
5.7
28.5
7.12
36.62
Vandenbroucke et al, 1994
Clin Med Cardiol FI
Risk of DVT in long-haul flights (>8h)
in economic class passengers
No stockings passengers, n=116
30%
RR=3.96
20%
10%
0%
F II
mutation
No F II
mutation
FV Leiden
No FV Leiden
The Lancet 2001
Haemostasis-related risk factors in
958 patients with DVT referred to
Thrombosis Center, Florence (1999-2000)
APCR
32.9%
Factor V Leiden
30.3%
Prothrombin polymorphism
12.6%
Inhibitors’ deficiences
3.2%
Centro Trombosi , FI
Clin Med Gen e Cardiol, FI
Percentuale di TV spiegate dalle
alterazioni trombofiliche ereditarie
note
1978
2%
1982
10%
1984
15%
1994
55%
1996
73%
Clin Med Cardio, Fi
Fasting Homocysteine levels in case-control studies
on VENOUS thrombosis
Brattstrom
den Heijer
Amundsen
Fermo
den Heijer
Cattaneo
Simioni
Ridker
ALL
1
From Cattaneo M, Thromb Haemost 2000
10
90
HOMOCYSTEINE
METABOLISM
Diet
Methionine
Tetrahydrofolate
SAM
dimethylglycine
Methionine Synthase
Vit.B12
MTHFR
5 CH3
Tetrahydrofolate
Remethylation
SAH
Betaine
Transulfuration
5,10 CH3
Tetrahydrofolate
HOMOCYSTEINE
CBS
Vit.B6
Cysteine
Fasting Homocysteine levels in case-control studies
on VENOUS thrombosis
Brattstrom
den Heijer
Amundsen
Fermo
den Heijer
Cattaneo
Simioni
Ridker
ALL
1
From Cattaneo M, Thromb Haemost 2000
10
90
Prevalence of MTHFR in the different populations
Europeans and Europeans derived
25
Mixed Asians
20
%
15
10
5
AU
AU
NL CDN
I
USA USA USA DK IRL USA BR
Africans
J
Abbate R et al, Thromb Haemost 1998
tHcy for Genotypes of C677T MTHFR
Mutation
Folate > 11.5 nmol/l
Folate < 11.5 nmol/l
(µmol/L)
Fasting tHcy
25
20
15
10
CC
CT
TT
MTHFR Genotypes
Girelli et al., Blood 1998
C677T mutation in the MTHFR gene and
risk of venous thrombosis: the VITA project
20
15
12.3%
13.1%
%
10
5
0
DVT patients
Controls
Tosetto et al, BJH 1997
Hyperhomocysteinaemia and
thrombophilic genotypes in DVT
Patients (n=111)
OR (95% CI)
Hyperhomocysteinemia
3.7 (1.4-9.6)
Hyperhomocysteinemia +
Factor V Leiden
29.9 (2-419)
Hyperhomocysteinemia +
Prothrombin mutation
49.8 (1.7-1471)
De Stefano V et al, BJH 1999
Haemostasis-related risk factors in
958 patients with DVT referred to
Thrombosis Center, Florence (1999-2000)
Hyperhomocysteinemia
36.3%
APCR
Factor V Leiden
32.9%
30.3%
Prothrombin polymorphism
12.6%
Inhibitors’ deficiences
3.2%
Centro Trombosi , FI
Clin Med Gen e Cardiol, FI
High levels of FVIII in venous thrombosis
25
= SINGLE episode of DVT
= RECURRENCE venous thromboembolism
20
OR
15
10
5
0
100-150
U/dl
150-175
U/dl
Kraaijenhagen, Thromb Haemost 2000
175-200
U/dl
>200
U/dl
Test consigliabili per
uno screening per trombofilia*
Resistenza alla Proteina C attivata (e/o Fattore V Leiden
Mutazione G20210A del gene della Protrombina
Antitrombina
Proteina C
Proteina S (dosaggio immunologico della frazione libera)
Omocisteina e ?
Ricerca fenomeno Lupus Anticoagulant (LAC)
Anticorpi anticardiolipina
Fattore VIII
*è opportuno avere un criterio di funzionalità epatica: eseguire PT
Raccomandazioni per lo screening
di laboratorio
Storia documentata di TEV in assenza di
circostanze a rischio trombotico elevato
(neoplasia o chirurgia ad alto rischio) o
TFS ricorrenti
o patologia gravidica (MEF 20 sett,aborti ?,
preeclampsia severa, IUGR) dopo esclusione di
altre cause
Storia documentata di trombosi arteriosa
(limitatamente al dosaggio omocisteina basale o alla
ricerca LAC/ACA)
Raccomandazioni per lo screening
di laboratorio
Donne asintomatiche con storia familiare positiva
per TEV o TFS ricorrenti prima della prescrizione
di estroprogestinici o di trattamento sostitutivo
ormonale o prima della programmazione della
prima gravidanza (senza la ricerca LAC/ACA) 1
Linee guida per l’esecuzione di
uno screening per trombofilia
A) In linea generale lo screening per trombofilia non va eseguito
durante*:
la fase acuta di un evento trombotico sia venoso che arterioso
la terapia anticoagulante (eparina, anticoagulanti orali)
malattie intercorrenti acute che possono influenzare i risultati
trattamento estro-progestinico
la gravidanza
in caso di epatopatie gravi
B) Si consiglia di eseguire lo screening per trombofilia a distanza
di almeno tre mesi dall’evento tromboembolico venoso acuto e
dopo la sospensione del trattamento anticoagulante da almeno
20-30 gg.
*tali controindicazioni non riguardano i test genetici
Raccomandazioni di profilassi
antitrombotica primaria
Profilassi con eparina LMW in tutti i
soggetti portatori di trait
trombofilico in occasione di chirurgia
(anche se a basso rischio),
ingessatura, immobilizazione
Raccomandazioni di profilassi antitrombotica
in gravidanza e puerperio
Profilassi per tutto il puerperio in tutte le donne
portatrici di trait trombofilico
Profilassi per tutta la gravidanza e il puerperio nelle
donne con storia di TEV o TFS
Profilassi per tutta la gravidanza nelle donne con
storia di patologia gravidica e presenza di trait
trombofilico
Profilassi per tutta la gravidanza e il puerperio nelle
donne con difetto di AT, PC,PS, omozigosi o difetti
multipli
Raccomandazioni di profilassi
antitrombotica secondaria a tempo
indeterminato
Pazienti con un episodio idiopatico di TEV e
presenza LAC/ACA ad alto titolo, malattia
neoplastica, presenza di traits trombofilici
combinati
Pazienti con due o più episodi idiopatici di TEV,
indipendentemente dall’esito dello screening
laboratoristico
Duration of OAT after VTE (ACCP CHEST
2004)
3 mo
First event with reversible or time-limited
risk factor
1A
6-12 mo
Idiopathic VTE, first event
to lifetime
1A
First event* with
Cancer until resolved
1C
Anticardiolipin antibody 1C
Combined deficiency
2C
AT,PC,PS
FV
Leiden
FII202210
mutation, hcy, VIII
2C
Recurrent event,
thrombophilia
idiopathic
2A
or
with
Controindicazioni a trattamento
estroprogestinico
Donne con storia di TEV o TFS o
trombosi arteriosa
Donne asintomatiche con storia familiare positiva per
TEV oTFS, e portatrici di trait trombofilico (in
particolare difetto di AT, PC, PS, omozigosi o
difetti multipli)
High levels of FXI in venous thrombosis
2.5
2.0
OR
1.5
1.0
0.5
0
1
Meijers JCM, NEJM 2000
2
3
Quartile
4
High levels of FIX in venous thrombosis
5.0
*= adjusted for age, sex and OC use
*
4.0
OR
3.0
*
2.0
1.0
0
*
*
<100
U/dl
100-125
U/dl
Van Hylckama Vlieg, Blood 2000
125-150
U/dl
>150
U/dl
Thromboresistant Properties of
Endothelium
FXa
Lipoprotein TFPI
TFPI
TFPI
Heparin
FVIIa
TFPI
HSPG
TF
FXa
TFPI
EC
Clin Med Gen Cardiol FI
Colman et al., 1994
Odds Ratios for DVT, by TFPI levels
DVT n=473,contr n=473
OR (95% CI)
TFPI free antigen
10th percentile
5 th percentile
2nd percentile
1.7 (1.1 - 2.6)
2.1 (1.1 - 4.1)
2.2 (0.89- 5.3)
TFPI total antigen
10th percentile
5 th percentile
2nd percentile
1.5 (0.98 - 2.3)
2.1 (1.1 - 4.1)
3.0 (1.3 - 7.2)
TFPI activity
10th percentile
5 th percentile
2nd percentile
1.1 (0.73 - 1.8)
1.6 (0.87 - 2.8)
2.4 (1.1 - 5.1)
Clin Med Card FI
Dahm A. et al. Blood, 2003
TAFI - Mechanism of Action
Pro-Carboxypeptidase
Thrombin
- COOH Lysine
TAFI
aTAFI
Fibrin
Clin Med Card FI
Modified Fibrin
(unlinked with
Lysine)
PLI
Endothelial Cells
PLG
t-PA
Risk for recurrent VTE according to TAFI level.
Cumulative probability of recurrence (%)
(P= .006, Wilcoxon rank sum test; P= .02, log rank test)
30
TAFI ≥75th percentile
20
10
0
No. of Patients of Risk
TAFI ≥75th percentile
TAFI <75th percentile
Clin Med Card –FI
TAFI <75th percentile
0
12
154
446
123
387
24
36
48
Months after discontinuation of anticoagulaton
100
331
65
261
41
195
60
27
139
Eichinger S et al., Blood 2004
Recurrent VTE after discontinuation of OAT
Cumulative probability
of recurrence
Factor V Leiden
0.2
NO Factor V Leiden
0.1
0.0
12
Clin Med Card –FI
Months
24
36
Eichinger et al, Thromb Haemostas 1997
Independent* risk factors for idiopathic VTE
2.1 (1.3-3.4)
Lp(a)>300
mg/L
4.0 (1.4-10.2)
aCL
4.1 (1.4-10.2)
Homocysteine
4.5 (2.5-8.0)
Factor V
Leiden
1
2
3
4
5
6
*Adjusted for acquired (trauma, surgery, use of oral
OR (95% CI)
contraceptives, pregnancy and puerperium, hormone
replacement therpay), and thrombophilic risk factors
7
8
9
10
Am J Med 2003
Independent* risk factors for recurrences
Factor V Leiden
3.7 (1.6-8.4)
+
FII
polymorphisms
5.0 (3.0-8.4)
Homocysteine
5.1 (3.1-8.4)
Lp(a)>300
mg/L
1
2
3
4
5
6
*Adjusted for acquired (trauma, surgery, use of oral
OR (95% CI)
contraceptives, pregnancy and puerperium, hormone
replacement therpay), and thrombophilic risk factors
7
8
9
10
Am J Med 2003
An association between atherosclerosis
and venous thrombosis
OR for carotid plaques in patients with
spontaneous vs secondary
Venous thrombosis =
2.4
95% CI
(1.4-4.0)
Paolo Prandoni et al., NEJM 2004
Has DD a predictive role for VTE
recurrences after OAT
withdrawal?
• Normal
DD levels at 3 m from
OAT withdrawal have a very high
NPV (95.6%) for VTE recurrence
Palareti 2001
Residual Vein Thrombosis and D-dimer are
independent risk factors for recurrence after a
first episode of VTE
Cosmi et al, O141
Residual Vein Thrombosis :HR 2.7 1.1-6
High D-Dimer :
HR 2.7 1.1-6.3
RVT and high D-Dimer: HR 5.1 2.3-9
Sources of variation in Ddimer testing
• Due to patient characteristics
• Extent of VTE
• Duration of symptoms
• Anticoagulant treatments
• Age
• Co-morbid conditions
Possible sources of D-dimers
• Venous clots
• Arterial clots
• Extravascular fibrin (ascitic fluid)
• Surgical lesions
• Large skin lesions
• Atherosclerotic lesions
• Large hematomas
Problemi
aperti
Trait trombofilico e malattia neoplastica
Trait trombofilico e tamoxifene
Trait trombofilico e fecondazione assistita
Trait trombofilico e viaggio aereo