Prof rosanna abbate univ di firenze
Download
1 / 75

Prof. Rosanna Abbate Univ.di Firenze - PowerPoint PPT Presentation


  • 109 Views
  • Uploaded on

Prof. Rosanna Abbate Univ.di Firenze. Incidence of VTE: The third most common vascular disease. Annual incidence (US data). Deep vein thrombosis (DVT) only 1,2. Pulmonary embolism (PE) with or without DVT 3. Up to 145/100,000. Up to 69/100,000. 1. Gillum RF. Am Heart J 1987;114:1262–4

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Prof. Rosanna Abbate Univ.di Firenze' - gore


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Prof rosanna abbate univ di firenze

Prof. Rosanna Abbate

Univ.di Firenze


Incidence of vte the third most common vascular disease
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 to145/100,000

Up to69/100,000

1. Gillum RF. Am Heart J 1987;114:1262–4

2. Anderson FA Jr, et al. Arch Intern Med1991;151: 933–8

3. Silverstein MD, et al. Arch Intern Med 1998;158:585–93


Circa l’80%

delle TVP è clinicamente silente2,3

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


Vte h eavy burden of long term complications

80%

17%

25%

2 years

74%

24%

30%

5 years

69%

30%

30%

8 years

VTE:Heavy burden of long-term complications

Long-term outcomes after a first DVT in symptomatic patients

Cumulative incidence

Survival

rate

Recurrent DVT

Post-thrombotic syndrome

Prandoni P, et al. Haematologica 1997; 82:423–428


Economic b urden of vte

PE1

DVT1

MI2

Stroke2

12500

0

2500

5000

7500

10000

Economic Burden of VTE

Direct inpatient costsof a VTE event are comparable with MI orstroke1,2

Additional long-term healthcare costs of a DVT: 75% of the initial cost3

$12,795

$9,337

$9,643

$6,367

Average cost per admission

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

500

females

400

300

Incidence (/100 000)

200

100

0

0-9

>80

9-19

20-29

30-39

40-49

50-59

60-69

70-79

Age (years)

Worchester study 1991

Clin Med Cardiol FI


Fattori di rischio di tev et
Fattori di rischio di TEV: Età

  • < 40 a. = 1 TEV su 10.000 soggetti/a.

  • 40-60 a. = 1 TEV su 1000 soggetti/a.

  • > 75 a. = 1 TEV su 100 soggetti/a.


Vte a large population at risk

All hospitalized

All major surgery

Abdominal surgery

Vascular surgery

Neurosurgery

Urology

Cardiac surgery

0

10

20

30

40

50

60

70

80

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 hospitalizedpatients have at least

three riskfactors

This can be

up to70%

in some wards

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

Trombosi

venosa

Stasi

Acquisita

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

Patients

Risk Factor (%)

Age ≥40 years 88.5

Obesity 37.8

History for venous thromboembolism 26.0

Cancer 22.3

Bed rest ≥5 days 12.0

Major surgery 11.2

Congestive heart failure 8.2

Varicose veins 5.8

Fracture (hip or leg) 3.7

Estrogen treatment 2.0

Stroke 1.8

Multiple trauma 1.1

Childbirth 1.1

Myocardial infarction 0.7

1 or more risks 96.3

2 or more risks 76.0

3 or more risks 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

Goldberg, 1987

Griffin, 1987

Monreal, 1988

Nordstrom, 1994

Ahmed, 1996

Hettiarachchi, 1997

Prandoni, 1992

Bastounis, 1996

Monreal, 1991

Ranft, 1991

8.8 %

3.7 %

3.5 %

8.5 %

4.8 %

1.5 %

4.0 %

6.0 %

9.1 %

10.6 %

11.5 %

0

5

10

15

Incidence of newly diagnosed malignancies (%)

Clin Med Cardiol FI

Prins et al, 1997


Risk factors for DVT: year in unselected cohorts of pts with confirmed VTE

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 year in unselected cohorts of pts with confirmed VTE

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 year in unselected cohorts of pts with confirmed VTE

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 year in unselected cohorts of pts with confirmed VTE

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
Fattori di rischio di TVP year in unselected cohorts of pts with confirmed VTE: IMMOBILIZZAZIONE

  • Rischio relativo = 11 volte

    (Leiden Thrombophilia Study)

  • Rischio attribuibile per tutte le TVP = 15%


Odds ratios on the risk of travel and thrombosis year in unselected cohorts of pts with confirmed VTE

for different duration categories of travelling

in patients with suspected

venous thromboembolism

Duration of travelling Patients with Patients without Pooled odds ratio

venous venous (95% CI)

thromboembolism thromboembolism

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 year in unselected cohorts of pts with confirmed VTE

We recommend that most patients with acute MI receive prophylactic or therapeutic anticoagulant therapy with sc LDUH or iv heparin (GRADE 1A)

Ischemic Stroke

  • For patients with ischemic stroke and impaired mobility, we recommend the routine use of LDUH, LMWH, or the heparinoid, danaparoid (all GRADE A)

  • 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 Conference2001

Clin Med Cardio, Fi


Risk factors for VTE-Medical patients year in unselected cohorts of pts with confirmed VTE

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


APC year in unselected cohorts of pts with confirmed VTE

THROMBOMODULIN

Protein s

aPL

Thrombin

Protein C

TF

PAI

PGI2

EC


Criteri clinici
CRITERI CLINICI year in unselected cohorts of pts with confirmed VTE

  • 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:

  • Una o più morti fetali oltre la 10° settimana;

  • Uno o più parti prematuri prima della 34° settimana, accompagnati da preeclampsia o severa insufficienza placentare;

  • Tre o più aborti spontanei in assenza di anomalie ormonali o cromosomiche prima della 10° settimana.


CRITERI PER LA DIAGNOSI year in unselected cohorts of pts with confirmed VTEDEL 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
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

Long-term Anticoagulation CLINICASixth 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)


Moderate intensity inr 2 0 3 0 high intensity inr 3 1 4 0

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) prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome

4.2

EP di 3° generazione (Desogestrel,Gestodene)

9.2

Rischio relativo medio per TEV dell’uso di EP (rispetto al non uso di EP)


Risk factors for DVT: prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome

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

Clin Med Cardiol FI

NHI Consensu Conference, 1986


0 prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome

1

2

3

4

5

Hormone Replacement Therapy Risks

Venous TE and HRT use

Daly et al., Lancet 1996

3.5

Venous TE and HRT use

Jick et al., Lancet 1996

3.3

Pulmonary Embolism and HRT use

Grodstein et al., Lancet 1996

2.1

RELATIVE RISK

Clin Med Card FI


TVP: fattori di rischio prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome

Thromb Haemost 2001 86: 452-63


Relative risk of non-fatal venous prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome

Thromboembolism in subjects of the

VITA project( cross-sectional study,n= 15055)

Odds ratio Corrected odds ratio

(95% CI) (95% CI)

Previous SVT4.9 (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 0.7 (0.4-1.2) 0.5 (0.3-0.9)

Upper-tertile 1.7 (1.1-2.6) 2.9 (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 risk factors(%) of inherited thrombophilic

Syndromes in the general population and

In patients with venous thrombosis

General Unselected patients selected patients

Population with venous thrombosis with venous thrombosis*

Syndrome

AT deficiency 0.02-0.17 1.1 0.5-4.9

PC deficiency 0.14-0.5 3.2 1.4-8.6

PS deficiency - 2.2 1.4-7.5

APC resistance 3.6-6.0 21.0 10-64

Prothrombin 1.7-3.06.2 18

G20210A

* 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 risk factors

Via estrinseca

Superficie di contatto

XII

lesione

XIIa

XI

IX

XIa

TF

+

VIIa

IXa

Membrana delle

piastrine

+

VIII

X

APCR

Membrana delle

piastrine

Complesso

protrombinasico

Xa

+ PS

+ PS

Va

Leiden

Proteina C

Attivata

Va

Trombina

Protrombina


Estimated population incidence of first DVT in women aged 15-49, according to presence of Factor V Leiden mutation and use of OC

Factor V Leiden neg

Non OC use

Current OC use

Factor V Leiden pos

Non OC use

Current OC use

Patients

36

84

10

25

Person-

yrs

437870

275858

17515

8757

Incidence/

10000/yrs

0.8

3.0

5.7

28.5

OR

1

3.75

7.12

36.62

Vandenbroucke et al, 1994

Clin Med Cardiol FI


Risk of DVT in long-haul flights (>8h) 15-49, according to presence of Factor V Leiden mutation and use of OC

in economic class passengers

No stockings passengers, n=116

30%

RR=3.96

20%

F II

mutation

10%

No F II

mutation

0%

FV Leiden

No FV Leiden

The Lancet 2001


Haemostasis-related risk factors in 15-49, according to presence of Factor V Leiden mutation and use of OC

958patients 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 ereditarie note

on VENOUS thrombosis

Brattstrom

den Heijer

Amundsen

Fermo

den Heijer

Cattaneo

Simioni

Ridker

ALL

1

10

90

From Cattaneo M, Thromb Haemost 2000


HOMOCYSTEINE METABOLISM ereditarie note

Diet

Methionine

Tetrahydrofolate

dimethylglycine

SAM

Methionine Synthase

Vit.B12

5,10 CH3

Tetrahydrofolate

Betaine

SAH

MTHFR

HOMOCYSTEINE

5 CH3

Tetrahydrofolate

Transulfuration

CBS

Vit.B6

Remethylation

Cysteine


Fasting Homocysteine levels in case-control studies ereditarie note

on VENOUS thrombosis

Brattstrom

den Heijer

Amundsen

Fermo

den Heijer

Cattaneo

Simioni

Ridker

ALL

1

10

90

From Cattaneo M, Thromb Haemost 2000


Prevalence of MTHFR in the different populations ereditarie note

Abbate R et al, Thromb Haemost 1998


tHcy for Genotypes of C677T MTHFR Mutation ereditarie note

Folate > 11.5 nmol/l

Folate < 11.5 nmol/l

25

Fasting tHcy

(µmol/L)

20

15

10

CC

CT

TT

MTHFR Genotypes

Girelli et al., Blood 1998


C677T mutation in the MTHFR gene and ereditarie note

risk of venous thrombosis: the VITA project

20

13.1%

15

12.3%

%

10

5

0

Controls

DVT patients

Tosetto et al, BJH 1997


Hyperhomocysteinaemia and ereditarie note

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 ereditarie note

958patients with DVT referred to Thrombosis Center, Florence (1999-2000)

Hyperhomocysteinemia 36.3%

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


High levels of FVIII in venous thrombosis ereditarie note

= SINGLE episode of DVT

= RECURRENCE venous thromboembolism

25

20

15

OR

10

5

0

100-150

U/dl

150-175

U/dl

175-200

U/dl

>200

U/dl

Kraaijenhagen, Thromb Haemost 2000


Test consigliabili per ereditarie note

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 ereditarie note

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 ereditarie note

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

Familiari di primo grado di soggetti diagnosticati portatori di trombofilia ereditaria 2


Linee guida per l’esecuzione di ereditarie note

uno screening per trombofilia

  • 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 ereditarie note

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 puerperio

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 puerperio(ACCP CHEST 2004)

First event with reversible or time-limited risk factor 1A

3 mo

Idiopathic VTE, first event 1A

6-12 mo

to lifetime

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, idiopathic or with thrombophilia 2A


Controindicazioni a trattamento puerperio

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 puerperio

2.5

2.0

1.5

OR

1.0

0.5

0

1

2

3

4

Quartile

Meijers JCM, NEJM 2000


High levels of FIX in venous thrombosis puerperio

*= adjusted for age, sex and OC use

5.0

*

4.0

3.0

*

OR

2.0

*

*

1.0

0

<100

U/dl

100-125

U/dl

125-150

U/dl

>150

U/dl

Van Hylckama Vlieg, Blood 2000


Thromboresistant Properties of Endothelium puerperio

FXa

Lipo-

protein

TFPI

TFPI

TFPI

Heparin

TF

FVIIa

FXa

HSPG

TFPI

TFPI

EC

Colman et al., 1994

Clin Med Gen Cardiol FI


Odds Ratios for DVT, by TFPI levels puerperio

DVT n=473,contr n=473

OR (95% CI)

TFPI free antigen

10th percentile 1.7 (1.1 - 2.6)

5 th percentile 2.1 (1.1 - 4.1)

2nd percentile2.2 (0.89- 5.3)

TFPI total antigen

10th percentile 1.5 (0.98 - 2.3)

5 th percentile 2.1 (1.1 - 4.1)

2nd percentile3.0 (1.3 - 7.2)

TFPI activity

10th percentile 1.1 (0.73 - 1.8)

5 th percentile 1.6 (0.87 - 2.8)

2nd percentile2.4 (1.1 - 5.1)

Dahm A. et al. Blood, 2003

Clin Med Card FI


TAFI - Mechanism of Action puerperio

Thrombin

PLG

aTAFI

TAFI

t-PA

Pro-Carboxypeptidase

- COOH -

Lysine

Modified Fibrin

(unlinked with

Lysine)

PLI

Fibrin

Endothelial Cells

Clin Med Card FI


Risk for recurrent VTE according to TAFI level. puerperio

(P= .006, Wilcoxon rank sum test; P= .02, log rank test)

30

20

10

0

TAFI ≥75th percentile

Cumulative probability of recurrence (%)

TAFI <75th percentile

0 12 24 36 48 60

Months after discontinuation of anticoagulaton

No. of Patients of Risk

TAFI ≥75th percentile 154 123 100 65 41 27

TAFI <75th percentile 446 387 331 261 195 139

Clin Med Card –FI Eichinger S et al., Blood 2004


Recurrent VTE after discontinuation of OAT puerperio

Factor V Leiden

0.2

NO Factor V Leiden

Cumulative probability

of recurrence

0.1

0.0

12

24

36

Months

Clin Med Card –FI Eichinger et al, Thromb Haemostas 1997


Independent* risk factors for puerperioidiopathic 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

7

8

9

10

*Adjusted for acquired (trauma, surgery, use of oral contraceptives, pregnancy and puerperium, hormone replacement therpay), and thrombophilic risk factors

OR (95% CI)

Am J Med 2003


Independent* risk factors for puerperiorecurrences

Factor V Leiden

+

FII

polymorphisms

3.7 (1.6-8.4)

5.0 (3.0-8.4)

Homocysteine

5.1 (3.1-8.4)

Lp(a)>300 mg/L

1

2

3

4

5

6

7

8

9

10

Am J Med 2003

*Adjusted for acquired (trauma, surgery, use of oral contraceptives, pregnancy and puerperium, hormone replacement therpay), and thrombophilic risk factors

OR (95% CI)


An association between atherosclerosis puerperio

and venous thrombosis

OR for carotid plaques in patients with

spontaneous vs secondary

Venous thrombosis = 2.495% CI(1.4-4.0)

Paolo Prandoni et al., NEJM 2004


Has dd a predictive role for vte recurrences after oat withdrawal
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 VTECosmi 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 d dimer testing
Sources of variation in D-dimer testing factors for recurrence after a first episode of VTE

  • Due to patient characteristics

  • Extent of VTE

  • Duration of symptoms

  • Anticoagulant treatments

  • Age

  • Co-morbid conditions


Possible sources of d dimers
Possible sources of D-dimers factors for recurrence after a first episode of VTE

  • Venous clots

  • Arterial clots

  • Extravascular fibrin (ascitic fluid)

  • Surgical lesions

  • Large skin lesions

  • Atherosclerotic lesions

  • Large hematomas


Problemi aperti factors for recurrence after a first episode of VTE

Trait trombofilico e malattia neoplastica

Trait trombofilico e tamoxifene

Trait trombofilico e fecondazione assistita

Trait trombofilico e viaggio aereo


ad