Download Thrombosis and cancer

Thrombosis and cancer
Dr Galila Zaher
Consultant Hematologist
MRCPath
Oct 2003
Venous thrombosis and cancer are two
way clinical association.
 Pathgenisis of thrombosis is different .
 The frequency is greater.
 The management required is more
complex.
Pathogenesis
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Tumor cells express pro-coagulant TF.
TF :receptor &cofactor for FVIIa.
TF expressed in pancreatic adeno-carcemona.
TF: correlates with the degree of differentiation .
TF: associated with switch in angiogenic balance & up
regulation of vascular endothelial growth factor .
TF-VII up-regulates palsminogen activator receptor
promoting tumor cell invasion.
FXa :over expression of the angiogenesis.
Thrombin binding to its receptors upregulates TF
expression.
VTE and occult cancer
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Idiopathic VTE have an increased incidence of
subsequently developed cancer .
The standardized incidence ratio for cancer
in patients with VTE is 4.4.
The SIRs are highest in the first 6m & drop
to 1 beyond 12m.
The cumulative probability of cancer over 6Y
FU in idiopathic VTE is 17% Vs 5% in
secondary VTE.
Extensive Investigations for
underlying cancer
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The potential benefit of screening must be
weighed against potential harms.
Procedure related morbidity.
The psychological burden of false positive
test.
The cost of screening.
Small randomized trail :no statistically
significant difference in cancer related
mortality .
It is premature to recommend extensive
screening in patients who present with
idiopathic VTE.
Prevention of thrombosis
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Surgical prophylaxis: meta-analysis of trials
comparing LMWH &UFH in high –risk surgery
included cancer patients :
Evidence that once daily LMWH is as safe
&effective as UFH.
Incidence of venographic DVT can be reduced
with extended out of hospital prophylaxis.
Extended prophylaxis in cancer surgery there
is a significant reduction in DVT from 12%
with placebo Vs 4% with extended prophylaxis
.”Enoxacan II”
Prevention of thrombosis
Medical cancer patients:
 Fewer data are available on prophylaxis
in ambulatory cancer patients.
 PMH of VTE with breast cancer
,aromatase inhibitor has much lower risk
of thrombosis than tamoxifen .
 Low dose warfarin for the prevention of
thrombo-embolism in cancer patients.
” Levine”
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Prevention of thrombosis
Central vein catheter thrombosis:
 Small trials Low dose warfarin or
LMWH :
demonstrated significant reduction in
catheter thrombosis.
Randomized trials :no difference .
 Routine prophylaxis is not practiced .
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Treatment of VTE
Difficult :
 Increased risk of recurrence(27%/y Vs
9) .
 Increased anticoagulant induced
bleeding x6.
 Both occur predominantly during the
first month of anticoagulation
 Increased mortality compared to cancer
without VTE.
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Initial Treatment of DVT
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Meta-analysis:LMWH is as safe & more effective
than UFH .
20% were cancer patients.
it is reasonable to generalize the resuls to cancer
patients.
LMWH :SC ,no need for monitoring improve the
quality of life.
Home treatment :comparable.
LMWH at home in cancer patient is recommended
positive impact on the quality of life.
Compliance ,reliability &good support system.
Initial Treatment of PE
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Few trials comparing LMWH&UFH.
Case Presentation
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24 Dec: 1998
46 Years old Egyptian patient
E.R. admission.
Bilateral leg pain.
Red discoloration.
Risk factor
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No surgery, No immobilization
No bedridden, No trauma.
FH : diabetics mother.
HT: On Renetic- Adalat .
No symptoms of PE.
Non-smoker Teacher
Upon Examination
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Leg Swollen.
Lf : 45cm Rt : 38 cm
Warm tender.
Heart rate 70/m RR 20/m BP-145/90
Investigations
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Duplex U/S.
Sub acute thrombosis involving DVT
Superficial Femoral vein – popliteal vein
Anterior & post tibial veins.
Management
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Standard Heparin started 24/12/02
5000 IVI.
1.5 x APTT control : 26/12.
Thrombophilia Screen :26/1201.
LFT , U&E Normal .
Hepatitis Screen Negative
Follow up
OAC for 6m.
 Thrombophilia Screen :
Unprovoked DVT, Obesity.
 Off Wanferin x 6 w
 PC ,PS ,AT,APCR,ACA IgG - IgM :Negative
ANA , DNA CRP, Rhd Factor :Neg.
 LA. Screen & Confirmatory + ve
April 2001
Abd US : Rt upper pole renal mass.
 CT & biopsy are recommended
Cortical lesion confined to the organ
 Renal cell adeno-carcinoma.
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APL SECONARY TO CANCER
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Lupus type anticoagulant in a patient with
renal cell carcinoma
An autoimmune paraneoplastic syndrome.
J Urol 2002 May;167(5):2129 Ather MH, Mithani S, Bhutto S, Adil S.
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woman with pulmonary embolism and positive
lupus anticoagulant before the diagnosis of
renal cell carcinoma.
J Urol 1994 Sep;152(3):941-2 Papagiannis A, Cooper A, Banks J.
ovarian cancer.
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APS before ovarian endometrial
adenocarcinoma.
widespread thromboembolism .
No respond to anticoagulant treatment.
The paraneoplastic nature is suggested by
the disappearance of both thromboembolism
and APL only after surgical removal of the
cancer.
CLL& Lung cancer
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Autoimmune complications of CLL:
APL (LA,ACA).
 Anti-factor VIII inhibitors.
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Ann Ital Med Int 1999 Jan-Mar;14(1):46-50
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The lung cancer may trigger catastrophic APS.
Occlusion of the superior mesenteric artery.
Nippon Geka Gakkai Zasshi 1999 Feb;100(2):228-30