Thrombotic complications of panreatic cancer a classical knowledge revisited
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THROMBOTIC COMPLICATIONS OF PANREATIC CANCER: A CLASSICAL KNOWLEDGE REVISITED. D. L . DUMITRASCU, O. SUCIU, C. GRAD, D. GHEBAN 2 ND MEDICAL DEPT. UMPh IULIU HATIEGANU CLUJ ROMANIA. Cluj, Romania. Armand Trousseau (1801­1867).

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THROMBOTIC COMPLICATIONS OF PANREATIC CANCER: A CLASSICAL KNOWLEDGE REVISITED

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Thrombotic complications of panreatic cancer a classical knowledge revisited

THROMBOTIC COMPLICATIONS OF PANREATIC CANCER: A CLASSICAL KNOWLEDGE REVISITED

D. L. DUMITRASCU,

O. SUCIU,

C. GRAD,

D. GHEBAN

2ND MEDICAL DEPT.

UMPh IULIU HATIEGANU CLUJ

ROMANIA


Cluj romania

Cluj, Romania


Armand trousseau 1801 1867

Armand Trousseau (1801­1867)


Looking for this association and its consequences for clinical practice

Looking for this association and its consequences for clinical practice


Thrombotic complications of panreatic cancer a classical knowledge revisited

  • “In conditions of cachexia, a special state of the blood occurs which predispose to spontaneous coagulation”

    • Trousseau

      1865


Thrombotic complications of panreatic cancer a classical knowledge revisited

Jaundice

Pancreas CC

Thrombosis of aorta


Thrombotic complications of panreatic cancer a classical knowledge revisited

Pancreatic CC

Thrombosis

Pancreas


Thrombotic complications of panreatic cancer a classical knowledge revisited

longitudinal and transversal section of popliteal vein: recent thrombosis, complete obstruction of popliteal vein


Thrombotic complications of panreatic cancer a classical knowledge revisited

transversal section of common femural vein at femural bifurcation: recent thrombosis, complet obstruction (duplex color)


Epidemiology

Epidemiology

  • Incidence of thrombosis:

    • in cancer: 5-60%

  • 2x higher in cancer pts vs general population

  • 20% pts DVT have dg cancer


Clinical types of thrombosis

Clinical types of thrombosis:

  • Superficial migratory thrombophlebitis (Trousseau syndrome)

  • Idiopathic deep venous thrombosis

  • Nonbacterial thrombotic endocarditis

  • Intravascular disseminated coagulation

  • Thrombotic microangiopathy (thrombocitary thrombocytopenic purpura and the hemolitic-uremic syndrome)

  • Arterial thrombosis


Localisat i on of cancer

Localisation of cancer


Pathogenesis virchow s triad

PathogenesisVirchow’s triad

  • Alterations in blood flow

  • Vascular endothelial injury

  • Alterations in the constituents of the blood

  • Patients with cancer : hypercoagulable state >> substances with procoagulant activity: tissue factor, cancer procoagulant


Pat h ogene sis

Pathogenesis

  • Hypercoagulability

    • Abnormal coagulation tests

    • Thrombine generated in excess

    • Tumour cells have direct procoagulant effect

    • Tissue factor activate F IX and FX initiating coagulation

    • Tumoral procoagulant: a Ca-dependent cistein-protease


Pathogenesis

Pathogenesis

  • The factor V Leiden mutation, a mutation of the F5 gene (gene ID: 2153), causes partial resistance of this coagulation factor to the inactivating effects of activated protein C, a protein encoded by the PROC gene (gene ID: 5624)

  • 5% population RR 3-8


Pathogenesis1

Pathogenesis

  • The prothrombin 20210A mutation found to be associated with elevated prothrombin levels

  • 2% population, RR 2.0


Pathogenesis2

Pathogenesis

  • The endothelial cells may become procoagulant under the influence of proinflammatory cytokinases or other peptides: TNF & IL-1 increase the expression of adhesion molecules for leukocytes, PAF and tissue factor

  • TNF decreases the endothelial fibrinolytic activity, increases endothelial production of IL-1, increases the expression of thrombomoduline (which diminishes the activation of anticoagulant proteine C).


Other mec h anism s

Other mechanisms

  • Extrinsec compression

  • Vascular invasion


Trousseau syndrome

TrousseauSyndrome


Pancreatic carcinoma and dvt

PANCREATIC CARCINOMA and DVT

  • N=202

  • Venous THROMBOSIS: 108.3 PER 1000 PATIENT-YEARS (~11%)

  • Thrombosis: 58.6-FOLD INCREASE

  • CHEMOTHERAPY: 4.8-FOLD

  • RADIOTHERAPY: 1.0

  • POSTOPERATIVE: 4.5-FOLD

  • METASTASIS: 1.9-FOLD

    Blom et al Eur. J. Cancer 410, 2006


Cancer in 1383 cases of phlebitis venography nordstrom et al bmj 1994

CANCER IN 1383 CASES OF PHLEBITIS VENOGRAPHY + Nordstrom et al BMJ 1994

<6mo >6 mo

  • ALL CANCER 66 84

  • Oesophagus + stomac: 3 4

  • Intestinal 7 10

  • Liver 5 3

  • Gallbladder 5 1

  • PANCREAS 6 2


Sorensen et al nejm 1998

Sorensen et al NEJM 1998

  • 15,348 patients with DVT and 11,305 patients with pulmonary embolism

  • 1737 cases cancer in the cohort with deep venous thrombosis, compared with 1372 expected cases (standardized incidence ratio, 1.3);

  • Among the patients with pulmonary embolism, standardized incidence ratio was 1.3,

  • The risk was substantially elevated only during the first six months of follow-up and declined rapidly

  • 40% of patients given a diagnosis of cancer within one year after hospitalization for thromboembolism had distant metastases at the time of the diagnosis

  • Strong associations with cancers: pancreas, ovary, liver (primary hepatic cancer), brain.


Thrombotic complications of panreatic cancer a classical knowledge revisited

Risk of Venous Thrombosis per Type of Malignancy for Patients With a Diagnosis of Malignancy Within 5 Years Before Diagnosis of Venous Thrombosis

Bloom et al 2005

Type of Malignancy

No. of Patients/No. of Control

Odds Ratio (95% CI)/Adjusted Odds Ratio(95% CI)

No malignancy 1.00 1.00

Men 1279 /1038

Women 1552/ 1024

Malignancy

All hematological cancer 37/ 1 26.2 (3.6-191.4)/ 28.0 (4.0-199.7)

Gastrointestinal malignancies

Bowel 46/ 2 16.8 (4.1-69.1)/ 16.4 (4.2-63.7)

Pancreas 2/ 0 ND ND

Stomach 2 /0 ND ND

Esophagus 2/ 0 ND ND

All gastrointestinal cancer 52/ 2 18.9 (4.6-77.8)/ 20.3 (4.9-83.0)


Risk factors

Risk factors

  • Advanced age

  • Caucasians

  • Comorbidities

  • History of DVT

  • Location of cancer

  • First 6 months after cc dx

  • Metastasis

  • Recent surgery, current hospitalization, chemotherapy, central venous catheters, sepsis.


Prognosis

Prognosis

  • Poorer in pts with cancer (incl. pancreatic cancer + DVT) vs cancer (including pancreatic cancer without DVT (Alcalay et al J Clin Oncol 2006)


Prophylaxis

Prophylaxis

  • LMWH 5000 iu once a day

    (Bergquist et al Br J Surg 1995)

  • LMWH superior to heparin

    (Mismetti et al Br J Surg 2001)

  • Long-term: 4 weeks postop. superior to 1 week

    (Rasmussen et al Blood 2003)


Conclusions

Conclusions

  • Pts with pancreatic cancer have higher risk to develop thrombotic events

  • This contribute to their morbitiy nd mortality

  • These complications should be actively searched in order to improve life expectancy and qol

  • Thromboprofilaxis of pts with pancreatic cancer refered to surgery or having catheters is very important


Questions

QUESTIONS

  • Is pancreatic cancer associated with DVT?

  • YES

  • NO


Shall we screen pts with dvt recurrent for occult malignancy including pancreatic cc

Shall we screen pts with DVT (recurrent) for occult malignancy including pancreatic cc?

  • YES

  • NO


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