Hypercoagulable State of Malignancy

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Hypercoagulable State of Malignancy

• JHU/ Sinai Internal Medicine Program

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Introduction

• Clinical thromboembolism occurs in approximately
  11 of patients with cancer
• Second leading cause of death in patients with
  overt malignant disease
• Lung cancer accounts for the largest number of
  thromboembolic events
• Most commonly associated with adenocarcinoma
  compared to squamous cell carcinoma

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Hypercoagulable Disorders

• Migratory superficial thrombophlebitis
  (Trousseaus sx)
• Idiopathic deep venous thrombosis
• Nonbacterial thrombotic endocarditis
• Disseminated intravascular coagulation
• Thrombotic microangiopathy (HUS)
• Arterial thrombosis

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Trousseaus Syndrome

• First suggested in 1865 by Trousseau.
• Rare variant of venous thrombosis characterized
  by a recurrent and migratory pattern and
  involvement of superficial veins, frequently in
  arms and chest.
• Occurs in up to 10 of patients with pancreatic
  carcinoma.
• Heparin treatment of choice, Coumadin no
  improvement.

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Idiopathic Venous Thrombosis

• Large Dutch population based case control study
  of 3220 patients found
• - overall risk of VTE was significantly
  increased in patients with malignancy (adjusted
  OR 6.7)
• - patient with metastases had a higher risk of
  VTE (adjusted OR 19.8)
• - hematologic malignancies risk of VTE (adjusted
  OR 28), lung cancer (adjusted OR 22) and breast
  (OR 4.9)
• - metastatic disease at the time of diagnosis is
  the largest predictor of VTE.

Blom, et al. Malignancies, prothrombotic
mutations and the risk of VTE. JAMA 2005 293
715.
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Should we screen?

• Should we screen for malignancy in patients with
  idiopathic DVT.
• Several studies however there is a lack of
  prospective studies demonstrating improved
  survival with aggressive diagnostic testing.
• Recurrent thrombosis and abnormal clinical
  findings during an initial clinical eval should
  prompt further investigation.

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Treatment

• Treatment is associated with both benefit and a
  high rate of complications
• Major observations in multiple studies show
• - the overall incidence of recurrent VTE was
  three times higher and that of major bleeding 6.5
  times higher among those with malignancy.

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LMW Heparin vs. Warfarin

• CANTHANOX Trial
• - compared 3 months of therapy with either
  warfarin or enoxaparin in cancer patients with
  DVT, PE or both.
• - warfarin arm had a 20 treatment failure.
• - warfarin arm had a higher bleeding risks.

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7th ACCP Guidelines

• Recommendations
• GRADE 1A
• - For patients with advanced malignancy, a
  reasonable quality of life and life expectancy,
  and VTE, we recommend the use of a LMW heparin
  over the use of oral anticoagulants
• - We recommend that such anticoagulation be
  given for an indefinite period if metastatic
  disease is present or if the patient is receiving
  chemotherapy or until the cancer is resolved.

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LMW Heparin vs. Warfarin

• CLOT Trial
• - multicenter international randomized clinical
  trial compared 6 mos of treatment with dalteparin
  or warfarin in 672 patients with cancer and acute
  symptomatic VTE.
• - no significant difference in major bleeding
  risks.
• - Dalteparin had significant reduction in
  cumulative rate of recurrent VTE.

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Nonbacterial Thrombotic Endocarditis

• Microscopic aggregate of platelets to large
  vegetations on heart valves.
• Cancer in as many as 75 of cases.
• Majority are adenocarcinomas
• Clinical manifestations sec to emboli spleen,
  kidney, extremities and CNS.
• Preferred diagnostic test is TEE.

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7th ACCP Guidelines

• NBTE and emboli should receive full dose unfrac
  IV or SQ heparin therapy.
• Full dose unfrac heparin therapy in patients with
  DIC or debilitating disease with aseptic vegs on
  Echo.
• Acg to continue indefinitely.

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Thank You