Hypercoagulable State

1
Hypercoagulable State

• Victor Ghobrial, MD
• Morning Report 5/30/00

2
HPI

• Pt is 58 yrs WF admitted to Hospital C/O
  dysphagia, orthopnea and cyanosis.
• She has difficulty swallowing - more to solid
  foods.
• She has puffiness of her eye lids B/L

3
PMH

• Metastatic Ovarian Cancer
• Endometriosis
• S/P total hysterectomy
• S/P ileostomy

4
History

• Meds
• Prilosec - Lorazepam - Megestrol - Leukine - Pro
  chlorpromazine
• Social Hx
• No ETOH or Smoking

5
Phsical Exam

• Temp B/P Pulse RR Pox
  98.5 110/ 70
  72 16 97
• HEENT Atraumatic, Puffy eyelids, Purple
  discoloration of face
• Neck Engorged veins, no lymphadenopathy
• Ht RRR S1S2 audible, no murmurs

6
Physical Exam

• Lungs CTAs B/L
• Abd Soft, ve BS, no organomegally
• Ex LE edema 2, Lt arm swelling no tenderness or
  erythema
• Neuro AAOX 3, no focal deficits

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• Your Thoughts ...

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Studies

• Labs WNL
• CXR
• CT Neck Chest

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Hypercoagulable Disorders in Malignancy

• Patients with cancer are in a hypercoagulable
  state.
• The spectrum ranges from just abnormal
  coagulation tests to massive thromboembolism

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Presentation

• Migratory superficial thrombophlebitis
  (Trousseau's syndrome)
• Idiopathic deep venous thrombosis and other
  venous thrombosis
• Nonbacterial thrombotic endocarditis
• Disseminated intravascular coagulation (DIC)
• Thrombotic microangiopathy (eg, hemolytic-uremic
  syndrome)

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Incidence

• Clinical thromboembolism occurs in as many as 11
  percent of patients .
• It is the second leading cause of death in
  patients with overt malignant disease.
• One study, for example, found evidence of
  thrombosis of 30 percent in patients who died of
  pancreatic cancer

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TROUSSEAU'S SYNDROME

• An association between venous thrombosis and
  malignancy was first suggested in 1865 by
  Trousseau.
• He subsequently developed unexplained deep venous
  thrombosis followed a year later by gastric
  carcinoma.

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Trousseau's syndrome

• Migratory superficial thrombophlebitis,
  phlegmasia alba dolens.
• It is rare involvement of superficial veins.
• Unusual sites such as the arm
• Occult tumor which is not always detectable at
  the time of presentation.
• It is usually adenocarcinoma.

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Trousseau's Syndrome

• Pancreas 24 percent
• Lung 20 percent
• Prostate 13 percent
• Stomach 12 percent
• Acute leukemia 9 percent
• Colon 5 percent

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Idiopathic Venous Thrombosis

• Clinically significant incidence of malignancy,
  often diagnosed within the first six months after
  presentation with thrombosis

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Venous Thromboembolism

• Presenting sign of pancreatic and prostate
  cancer.
• Occurs late in the course of breast, lung,
  uterine, or brain cancer.

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Pt with DVT ..

• Is extensive screening beneficial ?
• Two studies on 136 326 Pts.
• All pts with DVT and malignancy had obvious
  abnormality on their clinical data warranting
  malignancy.

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evaluation of patients

• Should be limited to a careful history, a
  complete physical examination and routine
  laboratory testing.
• A routine aggressive search for malignancy in all
  patients does not appear to be warranted.

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Hepatic Vein and Portal Vein Thrombosis

• Thrombosis of the hepatic vein (the Budd-Chiari
  syndrome) or portal vein may be associated with
  myeloproliferative disorders (such as
  polycythemia vera).
• Hepatic vein thrombosis is also associated with
  renal cell and adrenal carcinomas and hepatomas

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Nonbacterial Thrombotic Endocarditis

• Microscopic aggregates of platelets to large
  vegetations on the heart valves (most often
  aortic and mitral)
• In autopsy series, cancer has been found in as
  many as 75 of cases.
• Adenocarcinomas
• Abnormal aggregation of platelets.

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Disseminated Intravascular Coagulation

• The most common coagulopathy associated with
  malignancy
• Malignancy is the third most frequent cause of
  DIC after infection and trauma
• Reported in 15 advanced disease and in most
  patients with acute promyelocytic leukemia

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Thrombotic Microangiopathy (TMA)

• Microangiopathic hemolytic anemia
  thrombocytopenia, microvascular thrombotic
  lesions
• The two major syndromes are thrombotic
  thrombocytopenic purpura and the hemolytic-uremic
  syndrome

23
Microangipathic smear Peripheral blood smear
from a patient with a microangiopathic hemolytic
anemiawith marked red cell fragmentation. The
smear showsmultiple helmet cells (small arrows),
other fragmented red cells (large arrows) the
platelet number is reduced and the large platelet
in the center (red arrow) suggests that the
thrombocytopenia is to to enhanceddestruction.
Some small spherocytes are also seen (blue
arrows). Courtesy of Carola von Kapff.
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TMA

• Direct platelet consumption, endothelial injury
  or primary platelet activation by large von
  Willebrand factor multimers .
• The most important aspect of treatment of
  malignancy-related TMA is reduction of the tumor
  burden.

25
Pathogenesis

• Tissue factor transmembrane protein, complex
  with factor VII to activate factor IX and factor
  X
• Cancer procoagulant Ca dependent cysteine
  protease activates factor X directly
• Platelets Increased reactivity secondary to
  clonal abnormalities or tumor-platelet
  interactions
• Endothelial cells Become procoagulant under the
  influence of inflammatory cytokines (TNF) (IL)

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Comorbid Factors

• Vascular stasis
• Sepsis
• Advanced age
• Antineoplastic agents

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Therapy

• Anticoagulant therapy
• Fibrinolytic therapy, catheter directed Urokinase
• Surgical therapy, reserved for septic emboli