Hematology Rounds 121208

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Hematology Rounds12-12-08

• Scot Hickman, M.D.
• Suresh Vedantham, M.D.

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Disclosure Scot Hickman, M.D.
Dr. Scot Hickman has no relevant financial
interests to disclose.
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64 year old Caucasian male presented in mid
August of this year complaining of a 2 day
history of a swollen, purple right ankle.

• HPI The patient was in otherwise good with no
  significant past or present medical history. Two
  weeks prior to presentation he drove to WI to
  help repair pier damage to his friends lake side
  home pier. The drive was 6 hours and he stopped
  once or twice for food and gas. This was a trip
  he has probably driven over 100 times over the
  past several decades. The following morning he
  spent at least 4 hours on his hands and knees
  drilling pier sections. That afternoon he spent
  several hours climbing up and down a ladder
  cleaning 2nd story gutters. Following this he
  developed pain on the lateral side of his right
  knee that was not tender to palpation or movement
  of the knee. This resolved by morning at which
  time he returned to St. Louis again stopping at
  least twice. The following week he returned to
  this WI cottage with his family for a weeks
  vacation. The final day of this vacation, he
  noticed some mild swelling of his lower leg and
  ankle and some purple discoloration of his ankle.
  He denied pain, fevers, chills, and night
  sweats. Upon returning to St. Louis the
  following day, he sought medical advice.
•  

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• PMH As noted, this was unremarkable except for
  a basal cell carcinoma of the forehead in the
  1980s that was surgically removed, and a history
  of frequent palpations for 6-8 months that were
  evaluated about 2 years ago. EKG showed frequent
  APCs and these and all palpations resolved
  shortly after an expensive cardiac echo was
  obtained and found to be normal.
•  
• MEDs Aspirin prn but usually daily
•  
• FH No family history of thromboembolic
  disease. He is married and has two children
  (males).
•  
• SH He is a lifetime non-smoker and he denied
  illicit drug use. He does drink beer and wine
  but was vague about amounts

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PE His vital signs were normal. His physical
examination was likewise normal with the
exception of the examination of his right lower
extremity. There was mild/minimal swelling and
erythema from just below the right mid-calf to
and including the ankle. There was 1cm
erythematous collateral vessel on the dorsum of
his foot and the medial aspect of his right lower
ankle was purple. On close inspection, the
purple discoloration of his ankle appeared to be
due to multiple small collateral vessels. Labs
including CBC, CMP, PT/INR, and aPTT were within
normal limits. Duplex Venous Evaluations of the
lower extremities did not reveal any DVTs in the
left lower extremity. In addition, no DVT was
detected in the right thigh. However Doppler
evaluation of the right lower extremity revealed
thrombus in the posterior tibial vein and in the
popliteal vein. In addition, one set of
gastrocnemius veins was thrombosed.
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Which of the following is now accepted as the
most appropriate therapy option for this patient
at this time?

• Warfarin alone
• Warfarin started on day one and unfractionated
  heparin given for at least 5 days and until the
  INR is 2.0 for 24 hours
• Since the thrombi are below the knee,
  anticoagulation isn't absolutely necessary.
  Treat with anti-inflammatory agents only, thereby
  avoiding the potential side effects of
  anticoagulation
• Warfarin started on day one and low molecular
  weight heparin given for at least 5 days and
  until the INR is 2.0 for 24 hours
• Catheter-Directed Thrombolysis

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ADVANTAGES OF LOW MOLECULAR WEIGHT HEPARIN

• Can be administered on an outpatient basis 
• Doesnt require monitoring 
• Lower incidence of HIT 
• Lower overall COST

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DISTAL vs. PROXIMAL VEIN DVTs

• The popliteal vein is considered a proximal leg
  vein mainly because the risk of PEs from a
  popliteal vein thrombosis is high, equal to or
  approaching the risk from thrombi in the thigh
  deep veins.
• Patients with DVTs in other calf veins must be
  anticoagulated because there is 20-30 rate of
  extension/propagation to involve the popliteal
  vein.
• There is a high rate of recurrence of symptomatic
  calf vein DVTs if the initial episode is not
  treated (20 compared to 5-10 in treated
  patients).

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The association between venous thromboembolism
(VTE) and cancer is well known and frequently
observed. In the patient, who has no history of
cancer, what additional studies should be done to
evaluate for a hidden cancer?

• Other than the clinical history, physical
  examination, routine labs, a chest x-ray should
  be obtained 
• No additional testing is needed 
• Pan CT scanning 
• PET scan

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VTE and CANCER

• 1. There is a higher incidence of cancer
  (including hidden cancer) in patients with VTE
  than in the general population.
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• 2. There is a higher incidence of underlying or
  hidden cancer in patients with idiopathic VTE
  than in those with additional risk factors.
•  
• 3. Cancer found shortly after a diagnosis of VTE
  is associated with a very poor prognosis.
•  
• 4. Evaluations from the RIETE Registry have
  identified a subgroup of VTE patients with a
  higher risk for hidden cancer.

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There are genetic and acquired causes of
thrombophilia. In this patient, which of the
following should be obtained for thrombophilia
screening?

• The Leiden mutation of factor V 
• The G20210A mutation of prothrombin 
• The antiphospholipid syndrome (Lupus
  anticoagulant) 
• all of the above (a, b, c) 
• no testing is indicated

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The clinical course and therapy options differ
depending on whether a DVT is provoked or
unprovoked. Did the patient have a provoked
DVT?

• Yes 
• No

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Provoked DVTs

• Reversible Provoking Risk Factors
• Major surgery, hospitalization, or plaster cast
  immobilization, all within 1 month of DVT
  diagnosis
• Minor estrogen therapy, pregnancy, prolonged
  travel (eg, gt8h), or any of the major factors
  when occurring 1-3 months before the diagnosis of
  DVT

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Everyone recognizes it is important to begin
anticoagulation as soon as possible in a patient
with a new diagnosis of a DVT. What are the
benefits of rapid and adequate anticoagulation?

• Relief of any acute symptoms
• Prevention of PEs
• Prevention of recurrent DVTs
• Prevention of postthrombotic syndrome
•  All of the above

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The patient has tolerated warfarin therapy well
although his weekly dose of 75mg/week is on the
high side. His INR has remained between 2.0 and
3.0 for weeks. How long should he take warfarin?

• Although its a proximal vein DVE, its still
  below the knee so 6 weeks of anticoagulation is
  more than enough
•  3 months
•  6 months
•  12 months
•  Indefinitely

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Prandoni, P, et al. Ann Intern Med.
1996125(1)1-7
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• This is one of the most controversial questions
  for the management of DVTs. Longer therapy
  appears to be better than shorter, although the
  risk for recurrent DVTs is increased after
  warfarin is discontinued regardless of the length
  of time warfarin is taken. The minimum
  requirement is 3 months. ACCP guidelines are
  as follows
• 2.1.2. For patients with unprovoked DVT, we
  recommend treatment with a VKA for at least 3
  months (Grade 1A). We recommend that after 3
  months of anticoagulant therapy, all patients
  with unprovoked DVT should be evaluated for the
  risk-to-benefit ratio of long-term therapy (Grade
  1C). For patients with a first unprovoked VTE
  that is a proximal DVT, and in whom risk factors
  for bleeding are absent and for whom good
  anticoagulant monitoring is achievable, we
  recommend long-term treatment (Grade 1A).
• This is a recent guideline, but already others
  have disagreed with this proposal (see
  Up-To-Date).

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Which of the following have been shown to predict
recurrent DVTs?

• D-dimer testing after 3-4 months of adequate
  anticoagulation 
• Doppler studies after 3 months of adequate
  anticoagulation 
• Neither of the above 
• Both of the above

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For the patient, PTS stands for

• Parent Teachers Society
• Post Traumatic Syndrome 
• Postthrombotic syndrome

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• PTS stands for PostThrombotic Syndrome. This
  syndrome includes a number of leg symptoms and
  signs in patients who have had DVTs. PTS occurs
  in 20 to 50 of patients after an acute DVT. As
  previously indicated, the initial treatment of
  acute DVT (adequate anticoagulation) may
  influence the presence and severity of PTS.
  Symptoms include swelling and pain of the lower
  extremity, ambulatory discomfort, and skin
  pigmentation. The severity of symptoms can vary
  over time, with the most extreme manifestation
  being venous ulceration of the lower extremity.

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• How can PTS be prevented?
•  
• Certainly adequate and prompt anticoagulation
  helps to prevent PTS. In addition below-knee
  elastic compression stockings appear to reduce
  the incidence of the postthrombotic syndrome.
  Other more invasive options are being studied.

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Cumulative incidence of the post-thrombotic
syndrome in patients wearing elastic stockings
and those in the control group
Prandoni, P. et. al. Ann Intern Med
2004141249-256