Thrombosis Medicine Residents 2009

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Thrombosis Medicine Residents 2009 Powered By Docstoc
					   Anticoagulation 101
        Neil A. Lachant, MD
   Chief, Section of Hematology
   Director, Thrombosis Program
      Cooper Cancer Institute
       Professor of Medicine
UMDNJ Robert Wood Johnson Medical
               School
         Venous Thrombosis
        Magnitude of the Problem
• No national data
• Incidence
   – 1- 2/1,000
   – 300,000 - 600,000 new cases per year
   – increasing as population ages
      • life expectancy 78 years
Incidence of VTE
  Age    Incidence

  <10    1:100,000

   20    1:10,000

   50    1:1,000

   80    1:100
             Manifestations
• 2/3 DVT
   – 50- 80% post-phlebitic syndrome

• 1/3 pulmonary emboli
   – 30% mortality
   – 30,000 – 60,000 deaths per year
A 22 yo female presents with an iliofemoral DVT. Her
    aPTT is 37 sec (nl <32) and she is found to have a
    lupus anticoagulant. She weighs 55 kg and her
    creatinine is 0.5 mg/dl. She is started on weight -
    based UFH. Her aPTT at 4 hrs is 123 s. She could
    be anticoagulated by all of the following EXCEPT:

   1. Decrease UFH with aPTT goal of 1.5-2.5 x her
            baseline
   2. UFH monitoring heparin level
   3. UFH correlating heparin level with the aPTT
   4. LMWH without monitoring
   5. Fondaparinux without monitoring
A 22 yo female presents with an iliofemoral DVT. Her
    aPTT is 37 sec (nl <32) and she is found to have a
    lupus anticoagulant. She weighs 55 kg and her
    creatinine is 0.5 mg/dl. She is started on weight -
    based UFH. Her aPTT at 4 hrs is 123 s. She could
    be anticoagulated by all of the following EXCEPT:

   1. Decrease UFH with aPTT goal of 1.5-2.5 x her
            baseline
   2. UFH monitoring heparin level
   3. UFH correlating heparin level with the aPTT
   4. LMWH without monitoring
   5. Fondaparinux without monitoring
      Heparin Therapy in APLS
• Lupus anticoagulant with prolonged baseline aPTT
   – use LMWH
   – use standard weight-based unfractionated heparin
     dosing
      1. correlate aPTT with heparin level (3-4 points)
              use aPTT range that corresponds to
              therapeutic heparin level (0.3 – 0.7 iu/ml)
      2. follow thrombin time if standardized in your lab
       140                                  Patient

       120

       100
                                            Normal
       80
aPTT




       60
       40

       20

        0
             0   0.2       0.4        0.6       0.8
                   Heparin Level (u/ml)
• A 34 year old African American male presents
  with a femoral DVT. He is given a 5000 u
  bolus of UFH and is started on a heparin drip
  at 1000 u/hr. The aPTT remains
  subtheraputic despite an increase to 1800
  u/hr. A hematology consult is obtained on the
  3rd hospital day for “inability to be
  anticoagulated”.
•    What is the most appropriate goal for UFH:
    1. aPTT ratio 1.5 - 2.5 x baseline
    2. aPTT that correlates with heparin level
            of 0.3 - 0.7 u/ml
    3. Whatever the lab computer says the
                  therapeutic range is
•    What is the most appropriate goal for UFH:
    1. aPTT ratio 1.5 - 2.5
    2. aPTT that correlates with heparin level
            of 0.3 - 0.7 u/ml
    3. Whatever the lab computer says the
                  therapeutic range is
                       Effect of Thromboplastin on
             6
                              aPTT Ranges

             5
aPTT Ratio




             4




             3




             2




             1
                 20   40   60   80      100       120       140   160   180   200

                                           aPTT
                                     (Anti-Xa 0.3 - 0.7 IU/ml)
                       Effect of Thromboplastin on
             6
                              aPTT Ranges

             5
aPTT Ratio




             4




             3




             2




             1
                 20   40   60   80      100       120       140   160   180   200

                                           aPTT
                                     (Anti-Xa 0.3 - 0.7 IU/ml)
• Review of the patients records shows that he weighs
  150 kg. His current aPTT is 38 sec (normal < 37.1)
  with an infusion rate of 1800 u/hr. The most
  appropriate rate for the UFH infusion is:
   1. 2700 u/hr (18 u/kg/hr)
   2. 2000 u/hr (18 u/kg/hr capped for patient size)
   3. Continue at 1800 u/hr
   4. Switch to LMWH because UFH doses above
      2000 u/hr are too dangerous to use
• Review of the patients records shows that he weighs
  150 kg. His current aPTT is 38 sec (normal < 37.1)
  with an infusion rate of 1800 u/hr. The most
  appropriate rate for the UFH infusion is:
   1. 2700 u/hr (18 u/kg/hr)
   2. 2000 u/hr (18 u/kg/hr capped for patient size)
   3. Continue at 1800 u/hr
   4. Switch to LMWH because UFH doses above
      2000 u/hr are too dangerous to use.
                   UFH Dosing

Anti-Xa                                 APTT
Initial dose            80 u/kg bolus, then 18 u/kg/hr
< 0.15                  80 u/kg bolus, increase 4 u/kg/hr
0.15 – 0.29             40 u/kg bolus, increase 2 u/kg/hr
0.30 – 0.70             No change
0.71 – 0.85             Decrease infusion by 2 u/kg/hr
> 0.85                  Hold 1 hr, decrease infusion by 3
                        u/kg/hr

 Adopted from Raschke Arch Int Med 156:1645, 1996
 Utilization management is pushing for discharge, but his
INR is only 1.6. The most appropriate recommendation
for the use of enoxaparin would be:
 1. 150 mg (1 mg/kg) sc q 12 hr
 2. 150 mg sc q 12 hr and check a heparin level
      immediately before the third dose
 3. 150 mg sc q 12 hr and check a heparin level 3.5 -
      4 hours after the third dose
 4. 225 mg (1.5 mg/kg) sc q 24 hr
 5. Enoxaparin contraindicated in a patient this large
 Utilization management is pushing for discharge, but his
INR is only 1.6. The most appropriate recommendation
for the use of enoxaparin would be:
 1. 150 mg (1 mg/kg) sc q 12 hr
 2. 150 mg sc q 12 hr and check a heparin level
      immediately before the third dose
 3. 150 mg sc q 12 hr and check a heparin level 3.5 -
      4 hours after the third dose
 4. 225 mg (1.5 mg/kg) sc q 24 hr
 5. Enoxaparin contraindicated in a patient this large
         Kinetics of LMWH

• Different for each LMH
• Doses not interchangable
   Low Molecular Weight Heparin
             Dosing

             Prophylactic     Therapeutic

Enoxaparin   40 mg q 24 h     1 mg/kg q12 h,
                                     or
                              1.5 mg/kg q 24 h
Daltaparin   2,500 or 5,000 u 200 u/kg q 24 h
             q 24 h

Tinzaparin                    175u/kg q 24 h
          LMWH in Obesity

• Relationship of intravascular volume
  and TBW is not linear
  – adipose tissue has a relative decrease in
    plasma volume compared to muscle
  – could lead to overdosing
        Weight in LMWH Studies

Actual weight dosed anti-Xa activity is not
significantly increased in obesity
Enoxaparin              <144 kg

Daltaparin              <190 kg

Tinzaparin              <165 kg
  Recommendations For the Use of
       LMWH in Obesity
• Patient should receive LMWH dose based on
  actual body weight
   – if < 150 kg,
       • monitoring not necessary on a routine
         basis
   – if > 150 kg,
       • check heparin level 3.5 - 4 hrs after 3rd
         or 4th dose
       • dose reduce if > 1.0 IU/ml
• A 24 yo dialysis dependant female is paraplegic. She
  receives enoxaparin 1 mg/kg q 12h for an acute DVT.
  One week later in rehab, she develops pain in her
  right shoulder. She is brought to the emergency
  room during the night with a 20 cm hematoma in her
  right supraclavicular fossa. What is her correct
  enoxaparin dose?

   A. 1 mg/kg q 12h
   B. 1 mg/kg qd
   C. Enoxaparin contraindicated with ESRD
• A 24 yo dialysis dependant female is paraplegic. She
  enoxaparin 1 mg/kg q 12h for an acute DVT. One
  week later in rehab, she develops pain in her right
  shoulder. She is brought to the emergency room
  during the night with a 20 cm hematoma in her right
  supraclavicular fossa. What is her correct
  enoxaparin dose?

   A. 1 mg/kg q 12h
   B. 1 mg/kg qd
   C. Enoxaparin contraindicated with ESRD
             LMWH
   Dosing in Renal Dysfunction
• LMWH accumulates as Ccr decreases
  – cutoff point varies between different LMWHs
  – Ccr 30 - 50
     • monitor heparin level if concern about dosing or
       bleeding
  – Ccr < 30
     • dose reduce
     • monitor heparin level
  – Ccr < 10
     • do not use LMWH under any circumstances
Enoxaparin Dosing with Renal
       Dysfunction
                         Ccr > 30        Ccr 10 - 30
Indication               ml/min          ml/min

Abdominal Surgery        40 mg qd        30 mg qd
Prophylaxis
Medical Prophylaxis      40 mg qd        30 mg qd

Orthopedic Prophylaxis   30 mg q 12h     30 mg qd

DVT and/or PE            1 mg/kg q 12h   1 mg/kg qd
• A 24 year old Hispanic female presents to her
  local hospital with left calf pain. Duplex
  shows a popliteal DVT. Therapy with UFH is
  initiated on Saturday. She is discharged on
  Sunday. Her only anticoagulation is 12 mg
  warfarin which she is told to start at 6 PM that
  night. She presents to Cooper Hospital on
  Monday evening with a leg that is painful and
  swollen to the groin. Duplex shows a DVT
  extending to the iliac vein.
• Which of the following statements about
  anticoagulation after VTE is/are true?
  1. Warfarin should only be given simultaneously
     with a heparin, DTI or other rapid acting
     anticoagulant
  2. Warfarin should be started at a dose of 5 - 7.5 mg
  3. Warfarin should be overlapped with heparin for a
     minimum of 5 days (no matter what the INR is)
  4. Heparin should be stopped when the INR > 2.0
     for 2 days or INR > 2.5
  5. All of the above
• Which of the following statements about
  anticoagulation after VTE is/are true?
  1. Warfarin should only be given simultaneously
     with a heparin, DTI or other rapid acting
     anticoagulant
  2. Warfarin should be started at a dose of 5 - 7.5 mg
  3. Warfarin should be overlapped with heparin for a
     minimum of 5 days (no matter what the INR is)
  4. Heparin should be stopped when the INR > 2.0
     for 2 days or INR > 2.5
  5. All of the above
A 60 year old female is taking a stable dose of
coumadin as prophylaxis for atrial fibrillation (INR
2.6). She develops a UTI and is treated with bactrim.
Two weeks later her INR is 6.9. She has no clinical
bleeding. Her coumadin is held. The most
appropriate adjunctive therapy would be:

    A.   Transfuse 4-6 units FFP
    B.   Transfuse 15 bags cryoprecipitate
    C.   Vitamin K 0.5 mg sc x 1
    D.   Vitamin K 10 mg sc x 1
    E.   Vitamin K 10 mg sc x 3d
    F.   Vitamin K 2.5 mg po x 1
    G.   No additional therapy is needed
A 60 year old female is taking a stable dose of
coumadin as prophylaxis for atrial fibrillation (INR
2.6). She develops a UTI and is treated with bactrim.
Two weeks later her INR is 6.9. She has no clinical
bleeding. Her coumadin is held. The most
appropriate adjunctive therapy would be:

    A.   Transfuse 4-6 units FFP
    B.   Transfuse 15 bags cryoprecipitate
    C.   Vitamin K 0.5 mg sc x 1
    D.   Vitamin K 10 mg sc x 1
    E.   Vitamin K 10 mg sc x 3d
    F.   Vitamin K 2.5 mg po x 1
    G.   No additional therapy is needed
         Reversal of Warfarin

• INR < 5.0, no bleeding
  – lower dose or
  – omit dose, restart at lower dose




                               Chest June, 2008
         Reversal of Warfarin

• INR > 5.0 but < 9.0, no significant bleeding
  – omit 1 or 2 doses and restart at lower dose, or
  – omit dose, give vitamin k 1-2.5 mg po, or
  – for rapid reversal (i.e., surgery) 3 - 5 mg po
    (INR should decrease in 24 hr)
      • can repeat vitamin k 1-2 mg po if goal not
        reached
         Reversal of Warfarin

• INR > 9.0, no significant bleeding
  – hold warfarin
  – give vitamin K 2.5 - 5 mg po (INR should be
    significantly reduced in 24 - 48 hrs)
  – additional vitamin k po if needed
  – resume warfarin when INR therapeutic
           Reversal of Warfarin

• Any INR > 3.0, serious bleeding
  –   hold warfarin
  –   vitamin k 10 mg slow iv infusion
  –   repeat every 12 hours as needed
  –   FFP, r-VIIa or prothrombin complex depending
      upon urgency of the situation
         Reversal of Warfarin

• Any INR > 3.0, life threatening bleeding
  – hold warfarin
  – fresh frozen plasma, r-VIIa or prothrombin
    complex
  – vitamin k 10 mg slow iv infusion
              Warfarin Pearls
• Coumadin if possible
  – If generic, keep track of brands
• Dose adjustment
  – Think in terms of a week
  – New warfarin dose = current dose x goal INR
                                       current INR
  – New dose = 35 mg x 2.5/5.0
  – New dose = 17.5 mg/week = 2.5 mg/day
                    IVC Filter
                   Indications
• Recent proximal DVT, and
   – Contraindication to anticoagulation
      • current or recent active GI bleed
      • intracranial bleed in last 5 days
      • recent neurologic or ophthalmologic surgery
      • cerebral metasteses at risk for bleeding
          – seminoma, melanoma, renal cell,
            choriocarcinoma
      • planned major surgery in next 4 weeks
      • severe, prolonged thrombocytopenia
• Recurrent pulmonary emboli while fully anticoagulated
         New Anticoagulants
• Pentasaccharide
  – Fondaprinux (Arixtra)
• Oral IIa inhibitors
  – ximelagatran
• Oral Xa-inhibitors
Fondaparinux (Arixtra)
Theoretical Models for Differential Effects
of Heparin and LMWH on Thrombin and
               Factor Xa
             Fondaparinux: 5 Saccharide Units

                                          Fondaparinux


                  AT      IIa       AT   Xa
              5                 5



                  Binds to AT   Binds
                   but not to   to AT
                   Thrombin
         New Anticoagulants
• Fondaparinux (Arixtra)
   – Synthetic pentasaccharide
   – Selective anti-Xa inhibitor
      • no anti-IIa activity
      • PT or PTT are insensitive
   – Renal excretion
   – T1/2 17 – 20 hrs
   – Does not bind PF4
      • One reported case of HIT
• FDA Approved
  –   hip and knee surgery prophylaxis
  –   treatment of DVT
  –   treatment of PE when started in hospital
  –   surgical DVT prophylaxis
• Fondaparinux dosing for DVT or PE
  – < 50 kg  5 mg qd sc
  – 50 – 100 kg 7.5 mg qd sc
  – >100 kg  10 mg qd sc


• Dose modification
  – Ccr 30 – 50, use with caution
  – Ccr < 30, contraindicated
• Because of long half-life, anticoagulant effect
  may last for 2 – 4 days after stopping
  fondaparinux with normal renal function

• Anti-Xa activity can be measured
   – ? <0.3 u/ml safe


• R-VIIa if severe bleeding

				
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