THROMBOPHILIA DVT PROPHYLAXIS VTE MANAGEMENT

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THROMBOPHILIA DVT PROPHYLAXIS VTE
MANAGEMENT

• DR. ASHISH
• Moderator DR. MEERA KHARBANDA

www.anaesthesia.co.in anaesthesia.co.in_at_gmail.c
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Thrombophilia

• Thrombophilia - propensity for thrombotic events
• Most often manifests clinically in form of venous
  thrombosis (frequently DVT of lower extremity)
• Thrombophilia may result from inherited or
  acquired conditions

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Heritable cause of thrombophilia

• Decreased anti thrombotic proteins
• Hereditary antithrombin deficiency
• Hereditary protein c deficiency
• Hereditary protein s deficiency

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Heritable cause of thrombophilia

• Due to increased prothrombotic proteins
• Factor V Leiden genetic polymorphism
• Prothrombin G20210A genetic polymorphism

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Acquired causes of thrombophilia

• Myeloproliferative disorders
• Malignancies
• Pregnancy OCP use
• Nephrotic syndrome patients
• Antiphospholipid antibodies

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Hypercoagulable States and Risk for
Perioperative Thrombosis

• High Risk  
• Heparin-induced thrombocytopenia (HIT) 
•  Antithrombin deficiency
•  Protein C deficiency 
•  Protein S deficiency
•  Antiphospholipid antibody syndrome

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• Hypercoagulable States and Risk for
• Perioperative Thrombosis
• Moderate risk
• Factor V Leiden genetic polymorphism
• Prothrombin G20210A genetic polymorphism 
• Hyperhomocysteinemia 
• Dysfibrinogenemia 
• Postoperative prothrombotic state  
• Malignancy  
• Immobilization

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• Random screening of asymptomatic patients for
  thrombotic risk has not proved cost effective or
  clinically efficacious
• Careful history focusing on prior thrombotic
  events, family H/O thrombosis, concurrent drug
  therapy offers greater predictive value than
  random screening.

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Common Inherited Thrombotic Disorders

• Factor V Leiden(activated protein C resistance)
• Point mutation of factor V gene
• Results in impaired inactivation of factor V by
  activated protein C
• Factor V leiden stays active in circulation gt N ,
  fostering increased thrombin generation
• Heterozygosity 5x 7x risk of VTE
• Homozygosity 80x risk of VTE

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Prothrombin gene G20210A mutation

• Prothrombin gene mutation nucleotide position
  20210 G ? A
• Elevated prothrombin levels and activity
• Increased risk of venous thrombosis
• Rare in Asians Africans

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Protein C deficiency

• Synthesis in the liver Vit-K dependent
• Inactivate factor? and factor?.
• It needs a cofactor protein S
• Protein C def. l/t overabundance of thrombin
• Risk of thrombosis if warfarin therapy started in
  absence of protective anticoagulation by heparin

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Protein S deficiency

• Synthesis in hepatocytes megakaryocytes
• Vit-K dependent
• Cofactor of activated protein C(APC)
• Protein C have shorter half life than Protein S

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Antithrombin ? deficiency

• Antithrombin (AT, also called AT III)
  defense against clot formation in healthy vessels
  or at the perimeter of a site of active
  bleeding
• Autosomal dominant trait
• Heterozygosity 20x risk of VTE
• Homozygosity Not compatible with life

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• In absence of coexisting precipitating
  conditions, absolute thrombotic risk secondary to
  heritable thrombophilia proves limited.
• In the presence of family history or test
  abnormality suggesting thrombophilia with no h/o
  thrombosis, risks a/w long-term preventive
  anticoagulation may outweigh potential benefits.

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• After a thrombotic complication, however,
  these patients most often are managed with
  life-long anticoagulation.

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Acquired thrombophilia- Antiphospholipid Syndrome

• Autoimmune disorder ch/by venous and/or arterial
  thromboses , recurrent pregnancy loss.
• 20 to autoimmune disorders such as SLE or RA, or
  occur in isolation.
• Mild prolongation of aPTT testing for lupus
  anticoagulant or anticardiolipin antibodies.

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Acquired thrombophilia- Antiphospholipid Syndrome

• No increased bleeding risk but risk of
  thrombosis.
• Isolated prolongation of an aPTT in preoperative
  patient consider - antiphospholipid syndrome.
• Risk of recurrent thrombosis - life-long
  anticoagulation.

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HIT

• Autoimmune-mediated drug reaction - 5 of pt.
  receiving heparin therapy.
• Heparin AT complex also binds to platelet
  factor 4 some pt. develop -
• Heparin- induced ab. that can cross react with
  this platelet binding site to produce platelet
  clumping and subsequent thrombocytopenia
• Can be triggered by low dose heparin as well as
  therapeutic dose heparin

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MALIGNANCY

• Adenocarcinomas of pancreas, colon, stomach,
  ovaries .
• Pathogenesis - release of procoagulant factor(s)
  by tumor, which directly activate factor X,
  endothelial damage by tumor invasion, and blood
  stasis.
• Lab No abnormalities or some combination of
  thrombocytosis, elevation of the fibrinogen
  level, and low-grade DIC.

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Pregnancy and OCP Use

• Incidence - 1 in 1500 pregnancies
• Risk of PE highest during 3rd trimester
  immediate postpartum period
• Antithrombin IIIdeficient women high risk
  -anticoagulated throughout pregnancy.
• Factor V Leiden and the prothrombin G20201A
  mutation a/w less risk.
• Women with one of these inherited traits not
  anticoagulated unless h/o PE or recurrent DVT

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Pregnancy and OCP Use

• Since low-dose estrogen OCP introduction
  -incidence decreased.
• Women - smoke, h/o migraine headaches, inherited
  hypercoagulable defect at increased risk
  (30-fold) of venous thrombosis, PE,
  cerebrovascular thrombosis.

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Nephrotic Syndrome Patients

• Risk of thromboembolic disease including renal
  vein thrombosis.
• D/t lt N levels of antithrombin III or PC 20
  renal loss of coagulation protein, factor XII
  deficiency, platelet hyperactivity, abnormal
  fibrinolytic activity, gt N levels of other
  coagulation factors.
• Hyperlipidemia and hypoalbuminemia - also
  possible etiologic factors

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Perioperative venous thromboembolism

• Without prophylaxis, incidence of
• DVT
• 14 in gynaecological surgery
• 22 in neurosurgery,
• 26 in abdominal surgery,
• 4560 in orthopaedic surgery.

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• Agency for health care research and quality have
  issued report stating that
• Prophylaxis for venous thromboembolism is
  single most important measure for ensuring
  patient safety in hospitalized patients

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Patients at risk for VTE

• Surgery major surgery abdominal ,
  gynecologic,urologic, orthopedic, neurosurgery,
  cancer related surgery
• Trauma multisystem trauma, spinal cord injury,
  spinal , of hip and pelvis
• Malignancy any malignanacy, risk higher
  during chemo radiotherapy
• Acute medical illness stroke, acute MI, heart
  failure,neuromuscular weakness syndrome(GBS)

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Patients at risk for VTE

• Patient specific risk factor H/o VTE, Obesity,
  increasing age gt 40yr, hypercoagulable state(
  estrogen therapy)
• ICU related factors prolonged mechanical
  ventilation, neuromuscular paralysis(drug
  induced), CVC, severe sepsis, consumptive
  coagulopathy, HIT

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Risk assessment model (RAM) from the ACCP

• Low risk
• Uncomplicated minor
• surgery in patients lt40 yr
• with no clinical risk factors
• Minor surgery performed under local anesthesia
  or spinal anesthesia last lt 30 min

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Risk assessment model (RAM) from the ACCP

• Moderate risk factor
• Major and minor surgery in
• pt. 4060 yr with no
• clinical risk factors
• Major surgery in pt.
• lt40 yr with no additional
• risk factors
• Minor surgery in pt.
• with risk factors
• Major surgery performed under GA and last gt 30
  min
• Other risk factor cancer , obesity, h/o VTE,
  estrogen t/t , hypercoagulable state

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Risk assessment model (RAM) from the ACCP

• High risk
• Major surgery in patients
• gt40 yr who have additional
• risk factors
• Major surgery performed under GA and last gt 30
  min
• Other risk factor cancer , obesity, h/o VTE,
  estrogen t/t, hypercoagulable state

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Risk assessment model (RAM) from the ACCP

• Very high risk
• Major surgery in pt.
• gt40 yr plus previous VTE or
• malignant disease or
• hypercoagulable state
• Elective major orthopaedic
• surgery or hip or
• stroke or spinal cord injury
• or multiple trauma

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THROMBOPROPHYLAXIS FOR GENERAL SURGERY
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Prophylaxis regimens

• LDUH1 - Unfractionated heparin 5000 u s.c every
  12 hr
• LDUH2 - Unfractionated heparin 5000 u s.c every
  8 hr
• LMWH1Enoxaparin 40 mg s.c O.D or Dalteparin 2500
  u s.c O.D
• LMWH2 Enoxaparin 30 mg s.c every 12 hr or
  Dalteparin 5000 u s.c O.D
• Mechanical aid Graded compression stockings or
  intermittent pneumatic compression

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Thrombprophylaxis for hip knee Sx.

• Procedures Elective hip knee arthroplasty,
  hip surgery
• Drug regimen Use any one of following
• LMWHEnoxaparin 30 mg s.c every12hr.Give 1st dose
  12-24hr before Sx. Or 6hr after Sx.
• Fondaparinaux 2.5mg s.c O.D .First dose 6-8hr
  after Sx.
• Adjusted dose warfarin to achieve INR of 2-3.
  Give first dose the evening before Sx.

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Thrombprophylaxis for hip knee Sx.

• Duration of thromboprophylaxis
• For elective hip knee surgery, prophylaxis
  should continue for 10 days after surgery
• B. For hip surgery , prophylaxis should
  continue for 28 to 35 days after surgery

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• Thromboprophylaxis for other conditions

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Prophylaxis regimens

• LDUH1 - Unfractionated heparin 5000 u s.c every
  12 hr
• LDUH2 - Unfractionated heparin 5000 u s.c every
  8 hr
• LMWH1Enoxaparin 40 mg s.c O.D or Dalteparin 2500
  u s.c O.D
• LMWH2 Enoxaparin 30 mg s.c every 12 hr or
  Dalteparin 5000 u s.c O.D
• Leg compression methods Graded compression
  stockings(GCS) or intermittent pneumatic
  compression(IPC)

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Methods of thromboprophylaxis

• Mechanical - External leg compression
• Graded compression stockings
• Intermittent pneumatic compression
• Pharmacologic
• Low dose unfractionated heparin
• Low molecular weight heparin
• Adjusted dose warfarin
• Fondaparinaux

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Graded compression stockings

• Thromboembolic deterrent (TED stockings)
• Create 18 mm Hg external pressure at ankles 8
  mm Hg in thigh
• Resulting 10 mm Hg pressure gradient driving
  force for venous outflow from legs
• Shown to reduce VTE when used alone for abdominal
  neurosurgery
• However considered least effective method not
  used alone for moderate high risk of VTE.

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Intermittent pneumatic compression

• Inflatable bladders that are wrapped around lower
  leg
• Inflated create 35 mmHg external compression at
  ankles 20 mmHg at thighs
• Create pumping action by inflating deflating at
  regular interval- augments venous outflow
• Used after intracranial Sx trauma victims who
  are at risk of bleeding

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Low dose unfractionated heparin

• Rationale for low dose heparin
• Heparin indirect acting drug
• Must bind to cofactor anti-thrombinIII(AT) to
  produce effect
• Heparin-AT complex inactivates factors
  IIa(thrombin), IXa, Xa, Xia XIIa
• Inactivation of IIa is sensitive Rn occur at
  heparin doses far below those needed for
  inactivation of other coagulation factors
• Small doses of heparin can inhibit thrombus
  formation without producing full anticoagulation

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Low dose unfractionated heparin

• Dosing regimen 5000 u b.d or t.d.s daily
• More frequent dosing (t.d.s) recommended for
  higher risk condition
• Surgical prophylaxis 1st dose 2hr before Sx.
• Postoperative prophylaxis continued for 7-10 days
  or untill pt. fully ambulating
• Effective thromboprophylaxis for high risk
  medical cond. most non-orthopedic surgical
  prophylaxis

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Low molecular weight heparin

• More potent more uniform anticoagulant activity
  than UFH.
• Advantage Less frequent dosing,lower risk of
  bleeding HIT
• No need for routine anticoagulant monitoring with
  full anticoagulant dosing
• Disadvantage 10 times more costly (per day)
  than UFH
• More effective than UFH for orthopedic procedures
  involving knee hip, major trauma including
  spinal cord injury

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Low molecular weight heparin

• Dose Enoxaparin O.D. 40 mg for moderate risk
  cond. B.D. 30 mg for high risk cond.
• Dalteparin O.D. dose 2500 U for moderate risk
  cond. 5000 U for high risk cond.
• Timing Non orthopedic Sx. 2 hr before Sx
• Orthopedic Sx. 6 hr after Sx
• Excreted primarily by kidney.
• Pt. in renal failureEnoxaparin dose reduced to
  40 mg o.d for high risk cond.
• No dose adjustment for Dalteparin

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Adjusted dose warfarin

• Vitamin K antagonist prevents carboxylation
  activation of coagulation factors II, VII, IX,
  and X
• Advantage
• Preop dose not increase bleeding tendency during
  Sx d/t delayed onset
• Can be continued after discharge if prolonged
  prophylaxis
• Disadv.
• Multiple drug interactions
• Monitoring lab test
• Difficulty adjusting doses d/t delayed onset

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Adjusted dose warfarin

• Dosing regimen
• Initial dose 10mg P.O. evening before Sx
• F/b 2.5 mg daily starting the evening after Sx.
• Dose adjusted keep INR 2-3

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Fondaparinux

• Synthetic anticoagulant, an anti-Xa
  pentasaccharide
• Predictable anticoagulant effect
• No lab. monitoring required.
• Prophylactic dose 2.5 mg O.D s.c. inj. given 6-8
  hr after Sx.
• Contraindication
• Severe renal impairment creatinine clearance lt
  30ml/hr.
• Wt. lt 50 kg marked increase in bleeding

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Natural course of thromboembolism

• DVT in lower extremity may arise in calf vein or
  in proximal veins
• Thrombous may extend proximally to iliac veins
  IVC
• Incidence of thrombosis in upper extremity
  increasing d/t widespread use of central venous
  catheter
• DVT may occur in deep pelvic vein or renal vein
• Can be thrombous formation in right side of heart
  d/t atrial fibrillation

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• Most clinically important fatal pulmonary
  embolism occurs from proximal than distal DVT in
  leg
• PE occur in 50 of pt. with proximal DVT, while
  asymptomatic thrombosis of leg vein is observed
  in 70 pt with PE
• On early ambulation, thrombus in deep veins may
  resolve completely

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• Post-thrombotic syndrome may develop in 25 of
  patients, 2yrs after initial diagnosis and proper
  t/t of DVT
• Inadequate t/t of DVT result in 20-30 risk of
  recurrent VTE collaterals develop parallel to
  thrombosed segment of vein

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Diagnostic approach to thromboembolism

• The Clinical evaluation
• Clinical presentation of acute pulmonary embolism
  is nonspecific
• No clinical or lab findings that will confirm
  or exclude diagnosis of pulmonary embolism

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Clinical lab findings in pt. with suspected
pulmonary thromboembolism

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Plasma d- dimer levels

• Quantitative plasma D-dimer ELISA rises - DVT or
  PE because of plasmin's breakdown of fibrin.
• Elevation of D-dimer indicates endogenous
  although often clinically ineffective
  thrombolysis.
• Sensitivity gt80 for DVT gt95 for PE.
• D-dimer is less sensitive for DVT than PE because
  DVT thrombus size is smaller.
• D-dimer is a useful "rule out" test.

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Plasma d- dimer levels

• It is normal (lt500 ng/mL) in more than 95 of
  patients without PE.
• In patients with low clinical suspicion of DVT,
  it is normal in more than 90 without DVT.
• D-dimer assay is not specific.
• Levels increase in patients with myocardial
  infarction, pneumonia, sepsis, cancer,
  postoperative state, and second or third
  trimester of pregnancy.

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Spiral CT scan

• Computed tomography (CT) of the chest with
  intravenous contrast is the principal imaging
  test for diagnosis of PE
• Pt. must be able to breath hold for 30sec
• Best suited for detecting clots in main pulmonary
  artery
• When imaging is continued below the chest to the
  knee, pelvic and proximal leg DVT can also be
  diagnosed by CT scanning.
• Sensitivty 93 specificity 97

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Radionuclide lung scan

• 2nd-line diagnostic test for PE.
• Used for patients who cannot tolerate i.v.
  contrast
• Small particulate aggregates of albumin labeled
  with a gamma-emitting radionuclide are injected
  i.v are trapped in the pulmonary capillary
  bed.
• Perfusion scan defect indicates absent or
  decreased blood flow, possibly d/t PE.
• High probability scan two or more segmental
  perfusion defects in presence of N ventilation.
• Diagnosis of PE is very unlikely in pt. with N
  and near-N scans but is about 90 certain in
  patients with high-probability scans.

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Pulmonary angiography

• Most accurate method for detecting pulmonary
  emboli.
• Invasive catheter-based diagnostic testing
  reserved for patients with technically
  unsatisfactory chest CTs.
• Definitive diagnosis of PE - intraluminal filling
  defect in more than one projection.
• Secondary signs of PE include abrupt occlusion
  ("cut-off") of vessels, segmental oligemia or
  avascularity, prolonged arterial phase with slow
  filling, or tortuous, tapering peripheral vessels

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ALGORITHM FOR DIAGNOSTIC IMAGING
SUSPECT DVT OR PE
ASSESS CLINICAL LIKELIHOOD
DVT
PE
NOT LOW
LOW
NOT HIGH
HIGH
D - DIMER
D-DIMER
NORMAL
HIGH
HIGH
NORMAL
IMAGING TEST NEEDED
NO DVT
NO PE
IMAGING TEST NEEDED
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CLINICAL DECISION RULES

• LOW CLINICAL LIKELIHOOD OF DVT IF THE POINT SCORE
  IS ZERO OR LESS

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CLINICAL DECISION RULES

• HIGH CLINICAL LIKELIHOOD OF PE IF POINT SCORE
  EXCEEDS 4

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ALGORITHM FOR DVT DIAGNOSIS
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Color duplex scan of DVT
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ALGORITHM FOR PE DIAGNOSIS
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Antithrombotic therapy

• Anticoagulation
• Initial t/t of thromboembolism that is not life
  threatening is anticoagulation with heparin
• Standard t/t of both DVT acute PE is UFH
  continuous i.v infusion using wt. based dosing

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Antithrombotic therapy

• UFH
• Target aPTT 23 times the upper limit of
  laboratory normal.
• Usually equivalent to aPTT of 6080 s.
• Nomograms based upon patient's wt. may assist in
  adjusting dose of heparin
• Give an initial bolus of 80 units/kg, f/b an
  initial infusion _at_18 units/kg/hr.
• Check aPTT 6 hr after infusion adjust heparin
  dose

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Antithrombotic therapy

• LMWH
• Therapeutic dose Enoxaparin 1mg/kg s.c inj.
  every 12hr
• Warfarin anticoagulation
• Pt. with reversible cause of VTE (major Sx.)
• Warfarin can be started on on first day of
  heparin therapy
• When INR 2-3 heparin can be discontinued
• Oral anticoagulation continued at least 3 months

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Thrombolytic therapy

• Reserved for life threatening cases of PE with
  hemodynamic instability
• Alteplase 0.6mg/kg over 15min
• Reteplase 10U i.v. bolus repeat in 30 min
• Contraindications intracranial disease, recent
  Sx., trauma.
• Overall major bleeding rate 10, including 13
  risk of intracranial hemorrhage.

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Inferior vena caval filters

• Mesh like filter device can be placed in IVC
• To trap thrombi that break loose from leg vein
  prevent them from trvelling to lungs
• Indications
• (1) active bleeding that precludes
  anticoagulation
• (2) recurrent venous thrombosis despite
  intensive anticoagulation.
• Inserted percutaneously through IJV or femoral
  vein are placed below renal vein if possible

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Neuraxial blockade in patients who have or will
receive anticoagulant prophylaxis (1) Neuraxial
anesthesia/analgesia should generally be avoided
in patients with known bleeding disorder (2)
Avoided in pt.whose preoperative hemostasis is
impaired by antithrombotic drugs
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• NSAIDs aspirin do not appear to
• increase risk of perispinal hematoma.
• Thienopyridine platelet inhibitors clopidogrel
  ticlopidine discontiue for 5 to 14 days
• Insertion of spinal needle or epidural catheter
  should be delayed at least 8 to 12 h after s.c.
  dose of heparin or a twice daily prophylactic
  dose of LMWH
• At least 18 h after O.D. LMWH injection

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(3) Anticoagulant prophylaxis delayed if
hemorrhagic aspirate (ie, a bloody tap)
encountered during initial spinal needle
placement. (4) Removal of an epidural catheter
should be done when the anticoagulant effect
is at a minimum (usually just before the next
scheduled s.c inj.). (5) Anticoagulant
prophylaxis should be delayed for at least 2 h
after spinal needle or epidural catheter
removal.
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• (6) If warfarin is used - continuous
• epidural analgesia not be used for longer than 1
  or 2 days because of unpredictable anticoagulant
  effect
• If prophylaxis with a VKA is
• used at the same time as epidural analgesia, INR
  should be 1.5 at time of catheter removal.

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• (7)Postoperative prophylaxis with fondaparinux -
  safe in pt. who have received a spinal anesthetic
• No safety data about its use along with
  postoperative continuous epidural analgesia.
• Long half-life of fondaparinux renal
• mode of excretion raise concerns about potential
  for
• accumulation ,in elderly d/t associated
  impairment of renal function.

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• With concurrent use of epidural analgesia
  anticoagulant prophylaxis, all patients should be
  monitored for s/s of cord compression.
• Progression of lower extremity numbness or
  weakness, bowel or bladder dysfunction, new
  onset of back pain.
• If spinal hematoma is suspected, diagnostic
  imaging and definitive surgical therapy performed
  rapidly to reduce the risk of permanent paresis.

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• THANK YOU

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