medical device class III

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(No Transcript)
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Product Description

• FlowLine Bipore vascular graft

• heparin coating of inner surface

• medical device class III

• wall thickness 0,4 mm (thin wall)
  0,7 mm (standard wall)
  length 100 - 1000 mm diameter
  5 - 10 mm

• helical PTFE-monofilament reinforcement

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Product Description

• guidelineJOTEC FlowLine Bipore Heparin Xmm TW
• coating not visible
• shelf life 2 years
• no resterilization
• nomenclature i.e. 15TW6006S

S fully reinforced N no reinforcement
length
diameter
FlowLine Bipore Heparin
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Product Description

• additional label FlowLine Bipore Heparin

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Indications

• Same indications as FlowLine Bipore
• primarily in the periperal vascular region
• femoralpopliteal
• axillofemoral
• iliacoiliacal
• tibial and peroneal arteria
• arteriovenous shunt prothesis in hemodialysis

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Contraindications

• same contraindications as FlowLine Bipore
• patients with hypersensitivity to heparin
• HIT Type II (heparin-induced
  thrombocytopenia)
• immunologic disease
• activation of platelets in presence of heparin
• 0,5 - 3 of patients after dosage of 20.000 IU/d
• occurence within 20 days
• decrease of platelets lt 50
• thrombosis and bleeding

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Thrombocytopenia

• lower incidence of HIT Type II with porcine
  heparin than with bovine heparin (0.4 vs 1.6)
• dependent of applied heparin dose

Warketing T., Kelton J., Prog Hemost Thromb 10,
1-34, 1991
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Thrombocytopenia

• Coating of FlowLine Bipore Heparin
• heparin from porcine intestinal mucosa
• release of at most 20 IU in the case of largest
  graft
• no complications may be expected!

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Heparin in General

• physiological coagulation inhibitor
• liver, lung and intestinal mucosa
• physiological blood concentration 100 µg/l
• enzymatic degradation by Heparinase
• half-life 90 120 min
• partially excretion by urine

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Functional Principle

• binding of Antithrombin III in the blood plasma
  inhibition of coagulation
• imitation of the antithrombotic effect of
  heparansulfateas in the case of the natural
  endothelium
• creation of a blood friendly surface by binding
  of selected plasma proteins

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Established Heparin Coatings
Name Producer Market entry Bonding Application
Carmeda BioActive Surface Medtronic 1985 covalent ECC, ventricular assist devices, central venous catheter, coronary stent, ePTFE vascular graft (Gore)
Duraflo II Baxter 1988 ionic ECC
Bioline Coating Jostra AG 1992 covalent with ionic interaction ECC, centrifugal pump, catheter, canules, tubes
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Heparin Coating of Vascular Grafts

• InterVascular
• InterGard Heparin

• W.L. Gore Associates
• GORE-TEX PROPATEN Vascular Graft

• JOTEC
• FlowLine Bipore Heparin

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Product Comparison
Product name Material Heparin Bonding Registration
InterGardTM Heparin Polyester Collagen porcine / high molecular ionic 1991
GORE-TEX Propaten ePTFE porcine / low molecular covalent 2002
FlowLine Bipore Heparin ePTFE porcine /high molecular covalent with ionic interaction 2003
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Structural Comparison
InterGard Heparin
GORE-TEX PROPATEN
ePTFE
Polyester
Collagen
Heparin Adhesive agent
Adhesive agent
Activated surface
Heparin
FlowLine Bipore Heparin
Heparin
Adhesive agent
ePTFE
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FlowLine Bipore Heparin Coating
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InterGard Heparin Coating

• ionic binding of high molecular heparin to
  polyester
• TDMAC (Tridodecyl-methyl-ammoniumchloride) as
  adhesive agent
• impregnation of heparinized polyester graft with
  collagen

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InterGard Heparin
Just a fractional amount of heparin in contact
with blood after implantation!
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InterGard Heparin

• in vitro stability of heparin coating over 4
  weeks with minimal loss after 7 days
• prospektive randomized clinical trial in
  comparison to uncoated ePTFE vascular graft
  (Devine et al.J Vasc Surg 2001)
• lower amputation rate (6 vs 17)
• significantly higher patency rates

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InterGard Heparin Randomized Clinical Trial
Product brochure InterGard Heparin P/N 7366/2
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GORE-TEX PROPATEN Vascular Graft Coating

• heparin coating of ePTFE vascular grafts
• surface activation
• application of adhesive agent
• covalent binding of low molecular heparin by
  end-point attachment
• interaction of active heparin sequences with
  circulating blood

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GORE-TEX PROPATEN Vascular Graft

• stability proven in vitro marginal heparin
  release within 24 h
• improved patency rates after 6 months ( Fig.
  1)
• Test animal dog
• Implantation site Arteria carotis shunt model
• Ø 3mm, length no statement
• no thrombus formation on bioactive surface after
  implantation for 2 h ( Fig. 2)

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FlowLine Bipore Heparin Coating

• alternating coating consisting of adhesive agent
  and high molecular heparin high
  heparin loading to the inner surface!
• synthetic protein as adhesive agent avoidance
  of toxic substances!
• covalent cross linking by EDC (carbodiimide)
  avoidance of toxic substances!
• covalent bonding and ionic interactions
  bioactive sequences freely accessible! stable
  bonding of heparin!

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FlowLine Bipore Heparin Coating

• no effect on the graft handling
• implantation technique
• anticoagulation
• no modification of mechanical features of ePTFE
  graft

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Dynamic Blood Test Using a Chandler Loop Model
H.P. Wendel Clinical Research Laboratory, Dept.
of Thoracic and Cardiovascular Surgery,
University of Tübingen
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Dynamic Blood Test Using a Chandler Loop Model
Platelets x103/µl
C Control P ePTFE graft H FlowLine Bipore
Heparin
C P H C P H C P H
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Dynamic Blood Test Using a Chandler Loop Model
ePTFE graft after 2 hours of blood contact
FlowLine Bipore Heparin after 2 hours of blood
contact
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Comparison of Product Range JOTEC vs GORE-TEX
JOTEC Thin Wall, w/o reinforcement JOTEC Thin Wall, w/o reinforcement JOTEC Thin Wall, w/o reinforcement Gore Thin Wall, w/o reinforcement
Length cm Ø mm Catalogue-No.
40 5 15TW4005N not available
50 678 15TW5006N15TW5007N15TW5008N 6not available8
80 678 15TW8006N15TW8007N15TW8008N 6not available8
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Comparison of Product Range JOTEC vs GORE-TEX
JOTEC Thin Wall, reinforced JOTEC Thin Wall, reinforced JOTEC Thin Wall, reinforced Gore Thin Wall, reinforced
Length cm Ø mm Catalogue-No.
40 5 15TW4005S not available
50 678 15TW5006S15TW5007S15TW5008S not availablenot availablenot available
70 5 15TW7005S not available6
80 678 15TW8006S15TW8007S15TW8008S 6not available8
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JOTEC Product Range
Thin Wall Thin Wall Thin Wall Thin Wall Standard Wall Standard Wall Standard Wall Standard Wall
w/oreinforcement w/oreinforcement reinforced reinforced w/o reinforcement w/o reinforcement reinforced reinforced
L cm Ø mm L cm Ø mm L cm Ø mm L cm Ø mm
10 5 10 5 20 67
40 5 40 5 40 5 - -
50 678 50 678 50 678 50 678
70 5 70 5 70 5 - -
80 678 80 678 - - 80 678
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Product Advantages

• coating of inner surface
• no toxic substances
• stable covalent binding of heparin
• bioactive heparin sequences freely accessible
• high permanent hemocompatibility
• widest product spectrum

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GORE-TEX PROPATEN Vascular Graft
Product brochure GORE-TEX PROPATEN June 2002
Fig. 1