JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
medical device class III
FlowLine Bipore vascular graft
heparin coating of inner surface
wall thickness: 0,4 mm (thin wall) 0,7 mm (standard wall) length: 100 - 1000 mm diameter: 5 - 10 mm helical PTFE-monofilament reinforcement
Product Description
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
guideline:JOTEC FlowLine Bipore Heparin Xmm TW
coating not visible
shelf life: 2 years
no resterilization
nomenclature: i.e. 15TW6006S
length diameter
S: fully reinforced N: no reinforcement
FlowLine Bipore Heparin
Product Description
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
additional label FlowLine Bipore Heparin
Heparin
covalent bonded
Product Description
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
Same indications as FlowLine Bipore®
primarily in the periperal vascular region
- femoralpopliteal
- axillofemoral
- iliacoiliacal
- tibial and peroneal arteria
arteriovenous shunt prothesis in hemodialysis
Indications
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
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 < 50%
- thrombosis and bleeding
Contraindications
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
lower incidence of HIT Type II with porcine heparin than
with bovine heparin (0.4% vs 1.6%)
dependent of applied heparin dose
Number of patients Thrombocytopenia(<50 000 / µl)
Thrombocytopenia (<100 000 / µl)
Thrombotic Complications
Full-Dose Heparin(> 20.000 IU/d)
7/981 (0,7%) 26/1080 (2,4%) 4/1080 (0,4%)
Low-Dose Heparin(< 15.000 IU/d)
0/362 (0%) 1/362 (0,3%) no
Warketing T., Kelton J., Prog Hemost Thromb 10, 1-34, 1991
Thrombocytopenia
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
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!
Thrombocytopenia
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
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
Heparin in General
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
binding of Antithrombin III in the blood plasma
inhibition of coagulation
imitation of the antithrombotic effect of heparansulfate
as in the case of the natural endothelium
creation of a „blood friendly“ surface by binding of
selected plasma proteins
Functional Principle
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
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
Established Heparin Coatings
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
InterVascular
InterGard™ Heparin
W.L. Gore & Associates
GORE-TEX® PROPATEN Vascular Graft
JOTEC
FlowLine Bipore® Heparin
Heparin Coating of Vascular Grafts
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
Product name Material Heparin Bonding Registration
InterGardTM Heparin
Polyester
Collagenporcine /
high molecular ionic 1991
GORE-TEX® Propaten
ePTFEporcine /
low molecularcovalent 2002
FlowLine Bipore® Heparin
ePTFEporcine /
high molecular
covalent with ionic interaction
2003
Product Comparison
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
InterGard™ Heparin
Polyester Collagen Heparin + Adhesive agent
GORE-TEX® PROPATEN
ePTFE
HeparinAdhesive agent
Activated
surface
FlowLine Bipore® HeparinHeparin
Adhesive agent ePTFE
Structural Comparison
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
ePTFE
Adhesive agent
Heparin
Covalent bonding
+
–
FlowLine Bipore® Heparin – Coating
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
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
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinInterGard™ Heparin
Just a fractional amount of heparin in contact with blood after implantation!
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinInterGard™ 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
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinInterGard™ Heparin – Randomized Clinical Trial
Product brochure InterGard Heparin P/N: 7366/2
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinGORE-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
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinGORE-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)
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinFlowLine Bipore® Heparin – Coating
alternating coating consisting of adhesive agent and high molecular heparin high heparin loading to the inner surface!
synthetic protein as adhesive agentavoidance 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!
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
FlowLine Bipore® Heparin – Coating
no effect on the graft handling
• implantation technique
• anticoagulation
no modification of mechanical features of ePTFE graft
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
H.P. Wendel Clinical Research Laboratory, Dept. of Thoracic and Cardiovascular Surgery, University of Tübingen
Dynamic Blood Test Using a Chandler Loop Model
37 °C
ePTFE graftØ: 6 mm, l: 50 cm
blood: 18 mlheparin: 1,2 IU/mlcontact time: 2h
37 °C
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
Platelets [x103/µl]
C P H C P H C P H
C: ControlP: ePTFE graft
H: FlowLine Bipore®
Heparin
Dynamic Blood Test Using a Chandler Loop Model
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinDynamic Blood Test Using a Chandler Loop Model
ePTFE graft after 2 hours of blood contact
FlowLine Bipore® Heparin after 2 hours of blood contact
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinComparison of Product Range JOTEC vs GORE-TEX
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 available
8
80 678
15TW8006N15TW8007N15TW8008N
6not available
8
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinComparison of Product Range JOTEC vs GORE-TEX
JOTEC Thin Wall, reinforced Gore Thin Wall, reinforced
Length [cm] Ø [mm] Catalogue-No.
40 5 15TW4005S not available
50678
15TW5006S15TW5007S15TW5008S
not availablenot availablenot available
70 5 15TW7005Snot available
6
80678
15TW8006S15TW8007S15TW8008S
6not available
8
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
Thin Wall Standard Wall
w/oreinforcement reinforced w/o reinforcement reinforced
L [cm] Ø [mm] L [cm] Ø [mm] L [cm] Ø [mm] L [cm] Ø [mm]
10 5 10 5 2067
40 5 40 5 40 5 - -
50678
50 678
50678
50678
70 5 70 5 70 5 - -
80678
80678
- - 80678
JOTEC Product Range
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
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
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® HeparinGORE-TEX® PROPATEN Vascular Graft
Product brochure GORE-TEX PROPATEN June 2002
Fig. 1
JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net
FlowLine Bipore® Heparin
GORE-TEX® PROPATEN Vascular Graft
Product brochure GORE-TEX PROPATEN June 2002
Fig. 2