Transcript دکتر عشقی-بندآورنده های موضعی خون-هموفیلی

LOCAL HEMOSTATIC AGENTS :
INDICATIONS AND APPLICATION IN BLEEDING
EVENTS
Peyman Eshghi MD.
Prof. of Pediatric hematology&oncology
Mofid Children Hospital
PCHD-RC
SBMU
[email protected] ; [email protected]
SHIRAZ-1393
CASE1
• 1.5 Y OLD BOY
• GLANZMAN THROMBASTHENIA
• NOSE BLEED ,NON-STOP FOR
HOURS WITH PRESSURE AND
POSITION
• NO PREVIOUS Tx
HOW TO MANAGE
RANDOM DONOR PLATELET
URGENTLY
SINGLE DONOR PLATELET REQUEST
DESMOPRESIN
TRANSAMINE
ORAL
IV
LOCAL
rFVIIa
OTHER
CASE2
• 2 Y OLD BOY
• SEVER HA ;NO INH
• REFFERED FOR CIRCUCISION
HOW TO MANAGE
FVIII30-50 U/KG PRE-OP;THEN
20U/KG Q8H FOR 3 DAYS;AND Q12-24
H TO 7 DAYS
FVIII30-50 U/KG PRE-OP;THEN
 FG AND OD FACTOR REPLACEMENT+TA
FOR10 DAYS
GB-TISS AND OD FACTOR
REPLACEMENT+TA FOR 10 DAYS
FVIII30-50 U/KG PRE-OP;THEN
FG +FVIII20U/KGQ8-12 H X3 DAYS+TA
FOR10 DAYS
GB-TISS +FVIII20U/KGQ8-12 H X3
DAYS+TA FOR 10 DAYS
Characteristics of an Ideal hemostatic agents :
1. Rapid and effective in control/cessation of bleeding from large arterial
and venous vessel
2. Easy preparation and application :no requirement for mixing or preapplication by patients, wounded victim, buddy, or medic; light weight
and durable;
3. Absorbability and biocompatibility (so as not to trigger immune or
inflammatory responses)
4. Long shelf life in extreme environments;
5. Inexpensive
6. Safe to use with no risk of injury to tissues or transmission of infection;
Morikawa, T. Am J Surg. 2001;182(2 Suppl):S29-S35
HEMOSTATIC INTERVENTION
• Mechanical & physical & thermal methods:
compression;elevation; Tourniquets; Clamps; electrocautery,;etc
• Local & chemical agents:
Absorbable topical
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Oxidized Cellulose
Gelatin Foam
Microfibrillar Collagen
Chitosan based dressing
Medicinal plant extract blood stopper
Minerals
Fibrin Sealants
Synthetic Sealants
Systemic coagulation agents/Pharmacotherapy
antifibrinolytics(transamine;etc.)
Desmopresin
hormone therapy
Vit K
Blood products:plasma/platelets/Cryo./CFs
Tranexamic acid and bleeding
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Tranexamic Acid (TXA) is a synthetic derivative of
the amino acid lysine.
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It has a very high affinity for the lysine binding
sites of plasminogen.
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It blocks these sites and prevents binding of
plasmin to the fibrin surface, thus exerting its
antifibrinolytic effect.
Oxidized regenerated cellulose (ORC ) [1942/1946]
• Wood pulp (oxidized regenerated cellulose) :Cellulose is first dissolved and then
made into a continuous fiber.
• ORC has longer fibers and is more uniform than cotton Gauzes and does not fray
or lint
• ORC presents multiple mechanisms of action, including:
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physical and mechanical actions in tamponade;
swelling and gel formation;
conferring hemostasis by decreasing the pH and acting as a caustic
surface interactions with proteins, platelets, intrinsic and extrinsic pathway activation.
• Never use this soaked in thrombin. The latter, in fact, interferes with its natural
action.
• The greatest use has been for the control of oozing and mild bleeding from broad
surfaces,
Mechanism of action
ORC
• One major advantage of oxidized cellulose is its definite and
potent action against a wide variety of pathogenic organisms,
both in vivo and in vitro: methicillin-resistant Staphylococcus aureus (MRSA),
methicillin- resistant Staphylococcus epidermidis (MRSE), vancomycin- resistant Enterococcus (VRE),
penicillin-resistant Streptococcus pneumoniae (PRSP),
• Disadvantages: Cord compression, interferes with bone healing,
encapsulation of fluid, foreign body reactions
Claudio Schonauer et al. The use of local ur Spine J (2004) 13 (Suppl. 1) : S89–S96agents: bone wax, gelatin, collagen, oxidized cellulose E
Regenerated Oxidized Cellulose
Chitosan-based dressing
Chitosan is a biodegradable,nontoxic,complex carbohydrate derived from chitin(a naturally occuring
substance from zeolites): when the deacetylation of chitin is above 70% the generic name”
Chitosan” is applied
• In the form of an acid salt it has a mucoadhesive activity
• It has a positive charge and it attracts RBCs and Platelets which have negative charge.
• prove to be useful for patients with coagulopathies or those who are therapeutically
anticoagulated
• directly influenced platelets by themselves and this effect was enhanced in the presence of
plasma.
• Upon acetylation, the chitosan layer became a strong activator of the alternative pathway of the
complement system , and also accelerated thrombin generation
• The freeze-dried Dressing augments its sealing action
• Also offers an antibacterial barrier
• Mar. Drugs 2010, 8
CBD;continue
• It should be applied with pressure for 3 minutes and then
release ; can be left on the wound for 48 h ; easily removed by
saline without disturbing the clot
• It can be use even for high flow ,high pressure bleeding:
combat operations; hemodialysis;etc
• No complications have been reported
• > 1030000 dressings have been distributed in US army
Wedmore I, et al. J Trauma. 2006;60:655–658
• It is stiff and the proper size should be applied
• Its domestic product is available as powder
Mechanism of Action of ChitoHem
Hydrophobically modified chitosan
Clinical investigation (Angiography)
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Experience in Kerman and Mofid children hospital
(2008)
• 23 cases were enrolled:
• 9 cases of congenital bleeding disorders:
4 VWD; 4 GT;1 FVII def.
• 14 other disorders(ALL; ITP; Malignancies; Fanconi anemia)
• Bleeding stopped in <5 min. :14/14 nose bleedings;3/3 gum or dental
bleedings; 1/3 wound bleedings
• 6 cases had consumped CFCs:24 rFVIIa (1.2 mcg);16 Humate
• Persistent control in hemophilia cases
Comparative study of LHAs in congenital bleeders (MCCCH-20011-12)
CBD
ORC
The time required for stanching
epistaxis
Tranexamic acid
<10 min
Number
(Percent)
6 (20.7%)
>10 min
Number
(Percent)
23 (79.3%)
EpiCell tampon (ORC)
12 (41.4%)
17 (58.6%)
ChitoHem (Chitosan reinforced )
24 (80%)
6 (20%)
statistically significant differences( Fisher's Exact Test) between chitosan-based product and
tranexamic acid (P<0.0001), and between chitosan-based product and ORC (P=0.013) but
not between tranexamic acid and ORC (P=0.155)
Cyanoacrylate Glues
 Clear, Ready for Use Transparent Liquid which is Rapidly
polymerized even in wet environment
 Polymerization at low temperature (about 45°C)
 2 types:
 1/ for O p e n and E n d o s c o p i c surgeries (GLUBRAN2)
 2/for skin (GLUBRAN Tiss)
Produce a Thin elastic layer of high tensile strength Firmly adheres to tissue
Anti septic barrier film
 is eliminated by hydrolytic breakdown
 Thin elastic layer of high tensile strength
 Firmly adheres to tissue
 Conforms naturally to the anatomy of the tissue
 Waterproof (it is not impaired by blood or organic fluid)
 Anti septic barrier
Polymerization at low temperature
 No human or animal product (no risk of viral
transmission)
 No swelling
Application
•Apply drop by drop on purposed area.
•Approximately one drop/cm2 is sufficient.
•Polymerization starts1-2 seconds after use, and after 60-90 seconds
will be completed.
•In normal surgical procedures, the film is eliminated by hydrolytic
breakdown, a process which duration varies according to tissue type
and quantity of glue applied.
Instruction for use
Instruction for use
Instruction for use
Instruction for use
Instruction for use
Types of fibrin sealant
Commercial fibrin sealant:
• Prepared from pooled plasma
• Viral reduction methods
 Potential Risk of blood-borne infections
 Allergic reaction
 Cost
Standardized concentration
Blood Bank produced:
• Autologous plasma
• Homologous :Single donor plasma OR
Qurantine Retested Plasma(QRP)
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Reduce OR Eliminate this risk
Less hyper sensitivity
Less cost
Variable concenteration
Less Availability & feasibility
Composition
 Fibrinogen (preglue)
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Thrombin (glue activator)
XIII
Anti fibrinolytic agent
Fibronectin
- cell attachment factor
- migrating fibroblasts
Thrombospondin
Vitronectin
Collagen
vwf
Clinical characteristic
• dries flexible;
• Absorbs in 7-14 days
• Rapid hemostasis and adhesion
• No swelling of product
• mixing may be required; up to 5 min prep time. Also available premixed.
Spray or drip; can be delivered laparascopically
• Available freeze dried or frozen
• Not for injection into vessels.
Review of a few of Studies on Clinical Use of Fibrin Sealant in
Hemophilia
-O. B. SHITTU Circumcision in haemophiliacs: the Nigerian experience .Haemophilia (2001), 7, 532±53
-Kavakli K, Aledort LA. Circumcision and haemophilia: a perspective. Haemophilia 1998; 4: 1±3.
-Martinowitz U, Varon D, Jonas P et al. Circumcision in haemophilia: the use of ®brin glue for the local haemostasis. J Urol 1992; 148: 855±7.
-Martinowitz U, Schulman S. Fibrin sealant in surgery of patients with a hemorrhagic diathesis. Thromb Haemost 1995; 74(1):486-92.
-Avanogmacru, et al. Low cost locally prepared fibrin glue for clinical applications: reported of145 cases. Committee of Bangkok International Hemophilia Training Center.J Med
Assoc Thai 1999; 82 (Suppl 1):S49-56.
-Gazda H, Grabowska A. [Topical treatment of oral bleeding in children with clotting disturbances]. Wiad Lek 1993; 46(3-4):111-5.
-Rakocz M, Mazar A, Varon D, et al. Dental extractions in patients with bleeding disorders. The use of fibrin glue. Oral Surg Oral Med Oral Pathol 1993; 75(3):280-2.
-Kavakli K, Kurugol Z, Goksen D, Nisli G.Should hemophiliac patients becircumcised? Pediatr Hematol Oncol 2000;17(2):149-53.
-Avanogmacr;Lu A, et al.Safer circumcision inpatients with Hemophilia:the use of fibrin glue for local hemostasis. BJU Int. 1999 Jan;83(1):91-4
Industrial Fibrin Sealant
• the fibrinogen, and now also the thrombin concentrates, are made by industrial
fractionation of batches of hundreds or thousands of litres of Human plasma.
• Viral safety: careful selection, testing(ELISA,NAT,PCR), Viral inactivation (solventdetergent, pasteurization ,vapour-heat treatment, nanofiltration)
• The fibrinogen concentrate is more than 80g/l
• Thrombin concentrate is typically over 500UNIH/ml
• Antifibrinolytic:
1-aprotinin:bovine origin
2-Tranexamic acid :the risk of potentially fatal neurotoxicity when used in contact
with the central nervous system
• Several Mode of Application:
-dual-syringe system,
-Longer single or dual Teflon tubes are used for endoscopic delivery;
-spray(for hemostasis of larger bleeding surfaces); expandable foams, and spray
powders (may provide the person with hemophilia the ability to rapidly attain control
of traumatic hemorrhages prior to hospital treatment);
- alternative layers of collagen and fibrinogen freeze-dried together as a composite
are also available in some countries for use as a surgical dressing.
• Prohibitively expensive at around US$130 for a 1-ml kit.
T/FI in each ml=
500NIH/80mg
Several fibrin sealants are in commercial production throughout the world,:
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Beriplast P (Aventis Behring, Marburg, Germany),
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Bolheal (Fujisawa, Osaka,Japan),
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Hemaseel APR (Haemacure Corporation, Sarasota,
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FL, USA),
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Quixil (Omrix, Brussels, Belgium),
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Tisseel (Baxter Immuno, Vienna, Austria)
Blood Bank Fibrin Sealant
• single plasma donations (Autologous or Homologous)
• There is also industerial Autologous FSs
• fibrinogen concentration is typically close to 20mg/ml , So The strength of the fibrin clot, is less than that of
industrial fibrin sealants,
• Bovine thrombin: risk of
1-immunological reactions (formation of cross reactive anti-factor V or anti-thrombin antibodies)
2-transmission of bovine infectious agents (CJD,etc.)
3-sever allergic reactions
• Prepare thrombin from single human plasma donations (at a concentration close to 50 UNIH/ml):
higher purity & lack this severe side effect
• Fibrin clot formation typically takes 2 to 10 seconds
T/FI in each ml=
500NIH/80mg
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Several fibrin sealants are in commercial production throughout the world,:
Beriplast P (Aventis Behring, Marburg, Germany),
Bolheal (Fujisawa, Osaka,Japan),
Hemaseel APR (Haemacure Corporation, Sarasota,
FL, USA),
Quixil (Omrix, Brussels, Belgium),
Tisseel (Baxter Immuno, Vienna, Austria)
Suggested protocole for circumcision in
hemophiliacs:
• Continiuos infusion of Factors for 3 days (30% Factor level)
• Circumcision
• suturing +FS
• Systemic antifibrinolytics for 10 days
Matinovitz et al,Haemophilia(1998),4,443-448
CASE1
• 1.5 Y OLD BOY
• GLANZMAN THROMBASTHENIA
• NOSE BLEED ,NON-STOP FOR
HOURS WITH PRESSURE AND
POSITION
• NO PREVIOUS Tx
HOW TO MANAGE
RANDOM DONOR PLATELET
URGENTLY
SINGLE DONOR PLATELET REQUEST
DESMOPRESIN
TRANSAMINE
ORAL
IV
LOCAL
rFVIIa
OTHER: ORC;CBA
CASE2
• 2 Y OLD BOY
• SEVER HA ;NO INH
• REFFERED FOR CIRCUCISION
HOW TO MANAGE
FVIII30-50 U/KG PRE-OP;THEN
20U/KG Q8H FOR 3 DAYS;AND Q12-24
H TO 7 DAYS
FVIII30-50 U/KG PRE-OP;THEN
 FG AND OD FACTOR REPLACEMENT+TA
FOR10 DAYS
GB-TISS AND OD FACTOR
REPLACEMENT+TA FOR 10 DAYS
FVIII30-50 U/KG PRE-OP;THEN
FG +FVIII20U/KGQ8-12 H X3 DAYS+TA
FOR10 DAYS
GB-TISS +FVIII20U/KGQ8-12 H X3
DAYS+TA FOR 10 DAYS