Recombinant Factor VIIA
Sridhar ,V.M.D.
Critical
Care,Anesthesiology
and Cardiology.
Introduction..
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Universal hemostatic agent.
Originally developed for treatment of
hemophiliac patients.
Those with inhibitory antibodies to Factor VIII
and Factor IX.
Normal Hemostasis
• First step in hemostasis is formation
of a platelet aggregate
• At the molecular level interaction of
coagulation factors takes place on the
surface of activated platelets
• The Tissue Factor–FVIIa complex is
the physiological activator of normal
hemostasis
Hemostasis
Subendothelial matrix
Nitric oxide
Endothelial cell
Coagulation Pathways
Intrinsic Pathway
Extrinsic Pathway
IX
Tissue Factor + VII
Contact
TF Pathway
TF-VIIa X
XI
Common Pathway
PL
XIIa HKa
Prothrombin
XIa
IXa
PL (Tenase)
VIIIa
PL
X
a Va
(Prothrombinase)
Protein C, Protein
S, Antithrombin III
XIII
Thrombin
Fibrinogen
Fibrin
(weak)
XIIIa
Fibrin
(strong)
Mechanism ..
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The first step in all coagulation –Formation of
Tissue Factor –Factor VIIa complex
formation.
This catalysis the coagulation cascade in
normal persons and as well as in bleeding
disorders.
Mechanism of Factor VIIa ..
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TF+VIIa ->Thrombin .
Which in turn activates platelets, and
activates Factor X to Factor Xa.
The activated platelets provide the template
for further Factor X activation.
General Instructions..
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Binding of rFVIIa occurs only to activated
platelets.
Action occurs only at the site of bleeding.
Effective doses 35 to 120mcg/kg.
Standard dose 90 mcg/kg.
Bolus infusion every 2 hrs.
Hemophiliac patients..
Treat with recom DNA Factor VIII and Factor
IX concentrates.
 Development of antibodies.
 Dose recommendation is 90 mcg/kg.
 Other options
a. Large doses of Factor VIII.
b. Prothrombin complex
c. Porcine Factor VIII.
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Platelet Disorders..
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Glanzmann Thrombasthenia.
Bernard- Soulier syndrome..
First correct with platelets, FFP and
Cryoprecipate.
Can use Desmopressin
Factor VIIa 50 to 100mcg/kg.
Liver Disorders..
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Coagulopathy in Liver Disorders..
Vit K dependent—FVII,C and S.
Treatment includes Vit K, FFP,
Desmopressin and platelets.
Dose 100mcg/kg.
Trauma and Surgery..
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Dose 60mcg/kg.
Used in intraoperative bleeding during liver
surgery and in pulmonary hemorrhage.
In Trauma
10 U PRBC
8 U PLTS
10 U Cryoprecipitate.
Then 100 mcg/kg ,repeat dose in 20 mns
Reversal of Anticoagulant Therapy..
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Can be used if Vit K not effective alone
Dose 20 and 90 mcg/kg.
Intracerebral Bleeding.
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Volume of bleeding ---direct correlation with
neurological outcomes.
Incorporation of Factor VII a reduces the rate
of hematoma formation.
Other Conditions..
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Type III Von willebrand disease.
Congenital factor VII def.
Factor XI and Factor IX def.
Extensive Burns.
Uremia.
Cardiac Surgery..
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Post operative bleeding is common.
In US 10 to 15%of all blood donated is used
by Cardiothoracic Surgery.
Has been used Prophylactically
Rescue Therapy.
Need of RCT.
Cost Factor.
Safety..
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Tissue Factor is in contact with plasma.
Tissue factor is up regulated on the surface
circulating monocytes (gram neg sepsis).
Tissue factor is expressed in the lipid core of
the plaque.
Do not use with activated protein C.
Use with caution when there is generalized
activation of the haemostatic mechanism.
Lab Tests in Trauma ..
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Repeat blood test after each 4 to 6 units
PRBC.
PT,APTT >1.5 X control 4 units FFP.
Fibrinogen <1g/l  10 units Cryoprecipitate.
Plt count <75k 4 units plts.
Consider Calcium chloride.
THE END