Download Prothrombin complex concentrate Octaplex

Prothrombin complex concentrate
Octaplex
Maude Latulippe, CCFP-EM res
Grand Rounds, FMC
CASE
• 73 year old male
• Hx CVA in 2007 and A fib on Coumadin
• Brought in by EMS for right sided
weakness and aphasia.
• Pt unable to walk
• Pt speaks limited English and follows a
few commands. No family is present.
On exam:
• Vitals 37.2, 100, 16, 167/98, 98% RA
• Glucometer 6.8
• Eyes open spontaneously. He has a right
lower face, arm and leg hemiparesis. He
is agitated.
• EKG: a fib
• Remainder of physical exam is noncontributory.
PMHX:
• Ischemic CVA in 2007
secondary to A fib and
subtherapeutic INR. Was left
MCA symptomatology
• A fib
• CHF
• Remote MI
• HTN
• PVD
• Chronic venous insufficiency
• Dyslipidemia
Meds:
• Warfarin
• Lipitor
• Micardis
• Ramipril
• Lasix
Post CT the patient deteriorates: GCS drops
to 7 (E2 M4 V1)
Breathing becomes more shallow and
appears less effective.
Eyes deviate to the left.
CBC, lytes, creat unremarkable
INR 3.6
PTT N
Management:
• Should vitamin K be given?
• How long does FFP take to work?
• What are the other disadvantages of FFP?
• What new blood product is the best
treatment for this patient?
• What are the other indications for
Octaplex- prothrombin complex
concentrate?
Objectives
• What is Prothrombin Complex
Concentrate (PCC)?
• Potential risk
• Advantages: PCC vs Vit K
PCC vs FFP
• How to use it? Indications/Protocol
PROTHROMBIN COMPLEX CONCENTRATE
• Contains FII, (FVII), FIX, FX, and
anticoagulant proteins C, S and
heparin
• Low volume (average 40cc)
• Administered rapidly, quick
onset of action
• No need for matching blood
group
• Room temperature
• Prepared using viral inactivation
method
• 1150$ per dose
Octaplex: Contains FII, FVII, FIX, FX in the ratio of approx. 1:1:1:1
Role of prothrombin complex
concentrates in reversing
warfarin anticoagulation: A
review of the literature, Cindy A.
Leissinger, Am. J. Hematol.
83:137–143, 2008
• Review of 14 studies
involving urgent warfarin
reversal with PCCs
• 460 patients
• 7 thrombotic complications =
1.5%
• … in patient with a pre prothrombotic co-morbidity
Journal of Thrombosis and Haemostasis, 2008
Single-arm prospective study was from Oct 05 to Nov 06 at 15
centers in Austria, Germany, Hungary, Israel, Lithuania, the
Netherlands, Poland, andSwitzerland.
43 patients with INR > 2 :
26 requiring interventional procedures
17 acute bleeding
Method:
• Vit K given prior to PCC infusion (88% pt)
• Dose Beriplex by INR INR Dose IU/kg
2-3.9
4-6
>6
25
35
50
• Concomitant tx with blood, plasma hold
for 30 min
Primary end point: - INR at 30 min
40/43 INR<1.3
3/43 INR=1.4
Plasma levels of coagulation factors and clotting inhibitors
following administration of Beriplex® P/N. F, factor.
Adverse events
• Adverse events in 25 pt (58%)
• Serious : 6 patients
– 3 died
1 death possibly related to treatment
• All other serious/non-serious AE not
related to treatment
New generation PCC
Thromboembolism risk
Better balance pro/anticoag
factor
No active phospholipid
No activated factor (FVIIa, FIXa)
Often only 1 dose required
Viral transmission
4 cases Parvovirus B19
seroconversions
Allergic reaction
Treatment options for reversal of oral
anticoagulants
Vitamin K
Application of vitamin K:
oral:
slow decrease of INR, start within 12-24 h
i.v. :
slow decrease of INR, start within 6-8 h
FIX and FX takes longer
Warfarin resistance for 1 week
Studies comparing PCC with Vit K
Treatment, time and INR
Fresh frozen plasma (FFP)
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15 ml/kg – 1050 ml in 70 kg patient
30-45 min from demand to start infusion
Blood group specific
Thawed
1-3h for reversal
Longer time to infuse
TRALI, infection, allergic reaction
200$/unit
Studies comparing PCC and FFP
Hematoma Growth and Outcome in Treated
Neurocritical Care Patients With Intracerebral
Hemorrhage Related to Oral Anticoagulant Therapy
Comparison of Acute Treatment Strategies Using
Vitamin K, Fresh Frozen Plasma, and Prothrombin
Complex Concentrates. Huttner Stroke 2006
• Retrospective review 55 pts ICH
-Group 1 (31pts): PCC +- FFP +- VitK
-Group 2 (18pts): FFP +- VitK
-Group 3 (6pts) VitK
• Outcomes
-Reversal of INR
-Hematoma growth (CT or MRI>33%)
-Neurological outcome (1 year)
• INR reversal (<2h)
-84% vs 39% vs 0% (p<0.01)
• Frequency of hematoma growth
-19.3% vs 33.3% vs 50% (p<0.01)
• Extent of hematoma growth
-44% vs 54% vs 59% (NS)
• Incidence of growth PCC vs No PCC
-19.3% vs 37.5% (p<0.01)
• No difference in outcome
PCC vs FFP
Favouring PCC
Rapid
No thawing
No blood group testing and matching
No volume limitation
fast application
Highly predictable effect (Antagonism of OAC)
No acute lung injury (TRALI)
Is INR a good test?
• Sensitive to FII, FVII and X
(but not FIX)
• Thromboelastography a better test?
Profile of clot formation in whole blood
Guidelines controversies
Indications for use (AHR)
1) For Warfarin reversal only in cases of
Urgent surgical procedure required
or
Massive bleeding – CNS, GI
2) INR >1.5
CONTRAINDICATION:
A. History HIT
Not recommended for*
A. Elective reversal of OAT pre-invasive procedure
B. Tx of elevated INRs without bleed or need for surgical
intervention
C. Massive transfusion
D. Coagulopathy associated with liver dysfonction
E. Recent Hx thrombosis, MI, recent ischemic stroke or
DIC
Special population: Pregnant/lactating women, pediatric,
congenital factor II and X deficient patients
*Evaluation case-by-case basis possible with hematologist/transfusion
medicine physician on call
PCC Dosage (Regional guidelines):
(less than the manufacturer’s recommended dose)
40mL (1000IU Factor IX activity) and Vit K 10mg IV
(Higher dose may be needed in extremes of INR or weight)
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Max 120mL (3000 IU)
Administration:
Initial rate 1mL/min x 10 min
max rate 3 mL/min
F-U: PT/INR 15 min post dose
Availability
• Octaplex available at FMC, PLC and RGH
• Any physicians who follow the protocol
can order Octaplex.
• An Octaplex request form must be
completed and faxed to the transfusion
Medicine department.
• Octaplex available very rapidly
Progress of case:
• FFP is ordered. 10mg IV Vitamin K given.
• Transfusion medicine is called to release
Octaplex from the blood bank.
• Octaplex 40cc (2 vials) given
• INR is reversed from 3.8 to 1.3 within 15
minutes of administration of Octaplex.
• The patient does not appear to worsen
clinically and does not require intubation.
• He is admitted to the Stroke Team. A CT
scan the next day unfortunately shows
significant progression of the bleed. The
patient has very poor neurological
function. Goals of care are changed to
comfort measures and he dies on the 10th
day after admission.
Take home point
• Octaplex is a Prothrombin Complex
Concentrate available in Calgary through
blood bank
• Contains FII, FVII, FIX, FX, protein C, protein S and
heparin
• Use if INR>1.5 + Massive bleeding (GI/ICH)
or Urgent surgical procedure needed
• C-I: HIT
• Give 2 vials (40cc) + vit K 10 mg IV
• Should be effective in less then 30 min, recheck INR
• Very sick patients with poor outcomes,
mortality/morbidity benefit still unproven
Special thanks
• Thanks to Dr Carey, Dr Dorrington, Dr
Shelagh Coutts (neuro) and Dr Rad
(hemato)
• Thanks to Carolyn Jursa, Octapharma
representant and to the department of
blood product FMC
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Prothrombin complex concentrate (Beriplex P/N) in severe bleeding:
experience in a large tertiary hospital, David Bruce,Tim JC Nokes,
Department of Haematology, Derriford Hospital, UK, critical care,2008
Prothrombin complex concentrate (Beriplex P/N) for emergency
anticoagulation reversal: a prospective multinational clinical trial.,
PABINGER, B. BRENNER J, Thromb Haemost 2008,
Warfarin-reversal: results of a phase III study with pasteurised, nanofiltrated
prothrombin complex concentrate, Ingrid Pabinger-Fasching , Medical
University of Vienna, Austria
Role of prothrombin complex concentrates in reversing warfarin
anticoagulation: A review of the literature, Cindy A. Leissinger, Philip M.
Blatt, American Journal of Hematology, 2008
Current Practices and Unresolved Questions Intracerebral Hemorrhage
Associated With Oral Anticoagulant Therapy, Steiner, Stroke 2006
Hematoma Growth and Outcome in Treated Neurocritical Care Patients
With Intracerebral Hemorrhage Related to Oral Anticoagulant Therapy
Comparison of Acute Treatment Strategies Using Vitamin K, Fresh Frozen
Plasma, and Prothrombin Complex Concentrates, Huttner, Stroke 2006
The use of PCC in Intensive Care Medicine, symposium Oct 2009, UK
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