2. Overview Introduction to Octapharma
Rationale for development of Octaplasma
Manufacturing of OctaplasmaTM
Safety and Efficacy of OctaplasmaTM in TTP
Why OctaplasmaTM?

3. Octapharma– Committed to Patient Care
Octapharma: one of the largest plasma product manufacturers
Commitment to coagulation disorders: >25 years
History of setting benchmarks for product and patient safety
First to apply SD-process
Patient in >80 countries treated with Octapharma products
Portfolio is divided into 3 areas:
Hematology (coagulation disorders)
Immunotherapy (immune disorders)
Intensive Care and Emergency Medicine

4. Our Commitment to Canada
Octaplex®: first PPC (prothrombin complex concentrate)
Wilate®: first double virally inactivated pd-VWF/FVIII concentrate
Octaplasma®: first SD-plasma
Octagam®: first liquid room temperature stable IVIG

5. 7. 2 million units of Octaplasma infused worldwide in ~2
7.2 million units of Octaplasma infused worldwide in ~2.4 million patients over two decades
Although plasma therapy saves lives and reduces morbidities in many clinical diseases and conditions, it is associated with certain risks.
Currently, the risk of transmission of infectious diseases through transfusion in Canada is minimal, because effective preventive strategies, including new laboratory tests, have been implemented. Nevertheless, many infectious agents, including viruses, bacteria, and parasites, can be transmitted through plasma transfusion.
Although transfusion transmitted infections have received the greatest attention, noninfectious adverse events remain the most common complications associated with transfusion. The majority of these noninfectious adverse events are immune mediated. They include: allergic reactions, anaphylactic reactions, TRAI, hemolysis etc.
Physiochemical reactions can also occur, specifically TACO and reactions due to various additives in the product.

6. OctaplasmaTM History Octaplasma was first approved in Germany in 1992
Has become the standard treatment for TTP/HUS patients throughout most of Europe and the UK
The clinical trial program comprised 1,385 patients
Production facilities are based in Vienna (Austria) and Stockholm (Sweden)

7. The Rational for Development of OctaplasmaTM
Reduce the risk of pathogen transmission
Transmission of human immunodeficiency virus (HIV)
Post-tranfusion hepatitis caused by
Hepatitis B / Hepatitis C virus
Meet the need for a cell free, standardized, high quality coagulation active plasma
To reduce adverse events
To improve the therapeutic accuracy of plasma treatment

8. Risks of Plasma Therapy
Fresh frozen plasma (FFP) transfusion plays a vital role in treatment of several specific clinical situations, however, FFP transfusion is not without complications
Pathogen transmissions and infections
Parasites
Bacteria
Viruses (especially HIV, HBV, and HCV)
Prions [e.g. variant Creutzfeldt-Jakob disease (vCJD)]
Immune-mediated transfusion reactions
Allergic reactions
Anaphylactoid and anaphylactic reactions
Transfusion-related acute lung injury (TRALI)
Haemolysis (anti-AB0s IgM and IgG, irregular antibodies)
Alloimmunisation (e.g. anti-D, anti-K, anti-HLA, anti-HNA)
Physicochemical reactions
Transfusion-associated circulatory overload (TACO)/fluid overload
Reactions due to additives (e.g. citrate toxicity)
Although plasma therapy saves lives and reduces morbidities in many clinical diseases and conditions, it is associated with certain risks.
Currently, the risk of transmission of infectious diseases through transfusion in Canada is minimal, because effective preventive strategies, including new laboratory tests, have been implemented. Nevertheless, many infectious agents, including viruses, bacteria, and parasites, can be transmitted through plasma transfusion.
Although transfusion transmitted infections have received the greatest attention, noninfectious adverse events remain the most common complications associated with transfusion. The majority of these noninfectious adverse events are immune mediated. They include: allergic reactions, anaphylactic reactions, TRAI, hemolysis etc.
Physiochemical reactions can also occur, specifically TACO and reactions due to various additives in the product.

9. OctaplasmaTM: Multiple Steps Ensures Safety
High
Donor
Plasma donation center
Manufacturing
Patient
Selection of plasma donors
Screening of donations (NAT tested: HIV, HBV, HCV)
Quality control measurements
Virus Inactivation/ Cell & Prion Removal
Screening of plasma pools (HIV, HBV, HCV)
Relative Risk
Product safety begins with plasma safety. Octapharma makes every effort to supply safe, optimal-quality products. Octapharma is always working to comply with the highest standards.
Precautions against viral transmission include multiple steps. Viral safety derives from three complementary approaches during manufacture, i.e. donor selection, testing of donations and plasma pools, and the introduction of viral inactivation and removal procedures in the course of manufacture, each of which requires strict adherence to good manufacturing practices.
In addition to the extremely rigorous donor selection process, all donations are qualified to ensure that plasma is accepted only from selected donors.
Qualified donation undergoes screening tests for infectious agents, for example nucleic acid testing (NAT) for HIV, HBV and HCV is done. Acceptable units are combined into minipools and a second round of NAT testing is performed.
During the manufacturing process, there are viral inactivation and removal steps to remove any potential contaminate.
Following this procedure, Octapharma ensures that the theoretical relative risk of transfusion-relevant infectious agents is reduced as much as possible at every step of the manufacturing process— from the time the plasma is received from the general population to the preparation of the final product.
Enveloped & Non-Enveloped Viruses
Low

10. Viruses Transmissible by Blood
Enveloped
HIV
HBV
Non-enveloped
Some viruses are enveloped, meaning that the capsid is coated with a lipid membrane known as the viral envelope The envelope may play a role in helping a virus survive and infect other cells. Viruses that lack envelopes (i.e., do not have nor need them) are termed non- enveloped. Non-enveloped viruses also constitute an important class of medically significant pathogens.
It is known that both enveloped and non-enveloped viruses can be transmitted via plasma.
Although non-enveloped viruses are not directly affected by SD treatment, the Octaplas manufacturing process has the capability to remove non-enveloped viruses during the removal of the SD reagents.
HAV
B19
2-3 log10 non-enveloped viruses can be removed during removal of SD reagents

11. Transfusion Related Lung Injury (TRALI)
No confirmed cases of TRALI with Octaplasma in 20 years
The incidence of TRALI has been reduced, but is still reported in Canada despite the introduction of male-only plasma
TRALI remains the leading cause of Transfusion related fatalities in North America which is approximately 30% 1,2
TRALI is significantly under diagnosed and consequently under reported due to the lack of awareness 3-5
3. Kleinman et al. Transfusion. 2004; 4. Kopko P.M. et al. JAMA. 2002; 5. Looney MR et al. CHEST. 2004

12. OctaplasmaTM - Efficacy in TTP
Scully et al. (2007)
12 episodes were performed using CPP only; 21 episodes exclusively used OctaplasmaTM.
No difference in the number of plasma exchange procedures between groups
17 CPP episodes had to be changed to OctaplasmaTM due to low age (n=1), severe allergic reactions to CPP (n=12) or due to refractory disease (n=4). This means that of the 29 episodes that started with CPP, as many as 12 (41%) had to be changed to Octaplasma® due to severe allergic reactions.
No significant thrombotic episodes, no detectable viral transmissions, no cases of TRALI
Scully et al., (2007) reviewed 50 acute TTP episodes to establish the efficacy and safety of cryosupernatant (CPP) and Octaplas®.
A total of 12 episodes (24%) were performed using CPP only and 21 (42%) episodes exclusively used Octaplas®.
In addition, 17 CPP episodes had to be changed to Octaplas® due to low age (n=1), severe allergic reactions to CPP (n=12) or due to refractory disease (n=4).
This means that of the 29 episodes that started with CPP, as many as 12 (41%) had to be changed to Octaplas® due to severe allergic reactions.
Allergic/urticarial and citrate reactions were more common with CPP than with Octaplas®.
It was reported that the number of citrate reactions and allergic (plasma) reactions were halved in those receiving only Octaplas® compared with CPP, the differences were both statistically significant.
The rate of allergic reactions here seems high for Octaplas® and it cannot be excluded that taking over the 12 episodes that experienced allergic reactions with CPP did cause a higher frequency for Octaplas® than what has been seen in other studies.
There was no documented viral transmission and no case of TRALI with Octaplas.
Scully et al., Vox Sang. 2007; 93(2);

13. Immune-mediated Reactions Caused by Plasmas+
Optimised integration
Cell removal & S/D treatment
Cell removal ÷
TRALI or +
Allergic rx. (urticaria)

14. Residual Blood Cells in Plasma
Fresh-frozen plasma
Cell and debris free - Removal of intracellular pathogens - Abolish cell-dependent adverse reactions
- Standardized bags
OctaplasmaTM

15. OctaplasmaTM demonstrates a low transfusion reaction rate
Serious Hazards of Transfusion Report (SHOT) 20101
Component
Febrile reactions, incidence per 100,000 units
Allergic or anaphylactic reactions, incidence per 100,000 units
Red cells
11.4
2.7
Platelets
10.2
18.4
Plasma
1.0
8.7
OctaplasmaTM
0.0
0.17
Ref 1 1.

16. OctaplasmaTM Tolerability - Finland
Rates of SAE: FFP vs. OctaplasmaTM in Finland in
Adverse events with FFP are common in large volume exchange procedures
Introduction of OctaplasmaTM in clinical use has decreased the rate of serious adverse events (SAE) by 84% (p=0.0005).
Authors concluded that OctaplasmaTM is a safe and well tolerated product1. 20
18.3
17.3
15.2
# of SAE’s/100,000
Units 10
Krusius et al., (2009) reported on the frequencies of adverse events from plasma transfusions in Finland over a 6 year period.
By the second half of 2007 Octaplas® had replaced FFP in the whole country.
Consistent with the documented Irish hemovigilance data, which experienced an 84% reduction in severe anaphalactic reactions (and documented experience in other countries), the Finnish Red Cross Blood Service reported that:
Introduction of Octaplas® in clinical use has decreased the rate of serious adverse reactions by 84%.
No TRALI reactions have been observed …. Based on these data, it can be concluded that Octaplas® is a safe and well‐tolerated product.
3.8
▲ SAE
Krusius et al.,, Sanguinis 2009;96 (Suppl. 1), 1–62.

17. OctaplasmaTM reduces both infectious and non-infectious risks of transfusions
The overall reduction in transfusion complications (-94%)1 for Octaplasma® compared to FFP is similar to published experience from Finland, -84%2 and Sweden, -85%3, Austria -94.6%
With no confirmed case of TRALI in 20 years and the significantly reduced risk for allergic reactions are major advantages that Octaplasma® has over FFP.
Expected transfusion complications were compared between Octaplas® and FFP.
Octaplas reduces not only infectious risk of transfusions but also the non-infectious risks. Compared to FFP, Octaplas reduces transfusion complications by 94% which is similar to published experience from Finland.
The abolished risk for TRALI and significantly reduced risk for and severity of allergic reactions are major advantages of that Octaplas® has over FFP.
Based on these data it can be concluded that Octaplas is a safe and well tolerated product.
1Svae et al, 2011; 2Krusius, 2009, 3Vaara & Nilsson 2010.
calculated risk, not actual

18. OctaplasmaTM Delivers
Virus-inactivated plasma for transfusion
Standardized levels of coagulation factors
Efficacy comparable to FP and CSP
Significant reduction of allergic reactions
Prevention of TRALI

19. OctaplasmaTM Currently Funded For:

20. OctaplasmaTM Request
Treating physician OR TM Medical Director need approval from local CBS medical director
Octaplasma sent from local CBS warehouse to hospital on patient specific bases
Form filled out, physician signed and faxed to CBS

21. Thank You

22. Manufacturing Process of OctaplasmaTM
Optimised integration of 630 to 1,520 single units of FFP
Fast thawing of the high quality FFP
PRE-VI
AREA
Cell and debris removal by filtration [1.0 µm]
S/D treatment [1% TNBP/ 1% Octoxynol-9, 30°C / hrs]
Liquid phase extraction of TNBP
POST-VI
AREA
Clear filtration [1.0 µm  0.45 µm]
Solid phase extraction of Octoxynol-9
Sterile filtration [0.45 µm µm]
STERILE AREA
Aseptic filling
Labelling and vacuum sealing
Freezing [-60°C] and storage [-30°C]
Full quality control and release

23. SD Treatment of OctaplasmaTM
Treatment with SD is widely used for ensuring the virus safety of plasma products.
SD mixtures disrupt the lipid membrane of enveloped viruses. Once disrupted, the virus can no longer bind to and infect cells.
SD is gentle to plasma proteins
SD treatment does not affect the final composition of OctaplasmaTM
Capacity to inactivate enveloped virus by the OctaplasmaTM SD treatment method
HIV
HBV
PRV
HSV-2
HCV
WNV
DHBV
VSV
≥ 7.2
≥ 6.0
≥ 6.3
≥ 5.0
≥ 5.8
≥7.3
≥ 7.5
Clearance factor of OctaplasmaTM (log 10)
Although enhancements in donor and blood screening have greatly reduced the risk of disease transmission through blood, transfusion-related infections and fatalities continue to occur, and emerging pathogens will continue to pose threats to the safety of the blood supply.
Several procedures for virus inactivation and removal have proven to be robust and to contribute substantially to blood product safety. Viral inactivation methods should be applied to all blood plasma-derived protein solutions.
SD mixtures disrupt the lipid membrane of enveloped viruses. Once disrupted, the virus can no longer bind to and infect cells. SD is a gentle process and does not affect the final characteristics of the product.
SD method is very effective at inactivating several enveloped viruses as shown in the table.
*adapted from Svae et al., 2011.

24. Non-lipid Enveloped Viral Safety
Immune antibodies in SD treated plasma neutralize viral particles and are of importance in avoiding clinical disease with HAV and parvovirus B191.
Octaplasma release specifications2:
Virus
Release Specifications
HAV PCR
Negative
Parvovirus B19 PCR
≤ 10.0 IU/µL
HAV-Ab
≥ 1 IU/mL
Parvovirus B19-Ab
≥ 22 IU/mL
Non‐enveloped viruses are not affected by the S/D treatment. It is unquestionable that naturally present immune neutralizing antibodies are very important barriers against the spread of many known and unknown viruses contaminating plasma pools.
The presence of these antibodies towards e.g. HAV and B19 in Octaplas results in immune neutralization of these viruses by blocking the viral capsid proteins essential for the viruses in their process of entering the host cells and passive immunization of patients, which both serve to prevent virus replication in vivo and thereby infection in patients .
Immune neutralisation has been acknowledged as an important safety mechanism against these viruses. The neutralization capacity is dependent on the specific antibody level versus the virus load and, thus, special safety measures have been incorporated for Octaplas in this respect.
The capacity to neutralize viruses in Octaplas by immune antibodies is very high and thereby prevents transmission and infections in the recipients.
Solheim BG et al. Transfusion 2000; 40: 84-90
Data on file

25. Non-lipid Enveloped Viral Safety by Immune Neutralization
Immune antibodies in OctaplasmaTM neutralize viral particles and are of importance in avoiding clinical disease with HAV and Parvovirus B19.
The capacity to neutralize non-enveloped viruses in OctaplasmaTM by immune antibodies is very high and thereby prevents transmission and infections in the recipients.
Capacity to neutralize non-enveloped viruses by immune antibodies
COX-B6
POL-1
HAV
HEV
B19
≥ 5.8
≥ 7.5
≥ 6.6
≥ 5.9
≥ 7.0
Clearance factor of OctaplasmaTM (log 10)
Non‐enveloped viruses are not affected by the S/D treatment. It is unquestionable that naturally present immune neutralizing antibodies are very important barriers against the spread of many known and unknown viruses contaminating plasma pools.
The presence of these antibodies towards e.g. HAV and B19 in Octaplas results in immune neutralization of these viruses by blocking the viral capsid proteins essential for the viruses in their process of entering the host cells and passive immunization of patients, which both serve to prevent virus replication in vivo and thereby infection in patients .
Immune neutralisation has been acknowledged as an important safety mechanism against these viruses. The neutralization capacity is dependent on the specific antibody level versus the virus load and, thus, special safety measures have been incorporated for Octaplas in this respect.
The capacity to neutralize viruses in Octaplas by immune antibodies is very high and thereby prevents transmission and infections in the recipients.

26. No Confirmed case of TRALI in 2 Decades
Octaplasma has eliminated the risk of TRALI: No detectable anti-leukocyte antibodies
Octaplasma reduces the risk of TRALI which remains a life threatening complication of TPE

27. Standardized Coagulation Factors
Some viruses are enveloped, meaning that the capsid is coated with a lipid membrane known as the viral envelope The envelope may play a role in helping a virus survive and infect other cells. Viruses that lack envelopes (i.e., do not have nor need them) are termed non- enveloped. Non-enveloped viruses also constitute an important class of medically significant pathogens.
It is known that both enveloped and non-enveloped viruses can be transmitted via plasma.
Although non-enveloped viruses are not directly affected by SD treatment, the Octaplas manufacturing process has the capability to remove non-enveloped viruses during the removal of the SD reagents.

28. TTP: ADAMTS13 & vWF Multimers
Parameters
Reference
Range FFP
OctaplasmaTM
Mean (n=3)  Std.dev.
ADAMTS13 antigen [IU/ml]
0.75 – 1.101
0.99  0.06
ADAMTS13 activity [IU/ml]
0.50 – 1.101
0.91  0.17
Factor H antigen [IU/ml]
0.48 ± 0.092
0.47 ± 0.03
Std.dev., standard deviation; 1Reference range assays,
2Heger P et al. Vox Sang 2007; 92:
(2010) Haemostasis Research Unit, University College London1
Reduced levels of HMW VWF in combination with well-conserved levels of ADAMTS-13 could be seen as a positive advantage in the treatment of patients with TTP
ADAMTS13, which is important for the physiological size and function of VWF multimers, was measured in Octaplas and in OctaplasLG.
The study revealed that Octaplas and OctaplasLG contain normal levels of ADAMTS13. There were no significant differences in ADAMTS13 activity and antigen levels between the two products.
In addition, Octaplas and OctaplasLG show a vWF multimeric pattern comparable to normal plasma.
Therefore, both products can substitute the missing or neutralized protease activity in TTP patients and thereby limit vWF-dependent (platelet-related) thrombosis.
Lawrie A.S. et al. Vox Sang 2010 (99):

29. OctaplasmaTM - Efficacy in TTP
Edel et al. (2010)
Efficacy and tolerability of Octaplasma has been studied in TTP
Overview: Retrospective analysis of 506 treatments (n=8) & 1999 L of plasma used over course of treatment
Efficacy parameters: Platelet count above 150 x 109 achieved; ADAMTS13 inhibitory antibodies were partially or completely removed by therapeutic plasma exchange
AEs: Use of S/D was well tolerable with no AEs and no thrombotic events

30. OctaplasmaTM Tolerability - Sweden

31. OctaplasmaTM Tolerability - Austria
Period (minus 2007 and 2008 – not reported)
Zero TRALIs among 267’000 Octaplas bags (FFP in 2009: 1:15’300)
94 allergic reactions in 112’600 FFP infusions, equivalent to 83 (95%CI = ) allergic reactions per 100’000 bags
12 allergic reactions in 267’000 Octaplas infusions, equivalent to 4 (95%CI = 1-10) allergic reactions per 100’000 bags

32. Answering TTP – Community Survey
82% of survey respondents cited at least 1 type of adverse reaction during TTP treatment
“Counting down the bags of donor plasma is all you can do to wait for it to end. You don't know if you will have an allergic reaction to the next bag and how severe that reaction might be until it happens. Just cross your fingers and hope you don't react.”
“Although the risk of contracting a disease from [FP] is supposed to be quite low, the sheer volume of plasma I have received each time I have relapsed increases the risk quite a bit, and that is always in the back of my mind. I do not know the exact amount I have received but I am sure it is upwards of 150 units per relapse (the last relapse lasted 3 months and was far more than that). A safer product would make me feel a lot less stress.”
Although transfusion transmitted infections have received the greatest attention, noninfectious adverse events remain the most common complications associated with transfusion. The majority of these noninfectious adverse events are immune mediated. They include: allergic reactions, anaphylactic reactions, TRAI, hemolysis etc.
Physiochemical reactions can also occur, specifically TACO and reactions due to various additives in the product.

33. OctaplasmaTM Coagulation Factor Levels
Heger A et al. Transfusion and Apheresis Science 2005; 33:

34. OctaplasmaTM Coagulation Factor Levels
Hellstern P et al. Transfus Med Hemother : 65-70

35. Octaplasma® reduces both infectious and non-infectious risks of transfusions
Risk per 1,000,000 plasma units
Reduction
Single‐donor FFP
Octaplas®
HIV
0.26 (0.16‐0.47)
-100%
HCV
0.30 (0.02‐0.52)
HAV
0.64 (0.43‐1.30)
TRALI death*
3.6 (3.3‐4.9)
HBV
4.6 (1.5‐7.1)
Allergic reactions death
6.6 (2.4‐14.4
0.5
-92%
TRALI all*
29 (15‐127)
B19
30 (18‐83)
Extra ALI*
1,227 (917‐1,852)
Allergic reactions severe
3,448 (2,857‐4,348)
292
Allergic reactions all
15,385 (14,286‐16,667)
1,053
-93%
Complications all
16,676 (15,239‐18,738
-94%
Infectious complications all
36 (20‐93)
Non-infections complications all
16,641 (15,218‐18,645)
Expected transfusion complications were compared between Octaplas® and FFP.
Octaplas reduces not only infectious risk of transfusions but also the non-infectious risks. Compared to FFP, Octaplas reduces transfusion complications by 94% which is similar to published experience from Finland.
The abolished risk for TRALI and significantly reduced risk for and severity of allergic reactions are major advantages of that Octaplas® has over FFP.
Based on these data it can be concluded that Octaplas is a safe and well tolerated product.
1Svae et al, 2011; 2Krusius, 2009
calculated risk, not actual

36. Manufacturing Comparison: Plas+SD vs Octaplasma®

37. Manufacturing Comparison: Plas+SD vs Octaplasma®

38. Active Ingredients: Proteins & Coagulation Factors

39. Active Ingredients: Inhibitors & Antibodies

40. Other Parameters: Non-lipid Related

41. Other Parameters: Lipid Related

42. Haemostatic Balance Comparison

43. Octaplasma use in Neonates, Obstetric and Gynaecological patients
41 neonates received 67 transfusions (18.4 mL/kg)
31 (76%) coagulopathy without haemorrhage (DIC or other)
8 (19%) clinical haemorrhage
38 obstetric and gynaecological patients received 57 transfusions (15.3 mL/kg)
36 (95%) haemorrhage
15 children with liver disease received 33 transfusions (38 mL/kg)
17 adult patients with end-stage liver disease transfused either following liver transplant or prior to other invasive procedures (10.2 mL/kg)

44. Efficacy in Single Factor Clotting Deficiency
Inbal et al.
Prospective and interventional study
A total of 11 patients, 8 with hereditary (2 FVII, 2 FX, 4 FXI deficiencies) and 3 with acquired complex coagulopathies, were treated with Octaplas®
The amount of Octaplas® infused ranged between 6-12 ml/kg
In all the 11 patients Octaplas® was sufficient to prevent or stop bleeding
Santagostino et al.
An open-label multicenter trial of Octaplas® involving 17 patients with inherited coagulation disorders (1 afibrinogenemia, 4 FV, 6 combined FV and FVIII, 1 FX and 5 FXI deficiencies)
Study evaluated the pharmacokinetics of the deficient factors and hemostatic efficacy of Octaplas®
The pharmacokinetic study used a median Octaplas® dose of 18 ml/kg (range: 15-20), whereas the treatment courses had a higher range with 6-29 ml/kg (median: 18)
Octaplas® was fully effective in 81% of patients. In the remaining patients bleeding was controlled by continuing or increasing treatment with Octaplas®
Treatment with Octaplas® was well tolerated and safe
Inbal et al., conducted a prospective study to evaluated the haemostatic efficacy and analyze the pharmacokinetcs of Octaplas in 8 patients with hereditary factor VII, X and XI deficiency and in 3 patients with acquired coagulation disorders.
Patients received Octaplas for treatment of haemarthrosis, menorrhagia or before surgical procedures.
In all patients with hereditary coagulopathies, an increase in the level of deficient factor following Octapls infusion was observed.
In all the patients Octaplas was sufficient to prevent or stop the bleeding.
An open-label multicenter trial conducted by Santagostino et al., evaluated the pharmacokinetics of the deficiency factors and hemostatic efficacy of Octapls in 17 patients with inherited coagulation disorders.
Treatment courses of Octaplas were judged fully effective in 81% of patients. In the remaining cases, mild bleeding occurred after major surgery in a FV deficient patient with a factor level of 43% and in a FXI deficient patient when factor levels were between 20-41%; and after minor surgery in a patient with FV and FVIII deficiency when factor levels were 41% and 18%, respectively. Bleeding was controlled by continuing or increasing treatment with Octaplas. Octaplas was well tolerated and safe.
Inbal et al., Blood Coagulation and Fibrinolysis. 1993; 4; ; Santagostino et al., Haematological. 2006; 91:

45. Octaplasma Dosing
The volume and frequency of plasma exchanges vary depending on the individual patient, the clinical situation and disease, but mL/kg of body weight is an acceptable starting dose
Example: 70kg patient
Condition
Dosage
Treatment Goal
Calculation
Number of Bags
TTP/HUS
1.5 plasma volume mL/kg daily for 1-8 weeks
Platelets 150 x 109/L
TBC
~200
Single Factor Deficiency (FV, FXI or FXIII)
12-15 mL/kg
25% of coagulation factor activity
70kg x 12mL = 840 mL/200mL bags
4.2
ADAMTS13, which is important for the physiological size and function of VWF multimers, was measured in Octaplas and in OctaplasLG.
The study revealed that Octaplas and OctaplasLG contain normal levels of ADAMTS13. There were no significant differences in ADAMTS13 activity and antigen levels between the two products.
In addition, Octaplas and OctaplasLG show a vWF multimeric pattern comparable to normal plasma.
Therefore, both products can substitute the missing or neutralized protease activity in TTP patients and thereby limit vWF-dependent (platelet-related) thrombosis.