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B Y A A R O N K E E N A N A N D J A S O N D E C A S T R O
A case study on the use of fibrinogen concentrate
in SLE induced coagulopathy
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Presentation
17 year old female
Blanching, erythematous rash with malar distribution
Bruising on hips, thighs and calves
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Bruising around Hip
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Blanching rash with malar distribution
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Initial Investigation Extended Thrombin time of 26 seconds (10-17 s)
Low Fibrinogen level <0.6g/L (1.8-4.4 g/L)
Extremely high levels of Anti-DsDNA (>50)
All other blood results relatively normal
Low levels of Complement C3 and C4
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Provisional Diagnosis
Systemic Lupus Erythematosus (SLE) • With hyperfibrinolysis • And significant subcutaneous bleeding
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Ongoing Subcutaneous Bleeding
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Treatment -Blood Bank Perspective
Cryoprecipitate Riastap 1g per dose
Fresh Frozen Plasma
DAY 1 0 2 DAY 2 0 2 DAY 3 0 0 DAY 4 0 0 DAY 5 0 DAY 6 0 23 10 DAY 7 0 18 10 DAY 8 0 10 DAY 9 0 1 0
8 <0.6 g/L 6 2.1 1.1 34 <0.6 0.7
20 8g if <3.0 80 5 bags p/h 14 4g/h
12 2.8g/L
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DAY 10 – Clinical Treatment Continues
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Systemic Lupus Erythematosus
• Autoimmune disorder;
• Diverse clinical manifestation
• No two patients tend to follow same disease progression
• Aetiology is still unclear
• Genetic; strong familial aggregation
• Hormonal;
• Environmental; chemical stimulants, bacterial and viral
• Sex; predominantly a female disease.
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• Antibodies directed at self molecules
• Cell nucleus
• Cytoplasm
• Cell surface
• Circulating IgG and Coagulation factors
• Antinuclear antibodies present in 95% patients
• Anti-double stranded DNA (dsDNA) and anti-Sm antibodies (Small nuclear Ribonucleoprotein)
• Unique to SLE patients
• Consequently key diagnostic requirement
• Anti-DNA titres vary over course of disease
• Contrastly Anti-Sm tend to remain the same
Systemic Lupus Erythematosus
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Systemic Lupus Erythematosus
● Autoimmune screen ● ANA 1:2560 (speckled, nucleolar) ● ANA 1: 640 (homogenous) ● dsDNA > 50 ● RNP / SSA / Ro / Ribosomal P all positive ● Smith / SSB / Scl-70 / Jo / ANCA all
negative ● C3 0.27 / C4 < 0.05 (both low)
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• Meriad of immune system irregularity;
• Polyclonal B-cell activation
• Increase immune complex formation (Low C3 and C4 levels)
• >T-Cell activity
• Excessive and uncontrolled
• Differentiation and activation of autoantibody producing B-Cells (final common pathway)
• Use of immunosuppressive drugs
• < Autoantibody production integral control measure
Systemic Lupus Erythematosus
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• Protein encoded by the Serine 1 gene on chromosome 7
• Tissue plasminogen activator and urokinase
• Activator of plasminogen
• PAI-1 rapidly and irreversibly bind to plasminogen activators
• Consequently resulting in fibrinolysis
Plasminogen activator inhibitor- 1
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• The predominant source of plasma PAI-1 is unclear
• Hepato- cytes, endothelial cells, adipocytes, and megakaryo- cytes able to synthesize and secrete PAI-1 into the circulation
• Varied plasma levels throughout the day
• Highest level in mornings
• Lowered levels in the evening
• Short half life of 10min
Plasminogen activator inhibitor- 1
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• Bleeding disorder associated with PAI-1 deficiency generally mild to moderate.
• PAI-1 autoantibodies resulting in more extreme bleeding episode
• Currently does not appear to be a reported case of SLE associated PAI-1 deficiency
• Current investigation to be completed and hopefully published
Plasminogen activator inhibitor- 1
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Fibrinogen Concentrate
• Lyophilised fibrinogen powder made from pooled human plasma
• Fibrinogen concentrates heat treated for viral deactivation.
• Registered name in Australia with Therapeutic Goods Administration is Riastap (c)
• Primary described use is for treatment of afibrinogenaemia, hypofibrinogenaemia and dysfibrinogenaemia.
• Conditions are very rare
• Other potential uses are being explored
• Riastap manufactured by CSL Behring from donor in the United States and Germany
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Fibrinogen Concentrate
• Fresh frozen plasma and cryoprecipitate;
• Common products for fibrinogen deficiency
• Safety and efficacy issues with products
• Viral transmission
• Volume overload
• Group specific products for patients
• Allergic reactions
• Fibrinogen concentrate offers potentially valuable alternative
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Time to reflect
• What can the laboratory learn from JV’s case?
• Knowledge of what alternative products may be available is valuable.
• Increased awareness of what unusual results may be suggestive of.
• What potential role can Riastap have as a product used within the hospital?
• Cost of product compared to potential use.
• Relevant literature to support use
• Evaluation of current use and waste of plasma products
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Acknowledgement
� Dr. Fiona Kwok � Dr. Emmanuel Favaloro � Dr. Gaurav Sutrave