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

Presentation

17 year old female

Blanching, erythematous rash with malar distribution

Bruising on hips, thighs and calves

Bruising around Hip

Blanching rash with malar distribution

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

Provisional Diagnosis

Systemic Lupus Erythematosus (SLE) • With hyperfibrinolysis • And significant subcutaneous bleeding

Ongoing Subcutaneous Bleeding

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

DAY 10 – Clinical Treatment Continues

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.

•  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

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)

•  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

•  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

•  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

•  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

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

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

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

Acknowledgement

�  Dr. Fiona Kwok �  Dr. Emmanuel Favaloro �  Dr. Gaurav Sutrave