Fibrinolytic and Thrombotic disorders (CH15 & 22) Flashcards
What is important to understand about the
fibrinolytic system ?
- it is in balance with the coagulation system
- if fibrinolytic activity is substantially increased bleeding may occur even if the coagulation system and platelets are functioning ok.
- activity may be increased due to increased plasminogen activators or reduced levels of fibrinolytic inhibitors
In what situation can fibrinolytic bleeding
occur at the same time as dysregulated hemostasis ?
- DIC
When would you consider working up
a patient for atypical or a disorder of fibrinolysis ?
- history of bleeding
- negative results on the more common coagulation assays
- bleeding due to abnormal fibrinolysis is rare
What is the clinical presenation in disorders
of fibrinolysis ?
- delayed bleeding after surgery, trauma or childbirth
- wound hematomas (can be severe)
What are acquired causes of
fibrinolytic disorders ?
- cirrhosis
- liver transplantation
- trauma
- cardiopulmonary bypass
- DIC
- treatment of thrombosis with excess plasminogen activators
IMP limitation of TEG
and ROTEM in evaluting fibrinolysis
- lack of evidence of lysis on these tests does not rule out moderately increased fibrinolysis that may be clinically significant
- ex:
- plasminogen active inhibitor I deficiency
What is the inheritance pattern
and general information about plasminogen activator inhibtor 1
deficiency?
- rare congenital disorder
- homozygous, autosomal recessive
- increased fibrinolysis leading to excessive bleeding
- PAI-1 antigen levels are undetectable in plasma samples
- means a complete deficiency
IMP: however patients with normal antigen and reduced activity, heterozygosity etc have been described
What is the clinical presentation of
PAI-1 deficiency?
- easy bruising
- menorrhagia
- moderate to severe delayed bleeding after surgery or minor trauma
- often have excessive wound hematomas
- bleeding episodes include intracranial bleeding or joint bleeding
What is unclear about PAI-1 deficiency in
either the antigen or activity ?
- if low normal antigen levels and activity do truly lead to increased bleeding
What should the lab evaluation of
PAI-1 include ?
- PAI-1 activity
- PAI-1 antigen
- total tPA antigen or tPA-PAI-1 complex
Note: samples should be drawn in the morning when PAI-1 is highest
GREAT chart p. 202
In patients with PAI-1 deficiency
why is the amount of tPA antigen reduced ?
- the tPA-PAI-1 complex will be decreased to absent
- majority of the tPA will be in the free, unbound form
- which gets cleared quickly by the liver
IMP: must demonstrate a low tPA antigen level or tPA-PAI-1 complex when diagnosing PAI-1 deficiency in addition to the low PAI-1 activity
When should a spurious result of
PAI-1 deficiency be suspected?
- low PAI-1 activity
- normal or high tPA antigen level
IMP: this denotes a sampling problem (may have prolonged tourniquet time etc)
What is similar between normal patients
and those with PAI-1 deficiency ?
- tPA activity
Since circulating, active tPA is similar between normal patients and
those with PAI-1 deficiency, why do PAI-1
deficiency patients bleed?
- PAI-1 binds to the clot surface and is important to inhibiting tPA activity at that junction
- so in PAI-1 deficiency the clot is more subject to thrombolysis and hence these patients bleed more
- despite equivalent levels of blood tPA activity
What types of deficiencies
of alpha-2 antiplasmin have been described ?
- homozygous (very rare)
- autosomal recessive
- moderate to severe bleeding
- heterozygous (rare)
- controversial amount of bleeding
- similar to PAI-1 deficiency (moderate)
- post-operative bleeding, wound hematomas
