Platelet Function Screening
Cortese Hassett, Ph.D. and
Franklin A. Bontempo, M.D.
dysfunction may be acquired, inherited, or induced by platelet inhibiting
agents. It is clinically
important to assess platelet function as a potential cause of a bleeding
diathesis, especially in critically ill patients who may develop
life-threatening hemorrhages. The
most common causes of platelet dysfunction are related to uremia, liver
disease, von Willebrand’s disease (vWD) and exposure to agents such as
acetyl salicylic acid (ASA, aspirin). Current
methods to assess platelet function include bleeding time (BT), aggregation
studies and whole blood in vitro
test systems such as the closure time (CT).
times are performed on a PFA-100, an instrument and test cartridge system in
which the process of platelet adhesion and aggregation following a vascular
injury is simulated in vitro.
This system allows for rapid evaluation of platelet function on
samples of anticoagulated whole blood.
Membranes consisting of Collagen/Epinephrine (CEPI) and
Collagen/Adenosine-5’-diphosphate CADP and the high shear rates generated
under standardized flow conditions, result in platelet attachment,
activation and aggregation, building a stable platelet plug at the aperture.
The time required to obtain full occlusion of the aperture is reported as
the closure time (CT) in seconds. The test is sensitive to platelet
adherence and aggregation abnormalities and allows the discrimination of
aspirin-like defects and intrinsic platelet disorder.
The CEPI membrane is used to detect platelet dysfunction induced by
intrinsic platelet defects (vWD, drug effects etc.).
Abnormalities result in prolongations of CT >175 seconds.
Follow-up testing using the CADP membrane enables the discrimination
of aspirin effects. The following table shows expected patterns observed
with CT on normal subjects and subjects with various disorders.
TIMES vs. BLEEDING TIMES
thrombocytopenias are accurately assessed by automated platelet counters,
qualitative platelet defects are presently difficult to diagnose.
The only global screening test for platelet and vascular functions is
the BT. BT is a bedside
procedure, is labor intensive, expensive and its accuracy is heavily
dependent on operator skills. A
critical review of BT concluded
that the utility of BT is not enhanced by recent standardization attempts;
that in individual patients there is no relationship between BT and platelet
counts; that the BT is not a specific indicator of platelet function and
that the BT is a poor indicator of surgical bleeding risk.
As a consequence many clinicians no longer use BT.
The noted deficiencies of BT lead to the development of an in
vitro device that globally measures platelet-related primary hemostasis.
Closure time is sensitive to platelet adherence and aggregation
abnormalities and therefore has increased sensitivity for von Willebrand’s
screening when compared to bleeding time.
Comparative studies at our facility support these findings:
CT was abnormal in 64% of patients diagnosed with vWD as compared to
43% by BT.
times are indicated when a disorder of platelet function is suspected by a
personal or family history of easy bruising, nose bleeds, menorrhagia, or
post-operative bleeding, especially following dental extractions or
tonsillectomy. It is not recommended as a screen for potential bleeding
risk. Closure times may be prolonged when the platelet count is
< 100,000/mm3 even if platelet function is normal.
In addition the CT will be prolonged when hematocrit levels are <
35%, due to the contributory effect of red blood cells on platelet behavior.
These restrictions should be considered prior to performing a closure time.
von Willebrand’s disease, inherited platelet disorders and evaluation of
acquired disorders of platelet function (hepatic disease, renal disease,
drug effects) are appropriate
clinical reasons for closure time screening.
It may also be useful to monitor the response of therapeutics, such
as DDAVP infusions, renal dialysis, platelet and antiplatelet drug therapy.
Abnormal closure times, indicating possible defective platelet function,
should be further investigated with standard platelet aggregation tests.
time is a test system to assess platelet-related primary hemostasis with
improved accuracy and reliability in comparison to bleeding time.
This assay is an important aid in the assessment of platelet
dysfunction and bleeding risk caused by uremia, von Willebrand’s disease,
congenital platelet disorders and exposure to agents such as aspirin.
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for von Willebrand’s disease with a new analyzer using high shear stress:
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