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Glanzmann’s thrombasthenia –
a rare congenital platelet function
defect
By Jun Teruya, M.D., D.Sc.
On Friday afternoon in June 2006, a 4-month-old girl came to the
Emergency Center with systemic purpura. The mother stated
through a Spanish interpreter that after the girl received
vaccine two weeks earlier, bleeding did not stop for a day or
two.
Laboratory tests showed normal hemoglobin and white cell count,
and increased platelet count of 630,000/mm3. Routine coagulation
tests such as prothrombin time, activated partial thromboplastin
time and fibrinogen were all normal. The hematologist who was
consulted for this case suspected a disorder of congenital
platelet function defect. Further tests to assess the platelet
function were ordered: platelet function analysis (PFA) and
thromboelastography (TEG).
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Conditions which may prolong PFA |
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Von Willebrand disease
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Congenital and acquired qualitative platelet disorders
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Medications
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Myeloproliferative disorders
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Low hematocrit (<25-30%)
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Thrombocytopenia
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Uremia
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High erythrocyte sedimentation rate
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By the time a new specimen was sent, the patient had a low
hemoglobin due to repeated blood specimen collections. The PFA
collagen/epinephrine was prolonged at >197 sec and collagen/ADP
was prolonged at >164 sec. TEG was markedly abnormal, showing
a decreased maximum amplitude (Figure). These results indicated definitive
diagnosis of congenital platelet function defect, provided a
medication effect such as aspirin, which may cause drug-induced
platelet dysfunction, is ruled out. On the same day, the
platelet aggregometry, a gold standard for a platelet function
test, was performed and the diagnosis of Glanzmann’s
thrombasthenia was strongly suspected.
The patient was treated with platelet transfusion, despite the
elevated platelet count, as well as red cell transfusion.
Eventually, all the bleeding symptoms stopped. The platelet
count was increased to 962,000/mm3 at that time. The diagnosis
was later confirmed as Glanzmann’s thrombasthenia by platelet
membrane receptor assay using flow cytometry.
Glanzmann’s thrombasthenia is a rare hereditary disorder that
causes systemic purpura, nosebleed, and sometimes intracranial
bleeding. It was first described by Glanzmann in 1918. Patients
with Glanzmann’s thrombasthenia have deficiency of a platelet
receptor, glycoprotein IIb/IIIa, which is a receptor for
fibrinogen. Since the fibrinogen should act as a bridge between
each platelet, because of the lack of the receptor a patient’s
platelets cannot effectively aggregate.
In the past at Texas Children’s Hospital, the only available
test for platelet function was a bleeding time test. Although
the bleeding time test has been used for more than 100 years,
more and more hospitals in the United States have stopped
offering the test due to the lack of reproducibility and
sensitivity to the platelet function. We completely stopped the
bleeding time test three years ago and now more reproducible and
sensitive tests such as PFA and TEG are available 24 hours a
day.
PFA and TEG
PFA is performed using PFA-100™, which is an instrument designed
to measure platelet-related hemostatic disorders in whole blood.
PFA utilizes approximately 1 mL of citrated whole blood through
a thin capillary tube and is tested under flowing physiologic
conditions. The amount of time in seconds required to occlude an
aperture membrane coated with collagen and either epinephrine or
ADP is called the closure time. It has been reported to be
useful as a screening test for von Willebrand disease, platelet
function defects, and monitoring of antiplatelet therapy. The
accompanying table lists the possible settings and hemostatic
disorders prolonging PFA. Since there are two cartridges to run,
the specimen requires two 2.7 mL blue top tubes.
TEG as a method of assessing primary and secondary hemostasis
and fibrinolytic function has existed for more then 50 years.
TEG has been revisited for liver transplant surgery and cardiac
surgery in the past 15 years. It has proven utility for
monitoring hemostatic and fibrinolytic derangements. However,
the utility of the TEG for outpatient setting has not been
advocated.
We have been using TEG for surgical cases and outpatients who
have bleeding symptoms of unknown etiology. It appears quite
useful since TEG can detect platelet dysfunction like in this
case, hyperfibrinolysis, which may be associated with
high tissue plasminogen activator or decreased alpha
2-antiplasmin, and factor XIII deficiency, which cannot be
measured by routine coagulation assays. The specimen requires
one 2.7 mL blue top tube.
No single coagulation test can assess overall hemostatic
function and predict bleeding during invasive procedures.
Therefore, concise personal and family history of bleeding is
the first and the most important method to detect coagulopathy.
This patient continues to have occasional gastrointestinal
bleeding, which required hospitalization twice since the first
presentation. Currently, effective treatment is limited to
platelet transfusion at this age. Desmopressin may be used for
Glanzmann’s thrombasthenia when she gets older. Desmopressin is
used to improve the platelet function by increasing a
circulating von Willebrand factor. It is unknown if desmopressin
is truly effective to minimize bleeding and bruising for this
patient since the reports are variable in terms of success. Use
of an antifibrinolytic agent, such as epsilon aminocaproic acid,
is anecdotal. In the future of her life, control of menstrual
bleeding will be a major problem.
Jun Teruya, M.D., D.Sc., is director of Blood Bank and
Coagulation at Texas Children's Hospital and associate professor
of Pathology and Pediatrics at Baylor College of
Medicine.
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TEG of the patient |
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Normal TEG |
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