| Glanzmann's
Thrombasthenia |
 |
Glanzmann's Thrombasthenia is a rare genetic bleeding disorder. It is
a disorder of platelet function and is caused by a deficiency or abnormality
in the membrane glycoprotein (GP) IIb-IIIa which is responsible for the
formation of a plug (haemostatic plug) which prevents further bleeding
of injured blood vessels. In effect the platelets do not stick together
adequately causing prolonged bleeding even from minor injuries. Despite
the abnormality of platelet function, the total platelet count is normal
and specialised platelet function tests are necessary to make the diagnosis.
Glanzmann's Thrombasthenia may be of variable severity. Some patients
(Type 1) are severely affected whilst others are less so (Type 2). The
genes for glycoprotein IIb and IIIa are on chromosome 17, but many genetic
mutations have already been described. Glanzmann's Thrombasthenia is
not always the result of the same mutation.
Normal handling of infants can cause superficial bruises. Epistaxis
(nose bleeds) in childhood and menstrual bleeding can cause problems.
Platelet transfusions can be used in cases of serious bleeding. However
antibodies against platelets can develop as a result of such transfusions.
Anti-platelet drugs such as aspirin should be avoided.
Bone marrow transplantation is the only curative form of treatment.
However this is generally considered more hazardous than the condition
except in exceptional circumstances.
Inheritance patterns
Autosomal recessive, carriers can now be detected.
Pre-natal diagnosis
This is possible at 18 plus weeks through a fetal blood sample. However
where the child is affected the fetal sampling carries a high risk
of haemorrhage and may be fatal. Unaffected or carrier fetuses will
not undergo any special risk from the testing. Genetic counselling
is available.
Medical text last updated August 2001 by Dr R F Stevens, Consultant
Haematologist/Oncologist, Royal Manchester Children's Hospital, Manchester,
UK.
GLANZMANN'S THROMBASTHENIA CONTACT GROUP
Marilyn Buxton Glanzmann's Thrombasthenia Contact Group 28 Duke Road
Newton Hyde
SK14 4JB Tel 0161 368 0219 e-mail: glanzmannsupport@btopenworld.com This
is a Contact Group founded in 1990.
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Authored by Mark J. Shumate,
M.D., M.P.H., Assistant Professor, Hematology/Oncology Division,
Emory University
Edited by Christopher D. Hillyer, M.D.,
Program Director, Transfusion Medicine and Hospital Blood Bank, Associate
Professor, Departments of Medicine and Pathology, Emory University
School of Medicine; F. Talavera, Pharm.D., Ph.D.,
Department of Pharmacy, Creighton University; Emmanuel C. Besa,
M.D., Professor, Department of Medicine, Section of Hematology
and Oncology, Medical College of Pennsylvania Hospital, MCP Hahnemann
University; Rajalaxmi McKenna, M.D., Director, Hemophilia
Center; Division of Hematology, Clinical Professor of Medicine, Hematology/Oncology
Faculty Foundation, Director, Cardeza Special Hematology and Hemostasis
Laboratories, Thomas Jefferson University and Hospital; and Michael
E. Zevitz, M.D., Director of Echocardiography Lab, Division
of Cardiology, Clinical Assistant Professor, Department of Medicine,
Finch University of Health Science/The Chicago Medical School
Background:
Glanzmann Thrombasthenia is a genetic platelet
disorder in which the platelet glycoprotein IIb/IIIa (GP IIb/IIIa)
complex is either deficient or present but dysfunctional. This defect
leads to defective platelet aggregation and subsequent bleeding. It
is rare and is inherited in an autosomal recessive pattern.
Pathophysiology:
Platelet aggregation at sites of vascular injury
requires expression of GPIIb/IIIa complex on the surface of the platelets
forming the platelet plug.
GPIIb/IIIa complex binds fibrinogen and/or von
Willebrand factor (vWF). Adjacent platelets are cross-linked through
GPIIb/IIIa - fibrinogen - GPIIb/IIIa complexes. When GPIIb/IIIa complex
functions abnormally, platelet aggregation is impaired and bleeding
occurs.
GPIIb/IIIa complex is a heterodimer that requires
calcium for the GPIIb and GPIIIa to associate normally. Both GPIIb
and GPIIIa are required for normal platelet function. A defect in either
one can lead to a bleeding disorder.
Platelet counts and platelet functions that do
not depend on GPIIb/IIIa are normal in thrombasthenic patients.
Frequency:
Mortality/Morbidity:
Bleeding problems can be severe, but the prognosis
remains good if platelet transfusion is available.
Age:
Thrombasthenia typically presents with mucocutaneous
bleeding at birth or early in infancy.
History:
- Bleeding from a condition which could cause
bleeding in an otherwise normal individual.
- Petechiae and ecchymoses, although spontaneous
petechiae are uncommon
- Menorrhagia, often worse at menarche
- Gingival bleeding worse with poor dental hygiene
Physical:
Examine the skin and oral mucosa for petechiae,
ecchymoses and any current bleeding.
Causes:
The disease is a genetic condition.
Other Problems to be Considered:
Afibrinogenemia
Autoantibodies to GPIIa/IIIb
Bernard-Soulier Syndrome and Other Qualitative Platelet Disorders such
as Gray Platelet Syndrome; Wiskott-Aldrich Syndrome; Platelet-Type von
Willebrand Disease; or Platelet Storage Pool Defects.
Lab Studies:
- Complete blood count, prothrombin time and partial
thromboplastin time
- The platelet count and other coagulation tests
should be normal.
- Bleeding times should be prolonged
- Platelet aggregation studies
- The primary platelet aggregation response
to platelet agonists such as ADP and epinephrine are decreased
while the response to ristocetin is normal. If the secondary platelet
aggregation response is abnormal, suspect a platelet storage pool
defect or an abnormality in platelet signal transduction
Histologic Findings:
Platelet morphology on peripheral blood smears
is normal
Medical Care:
- Thrombasthenia patients who are bleeding require
platelet transfusion.
- Because patients are likely to require multiple
transfusions during their lifetime, take care to avoid platelet
alloimmunization.
- Prevention is best accomplished by using leukocyte-depleted
blood products. Leukocyte depletion can be accomplished with mechanical
filtration. Only filtered blood products should be given.
- Use of HLA-matched platelets is a further
attempt in the prevention of platelet alloimmunization.
- Patients should be vaccinated for hepatitis
B, due to infectious risks associated with multiple transfusions,
- Avoid medications that effect platelet function,
such as aspirin and other NSAIDs.
- Consider oral contraceptives to control menorrhagia.
Surgical Care:
- To prevent excessive bleeding during surgery,
platelets should be transfused pre-operatively.
- Further platelet transfusions based on maintaining
hemostasis
Consultations:
A hematologist confirms the diagnosis and makes
transfusion recommendations.
Further Outpatient Care:
- Regular dental care is recommended to avoid
gingival bleeding.
Deterrence/Prevention:
- Avoid drugs which decrease platelet function
or coagulation such as the following:
- Ticlopidine or Clopidogrel
- GP IIb/IIIa antagonists such as abciximab
- Streptokinase, urokinase or tissue plasminogen
activator
- Volume expanders such as dextran or hydroxyethyl
starch
Complications:
- Bleeding complications of any type
Prognosis:
- With platelet transfusions for bleeding complications,
the prognosis is generally good.
Patient Education:
- Regular dental care is necessary to avoid gingivitis
and gingival bleeding.
CME Question 1: What is the inheritance
pattern of Glanzmann thrombasthenia?
A: Autosomal dominant
B: X-linked recessive
C: Autosomal recessive
D: Y-linked dominant
E: Glanzmann thrombasthenia is not a heritable disease
The correct answer is C: Glanzmann thrombasthenia is due to
defects in GPIIb or GPIIIa. Both of these protein`s genes are on
chromosome 17. Fifty percent activity of each protein is enough to
support normal platelet aggregation. Therefore, the disease is inherited
as an autosomal recessive trait.
CME Question 2: Which of the following
drugs can be safely given to a patient with thrombasthenia?
A: Aspirin
B: Ticlopidine
C: Heparin
D: Dipyridamole
E: Gentamicin
The correct answer is E: Aminoglycoside antibiotics such as
gentamicin do not alter platelet function, all of the other drugs
listed alter platelet function.
Pearl Question 1: What are the
results of a complete blood count in a Glanzmann thrombasthenia patient?
The correct answer is: The platelet and
white blood cell count would be normal. The red count may be decreased
due to bleeding and/or concomitant iron deficiency
Pearl Question 2: How do platelets
from a Glanzmann thrombasthenia patient appear on microscopic examination
of the blood smear?
The correct answer is: The platelets appear
normal.
Pearl Question 3: If an adult
patient with no family history of thrombasthenia or any previous bleeding
disorder develops a thrombasthenic-like condition, what should be considered
in the differential diagnosis?
The correct answer is: Autoantibodies against
GPIIb/IIIa have been described which result in a thrombasthenic-like
syndrome. This suspicion can be confirmed by demonstrating an inhibitor
of platelet function through mixing studies using normal plasma and
normal platelets.
Pearl Question 4: How can excessive
menorrhagia be managed?
The correct answer is: In addition to platelet
transfusion for acute bleeding, menorrhagia can be prevented with use
of oral contraception.
- George JN, Caen JP, Nurden AT:
Glanzmann's thrombasthenia: the spectrum of clinical disease. Blood
1990 Apr 1; PT - REVIEW, ACADEMIC(7): 1383-95[Medline].
- Malik U, Dutcher JP, Oleksowicz L:
Acquired Glanzmann's thrombasthenia associated with Hodgkin's lymphoma:
a case report and review of the literature. Cancer 1998
May 1; PT - REVIEW LITERATURE(9): 1764-8[Medline].
- Vuckovic SA: Glanzmann's
thrombasthenia revisited. J Emerg Med 1996 May-Jun; 14(3):
299-303[Medline].
| NOTE: |
|
Medicine is a constantly
changing science and not all therapies are clearly established.
New research changes drug and treatment therapies daily. The
authors, editors, and publisher of this textbook have used their
best efforts to provide information that is up-to-date and accurate
and is generally accepted within medical standards at the time
of publication. However, as medical science is constantly changing
and human error is always possible, the authors, editors,
and publisher or any other party involved with the publication
of this text do not warrant the information in this text is accurate
or complete, nor are they responsible for omissions or errors
in the text or for the results of using this information. The
reader should confirm the information in this text from other
sources prior to use. In particular, all drug doses, indications,
and contraindications should be confirmed in the package insert. |
Last Modified Date
: - Thursday, 14 December 2000
|
platelets
from such patients contained reduced amount or abnormal
forms of GP IIb/IIIa. The term "thrombasthenia"
means weak platelets. Glanzmann knew that the platelets
were "weak" because clots from such patients
did not shrink or express serum. Although they contained
normal numbers of platelets, these clots behaved as
if they contained no platelets. In the figure below,
PCF in samples from three such patients are compared
to a group of normals. The decrease in PCF is not subtle.
The
kinetics of PCF development in Glanzmann's thrombasthenia
are similar to those seen in blood treated with GP IIb/IIIa
inhibitors. Indeed, treatment with Reopro is thought
to induce a "Glanzmann's-type deficit".
has
only been recognized in dogs and has been found
in Otterhounds and Great Pyrenees.
The defect is due to absent or dysfunctional glycoprotein
IIb/IIIa on platelets. GPIIb/IIIa is the platelet
fibrinogen receptor and is essential for platelet
aggregation (mediated by fibrinogen). Affected
dogs have prolonged bleeding from minor wounds,
spontaneous epistaxis and readily form hematomas
at sites of injury or venipuncture. 
