AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. The condition is rare and is inherited in an autosomal recessive pattern. The disorder was first described by Dr. Eduard Glanzmann in 1918.

Pathophysiology

When an injury occurs, the GP IIb/IIIa receptors play an important role in platelets' adherence to the endothelium as well as platelet aggregation.

GP IIb/IIIa complex binds fibrinogen and/or von Willebrand factor (vWF). Adjacent platelets are cross-linked through GP IIb/IIIa-fibrinogen-GP IIb/IIIa complexes. When GP IIb/IIIa complex functions abnormally, platelet aggregation is impaired and bleeding occurs.

GP IIb/IIIa complex is a heterodimer that requires calcium for the GP IIb and GP IIIa to associate normally. Both GP IIb and GP IIIa are required for normal platelet function. A defect in either can lead to a bleeding disorder.

Platelet counts and platelet functions that do not depend on GP IIb/IIIa are normal in patients with thrombasthenia.

Frequency

International

Glanzmann thrombasthenia is quite rare and is inherited in an autosomal recessive manner. It is observed most often in populations with increased consanguinity.

Mortality/Morbidity

• Bleeding problems can be severe, but the prognosis remains good if platelet transfusion is available.

Age

• Patients with thrombasthenia typically present with mucocutaneous bleeding at birth or early in infancy.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Excessive bleeding after dental extraction (may often be the first sign)
• Petechiae and ecchymoses, although spontaneous petechiae are uncommon
• Menorrhagia, often worse at menarche
• Gingival bleeding, worse with poor dental hygiene
• Epistaxis
• Hemarthroses (rare)
• Family history of a bleeding disorder may or may not exist

Physical

• Examine the skin and oral mucosa for petechiae, ecchymoses, and any current bleeding.

Causes

• Glanzmann thrombasthenia is a genetic condition.
• Rare acquired forms caused by antibodies against GP IIb/IIIa have been described. One of these patients developed non-Hodgkin lymphoma and another had no underlying cause.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Afibrinogenemia
Autoantibodies to GP IIa/IIIb
Bernard-Soulier syndrome and other qualitative platelet disorders (eg, gray platelet syndrome, platelet-type von Willebrand disease, or platelet storage pool defects)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Complete blood count, prothrombin time, and activated partial thromboplastin time: The platelet count and other coagulation tests should be normal.
• Bleeding times should be prolonged.
• Platelet function analyzer 100 is a device that may be helpful in determining the cause of bleeding diathesis.
• Platelet aggregation studies
• • The primary platelet aggregation response to platelet agonists such as adenosine diphosphate (ADP), epinephrine, and collagen 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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Patients with Glanzmann thrombasthenia 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 platelets matched via human leukocyte antigen (HLA) is a further attempt to prevent platelet alloimmunization.
• Patients should be vaccinated for hepatitis B due to the infectious risks associated with multiple transfusions
• Avoid medications that affect platelet function, such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Consider oral contraceptives to control menorrhagia.
• Recombinant human-activated factor VII has been used in patients with antibodies to GP IIb/IIIa and/or human leukocyte antigen rendering transfusions ineffective.

Surgical Care

• To prevent excessive bleeding during surgery, platelets should be transfused preoperatively.
• Further platelet transfusions are considered based on maintaining hemostasis.
• Recombinant human-activated factor VIIa may be useful for preventing or controlling bleeding.

Consultations

A hematologist confirms the diagnosis and makes transfusion recommendations.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to induce active immunity, reduce morbidity, and prevent complications.

Drug Category: Vaccines, viral

Provide immunity against viral infections.

Drug Category: Oral contraceptives

Estrogen-progestin combinations. Reduce the secretion of LH and FSH from the pituitary by decreasing amount of gonadotropin-releasing hormones.

Drug Category: Coagulation factor VIIa

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Regular dental care is recommended to avoid gingival bleeding.

Deterrence/Prevention

• Avoid drugs that decrease platelet function or coagulation, such as the following:
• • Aspirin or other NSAIDs
  • Heparin
  • Warfarin
  • Ticlopidine or clopidogrel
  • GP IIb/IIIa antagonists such as abciximab
  • Streptokinase, urokinase, or tissue plasminogen activator
  • Volume expanders such as dextran or hydroxyethyl starch
  • Dipyridamole

Complications

• Bleeding complications of any type

Prognosis

• With platelet transfusions for bleeding complications, the prognosis generally is good.

Patient Education

• Regular dental care is necessary to avoid gingivitis and gingival bleeding.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to monitor for bleeding complications

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• George JN, Caen JP, Nurden AT. Glanzmann''s thrombasthenia: the spectrum of clinical disease. Blood. Apr 1 1990;75(7):1383-95. [Medline].
• Lombardo VT, Sottilotta G. Recombinant activated factor VII combined with desmopressin in preventing bleeding from dental extraction in a patient with Glanzmann''s thrombasthenia. Clin Appl Thromb Hemost. Jan 2006;12(1):115-6.
• Malik U, Dutcher JP, Oleksowicz L. Acquired Glanzmann''s thrombasthenia associated with Hodgkin''s lymphoma: a case report and review of the literature. Cancer. May 1 1998;82(9):1764-8. [Medline].
• Poon MC, Zotz R, Di Minno G, et al. Glanzmann''s thrombasthenia treatment: a prospective observational registry on the use of recombinant human activated factor VII and other hemostatic agents. Semin Hematol. Jan 2006;43(1 Suppl 1):S33-6.
• Tholouli E, Hay CR, O''Gorman P, Makris M. Acquired Glanzmann''s thrombasthenia without thrombocytopenia: a severe acquired autoimmune bleeding disorder. Br J Haematol. Oct 2004;127(2):209-13.
• Vuckovic SA. Glanzmann''s thrombasthenia revisited. J Emerg Med. May-Jun 1996;14(3):299-303. [Medline].

Article Last Updated: Jul 24, 2006