Glanzmann Thrombasthenia

Glanzmann Thrombasthenia is a rare genetic platelet disorder in which the platelet glycoprotein IIb/IIIa complex is either deficient or present but dysfunctional.  This defect leads platelets to fail to aggregate following stimulation, failing to form blood clots.  The condition is inherited in an autosomal recessive pattern of the two genes GPIIb and GPIIIa. GPIIb and GPIIIa exists together as a dimmer and once activated will bind to one end of fibrinogen.  Another platelet, with its own GPIIb/IIIa can then bind to the other end of the fibrinogen.  This allows the formation of a large collection or aggregation of bound platelets, commonly called a blood clot. In GT they are defective, the platelets can no longer bind with one another and the blood clot fails to form. It commonly presents in infancy or early childhood with multiple bruises and unrecognizable trauma.

The genetics underpinning the disease are very diverse, ranging from major deletions in the gene to single point mutations.  The disease is very rare, with only about 200 cases in the world (1995), of which only twelve have been solved at the genetic level.  The disease was found in 1918 where consanguineous marriages were common. Glanzmann’s is also found at a higher frequency among Iraqi Jews, French Gypsies and individuals of Arabic descent.

  • Common symptoms include:
  • Excessive bleeding after skin damage (dentist, surgery, accidents)
  • Spontaneous bleeding within the joints
  • Spontaneous bleeding within mucosal tissues
  • Mennorhagia- bleeding more severe during menstruation
  • Hemarthroses are rare

Glanzmann’s Thrombasthenia may be of variable severity on patients and if left untreated death might occur.

For prevention patients should be vaccinated to hepatitis B, due to infectious risk with multiple transfusions.  Patients should also avoid medications that effect platelet function, such as aspirin or other NSAIDS, Heparin, Wrafarin, Streptokinase and others.

Platelet transfusions can be used in cases of serious bleeding, however antibodies against it can develop as a result of such transfusions.  Normal handling of infants can cause superficial bruises and epistaxis is very common.  Bone marrow transplantation is the only curative form of treatment, but the surgery can be more hazardous than the condition except in exceptional circumstances.

Lab test has shown that blood count and platelet count can be normal and platelet morphology on peripheral blood smears are also normal.  In order to diagnose this disease, very specific testing has to be done.  Because patients are likely to require multiple transfusions during their lifetime, platelet alloimmunization is a concern.

David A. Wilcox, PhD, Assistant Professor of Pediatrics and Associate Investigator at the blood Research Institute has been doing research at the Medical College of Wisconsin and has used gene therapy to successfully correct a defect in the cells of individuals with Glanzmann.  The strategy used in the laboratory could one day be used to treat other disorders as well.  Dr. Wilcox is focusing on applying the technique to lab animals. He is working with researcher Richard Hynes from MIT , on mice purposely infected  with Glanzmann’s. Positive results in laboratory animals could lead to tests in People, however, we can’t say when that would be.  The need to develop a better method of treatment is due to the fact that patients with the disorder become unable to tolerate the transfusions of platelets.

SOURCES

Newman P.J., Poncz M. (1995) Inherited disorders of platelets. IN Scriver C.R., Beaudey A.L., Williams S.S., editors, Molecular and Metabolic basis of disease. McGraw&Hill Inc.
George JN, Caen JP,Nurden AT: Glanzmann’s Thronbasthenia: the clinical disease. Blood 1990 Apr 1; PT – REVIEW ACADEMIC (7):1 [Medline].

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