1. Bleeding in Paris-Trousseau syndrome
11q23 Family Conference
July, 2010

2. Paris-Trousseau Syndrome
Inherited disorder in which children may have:
Heart defects
Neurologic impairment
Growth delay
Low platelets
Due to deletion of the terminal
portion of chromosome 11q

3. Why does a deletion matter?
Normally there are 2 copies of each gene in the body, one from each parent
If one copy is lost, there may not be enough of the protein product for the cell to work normally
Even if the cell can work normally, any problem with the remaining copy can be disastrous
A deleted region of chromosome contains many genes

4. Fli-1 in megakaryocyte development
Fli-1 is one gene that is lost in Paris-Trousseau syndrome
Fli-1 is essential for megakaryocyte and platelet development
Fli-1 promotes platelet development and inhibits red
cells
Fli-1 X

5. Megakaryocytes Large cells in the bone marrow
Produce up to 150 billion circulating platelets each day, 1000 platelets/ MK

6. Proplatelet formation
Italiano, et al., J. Cell Biol. 1999

7. Platelet granules are important for their function
Alpha granules and dense granules contain substances that promote platelet aggregation and clotting
In the body, granules are released when platelets are activated
In the lab, platelet function is often tested by treating platelets with different chemicals that stimulate granule release and measuring platelet aggregation

8. How are platelets in Paris-Trousseau syndrome different?
PTS platelets have large, fused alpha granules, may have reduced dense granules
Normal
PTS
White, Platelets 2007

9. How are platelets in Paris-Trousseau syndrome different?
Platelet function in PTS is not well defined
Bleeding times may be prolonged even when platelet numbers are normal
Overall measurements of platelet function are normal but subpopulation of platelets with abnormal alpha granules do not release granules in response to thrombin
Fewer dense granules may cause storage pool deficiency
Breton-Gorius et al., Blood 1995; Grossfeld et al.,Am JMG 2004; White, Platelets 2007

10. Natural history of thrombocytopenia in PTS
Thrombocytopenia at birth may be severe (10-20,000/microliter; normal is >150,000)
With time (months-years), platelet counts improve in most to normal or near normal levels
Bleeding symptoms due to low platelets commonly include:
Bruising
Nosebleeds
Bleeding from tooth extractions or tonsillectomy
Heavy menses

11. Management of bleeding symptoms
Amicar
For dental procedures, mouth or nose bleeding
Use as a mouthwash or take as a pill or liquid
Oral contraceptives
For girls with heavy periods
DDAV P
May improve platelet aggregation
IV or nasal spray
Platelet transfusion
For serious bleeding or before major surgeries

12. Acknowledgements and resources:
Paul Grossfeld
Platelet Disorder Support Association