1. Inherited disorders of platelet function Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

2. Introduction • Platelets bind via glycoprotein 1b (GpIb) receptors to von Willebrand factor (vWF) on exposed extracellular matrix (ECM) …then they are activated shapechange granule release …Released adenosine diphosphate (ADP) and thromboxane A2 (TxA2) additional platelet aggregation through binding of platelet GpIIb-IIIa receptors to fibrinogen The primary hemostatic plug is now formed

3. 3 main groups • Defects of adhesion…Bernard-Soulier syndrome • Defects of aggregation…Glanzmann thrombasthenia • Disorders of platelet secretion (release reaction)… = storage pool disorders

4. Bernard-Soulier syndrome • Defective adhesion of platelets to subendothelialmatrix • Caused by an inherited deficiency of the platelet membrane glycoprotein complex Ib-IX …this glycoprotein is a receptor for vWF • Often severe bleeding tendency

5. Glanzmann thrombasthenia • Defective platelet aggregation • Autosomal recessive • The platelets fail to aggregate in response to adenosine diphosphate (ADP), collagen, epinephrine, or thrombin because of deficiency or dysfunction of glycoprotein IIb-IIIa, an integrin that participates in “bridge formation” between platelets by binding fibrinogen • Often severe bleeding tendency

6. Disorders of platelet secretion (release reaction) • Defective release of certain mediators of platelet activation, such as thromboxanes and granule-bound ADP

7. Just to remember • Uremia is a cause of acquired platelet dysfunction …It affects platelet adhesion, aggregation & release reaction

8. Thank You