Qualitative platelet disorders.

1. Larry D Brace, PhD[⇑][1] 1. is Associate Professor Emeritus, University of Illinois at Chicago, Chicago IL 1. Address for correspondence: Larry Brace PhD, Professor Emeritus, University of Illinois at Chicago, 11285 Plainfield Road, Indian Head Park IL 60525. (708) 246-7150. lbrace{at}uic.edu. Upon completion of this article, the reader will be able to: 1. recognize the clinical presentation of patients with dysfunctional platelets. 2. describe the defect in each of the following hereditary disorders: Glanzmann thrombasthenia and Bernard-Soulier syndrome (BSS). 3. distinguish among the following types of hereditary platelet disorders: membrane receptor abnormality, secretion disorder, and storage pool deficiency. 4. ror each of the inherited platelet disorders listed, name useful laboratory tests and recognize diagnostic results. 5. Discuss general mechanisms of action for antiplatelet drugs. 6. explain the effects of paraproteins on platelet function. 7. describe the effect of aspirin, clopidogrel, and αIIb/β3 inhibitors on platelet function. 8. discuss the mechanism of the platelet defects associated with myeloproliferative diseases, uremia, and liver disease. Mucocutaneous bleeding in a patient whose platelet count is normal suggests a disorder of platelet function. Congenital and acquired disorders may cause abnormalities in each phase of platelet function: adhesion, aggregation, and secretion. The qualitative disorders are detected and monitored using platelet aggregometry.1 Qualitative disorders are summarized in Table 1. Bernard-Soulier (giant platelet) syndrome Bernard-Soulier syndrome (BSS) usually manifests in infancy or childhood with mucocutaneous hemorrhage characteristic of defective platelet function: ecchymoses, epistaxis, and gingival bleeding. BSS is inherited as an autosomal recessive disorder in which the glycoprotein (GP) Ib/IX/V complex exhibits abnormal function. Heterozygotes with about 50% of normal levels of GP Ib, GP V, and GP IX have normal platelet function. Homozygotes have moderate to severe bleeding characterized by enlarged platelets, thrombocytopenia, and decreased platelet survival. Platelet counts range from 40,000/μL to near-normal.2 Platelets typically are five to eight μm in diameter although a few reach 20 μm. Viewed by electron microscopy, BSS platelets contain a larger number of cytoplasmic vacuoles and membrane complexes.3-5 Four glycoproteins are required to form the GP Ib/IX/V complex: GP Ibα, GP Ibβ, GP IX, and GP V. These are present in the ratio of 2:2:2:1. The gene for GP Ibα is located on chromosome 17, the gene for GP Ibβ is located on chromosome 22, and the genes for GP IX and GP V are on chromosome 3. For surface expression of the complex, it seems that synthesis of three proteins, GP Ibα, GP Ibβ, and GP IX,… ABBREVIATIONS: ADP = adenosine diphosphate; BSS = Bernard-Soulier syndrome; GP = glycoprotein; GSA = guanidinosuccinic oxide MPDs = myeloproliferative disorders; NO = nitric oxide; NSAIDs = non-steroidal anti-inflammatory drugs; TXA2 = thromboxane A2; VWD = von Willebrand disease; VWF = von Willebrand factor. Upon completion of this article, the reader will be able to: 1. recognize the clinical presentation of patients with dysfunctional platelets. 2. describe the defect in each of the following hereditary disorders: Glanzmann thrombasthenia and Bernard-Soulier syndrome (BSS). 3. distinguish among the following types of hereditary platelet disorders: membrane receptor abnormality, secretion disorder, and storage pool deficiency. 4. ror each of the inherited platelet disorders listed, name useful laboratory tests and recognize diagnostic results. 5. Discuss general mechanisms of action for antiplatelet drugs. 6. explain the effects of paraproteins on platelet function. 7. describe the effect of aspirin, clopidogrel, and αIIb/β3 inhibitors on platelet function. 8. discuss the mechanism of the platelet defects associated with myeloproliferative diseases, uremia, and liver disease. [1]: #corresp-1