Inherited platelet disorders

Haemophilia. 2012 Jul;18 Suppl 4:154-60. doi: 10.1111/j.1365-2516.2012.02856.x.


Inherited diseases of the megakaryocyte lineage give rise to bleeding when platelets fail to fulfill their hemostatic function upon vessel injury. Platelet defects extend from the absence or malfunctioning of adhesion (GPIb-IX-V, Bernard-Soulier syndrome) or aggregation receptors (integrin αIIbβ3, Glanzmann thrombasthenia) to defects of primary receptors for soluble agonists, secretion from storage organelles, activation pathways and the generation of procoagulant activity. In disorders such as the Chediak-Higashi, Hermansky-Pudlak, Wiskott-Aldrich and Scott syndromes the molecular lesion extends to other cells. In familial thrombocytopenia (FT), platelets are produced in insufficient numbers to assure hemostasis. Some FT affect platelet morphology and give rise to the 'giant platelet' syndromes (e.g. MYH9-related diseases) with changes in megakaryocyte maturation within the bone marrow and premature release of platelets. Diseases of platelet production may also affect other cells and in some cases interfere with development and/or functioning of major organs. Diagnosis of platelet disorders requires platelet function testing, studies often aided by the quantitative analysis of receptors by flow cytometry and fluorescence and electron microscopy. New generation DNA-based procedures including whole exome sequencing offer an exciting new perspective. Transfusion of platelets remains the most common treatment of severe bleeding, management with desmopressin is often used for mild disorders. Substitute therapies are available including rFVIIa and the potential use of thrombopoietin analogues for FT. Stem cell or bone marrow transplantation has been successful for several diseases while gene therapy shows promise in the Wiskott-Aldrich syndrome.

Publication types

  • Review

MeSH terms

  • Blood Coagulation Disorders, Inherited / diagnosis
  • Blood Coagulation Disorders, Inherited / genetics*
  • Blood Coagulation Disorders, Inherited / therapy
  • Blood Platelet Disorders / diagnosis
  • Blood Platelet Disorders / genetics*
  • Blood Platelet Disorders / therapy
  • Humans
  • Platelet Membrane Glycoproteins / physiology
  • Signal Transduction


  • Platelet Membrane Glycoproteins