Functional Platelet Disorders

Clinical Background

Platelet dysfunction is frequently associated with excessive bleeding and can be acquired or inherited.

Epidemiology

All inherited disorders are rare
Age - age of onset depends on disorder

Inherited Platelet Disorders -- Clinical Presentation
Disorder	Defect	Clinical Presentation (in order of frequency)
Bernard-Soulier syndrome	Platelet GPIb-IX-V complex (Disorder of adhesion)	Epistaxis, ecchymoses, menorrhagia, gingival hemorrhage, gastrointestinal bleeding
von Willebrand disease	vWF deficiency (Disorder of adhesion)	Epistaxis, ecchymoses, menorrhagia, gingival hemorrhage
Glanzmann thrombasthenia	Platelet glycoprotein Alpha II beta III (Disorder of aggregation)	Menorrhagia, ecchymoses, epistaxis, gingival hemorrhage
Oculocutaneous albinism (Hermansky-Pudlak syndrome)	Lack of giant granules in platelets (Disorder of granule release)	Oculocutaneous albinism Excessive mucosal bleeding Deposition of ceroid lipofuscin in organs
Chediak-Higashi syndrome	Deficiency of storage pools of ADP and serotonin & decreased dense bodies in platelets (Disorder of granule release)	Recurrent infections Loss of pigment in hair and skin CNS ataxia common Excessive mucosal bleeding
Gray-platelet syndrome	Deficiency of alpha granules in platelets (Disorder of granule release)	Mild mucosal bleeding
Delta storage pool deficiency	Abnormal dense granules in platelets (Disorder of granule release)	Frequently a part of other syndromes such as Wiskott Aldrich, Chediak-Higashi Mild mucosal bleeding

Acquired disorders include

Disorders of adhesion
- Uremia
- Acquired von Willebrand disease
Disorders of aggregation
- Fibrin degradation product inhibition
- Dysproteinemias
- Drugs (ticlopidine)
Disorders of granule release
- Cardiopulmonary bypass
- Drugs (aspirin, NSAIDs)
- Myeloproliferative disorders

Risk Factors

Genetics - most are inherited as autosomal recessive traits

Pathophysiology

Platelets circulate in the blood as small disc-shaped cells
Functions
- Aggregate in response to a variety of stimuli and secrete substances such as adenosine diphosphate (ADP)
- Adhere to and spread on damaged endothelial surfaces and aggregate with one another
- Normal platelet count is 150,000 to 450,000 µL
Patients with thrombocytopenia will have abnormalities in aggregation even in the face of normal platelet function

See Also

Disseminated Intravascular Coagulation - DIC

Hemophilia - Factor VIII Carrier

Neonatal Alloimmune Thrombocytopenia - NAIT

Von Willebrand Disease - vWD

References

General References

Asselta R, Duga S, Tenchini ML. The molecular basis of quantitative fibrinogen disorders. J Thromb Haemost. 2006;4(10):2115-2129.

Balduini CL, Savoia A. Inherited thrombocytopenias: molecular mechanisms. Semin Thromb Hemost. 2004;30(5):513-523.

Di Pietro SM, Dell'Angelica EC. The cell biology of Hermansky-Pudlak syndrome: recent advances. Traffic. 2005;6(7):525-533.

Gunay-Aygun M, Huizing M, Gahl WA. Molecular defects that affect platelet dense granules. Semin Thromb Hemost. 2004;30(5):537-547.

Hayward CP, Rao AK, Cattaneo M. Congenital platelet disorders: overview of their mechanisms, diagnostic evaluation and treatment. Haemophilia. 2006;12 Suppl 3:128-136.

Neerman-Arbez M. Molecular basis of fibrinogen deficiency. Pathophysiol Haemost Thromb. 2006;35(1-2):187-198.

Nurden AT, Nurden P. The gray platelet syndrome: clinical spectrum of the disease. Blood Rev. 2007;21(1):21-36.

Nurden AT. Qualitative disorders of platelets and megakaryocytes. J Thromb Haemost. 2005;3(8):1773-1782.

Packham MA, Mustard JF. Platelet aggregation and adenosine diphosphate/adenosine triphosphate receptors: a historical perspective. Semin Thromb Hemost. 2005;31(2):129-138.

Peyvandi F, Kaufman RJ, Seligsohn U, Salomon O, Bolton-Maggs PH, Spreafico M, Menegatti M, Palla R, Siboni S, Mannucci PM. Rare bleeding disorders. Haemophilia. 2006;12 Suppl 3:137-142.

Poon MC, Zotz R, Di Minno G, Abrams ZS, Knudsen JB, Laurian Y. Glanzmann's thrombasthenia treatment: a prospective observational registry on the use of recombinant human activated factor VII and other hemostatic agents. Semin Hematol. 2006;43(1 Suppl 1):S33-S36.

Ramasamy I. Inherited bleeding disorders: disorders of platelet adhesion and aggregation. Crit Rev Oncol Hematol. 2004;49(1):1-35.

Saito H, Matsushita T, Yamamoto K, Kojima T, Kunishima S. Giant platelet syndrome. Hematology. 2005;10 Suppl 1:41-46.

Seligsohn U. Glanzmann thrombasthenia: a model disease which paved the way to powerful therapeutic agents. Pathophysiol Haemost Thromb. 2002;32(5-6):216-217.

Shiflett SL, Kaplan J, Ward DM. Chediak-Higashi Syndrome: a rare disorder of lysosomes and lysosome related organelles. Pigment Cell Res. 2002;15(4):251-257.

White GC. Congenital and acquired platelet disorders: current dilemmas and treatment strategies. Semin Hematol. 2006;43(1 Suppl 1):S37-S41.

Medical Reviewers

Rodgers, George M. III, M.D., Ph.D. Medical Director, Hemostasis/Thrombosis at ARUP Laboratories; Professor, Medicine, Adjunct Professor, Pathology, University of Utah

Comprehensive Review: November 2007
Last Update: September 2008

Inherited Platelet Disorders -- Diagnosis
Disorder	Diagnosis
Bernard-Soulier syndrome	Platelets - decreased numbers; giant sized platelet Aggregation studies - abnormal response to ristocetin
von Willebrand disease	Platelets - normal numbers
Glanzmann thrombasthenia	Platelets - normal numbers Bleeding time - prolonged Aggregation studies - no response to epinephrine; platelet shape change to ADP, thrombin, collagen
Oculocutaneous albinism (Hermansky-Pudlak syndrome)	Platelets - normal numbers Bleeding time - prolonged Aggregation studies - secondary with response to thrombin abnormal
Chediak-Higashi syndrome	Platelets - normal numbers Bleeding time - increased Aggregation studies - secondary with decreased response to adenosine diphosphate (ADP)
Gray-platelet syndrome	Platelets - decreased numbers; large gray platelets on peripheral smear Aggregation studies - abnormal to collagen and thrombin
Delta storage pool deficiency	Platelets - normal numbers Bleeding time - prolonged Aggregation studies - abnormal to secondary stimulation