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Disease Categories > Hematologic Disease

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Functional Platelet Disorders

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
Disorder	Defect	Clinical Presentation (in order of frequency)	Diagnosis
Bernard-Soulier syndrome	Platelet GPIb-IX-V complex (Disorder of adhesion)	Epistaxis, ecchymoses, menorrhagia, gingival hemorrhage, gastrointestinal bleeding	Platelets – decreased numbers; giant sized platelet Aggregation studies – abnormal response to ristocetin
von Willebrand disease	vWF deficiency (Disorder of adhesion)	Epistaxis, ecchymoses, menorrhagia, gingival hemorrhage	Platelets – normal numbers
Glanzmann thrombasthenia	Platelet glycoprotein Alpha II beta III (Disorder of aggregation)	Menorrhagia, ecchymoses, epistaxis, gingival hemorrhage	Platelets – normal numbers Bleeding time – prolonged Aggregation studies – no response to epinephrine; platelet shape change to ADP, thrombin, collagen
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	Platelets – normal numbers Bleeding time – prolonged Aggregation studies – secondary with response to thrombin abnormal
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	Platelets – normal numbers Bleeding time – increased Aggregation studies – secondary with decreased response to adenosine diphosphate (ADP)
Gray-platelet syndrome	Deficiency of alpha granules in platelets (Disorder of granule release)	Mild mucosal bleeding	Platelets – decreased numbers; large gray platelets on peripheral smear Aggregation studies – abnormal to collagen and thrombin
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	Platelets – normal numbers Bleeding time – prolonged Aggregation studies – abnormal to secondary stimulation

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

Hemophilia - Factor VIII Carrier

Von Willebrand Disease - vWD

Test Name and Number	Recommended Use	Limitations	Follow Up
Platelet Aggregation Studies 0030160 Method: Aggregation	Evaluate patients with inherited qualitative platelet disorders Evaluate patients with mucocutaneous bleeding of a life-long nature but who have a normal platelet count Evaluate patients for aspirin resistance	This is a time-sensitive test Do not order this test if platelets are decreased <100,000/mL	If all studies are normal and platelet dysfunction is still a possibility, order one or all of the following: von Willebrand factor assays, platelet granule content measures and membrane glycoprotein presence
CBC with Platelet Count 0040002 Method: Automated Cell Count	Identify thrombocytopenia
Immunohistochemistry Stain Offering arup005 Method: Immunohistochemistry	For fixed tissue samples, consultative services as well as immunohistochemical staining for CD42b are available

Test Name and Number	Comments
Platelet Antigen 1 Genotyping (HPA-1) 0051309 Method: Polymerase Chain Reaction/Fluorescence Monitoring

General References

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

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

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

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

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

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

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

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

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

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. (Link to PubMed)

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. (Link to PubMed)

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

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

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

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. (Link to PubMed)

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

Reviewed by

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: November 2007

Functional Platelet Disorders

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