Thrombocytopenic Disorders

Thrombocytopenia, Idiopathic Thrombocytopenic Purpura (ITP)

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

Platelet count <100-150 x 109/L

Laboratory Testing

  • Level of medical urgency determines which tests might be ordered and urgency of ordering those tests (eg, acutely ill patient versus ambulatory patient versus pregnant patient)
  • Initial testing
    • Confirm thrombocytopenia – repeat CBC with peripheral smear
      • Rule out pseudothrombocytopenia – platelet clumping visible on smear from ethylenediaminetetraacetic acid (EDTA) sample
        • Repeat testing using citrated blood
      • Peripheral smear may give clues as to cause of thrombocytopenia
    • Chemistry and urine testing to evaluate potential hemolysis
    • Disseminated intravascular coagulation (DIC) testing if clinically indicated – prothrombin time (PT), partial thromboplastin time (PTT), D-dimer
    • ​Consider drugs that may be causing thrombocytopenia (eg, heparin, cimetidine, amiodarone)
  • Secondary testing should be performed based on history and clinical presentation
    • Neonatal thrombocytopenia – refer to neonatal alloimmune thrombocytopenia
    • Thrombocytopenia or thromboses following administration of heparin – refer to heparin-induced thrombocytopenia
    • Childhood onset of thrombocytopenia – various studies may be necessary to evaluate the varied causes of congenital thrombocytopenia
    • Idiopathic thrombocytopenic purpura suspected – if patient meets clinical diagnostic criteria, testing for direct platelet antibodies aids in confirming diagnosis of autoimmune thrombocytopenia
  • Other possible testing based on clinical scenario

Differential Diagnosis

Refer to Pathophysiology section in Clinical Background section

Epidemiology

Pathophysiology

  • Causes can be subdivided into categories
    • Pseudothrombocytopenia – associated with ethylenediaminetetraacetic acid (EDTA) (found in purple top collection tube) initiating platelet clumping and spuriously decreased platelet count
    • Decreased platelet production
      • Congenital
      • Bone marrow disorders (eg malignancy, ineffective thrombopoiesis, or bone marrow failure)
      • Chemical or toxin mediated (eg, ionizing radiation, chemotherapy)
      • Infectious  (eg, parvovirus B19, adenovirus, Epstein Barr virus [EBV], HIV)
    • Increased platelet destruction
    • Splenic sequestration
      • Spleen harbors up to 30% of platelets
      • Splenomegaly can reduce count via sequestration
    • Dilution
      • Following major surgery
      • Following large transfusion of blood products lacking platelets

Clinical Presentation

  • Bleeding tendency
  • Easy bruisability, petechia, purpura
  • Other signs and symptoms are based on the specific etiology for thrombocytopenia – refer to TMA, HIT, and NAIT topics
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Heparin-Induced Thrombocytopenia (HIT) PF4 Antibody, IgG with Reflex to Serotonin Release Assay (Heparin Dependent Platelet Antibody), Unfractionated Heparin 2012181
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Serotonin Release Assay

Limitations 

Occasional false negatives occur with HIT testing; does not exclude HIT if clinical suspicion is high

Results should always be correlated with clinical findings

Serotonin Release Assay (Heparin Dependent Platelet Antibody), Unfractionated Heparin 2005631
Method: Qualitative Serotonin Release Assay

Limitations 

Occasional false negatives occur; does not exclude HIT if suspicion is high

Results should always be correlated with clinical findings

Heparin-Induced Thrombocytopenia (HIT) PF4 Antibody, IgG 2012179
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Platelet Associated Antibodies, Direct Assay 0095614
Method: Qualitative Flow Cytometry

Limitations 

Does not distinguish between autoantibodies and alloantibodies

Does not identify specific types of antiplatelet antibodies, such as those against HPA-1a

Platelet Antibodies, Indirect 0051050
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Platelet Antigen Genotyping Panel 0051308
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

HPA alleles, other than those tested, are not determined

Bloody amniotic fluid specimens may give false-negative results because of maternal cell contamination

Diagnostic errors can occur due to rare sequence variations

ADAMTS13 Activity 0030056
Method: Chromogenic Assay

Limitations 

Mild to moderate ADAMTS13 deficiency may be seen in a variety of medical conditions

Prothrombin Time 0030215
Method: Electromagnetic Mechanical Clot Detection

Partial Thromboplastin Time 0030235
Method: Electromagnetic Mechanical Clot Detection

Thrombin Time with Reflex to Thrombin Time 1:1 Mix 0030260
Method: Electromagnetic Mechanical Clot Detection

D-Dimer 0030057
Method: Immunoturbidimetry

Limitations 

Presence of rheumatoid factor may lead to false-positive results; test should not be used to rule out venous thromboembolism (VTE)

Fibrinogen 0030130
Method: Electromagnetic Mechanical Clot Detection

Platelet Aggregation Studies 0030160
Method: Qualitative Aggregation

Limitations 

This test is available only for local clients due to short sample stability time

von Willebrand Panel 0030125
Method: Electromagnetic Mechanical Clot Detection/Platelet Agglutination/Microlatex Particle-Mediated Immunoassay

Guidelines

Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA, American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011; 117(16): 4190-207. PubMed

General References

Arnold DM, Smith JW, Kelton JG. Diagnosis and management of neonatal alloimmune thrombocytopenia. Transfus Med Rev. 2008; 22(4): 255-67. PubMed

Balduini CL, Savoia A. Genetics of familial forms of thrombocytopenia. Hum Genet. 2012; 131(12): 1821-32. PubMed

Chapman K, Seldon M, Richards R. Thrombotic microangiopathies, thrombotic thrombocytopenic purpura, and ADAMTS-13. Semin Thromb Hemost. 2012; 38(1): 47-54. PubMed

Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012; 120(20): 4160-7. PubMed

Favaloro EJ, Lippi G, Franchini M. Contemporary platelet function testing. Clin Chem Lab Med. 2010; 48(5): 579-98. PubMed

Geddis AE. Inherited thrombocytopenias: an approach to diagnosis and management. Int J Lab Hematol. 2013; 35(1): 14-25. PubMed

George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014; 371(7): 654-66. PubMed

Ghanima W, Godeau B, Cines DB, Bussel JB. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood. 2012; 120(5): 960-9. PubMed

Heikal NM, Smock KJ. Laboratory testing for platelet antibodies. Am J Hematol. 2013; 88(9): 818-21. PubMed

Nurden AT, Fiore M, Pillois X, Nurden P. Genetic testing in the diagnostic evaluation of inherited platelet disorders. Semin Thromb Hemost. 2009; 35(2): 204-12. PubMed

Nurden AT, Freson K, Seligsohn U. Inherited platelet disorders. Haemophilia. 2012; 18 Suppl 4: 154-60. PubMed

Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol. 2013; 161(1): 3-14. PubMed

Sekhon SS, Roy V. Thrombocytopenia in adults: A practical approach to evaluation and management. South Med J. 2006; 99(5): 491-8; quiz 499-500, 533. PubMed

Shenkman B, Einav Y. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification. Autoimmun Rev. 2014; 13(4-5): 584-6. PubMed

Smock KJ, Perkins SL. Thrombocytopenia: an update. Int J Lab Hematol. 2014; 36(3): 269-78. PubMed

Strong NK, Eddleman KA. Diagnosis and management of neonatal alloimmune thrombocytopenia in pregnancy. Clin Lab Med. 2013; 33(2): 311-25. PubMed

Visentin GP, Liu CY. Drug-induced thrombocytopenia. Hematol Oncol Clin North Am. 2007; 21(4): 685-96, vi. PubMed

Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008; 6(8): 1304-12. PubMed

Wirth SM, Macaulay TE, Armitstead JA, Steinke DT, Blechner MD, Lewis DA. Evaluation of a clinical scoring scale to direct early appropriate therapy in heparin-induced thrombocytopenia. J Oncol Pharm Pract. 2010; 16(3): 161-6. PubMed

Smock KJ. The role of ADAMTS13 testing in the work up of suspected thrombotic thrombocytopenic purpura. American Association for Clinical Chemistry. [Published Apr 2016; Accessed: Apr 2017]

Medical Reviewers

Last Update: September 2017