Thrombocytopenic Disorders

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

Indications for Testing

  • Platelet count <100-150 X 109/L

Laboratory Testing

  • Level of medical urgency will determine 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 EDTA sample
        • Repeat testing using citrated blood
      • Peripheral smear may give clues to cause of thrombocytopenia
    • Chemistry and urine testing to evaluate potential hemolysis
    • Disseminated intravascular coagulation (DIC) testing if clinically indicated – PT, 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 topic
    • Thrombocytopenia or thromboses following administration of heparin – refer to heparin-induced thrombocytopenia topic
    • 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 the diagnosis of autoimmune thrombocytopenia
  • Other possible testing based on clinical scenario

Differential Diagnosis

  • See Pathophysiology section in Clinical Background

Epidemiology

Pathophysiology

  • Causes can be subdivided into categories
    • Pseudothrombocytopenia – associated with EDTA (found in purple top) 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, 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 

SRA is a technically demanding, functional assay; extra turnaround time required

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

Platelet Antibodies, Indirect with Reflex to Identification 0051718
Method: Enzyme-Linked Immunosorbent Assay

Limitations 

Recommend testing on maternal sample as unbound platelet antibodies may not be detected in neonatal serum

Detection of a platelet antibody is not diagnostic for NAIT

Antibodies to HPA-4b (Penb) may not be detected

Antibodies to platelet antigens not listed will not be detected

Detects both alloantibodies and autoantibodies but will not distinguish between them

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 

Specimen must be drawn prior to beginning plasma infusion or exchange

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

Limitations 

Normal result does not rule out DIC

D-Dimer 0030057
Method: Immunoturbidimetry

Limitations 

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

Fibrinogen 0030130
Method: Electromagnetic Mechanical Clot Detection

Limitations 

Normal result does not rule out DIC

Platelet Aggregation Studies 0030160
Method: Qualitative Aggregation

Limitations 

This is a time-sensitive test – this test is only available for local clients due to 4-hour sample stability

Do not order this test if platelets are decreased (<100,000/μL)

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: April 2017