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
- Schistocytes – microangiopathic process
- Nucleated RBCs – post splenectomy
- Spherocytes – hereditary spherocytosis or immune-mediated hemolytic anemia
- Leukocytosis with bands – sepsis
- Immature WBCs – leukemia
- Multi-lobed hypersegmented neutrophils – B12 deficiency
- Rule out pseudothrombocytopenia – platelet clumping visible on smear from EDTA sample
- 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)
- Confirm thrombocytopenia – repeat CBC with peripheral smear
- 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
- HIV testing
- HCV testing
- Connective tissue disease evaluation
- Liver disease evaluation
Differential Diagnosis
- See Pathophysiology section in Clinical Background
Epidemiology
- Incidence
- Congenital thrombocytopenia – rare
- Heparin-induced thrombocytopenia (HIT) – 0.5-5% of patients receiving heparin
- Neonatal autoimmune thrombocytopenia (NAIT) – 1/2,000 pregnancies
- Thrombotic microangiopathies (TMA) – 1-2/million
- Idiopathic thrombocytopenic purpura (ITP) – ~2-5/100,000
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
- Immune-mediated
- ITP
- HIT
- NAIT
- Drug-induced (eg, amiodarone, cimetidine, digoxin, furosemide, anticonvulsants, sulfonamides, quinidine, penicillins, vancomycin)
- Connective tissue disease
- Post-transfusion purpura
- Non-immune-mediated
- TMA – TTP, HUS, and aHUS
- Disseminated intravascular coagulation (DIC)
- Sepsis
- Cardiac valves
- HELLP syndrome
- Immune-mediated
- 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
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
Gold standard reflex test for confirming diagnosis of HIT
Reflex pattern – if HIT PF4 antibody, IgG is 0.400 O.D. or greater, SRA (heparin dependent platelet antibody), testing is added
Clinical sensitivity/specificity – >90% for SRA
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
Gold standard test for diagnosis of HIT
Clinical sensitivity/specificity – >90%
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
Recommended initial screening test for heparin-PF4 antibodies that cause HIT
Confirmation with SRA may be necessary based on clinical presentation
Platelet Associated Antibodies, Direct Assay 0095614
Method: Qualitative Flow Cytometry
Support the diagnosis of autoimmune thrombocytopenia (AITP)
Platelet Antibodies, Indirect with Reflex to Identification 0051718
Method: Enzyme-Linked Immunosorbent Assay
Not recommended for the diagnosis of ITP
Preferred test for platelet-specific antibodies in suspected fetal or neonatal alloimmune thrombocytopenia, posttransfusion purpura, or multiplatelet transfusion refractoriness
Glycoproteins include
- GPIIb/IIIa complex including HPA-1a (PlA1), HPA-1b (PlA2), HPA-3a (Baka), HPA-3b (Bakb), and HPA-4a (Pena)
- GPIa/IIa complex (HPA-5a and HPA-5b) and antibodies against GPIb/IX and GPIV
Reflex pattern – if platelet antibodies directed toward GP IIb/IIIa are present, additional testing identifies the specific GP IIb/IIIa epitope
- HPA-1a/1b
- HPA-3a/3b
- HPA-4a
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
Assess risk for NAIT; may be ordered for parental, fetal, or neonatal genotyping
Clinical sensitivity/specificity – unknown
Gene included – HPA
Antigens tested include a and b variants of HPA-1 through -6 and HPA-15
Refer to Additional Technical Information document for further content
Tests may be ordered individually or as a panel; test performed with whole blood, amniotic fluid, or cultured amniocytes
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
Assist in diagnosing congenital or inherited thrombotic thrombocytopenic purpura (TTP)
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
Initial test for suspected bleeding disorder
Partial Thromboplastin Time 0030235
Method: Electromagnetic Mechanical Clot Detection
Initial test for suspected bleeding disorder
Thrombin Time with Reflex to Thrombin Time 1:1 Mix 0030260
Method: Electromagnetic Mechanical Clot Detection
Assist in diagnosing dysfibrinogenemia or abnormalities with fibrin polymerization
Screen samples for the presence of heparin or direct thrombin inhibitors
Reflex pattern – if TT is elevated, then TT 1:1 mix will be added
Normal result does not rule out DIC
D-Dimer 0030057
Method: Immunoturbidimetry
Aid in diagnosing and following DIC
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
Determine if fibrinogen deficiency is a potential cause of bleeding
Normal result does not rule out DIC
Platelet Aggregation Studies 0030160
Method: Qualitative Aggregation
Evaluate patients with suspected inherited qualitative platelet disorders or patients with lifelong platelet-type bleeding
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
Recommended panel for the initial workup of suspected von Willebrand disease (VWD)
Panel includes VWF antigen, ristocetin cofactor activity, and factor VIII activity
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