Thrombocytopenic Disorders

Thrombocytopenic disorders include congenital thrombocytopenia, heparin-induced thrombocytopenia (HIT), neonatal alloimmune thrombocytopenia (NAIT), thrombotic microangiopathies (TMA), and idiopathic thrombocytopenic purpura (ITP). The level of medical urgency determines which tests might be ordered and the urgency of ordering those tests (eg, acutely ill patient versus ambulatory patient versus pregnant patient).

Diagnosis

Indications for Testing

Platelet count <100-150 x 109/L

Laboratory Testing

  • 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 in Background.

Background

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

ARUP Lab Tests

Gold standard reflex test for confirming diagnosis of HIT

Reflex pattern: if HIT PF4 antibody, IgG is 0.400 optical density (OD) or greater, serotonin release assay (SRA) 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

Gold standard test for diagnosis of HIT

Clinical sensitivity/specificity: >90%

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

Results should always be correlated with clinical findings

 

Recommended initial screening test for heparin-PF4 antibodies that cause HIT

Confirmation with SRA may be necessary based on clinical presentation

Support diagnosis of autoimmune thrombocytopenia (AITP)

Does not distinguish between autoantibodies and alloantibodies

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

Not recommended for diagnosis of immune thrombocytopenic purpura (ITP)

Use to detect platelet-specific antibodies in suspected fetal or neonatal alloimmune thrombocytopenia, posttransfusion purpura, or multiplatelet transfusion refractoriness

Assess risk for fetal or neonatal alloimmune thrombocytopenia; may be ordered for parental, fetal, or neonatal genotyping

Refer to Platelet Antigen Genotyping Panel Test Fact Sheet for further content

Test performed with whole blood, amniotic fluid, or cultured amniocytes

Bloody amniotic fluid specimens may give false-negative results due to maternal cell contamination

Diagnostic errors can occur due to rare sequence variations

Genes included: human platelet antigens (HPA) genes (GP1BA, ITGA2B, ITGB3, ITGA2, ITGB3, and CD109)

​Antigens tested include a and b variants of HPA-1 through -6 and HPA-15

Reflexive panel to assist in diagnosis of thrombotic thrombocytopenic purpura (TTP) and in distinguishing between inherited and acquired forms of TTP

Assist in diagnosing congenital or inherited thrombotic thrombocytopenic purpura (TTP)

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

Assist in distinguishing between inherited and acquired forms of thrombotic thrombocytopenic purpura (TTP)

Recommended initial test for the identification of autoantibodies to ADAMTS13; more specific for acquired TTP than ADAMTS13 antibody test

If TTP is suspected but antibodies are not identified by inhibitor test, ADAMTS13 antibody testing is recommended

Assist in distinguishing between inherited and acquired forms of thrombotic thrombocytopenic purpura (TTP)

Not recommended as the initial test for identification of autoantibodies to ADAMTS13; ADAMTS13 antibody test is less specific for acquired TTP than the inhibitor test

Order when acquired TTP is suspected but antibodies are not identified by the ADAMTS13 inhibitor test

Initial test for suspected bleeding disorder

Assist in diagnosing dysfibrinogenemia or abnormalities with fibrin polymerization

Screen samples for the presence of heparin or direct thrombin inhibitors

Reflex pattern: if thrombin time (TT) is elevated, then TT 1:1 mix will be added

Aid in diagnosing and following disseminated intravascular coagulation (DIC)

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

Determine if fibrinogen deficiency is a potential cause of bleeding

Evaluate patients with suspected inherited qualitative platelet disorders or patients with lifelong platelet-type bleeding

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

Recommended panel for the initial workup of suspected von Willebrand disease (VWD)

Panel includes von Willebrand factor (VWF) antigen, ristocetin cofactor activity, and factor VIII activity

Related Tests

Use to confirm thrombocytopenia

Platelet clumping suggests pseudothrombocytopenia

Not recommended to screen for heparin-PF4 antibodies that cause HIT; preferred test is HIT PF4 antibody, IgG

Medical Experts

Contributor
Contributor

Smock

Kristi J. Smock, MD
Kristi J. Smock, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®

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