Thrombocytopenia laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Farbod Zahedi Tajrishi, M.D. [2]
Overview
On a CBC, platelet count < 150,000 per µm3 is considered as thrombocytopenia. Pseudothrombocytopenia, meaning a falsely reported low platelet count, should be ruled out before confirming thrombocytopenia and performing further diagnostic tests. A peripheral blood smear and/or repeating the CBC using a non-EDTA anticoagulant help to do so. Other laboratory findings on CBC and PBS are usually of great benefit and could narrow down the wide range of differential diagnoses for thrombocytopenia. Further laboratory testing are only recommended when these tests are already performed and suggestive of a condition. As thrombocytopenia is closely associated with HIV and HCV infections, adults with new-onset thrombocytopenia should be evaluated for these two conditions
Laboratory Findings
Laboratory tests might include: full blood count (CBC), liver enzymes, renal function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear.
CBC:
On a CBC, platelet count < 150,000 per µm3 is considered as thrombocytopenia. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply any form of disease. The number of platelets in a blood sample also decreases quickly with time and a low platelet count may be caused by a delay between sampling and analysis.
- Pseudothrombocytopenia:
Pseudothrombocytopenia simply means a false low platelet count. It usually occurs when platelet clumps are formed in blood samples and as a result the automated counter devices consider them as other entities (eg. leukocytes) by mistake. Several conditions can cause pseudothrombocyopenia. For instance:
- Blood samples that are not mixed or anticoagulated appropriately
- Exposure of blood samples to the EDTA anticoagulant in the collection tube
Note that a small proportion of the general population (~0.1%) have EDTA-dependent anti-platelet autoantibodies that can also result in platelet clumping. EDTA induces the dissociation of GPIIb/IIIa, which in turn exposes a concealed epitope on platelet membrane GPIIb/IIIa. This epitope causes the production of the aforementioned anti-platelet autoantibodies.[1][2][3][4][5][6]
- Platelet satellitism; i.e. rosette formation of platelets around WBCs (whether normal WBCs or lymphoma cells).[7][8][9][10]
- A peripheral blood smear and/or repeating the CBC using a non-EDTA anticoagulant help distinguish pseudothrombocytopenia. After ruling out pseudothrombocytopenia, one of these findings may be present in the CBC:
| Laboratory finding | Examples of associated conditions | Further explanations |
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| isolated thrombocytopenia |
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| thrombocytopenia + anemia |
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Combined anemia and thrombocytopenia may occur if there has been longstanding bleeding (eg, gastrointestinal). Combined anemia and thrombocytopenia also raises the possibility of systemic disorders.
Note that some of the mentioned conditions can coexist. |
| thrombocytopenia + leukocytosis |
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| thrombocytopenia + anemia + leukopenia (pancytopenia) | - | - |
| pseudothrombocytopenia | - | - |
Repeat CBC
A repeat CBC is indicated in the following conditions:
- outpatients with isolated mild thrombocytopenia (platelet count = 100,000 to 149,000 per µL), since platelet counts will improve in some of these patients without any interventions. [11]
- asymptomatic patients (eg, no signs of bleeding and no comorbidities) with moderate thrombocytopenia (platelet count = 50,000 to 100,000 per µL)
Peripheral blood smear
Peripheral blood smear is a useful test to exclude pseudothrombocytopenia and even to determine the underlying cause of thrombocytopenia. Abnormal cell morphologies on a PBS could be diagnostic; for instance:
| Finding on PBS | suggested diagnosis |
|---|---|
| Giant platelets | congenital platelet disorders such as Bernard-Soulier syndrome |
| Schistocytes | microangiopathic processes: |
| Nucleated RBCs and Howell-Jolly bodies |
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| Spherocytes |
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| Leukoerythroblastic findings, teardrop cells, nucleated RBCs, or immature granulocytes | bone marrow infiltration |
| Bandemia (left shift) and/or toxic granulations | infection |
| Immature/dysplastic WBCs | |
| Hypersegmented neutrophils | megaloblastic process |
HIV and HCV testing
As thrombocytopenia is closely associated with HIV and HCV infections, adults with new-onset thrombocytopenia should be evaluated for these two conditions.[12][13]
Further lab tests
Additional testing is necessary only when there are other findings as well as thrombocytopenia that suggest specific conditions. For example, findings suggestive of SLE or APS may lead to appropriate antibody testing or signs of liver disease may prompt for measurements of liver enzymes and liver function testing.
References
- ↑ Savage RA (1984). "Pseudoleukocytosis due to EDTA-induced platelet clumping". Am J Clin Pathol. 81 (3): 317–22. PMID 6422738.
- ↑ Payne BA, Pierre RV (1984). "Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences". Mayo Clin Proc. 59 (2): 123–5. PMID 6422167.
- ↑ Pegels JG, Bruynes EC, Engelfriet CP, von dem Borne AE (1982). "Pseudothrombocytopenia: an immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate". Blood. 59 (1): 157–61. PMID 6797491.
- ↑ Casonato A, Bertomoro A, Pontara E, Dannhauser D, Lazzaro AR, Girolami A (1994). "EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA". J Clin Pathol. 47 (7): 625–30. PMC 502090. PMID 8089218.
- ↑ Bartels PC, Schoorl M, Lombarts AJ (1997). "Screening for EDTA-dependent deviations in platelet counts and abnormalities in platelet distribution histograms in pseudothrombocytopenia". Scand J Clin Lab Invest. 57 (7): 629–36. PMID 9397495.
- ↑ Fiorin F, Steffan A, Pradella P, Bizzaro N, Potenza R, De Angelis V (1998). "IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb". Am J Clin Pathol. 110 (2): 178–83. PMID 9704616.
- ↑ Cesca C, Ben-Ezra J, Riley RS (2001). "Platelet satellitism as presenting finding in mantle cell lymphoma. A case report". Am J Clin Pathol. 115 (4): 567–70. doi:10.1309/75CQ-V7UX-4QX8-WXE7. PMID 11293905.
- ↑ Montague N, Blackwelder P, Alsayegh H, Ochoa R, Vial X, Byrne GE (2013). "Platelet satellitism and dual surface immunoglobulin light-chain expression in circulating splenic marginal zone lymphoma cells". Ann Diagn Pathol. 17 (1): 117–22. doi:10.1016/j.anndiagpath.2011.06.001. PMID 21889383.
- ↑ Bobba RK, Doll DC (2012). "Platelet satellitism as a cause of spurious thrombocytopenia". Blood. 119 (18): 4100. PMID 22701880.
- ↑ Podda GM, Pugliano M, Femia EA, Mezzasoma AM, Gresele P, Carpani G; et al. (2012). "The platelet count in EDTA-anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories". Am J Hematol. 87 (7): 727–8. doi:10.1002/ajh.23216. PMID 22674424.
- ↑ Stasi R, Amadori S, Osborn J, Newland AC, Provan D (2006). "Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia". PLoS Med. 3 (3): e24. doi:10.1371/journal.pmed.0030024. PMC 1326262. PMID 16401142.
- ↑ Weksler BB (2007). "Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease". Aliment Pharmacol Ther. 26 Suppl 1: 13–9. doi:10.1111/j.1365-2036.2007.03512.x. PMID 17958515.
- ↑ Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA; et al. (2011). "The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia". Blood. 117 (16): 4190–207. doi:10.1182/blood-2010-08-302984. PMID 21325604.