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.

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. 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. [41-47].

• Platelet satellitism; i.e. rosette formation of platelets around WBCs (whether normal WBCs or lymphoma cells) [48-52].

- 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
isolated thrombocytopenia	normal variation ITP
thrombocytopenia + anemia	chronic bleeding (eg, gastrointestinal) infection/sepsis malignancies DIC TTP HUS autoimmune diseases bone marrow disorders (eg, MDS) drug-induced thrombotic microangiopathy folate deficiency vitamin B12 deficiency copper deficiency	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	infecton/sepsis chronic inflammation malignancy
thrombocytopenia + anemia + leukopenia (pancytopenia)
pseudothrombocytopenia

Repeat CBC — A platelet count that does not make sense within the context of the clinical findings should be repeated before extensive evaluation is undertaken.

●For symptomatic patients (eg, signs of bleeding) or those with severe thrombocytopenia (ie, <50,000/microL), such retesting should be performed immediately.

●For asymptomatic patients (eg, non-bleeding, no associated comorbidities) with moderate thrombocytopenia (ie, 50,000 to 100,000/microL), testing may be repeated in one to two weeks, provided the patient is advised to report immediately any changes in clinical status or bleeding during this interval.

●For outpatients with isolated mild thrombocytopenia (ie, 100,000 to 149,000/microL), testing may be repeated in one or more months, as a small percent of these patients will develop a normal platelet count with observation only. An exception is a patient recently started on a new medication, new clinical findings, or other abnormalities on the CBC, because mild thrombocytopenia may be a sign of an evolving disorder (eg, drug-induced or heparin-induced thrombocytopenia, drug-induced thrombotic microangiopathy).

The default diagnosis in an asymptomatic patient with isolated thrombocytopenia (ie, no bleeding or signs of other acute illness, normal values on the remainder of the CBC, unremarkable peripheral blood smear) is primary immune thrombocytopenia (ITP), provided other causes of thrombocytopenia have been eliminated (eg, HIV infection, drug-induced thrombocytopenia, myelodysplasia).

In contrast, the diagnostic possibilities are more extensive for a symptomatic patient and/or a patient with thrombocytopenia in the setting of other hematologic abnormalities.

●Combined leukopenia, anemia, and thrombocytopenia (ie, pancytopenia) is discussed in detail separately. (See "Clinical manifestations and diagnosis of the myelodysplastic syndromes".)

Peripheral blood smear — Review of the peripheral blood smear is used to exclude pseudothrombocytopenia and to evaluate morphologic abnormalities of blood cells that could be useful in determining the cause of thrombocytopenia.

As an example, giant platelets (picture 5) may suggest a congenital platelet disorder (eg, MYH-9-related disorders, Bernard Soulier syndrome [BSS]); these may be counted as red blood cells by some automated counters. (See "Congenital and acquired disorders of platelet function", section on 'Giant platelet disorders'.)

RBC and WBC abnormalities — Abnormal RBC and WBC morphologies may suggest a specific condition.

Examples include the following:

●Schistocytes (picture 7) suggest a microangiopathic process (eg, DIC, TTP, HUS, DITMA).

●Nucleated RBCs (picture 8), and Howell-Jolly bodies (picture 9), may be seen post-splenectomy or occasionally in patients with poor splenic function.

●Spherocytes (picture 10 and picture 11) suggest immune-mediated hemolytic anemia or hereditary spherocytosis.

●Leukoerythroblastic findings (picture 12), teardrop cells (picture 13), nucleated RBCs, or immature granulocytes suggest an infiltrative process in the bone marrow.

●Leukocytosis with a predominance of bands (left shift) and/or toxic granulations suggest infection (picture 14).

●Immature WBCs (eg, myeloblasts) (picture 15) or dysplastic WBCs (picture 16) suggest leukemia or myelodysplasia.

●Multi-lobed/hypersegmented neutrophils (ie, >5 lobes) (picture 17) suggest a megaloblastic process (eg, B12/folate/copper deficiency).

HIV and HCV testing — Thrombocytopenia has been identified as an important "indicator condition" for HIV infection [20]. Thus, adults with new thrombocytopenia should have HIV testing if not done recently. (See "Hematologic manifestations of HIV infection: Thrombocytopenia and coagulation abnormalities", section on 'Incidence and causes of thrombocytopenia' and "Screening and diagnostic testing for HIV infection".)

Thrombocytopenia may also be seen with hepatitis C virus (HCV) infection; testing is appropriate for adults with thrombocytopenia if not done recently. (See "Screening for chronic hepatitis C virus infection".)

Other laboratory testing — Aside from the testing mentioned above (CBC, review of peripheral smear, HIV and HCV testing), no additional laboratory testing is absolutely required in a patient with isolated thrombocytopenia. However, additional testing may be warranted in patients with other findings.

Examples of findings that may trigger other laboratory testing include the following:

●Symptoms or findings of systemic autoimmune disorders (eg, systemic lupus erythematosus [SLE], anti-phospholipid syndrome [APS]) may prompt testing for anti-nuclear antibodies or anti-phospholipid antibodies, respectively. We do not test for these in patients with isolated thrombocytopenia and no signs or symptoms suggestive of SLE or APS.

●Findings of liver disease should prompt measurements of hepatic enzymes and possibly tests of liver synthetic function (eg, albumin, coagulation testing), depending on the severity of the liver disease. (See "Liver biochemical tests that detect injury to hepatocytes" and "Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin time)".)

●Thrombosis should prompt consideration of DIC, heparin-induced thrombocytopenia (HIT), and APS. Depending on the site of thrombosis and other hematologic findings, paroxysmal nocturnal hemoglobinuria (PNH) may also be a consideration. Testing for these conditions is discussed separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Diagnosis of antiphospholipid syndrome" and "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults" and "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria".)

●Microangiopathic changes on the peripheral smear should prompt coagulation testing (eg, PT, aPTT, fibrinogen) and measurement of serum lactate dehydrogenase (LDH) and renal function to evaluate for DIC, TTP, or HUS; with subsequent evaluation based on the results.