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Thrombocytopenia is a common clinical condition with a broad differential diagnosis, and identifying its etiology involves careful assessment of both clinical characteristics and the results of well-chosen laboratory tests. Thrombocytopenic disorders include numerous causes of decreased platelet production or increased platelet destruction and encompass conditions such as congenital thrombocytopenia, disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), neonatal alloimmune thrombocytopenia (NAIT), thrombotic microangiopathies (TMAs), antiphospholipid syndrome (APS), and primary immune thrombocytopenia, previously referred to as idiopathic thrombocytopenic purpura (ITP). Thrombocytopenic disorders can be life threatening, with increased bleeding or even thrombotic risk, depending on the underlying cause, and the clinical context (e.g., an acutely ill, pregnant, or ambulatory patient) helps to determine which tests should be ordered and with what urgency. Initial and essential laboratory tests in all cases include a CBC and a peripheral blood smear, which can provide important clues about the etiology of thrombocytopenia. , Subsequent testing is guided by the clinical presentation and the results of initial laboratory tests and may involve chemistry, urine, hematology, coagulation, and antibody tests, among others.
Quick Answers for Clinicians
Pseudothrombocytopenia is a spurious thrombocytopenia that occurs due to in vitro platelet clumping when there is insufficient anticoagulation within collection tubes or blood is collected in ethylenediaminetetraacetic acid (EDTA). , This leads to an underestimation of platelet counts, which may result in misdiagnosis of pseudothrombocytopenia as true thrombocytopenia. The problem can be resolved by reviewing a peripheral smear to detect platelet clumping and to manually estimate the true platelet count, or by recollecting a specimen using an alternative anticoagulant such as sodium or heparin citrate.
Bleeding risk usually does not occur until the platelet count falls below 50-100 x 109/L. Major bleeding due to thrombocytopenia generally does not occur until the platelet count is <20 x 109/L. If there is platelet dysfunction or if antiplatelet medications are present, bleeding can occur at higher platelet counts than these thresholds. It is important to note that normal platelet counts vary among populations, so these ranges are approximations rather than fixed values. Consequently, there is no consensus on a platelet count that guarantees no risk of bleeding.
Disseminated intravascular coagulation (DIC) (associated with bleeding and/or thrombosis), antiphospholipid syndrome (APS), thrombotic microangiopathies (TMAs) such as thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) are associated with increased thrombotic risk. Thrombocytopenia can result from many underlying disorders, and close correlation with clinical and laboratory information is necessary for accurate diagnosis and assessment of bleeding or thrombotic risk.
Primary immune thrombocytopenia, previously referred to as idiopathic thrombocytopenic purpura, is a diagnosis of exclusion. Patients with primary immune thrombocytopenia may demonstrate reduced platelet counts without an obvious underlying cause. Autoantibodies result in platelet destruction but also can suppress bone marrow platelet production. Diagnosis is generally based on clinical features, CBC, and evaluation of the peripheral blood smear to rule out other hematologic conditions.
Indications for Testing
Testing for thrombocytopenic disorders should be considered in patients with platelet counts <100-150 x 109/L.
Laboratory Testing
Diagnosis
CBC and Peripheral Smear
The first step in a workup for a suspected thrombocytopenic disorder is to rule out pseudothrombocytopenia by repeating the CBC and/or performing peripheral smear review. , A peripheral smear review can identify platelet clumping and enable a manual estimation of the platelet count. Repeating the CBC using an anticoagulant other than ethylenediaminetetraacetic acid (EDTA), such as sodium or heparin citrate, can yield a more accurate measurement of platelet count by automated analyzers.
Once thrombocytopenia is confirmed, results should be considered in light of the clinical context (e.g., newborn, pregnant, or asymptomatic patient; bleeding or thrombosis; other cytopenias; current medical conditions and medications), which provides essential clues as to the etiology.
The peripheral smear review can also provide clues. For example, the presence of schistocytes may indicate a microangiopathic process, such as DIC or thrombotic thrombocytopenic purpura (TTP), but is not a sensitive or specific finding for these disorders.
A workup for hemolysis and coagulation disorders may also be helpful during initial evaluation. Testing for DIC, an acquired condition that results in widespread clotting (particularly in small vessels) and consumption of coagulation factors and platelets, should be performed in all hospitalized patients with thrombocytopenia. Refer to the ARUP Consult Disseminated Intravascular Coagulation (DIC) topic for additional information about testing for this condition.
Testing to Determine Etiology
Secondary testing should be performed based on the patient’s history and clinical presentation to identify the cause of the thrombocytopenia. Thrombocytopenic disorders are generally associated with either decreased platelet production or increased platelet destruction. The following table presents some potential causes of thrombocytopenia. For more information about testing for specific disorders, refer to the individual ARUP Consult topics linked in the table.
Decreased Platelet Production or Function | |
|---|---|
| Cause | Comments |
| Bone marrow abnormalities | Include congenital disorders and acquired causes associated with myeloid malignances Not typically considered in initial workup until more common causes of thrombocytopenia are ruled out Diagnosis requires evaluation of megakaryocytic numbers and morphology |
| Chemical or toxin | Chemotherapeutic agents, ionizing radiation, antimetabolites, and alcohol use disordera can suppress bone marrow platelet production |
| Congenital thrombocytopenia | Rare but important to consider if there is a family history of bleeding or persistent, unexplained thrombocytopenia in infants and children Examples: Alport syndrome, Bernard-Soulier syndrome, Fanconi anemia, gray platelet syndrome, MYH9-related disorders, Wiskott-Aldrich syndrome , |
| Hepatic diseasea | The majority of patients with chronic hepatic disease demonstrate thrombocytopenia |
| Infection | Infections causative for thrombocytopenia are mainly viral, but bacterial and protozoal infections can also be causative, particularly in infants and young children Examples: measles, mumps, CMV, hepatitis, varicella-zoster virus, parvovirus B19, adenovirus, Epstein-Barr virus, HIV |
| Nutritional deficiencies | Vitamin B12 and folate |
| Increased Peripheral Consumption | |
| Cause | Comments |
| Autoimmune disorders | Examples: APS, rheumatoid arthritis, systemic lupus erythematosus |
| DICa | Results in widespread clotting in the bloodstream, consumption of coagulation factors and platelets, and activation of fibrinolysis Clinical presentation is dependent on underlying disease (e.g., sepsis, hematologic malignancies) |
| Drug-induced thrombocytopenia | Diagnosis relies on detailed history of medication exposure (e.g., OTC drugs, herbal remedies, supplements) and thrombocytopenia onset Typically resolves within 7-10 days of causative medication discontinuation; if not, alternative diagnosis should be considered |
| HIT | HIT is strongly suspected if a patient develops new thrombocytopenia 5-10 days after heparin exposure Typically results in a 50% drop from baseline platelet count and warrants emergency care |
| NAIT | Results from maternal alloantibodies that form in response to paternally inherited fetal platelet antigens |
| Posttransfusion purpura | Rare blood transfusion complication characterized by severe thrombocytopenia that manifests 5-14 days after platelet transfusion |
| Primary immune thrombocytopenia | Thrombocytopenia in absence of chronic medical conditions or acute infections There is no specific diagnostic laboratory test for primary immune thrombocytopenia; it is typically a diagnosis of exclusion |
| Sepsisa | Significant cause of ICU-acquired thrombocytopenia |
| TMAs | Characterized by microangiopathic hemolytic anemia, thrombocytopenia, and thrombosis Uncommon but require prompt diagnosis and possibly emergency care due to high mortality risk if untreated Examples: TTP, HUS, HELLP syndrome |
| Miscellaneous | |
| Cause | Comments |
| Dilutional thrombocytopenia | Presents after major surgery or with transfusion of large volumes of nonplatelet-containing blood |
| Gestational thrombocytopenia | Most common cause of thrombocytopenia in pregnancy Characterized by mild or moderate thrombocytopenia , that typically presents in second trimester |
| Pseudothrombocytopenia | Artificially reduced platelet counts due to platelet clumping in collection tubes |
| Splenomegaly | Thrombocytopenia caused by splenic sequestration |
aAssociated with multiple causative mechanisms of thrombocytopenia. CMV, cytomegalovirus; HELLP, hemolysis, elevated liver enzymes, and low platelet count; HUS, hemolytic uremic syndrome; ICU, intensive care unit; OTC, over the counter | |
The following table summarizes the typical test results seen in patients with DIC, TTP, and HIT. Refer to the linked ARUP Consult topics for more information about testing for these conditions.
| Disorder | CBC/Blood Smear | PT/aPTT/Fibrinogen Tests | Other Tests |
|---|---|---|---|
(fibrin clots) | Anemia Thrombocytopenia Schistocytes | Prolonged clotting times Decreased fibrinogen | Markedly elevated D-dimer |
(platelet-rich clots) | Anemia Thrombocytopenia Schistocytes (present in large numbers) | Normal or minimal abnormalities | ADAMTS-13 <10% of normal ADAMTS-13 antibodies in acquired form |
(platelet activation, then thrombin/fibrin formation) | Thrombocytopenia | Normal or minimal abnormalities in most cases, although some cases have more pronounced abnormalities | Strongly positive ELISA for heparin-platelet factor 4 antibodies Positive SRA |
| aPTT, activated partial thromboplastin time; ELISA, enzyme-linked immunosorbent assay; PT, prothrombin time; SRA, serotonin-release assay | |||
ARUP Laboratory Tests
References
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Smock KJ, Perkins SL. Thrombocytopenia: an update. Int J Lab Hematol. 2014;36(3):269-278.
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Gauer RL, Whitaker DJ. Thrombocytopenia: evaluation and management. Am Fam Physician. 2022;106(3):288-298.
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Pène F, Russell L, Aubron C. Thrombocytopenia in the intensive care unit: diagnosis and management. Ann Intensive Care. 2025;15(1):25. Published online Feb 2025.
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Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.
For more information about disorder-specific testing, refer to the ARUP Consult Disseminated Intravascular Coagulation, Heparin-Induced Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Thrombotic Microangiopathies topics.