Thrombocytopenic Disorders

Last Literature Review: May 2025 Last Update:

Medical Experts

Contributor

Moser

Karen A. Moser, MD
Associate Professor of Pathology (Clinical), University of Utah
Medical Director, Hematopathology and Hemostasis/Thrombosis Laboratory, ARUP Laboratories
Contributor

Smock

Kristi J. Smock, MD
Professor of Pathology (Clinical), University of Utah
Vice President, ARUP Institute for Clinical and Experimental Pathology®
Medical Director, Hemostasis/Thrombosis Laboratory, ARUP Laboratories

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

What is pseudothrombocytopenia?

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. 

What platelet counts are typically associated with increased bleeding risk?

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. 

Which thrombocytopenic disorders are associated with an increased thrombotic risk?

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.

Can primary immune thrombocytopenia be diagnosed by a specific laboratory test?

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.

Possible Causes of Thrombocytopenia

Decreased Platelet Production or Function

CauseComments
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 toxinChemotherapeutic 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 

Multiple modes of inheritance 

Examples: Alport syndrome, Bernard-Soulier syndrome, Fanconi anemia, gray platelet syndrome, MYH9-related disorders, Wiskott-Aldrich syndrome , 

Hepatic diseaseaThe 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 deficienciesVitamin B12 and folate 
Increased Peripheral Consumption
CauseComments
Autoimmune disordersExamples: 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 

NAITResults from maternal alloantibodies that form in response to paternally inherited fetal platelet antigens 
Posttransfusion purpuraRare 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 

SepsisaSignificant 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
CauseComments
Dilutional thrombocytopeniaPresents 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 

PseudothrombocytopeniaArtificially reduced platelet counts due to platelet clumping in collection tubes 
SplenomegalyThrombocytopenia 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

Sources: Smock, 2014 ; Gauer, 2022 ;Pène, 2025 

The following table summarizes the typical test results seen in patients with DICTTP, and HIT. Refer to the linked ARUP Consult topics for more information about testing for these conditions.

Summary of Typical Test Results in DIC, TTP, and HIT
DisorderCBC/Blood SmearPT/aPTT/Fibrinogen TestsOther Tests

DIC

(fibrin clots)

Anemia

Thrombocytopenia

Schistocytes

Prolonged clotting times

Decreased fibrinogen

Markedly elevated D-dimer

TTP

(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

HIT

(platelet activation, then thrombin/fibrin formation)

ThrombocytopeniaNormal 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

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.

References