INTRODUCTION — Thrombocytopenia, defined as a platelet count <150,000/microL, is clinically suspected when a child develops characteristic clinical symptoms, which include a petechial rash, easy bruising or bleeding, or mucosal hemorrhage. Thrombocytopenia is often asymptomatic and may present as an incidental finding during routine evaluation or during laboratory investigations performed for other reasons. A common cause of thrombocytopenia in children is immune thrombocytopenia (ITP), for which the consensus definition is more restrictive, requiring a platelet count <100,000/microL [1].

Our approach to the evaluation of thrombocytopenia in children will be reviewed here. Other topic reviews with information relevant to the child with thrombocytopenia include the following:

●(See "Causes of thrombocytopenia in children".)

●(See "Neonatal thrombocytopenia: Etiology".)

●(See "Approach to the child with bleeding symptoms".)

●(See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis".)

●(See "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children".)

●(See "Inherited aplastic anemia in children and adolescents".)

●(See "Congenital and acquired disorders of platelet function".)

PLATELET COUNT AND BLEEDING RISK — Bleeding risk generally increases with a low platelet count. This is because circulating platelets fulfill many critical hemostatic functions, including adhesion to sites of vascular injury, secretion of mediators of hemostasis, and aggregation via fibrinogen binding (figure 1). (See "Platelet biology", section on 'Overview of platelet function'.)

The normal platelet count for children ranges from approximately 150,000 to 450,000/microL [2]. In general, the risk of bleeding does not increase until the platelet count falls well below 100,000/microL, though it depends somewhat on the cause of thrombocytopenia. For example, surgical bleeding solely due to a decreased platelet count typically occurs only if the platelet count is <50,000/microL and spontaneous bleeding typically does not occur until the platelet count is <20,000/microL.

The platelet lifespan ranges from 7 to 10 days, after which they are removed from the circulation by cells of the monocyte-macrophage system. Younger circulating platelets are generally larger and more hemostatically active. For example, at a platelet count of 20,000/microL, patients with immune thrombocytopenia (ITP) have a higher proportion of younger circulating platelets and, consequently, less severe bleeding symptoms than patients with a similar degree of thrombocytopenia due to a production defect such as bone marrow failure or malignancy. Thus, for a given platelet count, bleeding risk is generally higher in patients with thrombocytopenia due to impaired platelet production primarily due to an older circulating population of platelets. (See 'Reticulated platelets/immature platelet fraction' below.)

When thrombocytopenia is recognized or suspected, reasonable precautions to minimize bleeding risk should be implemented. This includes precautions to reduce the risk of traumatic injury, particularly head injury (eg, ensuring adult supervision during play; avoidance of contact and collision sports; and avoidance of other activities that pose high risk of head trauma with velocity such as trampolines or bounce houses or riding a bicycle, scooter, all-terrain vehicle, hoverboard, or similar vehicle without helmet). In addition, drugs that impair platelet function (eg, nonsteroidal antiinflammatory drugs) should be avoided. (See "Immune thrombocytopenia (ITP) in children: Initial management", section on 'General measures'.)

BLEEDING SYMPTOMS — Many children with mild or moderate thrombocytopenia may be asymptomatic, and thrombocytopenia may be first detected on a complete blood count (CBC) obtained for another reason. Patients with symptomatic thrombocytopenia generally present with cutaneous and/or mucosal bleeding (eg, easy bruising, petechiae, gingival bleeding, epistaxis). Some affected children with severe thrombocytopenia may have persistent, profuse bleeding from superficial cuts. In postmenarcheal females, thrombocytopenia may present as menorrhagia (excess menstrual flow) and/or metrorrhagia (uterine bleeding between periods). (See "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis", section on 'Causes of heavy menstrual bleeding'.)

The pattern of bleeding differs between patients with thrombocytopenia and those with disorders of coagulation factors, such as hemophilia. Patients with thrombocytopenia are more likely to have bleeding after minor cuts and less likely to have deep bleeding into tissues, muscles, and joints or to have delayed bleeding. In patients with thrombocytopenia, posttraumatic or postoperative surgical bleeding usually responds to local measures but may persist for hours or days after small injuries. In addition, petechiae are a characteristic finding in patients with thrombocytopenia, whereas patients with coagulation disorders tend not to have petechiae. (See "Clinical manifestations and diagnosis of hemophilia".)

Cutaneous bleeding — Cutaneous bleeding is usually manifested as petechiae or superficial ecchymoses. These cutaneous manifestations are sometimes known as "dry purpura." Petechiae are small, red, flat, discrete lesions attributable to red cells which have extravasated from capillaries (picture 1). They often occur in crops in dependent areas, are nontender, and do not blanch under pressure. Petechiae that are confluent form a type of purpura that is not palpable (in contrast with the palpable purpura seen in vasculitic disorders). (See "Vasculitis in children: Evaluation overview".)

Ecchymoses and hematomas are larger areas of bleeding into the skin (picture 2). The affected area of the skin is initially red or purple due to the presence of extravasated blood and then evolves to green, orange, and yellow due to breakdown of heme pigment by skin macrophages. Ecchymotic lesions in patients with thrombocytopenia are usually small, multiple, and superficial and may develop without trauma.

Mucosal bleeding — Mucosal bleeding is usually manifested as epistaxis, gingival bleeding, and bullous hemorrhage on the buccal mucosa (picture 3) but also may include gastrointestinal and genitourinary bleeding. Mucosal bleeding is sometimes known as "wet purpura." Thrombocytopenic patients with mucosal bleeding usually have cutaneous bleeding as well. Although not rigorously validated, the presence of wet purpura is widely perceived as the more serious of the two findings and a risk factor for potentially life-threatening hemorrhage [3,4].

Intracranial hemorrhage — Intracranial hemorrhage (ICH) is a rare but serious consequence of thrombocytopenia and is the most common cause of death in affected patients. When ICH occurs, it is often preceded by a history of head trauma. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Intracranial hemorrhage'.)

DIAGNOSTIC EVALUATION — The initial step in the evaluation of suspected thrombocytopenia in children is verification of a low platelet count. Once thrombocytopenia has been confirmed, the evaluation is focused on determining the underlying etiology so that directed therapeutic measures can be implemented. The evaluation includes a detailed history, complete physical examination, and laboratory testing.

Verification of thrombocytopenia — A platelet count that is inconsistent with the clinical presentation of the patient (such as a platelet count <20,000/microL in a patient with no petechiae or other abnormalities) should be confirmed before extensive evaluation is undertaken to ensure that the low platelet count is not due to artifact or laboratory error. This can be accomplished through repeating testing or, preferably, review of the peripheral blood smear by a qualified observer.

Spurious thrombocytopenia can be caused by improper collection, delayed processing, or inadequate anticoagulation of the blood sample, resulting in platelet clumps that are counted as leukocytes by automated cell counters. In addition, agglutination of platelets by ethylenediaminetetraacetic acid (EDTA)-dependent antibodies, which are normally present in 0.1 percent of adults, may cause a falsely low platelet count (referred to as pseudothrombocytopenia). EDTA exposes a normally concealed epitope on the platelet membrane, glycoprotein IIb/IIIa, which interacts with these antibodies, resulting in platelet clumping. Examination of the blood smear will demonstrate large clumps of agglutinated platelets or adherent platelets surrounding neutrophils. The presence of pseudothrombocytopenia can also be confirmed by collecting a blood sample in a non-EDTA anticoagulant tube such as sodium citrate and confirming a normal platelet count.

History — The history should document the onset, frequency, and severity of present and past bleeding symptoms. Other components of the history may provide clues to the underlying etiology of thrombocytopenia (table 1). (See "Causes of thrombocytopenia in children".)

●Bleeding symptoms – Details of any present or past bleeding symptoms, including whether there has been bruising with little or no trauma, prolonged bleeding from superficial cuts or wounds, epistaxis (including duration and frequency), visible blood in the urine or stool, bleeding from the gums, unexpected bleeding with surgical or dental procedures, and menorrhagia and metrorrhagia in postmenarcheal girls. The duration and onset of any bleeding symptoms may help to determine whether the thrombocytopenia is acquired or congenital [5]. (See 'Bleeding symptoms' above.)

●Systemic symptoms – Systemic symptoms (fever, bone pain, appetite change, weight loss, and decreased energy) may suggest a systemic disease process, such as malignancy or autoimmune disorder. In patients with these symptoms, an expeditious evaluation should be performed because of the serious potential morbidity and mortality associated with these conditions.

●Previous blood counts – Previous blood counts (if available) should be reviewed. A prior history of thrombocytopenia suggests the possibility of a congenital or chronic disorder, while a past pattern of normal platelet counts points toward an acquired condition.

●Prodromal illness – Immune thrombocytopenia (ITP) has been associated with environmental triggers such as viral infection and live virus vaccination (especially measles-mumps-rubella). (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Preceding illness or vaccination'.)

A prodromal illness that includes abdominal pain and diarrhea suggests the possibility of Shiga-toxin-associated hemolytic uremic syndrome (HUS). This disorder is caused by an enteric pathogen that produces Shiga toxin. HUS is characterized by hemolytic anemia, thrombocytopenia, and acute renal injury, usually developing 5 to 10 days after the onset of diarrhea. (See "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children".)

●Medication history – The patient's medications should be reviewed carefully because many drugs may lower the platelet count, including chemotherapeutic agents, heparin, and certain antiseizure medications and antibiotics. (See "Drug-induced immune thrombocytopenia".)

●Underlying disease – The patient's medical history should be reviewed for any underlying disorders that may be associated with thrombocytopenia, including cancer, sepsis, congenital heart disease, autoimmune disorders including systemic lupus erythematosus (SLE), immune deficiency syndromes, liver disease, or hypersplenism (table 1).

●Family history – A family history of thrombocytopenia and/or mucosal bleeding suggests the possibility of an inherited thrombocytopenia syndrome. Among the most common of these rare syndromes are macrothrombocytopenic disorders related to mutations of the MYH9 gene. A family history of high-frequency sensorineural hearing loss, glomerulonephritis, or presenile cataracts further suggests the possibility of MHY9-related disease. A family history of thrombocytopenia affecting males, severe eczema, or immunodeficiency or leukemia is suggestive of Wiskott-Aldrich syndrome [5,6]. (See "Wiskott-Aldrich syndrome" and "Causes of thrombocytopenia in children", section on 'Genetic causes of defective thrombopoiesis'.)

●Travel – Malaria should be considered in a child with fever, splenomegaly, and recent travel history to endemic areas.

●Dietary history – A child with a very restricted diet or malabsorptive disease may have a nutritional deficiency that causes the thrombocytopenia, such as iron, vitamin B12, or folate deficiency. Such deficiencies usually cause other abnormalities on the complete blood count (CBC). (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis" and "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency".)

Physical examination — The extent of the bleeding should be evaluated and documented in detail. Bleeding into the skin is one of the most common findings in patients with thrombocytopenia and may include petechiae, nonpalpable purpura, and ecchymoses (see 'Cutaneous bleeding' above). Sites of bleeding should be noted, especially dependent parts of the body. Serial examinations can monitor the patient's clinical course by noting changes in the number of petechiae or bleeding pattern within involved areas. In hospitalized patients, careful examination for bleeding should be performed at the sites of indwelling catheters, drains and incisions, areas of previous trauma, and exit sites of venous access devices. The gingival and oral cavity should be examined carefully for evidence of bleeding.

Other components of the physical examination that may provide clues to the underlying cause of thrombocytopenia include:

●Constitution and growth – Short stature is a common finding in inherited bone marrow failure syndromes. Other congenital abnormalities can be present in inherited thrombocytopenia syndromes such as radial and thumb abnormalities (thrombocytopenia absent radius, Fanconi anemia, IVIC syndrome), cleft palate (Jacobsen syndrome), and others. Clinodactyly, syndactyly, hip dysplasia, and radioulnar synostosis are other findings associated with specific inherited conditions. (See "Inherited aplastic anemia in children and adolescents" and "Causes of thrombocytopenia in children", section on 'Genetic causes of defective thrombopoiesis'.)

●Lymph nodes – Lymphadenopathy may be indicative of an underlying lymphoid malignancy with bone marrow infiltration, or a lymphoproliferative process such as autoimmune lymphoproliferative syndrome or hemophagocytic lymphohistiocytosis. (See "Peripheral lymphadenopathy in children: Etiology", section on 'Uncommon but important causes'.)

●Head, eyes, ears, nose, and throat

•Hearing – Sensorineural deafness in association with macrothrombocytopenia (thrombocytopenia with large or giant platelets) suggests the possibility of an MYH9-related disease. These autosomal dominant diseases also feature varying degrees and combinations of nephritis, cataracts, and leukocyte inclusions. (See "Causes of thrombocytopenia in children", section on 'Large or giant platelets' and 'Other tests' below.)

•Eyes and mouth – Cataracts are associated with one of the MYH9-related diseases (Fechtner syndrome). Oral leukoplakia (white patches or plaques of the oral mucosa due to squamous epithelium hyperplasia) is one of the three main clinical manifestations characteristic of dyskeratosis congenita (table 2) [7,8]. (See "Dyskeratosis congenita and other telomere biology disorders".)

●Abdomen – Splenomegaly, with or without hepatomegaly, from any cause can result in thrombocytopenia due to increased sequestration of the platelet mass. Important causes of splenomegaly include viral infections including Epstein-Barr virus, leukemia, lymphoma, and chronic liver disease with portal hypertension. (See "Approach to the child with an enlarged spleen".)

●Extremities – Joint swelling may be seen in patients with autoimmune disease such as SLE. In some cases of SLE, ITP or thrombotic thrombocytopenic purpura (TTP) may be the initial manifestation of this disorder. (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Hematologic'.)

Skeletal abnormalities may be indicative of specific syndromes associated with thrombocytopenia. For example, absent radii may be seen in patients with thrombocytopenia-absent radius syndrome and thumb abnormalities in patients with Fanconi anemia. (See "Inherited aplastic anemia in children and adolescents".)

●Skin – Cutaneous findings that may be associated with specific underlying causes of thrombocytopenia include eczema (Wiskott-Aldrich syndrome), pigmentary and nail dystrophic changes (dyskeratosis congenita), café-au-lait spots (Fanconi anemia (table 3)), and certain vascular tumors (Kasabach-Merritt syndrome). (See "Wiskott-Aldrich syndrome" and "Inherited aplastic anemia in children and adolescents" and "Tufted angioma, kaposiform hemangioendothelioma, and the Kasabach-Merritt phenomenon".)

Laboratory evaluation — The laboratory evaluation of thrombocytopenia begins with a CBC, which includes the platelet count and mean platelet volume (MPV), and evaluation of the peripheral blood smear.

Complete blood count — From the CBC, the platelet count and MPV should be noted, as well as evidence of any other cytopenias (anemia and leukopenia).

In a patient with thrombocytopenia, a mildly elevated or variable/unreportable MPV (as compared with the normal range of 7 to 10 fL) is consistent with a destructive etiology, including ITP. An MPV that is considerably higher than normal suggests one of the macrothrombocytopenia syndromes (eg, Bernard-Soulier syndrome or MYH9-related disorders). A low MPV (3 to 5 fL) is almost exclusively seen in patients with Wiskott-Aldrich syndrome or X-linked thrombocytopenia (table 4). These abnormalities should be further evaluated by visual examination of the peripheral blood smear since both platelet counts and calculated MPV from automated cell counters can be inaccurate when platelet size is outside of the reference range [9]. The presence of anemia (not readily explained by bleeding), especially if accompanied by macrocytosis, could be suggestive of a marrow failure process. Leukopenia or differential abnormalities should be explainable by recent infectious symptoms or evaluated further to rule out a hematologic malignancy. (See "Causes of thrombocytopenia in children".)

Peripheral blood smear — The peripheral blood smear must be carefully examined to estimate the platelet number, determine the platelet morphology and the presence or absence of platelet clumping, and assess whether there are associated white and red blood cell morphologic abnormalities.

The following findings are suggestive of a specific etiology for thrombocytopenia.

●Platelet size

•Variably sized with some large platelets is suggestive of an ongoing platelet destructive process leading to the increased proportion of younger and larger platelets (eg, ITP, TTP, hypersplenism).

•Uniformly large or giant platelets could suggest a congenital macrothrombocytopenia syndrome (picture 4). The MYH9-related diseases are variably associated with leukocyte inclusions (Dohle-like inclusions). (See "Causes of thrombocytopenia in children", section on 'Large or giant platelets'.)

•Small platelets in the appropriate clinical setting (eg, male patient with eczema and immunodeficiency) suggest Wiskott-Aldrich syndrome. X-linked thrombocytopenia should be considered in a patient with microthrombocytopenia without these associated features. (See "Wiskott-Aldrich syndrome" and "Causes of thrombocytopenia in children", section on 'Small platelets'.)

●Circulating blast cells suggest a leukemic process (picture 5). Blast cells on the peripheral blood smear may be difficult to distinguish from atypical lymphocytes that are sometimes present in a postviral case of ITP (picture 6).

●Fragmented erythrocytes (schistocytes) (picture 7) suggest a microangiopathic process, such as HUS, TTP, or disseminated intravascular coagulation. (See "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children", section on 'Microangiopathic hemolytic anemia' and "Diagnosis of immune TTP", section on 'MAHA and thrombocytopenia' and "Disseminated intravascular coagulation in infants and children".)

●Spherocytes (picture 8) may suggest autoimmune hemolytic anemia coupled with autoimmune-mediated thrombocytopenia (Evans syndrome). In these patients, the direct antiglobulin test (also known as the Coombs test) is usually positive. Less commonly, autoimmune-mediated neutropenia may also occur. (See "Autoimmune hemolytic anemia (AIHA) in children: Classification, clinical features, and diagnosis", section on 'Evans syndrome'.)

Reticulated platelets/immature platelet fraction — Reticulated platelets (RP) are the youngest circulating platelets, analogous to the relationship between reticulocytes and mature red blood cells. RPs can be quantified by flow cytometry or with automated measurement of the immature platelet fraction (IPF). Comparison of the IPF with RPs, as measured by flow cytometry, has shown good correlation [10]. Measurement of RPs can be used to assess platelet turnover or thrombopoiesis in different types of thrombocytopenia [11].

The IPF has been used in the following settings:

●To help distinguish between different causes of thrombocytopenia if the clinical picture is unclear [12,13]. The IPF is typically higher in thrombocytopenia caused by peripheral consumption/destruction than in production defects such as bone marrow failure syndromes.

●To evaluate bleeding risk in ITP (lower IPF correlates with increased bleeding risk) [12].

●As a marker of platelet recovery in patients treated with chemotherapy or following stem cell transplantation [14,15].

IPF is not available on all automated blood cell counters, though it is increasingly available on newer models. Additional details about this testing are provided separately. (See "Automated hematology instrumentation", section on 'Reticulated platelets'.)

Bone marrow examination — In most cases of isolated unexplained thrombocytopenia in children, a bone marrow examination is not required in the initial evaluation unless there are clinical features that suggest bone marrow infiltration or failure.

A bone marrow examination is indicated in patients with any of the following findings, which are suggestive of either marrow infiltration with abnormal cells or marrow hypocellularity:

●Systemic symptoms (eg, fever, weight loss, night sweats, bone pain) that can be consistent with an underlying malignancy

●Evidence of involvement of other blood cell lines (anemia or leukopenia) in the absence of a likely alternative explanation

●Presence of blasts on peripheral blood smear

Bone marrow assessment may also be performed to evaluate chronic, stable thrombocytopenia that is not completely consistent with ITP. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Indications for bone marrow examination'.)

Other tests — In many cases, the cause of thrombocytopenia can be determined based on the history, physical examination, and initial laboratory testing (CBC and blood smear). For example, in an otherwise well-appearing child who presents with sudden-onset mucocutaneous bleeding without other systemic signs or symptoms and with laboratory confirmation of isolated thrombocytopenia, a provisional diagnosis of ITP can be made. The initial evaluation in this setting is summarized in the table and discussed in detail separately (table 5). (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Initial evaluation'.)

The following tests may be useful in determining the cause of thrombocytopenia if it remains uncertain after the initial evaluation. These tests are generally selected based upon suggestive clinical and laboratory findings.

●For patients with evidence of hemolytic anemia on the peripheral blood smear (eg, spherocytes, schistocytes, or polychromasia suggestive of reticulocytosis), the following tests are appropriate:

•A direct antiglobulin test (also known as the Coombs test) is obtained to detect an autoimmune hemolytic anemia (see "Autoimmune hemolytic anemia (AIHA) in children: Classification, clinical features, and diagnosis" and "Autoimmune hemolytic anemia (AIHA) in children: Classification, clinical features, and diagnosis", section on 'Initial laboratory evaluation')

•D-dimer and fibrinogen levels are useful to diagnosis intravascular coagulation in a patient with schistocytes on the peripheral blood smear and/or vascular tumors on examination (see "Disseminated intravascular coagulation in infants and children")

•Other tests to evaluate for a microangiopathy include serum lactic dehydrogenase, creatinine, and ADAMTS13 activity (see "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children", section on 'Diagnosis' and "Causes of thrombocytopenia in children", section on 'Platelet activation and consumption')

●Patients with chronic thrombocytopenia or with features suggesting inherited bone marrow failure syndromes (eg, pancytopenia with short stature, café-au-lait spots, or other characteristic findings) should undergo specific testing for these disorders (in addition to a bone marrow biopsy, as described above). For example, the presence of increased chromosomal breakage in lymphocyte cultures with DNA cross-linking agents such as mitomycin C is diagnostic of Fanconi anemia. (See "Inherited aplastic anemia in children and adolescents".)

●Patients with giant platelets, and particularly those with a family history of thrombocytopenia, may have an MYH9-related disorder, which are autosomal dominant diseases that feature varying degrees and combinations of nephritis, cataracts, and leukocyte inclusions. MYH9 encodes the heavy chain A of non-muscle myosin of class II (NMMHC-IIA). The diagnosis of an MYH9-related disorder is confirmed by immunofluorescent identification of NMMHC-IIA protein aggregates in neutrophils [16]. Patients suspected of having an MYH9-related disease can also have molecular genetic testing to identify a mutation. There are important genotype-phenotype correlations that inform management and prognosis [17]. A list of clinical laboratories that perform this test is available at the GeneTests website. (See 'Physical examination' above and "Causes of thrombocytopenia in children", section on 'Large or giant platelets'.)

SUMMARY AND RECOMMENDATIONS

●Thrombocytopenia is defined as a platelet count <150,000/microL. Spontaneous bleeding usually does not occur until the platelet count is <20,000/microL. (See 'Platelet count and bleeding risk' above.)

●Symptomatic patients generally present with cutaneous (petechiae, nonpalpable purpura, ecchymoses) and/or mucosal (epistaxis, gingival bleeding, bullous hemorrhage, menorrhagia) bleeding. Intracranial hemorrhage (ICH) is a rare but serious consequence of thrombocytopenia and is the most common cause of death in these patients. When ICH occurs, it is often preceded by a history of head trauma. (See 'Bleeding symptoms' above.)

●The initial step in the evaluation of suspected thrombocytopenia in children is verification of the low platelet count. In particular, a platelet count that is inconsistent with the clinical presentation of the patient (eg, a platelet count <20,000/microL in a patient with no petechiae or other abnormalities) should be confirmed before extensive evaluation is undertaken to ensure that the low platelet count is not due to artifact or laboratory error. (See 'Verification of thrombocytopenia' above.)

●Once thrombocytopenia has been confirmed, the evaluation is focused on determining the underlying etiology so that directed therapeutic measures can be implemented. A wide variety of disorders can lead to thrombocytopenia in children (table 1); one of the most common is immune thrombocytopenia (ITP). The evaluation includes a detailed history, complete physical examination, and laboratory testing. (See 'Diagnostic evaluation' above and "Causes of thrombocytopenia in children".)

●Thrombocytopenia with systemic symptoms and/or the presence of lymphadenopathy or hepatosplenomegaly should raise suspicion for malignancy or other proliferative process; patients with these signs or symptoms should be evaluated expeditiously. (See 'History' above and 'Physical examination' above.)

●Laboratory evaluation of thrombocytopenia begins with a complete blood count (CBC) and evaluation of the peripheral blood smear. The blood smear must be carefully examined for estimation of platelet number and morphology (table 4), presence or absence of platelet clumping, and evaluation for associated white and red blood cell abnormalities. (See 'Complete blood count' above and 'Peripheral blood smear' above.)

●Bone marrow examination is generally not required for the initial evaluation in most cases of unexplained isolated thrombocytopenia in children. A bone marrow examination is indicated in patients with evidence of involvement of other blood cell lines (anemia, leukopenia, or peripheral blasts), systemic symptoms (eg, fever, weight loss, bone pain), abnormal physical examination findings (specifically, lymphadenopathy and/or organomegaly). (See 'Bone marrow examination' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Donald Yee, MD, who contributed to an earlier version of this topic review.