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Am Fam Physician. 2022;106(3):288-298

Patient information: See related handout on thrombocytopenia, written by the authors of this article.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Thrombocytopenia is a platelet count of less than 150 × 103 per μL and can occur from decreased platelet production, increased destruction, splenic sequestration, or dilution or clumping. Patients with a platelet count greater than 50 × 103 per μL are generally asymptomatic. Patients with platelet counts between 20 and 50 × 103 per μL may have mild skin manifestations such as petechiae, purpura, or ecchymosis. Patients with platelet counts of less than 10 × 103 per μL have a high risk of serious bleeding. Although thrombocytopenia is classically associated with bleeding, there are conditions in which bleeding and thrombosis can occur, such as antiphospholipid syndrome, heparin-induced thrombocytopenia, and thrombotic microangiopathies. Patients with isolated thrombocytopenia in the absence of systemic illness most likely have immune thrombocytopenia or drug-induced thrombocytopenia. In stable patients being evaluated as outpatients, the first step is to exclude pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the platelet count. If thrombocytopenia is confirmed, the next step is to distinguish acute from chronic thrombocytopenia by obtaining or reviewing previous platelet counts. Patients with acute thrombocytopenia may require hospitalization. Common causes that require emergency hospitalization are heparin-induced thrombocytopenia, thrombotic microangiopathies, and the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Common nonemergency causes of thrombocytopenia include drug-induced thrombocytopenia, immune thrombocytopenia, and hepatic disease. Transfusion of platelets is recommended when patients have active hemorrhage or when platelet counts are less than 10 × 103 per μL, in addition to treatment (when possible) of underlying causative conditions. It is important to ensure adequate platelet counts to decrease bleeding risk before invasive procedures; this may also require a platelet transfusion. Patients with platelet counts of less than 50 × 103 per μL should adhere to activity restrictions to avoid trauma-associated bleeding.

Normal platelet counts range from 150 to 450 × 103 per μL; however, some laboratories may specify a slightly different range. Males, older adults, and White populations tend to have lower platelet counts.1,2 Modifying normal platelet count ranges based on age, sex, and ethnicity has been proposed, but no consensus has been established.

RecommendationSponsoring organization
Do not test or treat for suspected heparin-induced thrombocytopenia in patients with a low pretest probability of heparin-induced thrombocytopenia.American Society of Hematology
Do not treat patients with immune thrombocytopenic purpura in the absence of bleeding or a very low platelet count.American Society of Hematology

This review defines mild thrombocytopenia as a platelet count from 100 to 150 × 103 per μL, moderate as 50 to 99 × 103 per μL, and severe when platelet counts are less than 50 × 103 per μL.


Thrombocytopenia can result from decreased bone marrow production of platelets, increased peripheral destruction of platelets, consumption of platelets in immune complexes or acute thrombi, splenic sequestration, or dilution or platelet clumping (Table 1).35

Decreased platelet production or function
Alcohol use disorder*
Bone marrow failure, suppression, or infiltration
Congenital platelet disorders
Drug-induced·nonimmune thrombocytopenia
Hepatic disease*
Myelodysplastic syndrome
Nutritional deficiencies (vitamin B12 and folate)
Increased peripheral consumption
Alloimmune destruction
Disseminated intravascular coagulation*
Drug-induced immune thrombocytopenia
Heparin-induced thrombocytopenia
Immune thrombocytopenia
Mechanical destruction
Paroxysmal nocturnal hemoglobinuria
Preeclampsia/HELLP syndrome
Thrombotic microangiopathy (thrombocytopenic purpura, hemolytic uremic syndrome, drug-induced thrombotic microangiopathy)
Vaccine-induced immune thrombotic thrombocytopenia
Alcohol use disorder*
Dilutional thrombocytopenia
Gestational thrombocytopenia
Hepatic disease*

Although thrombocytopenia is classically associated with bleeding, there are also conditions in which bleeding and thrombosis can occur. These include antiphospholipid syndrome, heparin-induced thrombocytopenia (HIT), thrombotic microangiopathies (i.e., thrombotic thrombocytopenic purpura and hemolytic uremic syndrome), and disseminated intravascular coagulation.6 The pathogenesis of these conditions relates to mechanisms such as the development of immune complexes promoting excessive thrombin production, endothelial wall injury with platelet microthrombi formation, or disproportionate consumption of coagulation factors.

Bleeding Risk

The risk of bleeding at different levels of thrombocytopenia is not linear; therefore, there is no consensus on a safe level at which bleeding will not occur. Additional variables such as coagulation disorders, medications, and systemic diseases further affect bleeding risk. Patients with platelet counts greater than 50 × 103 per μL are generally asymptomatic. Patients with counts from 20 to 50 × 103 per μL often experience easy bruising, petechiae, and prolonged bleeding associated with minimal trauma. A high risk of spontaneous bleeding usually occurs when platelet counts are less than 10 × 103 per μL, and thrombocytopenia at that level should be considered a hematologic emergency.7,8

The finding of isolated mild thrombocytopenia has a favorable prognosis. A prospective study followed 217 individuals with platelet counts ranging from 100 to 150 × 103 per μL over 10 years. In 64% of patients, platelet counts normalized or stayed mildly thrombocytopenic without sequelae. The probability of developing immune thrombocytopenia (ITP) or an additional autoimmune disorder was approximately 7% and 12%, respectively. Only 2% of the study participants developed myelodysplastic syndrome, all of whom were older adults.9

Inpatient Evaluation

The urgency for evaluating thrombocytopenia is dependent on severity and associated symptoms. Thrombocytopenia requires hospitalization and immediate evaluation if any of the following red flag findings are present: major bleeding, platelet count less than 10 × 103 per μL, evidence of hemolysis on peripheral smear, new neurologic or renal dysfunction, recent exposure to heparin products, associated coagulation abnormalities, or vascular findings (e.g., extremity pain, swelling, skin necrosis). Patients with concomitant life-threatening hemorrhage (e.g., intracranial, gastrointestinal, genitourinary), anemia, leukopenia, leukocytosis, or other associated severe illnesses (e.g., sepsis) also warrant urgent hospitalization.

Outpatient Evaluation

Without situations requiring hospitalization, thrombocytopenia is often an incidental finding on blood counts obtained in routine practice, and the cause is not immediately apparent. The challenge is distinguishing patients with pseudothrombocytopenia, acute vs. chronic thrombocytopenia, and those with platelet counts within the normal range who had a precipitous drop in platelet count (e.g., a decrease from 350 to 160 × 103 per μL). Figure 1 is an algorithm for the evaluation of thrombocytopenia.


Pseudothrombocytopenia occurs when the clumping of platelets in the collection tube leads to a false low platelet count. Clinicians should first determine if the low platelet count is accurate by repeating the test and recollecting the blood in a tube containing heparin or sodium citrate to avoid platelet aggregation, and requesting a manual platelet count to confirm if thrombocytopenia is present.10

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