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Overview of Platelet Disorders


David J. Kuter

, MD, DPhil, Harvard Medical School

Last full review/revision Jun 2020
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Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, which in turn shed platelets from their cytoplasm. Thrombopoietin is produced in the liver at a constant rate and its circulating level is determined by the extent to which circulating platelets are cleared, and possibly by bone marrow megakaryocytes. Platelets circulate for 7 to 10 days. About one third are always transiently sequestered in the spleen.

The platelet count is normally 140,000 to 440,000/mcL. However, the count can vary slightly according to menstrual cycle phase, decrease during near-term pregnancy (gestational thrombocytopenia), and increase in response to inflammatory cytokines (secondary, or reactive, thrombocytosis). Platelets are eventually destroyed by apoptosis, a process independent of the spleen.

Platelet disorders include

Any of these conditions, even those in which platelets are increased, may cause defective formation of hemostatic plugs and bleeding.

The risk of bleeding is inversely proportional to the platelet count and platelet function (see table Platelet Count and Bleeding Risk Platelet Count and Bleeding Risk Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes,... read more Platelet Count and Bleeding Risk ). When platelet function is reduced (eg, as a result of uremia, or use of nonsteroidal anti-inflammatory drug [NSAID] or aspirin), the risk of bleeding increases.


Etiology of Platelet Disorders

Thrombocythemia and thrombocytosis

Essential thrombocythemia Essential Thrombocythemia Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased platelet count, megakaryocytic hyperplasia, and a hemorrhagic or microvascular thrombotic tendency... read more is a myeloproliferative neoplasm Overview of Myeloproliferative Neoplasms Myeloproliferative neoplasms are clonal proliferations of bone marrow stem cells, which can manifest as an increased number of platelets, red blood cells (RBCs), or white blood cells (WBCs)... read more (previously myeloproliferative disorder) involving overproduction of platelets because of a clonal abnormality of a hematopoietic stem cell. There is no correlation between the platelet count and risk of thrombosis, but some patients with extreme thrombocytosis (ie, > 1,000,000/mcL) develop bleeding due to loss of high molecular weight von Willebrand factor multimers.

Reactive thrombocytosis Reactive Thrombocytosis (Secondary Thrombocythemia) Reactive thrombocytosis is an elevated platelet count (> 450,000/mcL [> 450,000 × 109/L]) that develops secondary to another disorder. (See also Overview of Myeloproliferative Neoplasms.) Some... read more is platelet overproduction in response to another disorder. There are many causes, including acute infection, chronic inflammatory disorders (eg, rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more Rheumatoid Arthritis (RA) , inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more , tuberculosis Tuberculosis (TB) Tuberculosis (TB) is a chronic, progressive mycobacterial infection, often with a period of latency following initial infection. TB most commonly affects the lungs. Symptoms include productive... read more Tuberculosis (TB) , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis ), iron deficiency Iron Deficiency Iron (Fe) is a component of hemoglobin, myoglobin, and many enzymes in the body. Heme iron is contained mainly in animal products. It is absorbed much better than nonheme iron (eg, in plants... read more , and certain cancers. Reactive thrombocytosis is not typically associated with an increased risk of thrombosis or bleeding.


  • Decreased platelet production

  • Increased splenic sequestration of platelets with normal platelet survival

  • Increased platelet destruction or consumption (both immunologic and nonimmunologic causes)

  • Dilution of platelets


Overall, the most common specific causes of thrombocytopenia include

Platelet dysfunction

Symptoms and Signs of Platelet Disorders

Platelet disorders result in a typical pattern of bleeding:

  • Multiple petechiae in the skin (typically most evident on the lower legs)

  • Scattered small ecchymoses at sites of minor trauma or venipuncture sites

  • Mucosal bleeding (oropharyngeal, nasal, gastrointestinal, genitourinary)

  • Excessive bleeding after surgery

Manifestations of Platelet Disorders

Heavy gastrointestinal bleeding and bleeding into the central nervous system may be life threatening. However, bleeding into tissues (eg, deep visceral hematomas or hemarthroses) rarely occurs with thrombocytopenia; instead, patients usually have immediate and superficial bleeding following an injury. Bleeding into the tissues (often delayed for up to a day after trauma) suggests a coagulation disorder (eg, hemophilia Hemophilia Hemophilias are common hereditary bleeding disorders caused by deficiencies of either clotting factor VIII or IX. The extent of factor deficiency determines the probability and severity of bleeding... read more ).

Diagnosis of Platelet Disorders

  • Clinical presentation of petechiae and mucosal bleeding

  • Complete blood count (CBC) with platelets, coagulation studies, peripheral blood smear

  • Sometimes bone marrow aspiration

  • Sometimes von Willebrand antigen and activity studies

Platelet disorders are suspected in patients with petechiae and mucosal bleeding. A CBC with platelet count, coagulation studies, and a peripheral blood smear are obtained. Excessive platelets and thrombocytopenia are diagnosed based on the platelet count; coagulation studies are normal unless there is a simultaneous coagulopathy. In patients with a normal CBC, platelet count, international normalized ratio (INR), and partial thromboplastin time (PTT), platelet or vessel wall dysfunction is suspected.

Pearls & Pitfalls

  • Suspect platelet or vessel wall dysfunction in patients with petechiae and/or hemorrhage but with normal platelet count and coagulation test results.


Peripheral smear examination is important in patients with thrombocytopenia because automated platelet counts sometimes show pseudothrombocytopenia due to platelet clumping caused by a reaction with the ethylenediaminetetraacetic acid (EDTA) reagent present in some blood collection tubes. Also, schistocytes may be seen, which can indicate thrombotic thrombocytopenic purpura Thrombotic Thrombocytopenic Purpura (TTP) Thrombotic thrombocytopenic purpura (TTP) is an acute, fulminant disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. Other manifestations may include alterations... read more Thrombotic Thrombocytopenic Purpura (TTP) (TTP), hemolytic-uremic syndrome Hemolytic-Uremic Syndrome (HUS) Hemolytic-uremic syndrome (HUS) is an acute, fulminant disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. HUS usually occurs in children... read more Hemolytic-Uremic Syndrome (HUS) (HUS), or disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more (DIC—see table Peripheral Blood Findings in Thrombocytopenic Disorders Peripheral Blood Findings in Thrombocytopenic Disorders Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes,... read more Peripheral Blood Findings in Thrombocytopenic Disorders ).

Bone marrow aspiration is indicated if the smear shows abnormalities other than thrombocytopenia, such as nucleated red blood cells (RBCs) or abnormal or immature white blood cells (WBCs). Bone marrow aspiration reveals the number and appearance of megakaryocytes and is the definitive test for many disorders that cause bone marrow failure. If the bone marrow is normal but the spleen is enlarged, increased splenic sequestration Thrombocytopenia Due to Splenic Sequestration Increased splenic platelet sequestration can occur in various disorders that cause splenomegaly. However, thrombocytopenia that occurs in advanced cirrhosis is mostly due to reduced thrombopoietin... read more is the likely cause of thrombocytopenia. If the bone marrow is normal and the spleen is not enlarged, excess platelet destruction is the likely cause.

The immature platelet fraction in peripheral blood is sometimes a useful measure in patients with thrombocytopenia, since it is elevated when the bone marrow is producing platelets and not increased when marrow platelet production is reduced, similar to the reticulocyte count in anemia.

Measurement of antiplatelet antibodies may be clinically useful in some patients to distinguish ITP from other causes of thrombocytopenia (1) Diagnosis reference Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes,... read more Diagnosis reference . HIV testing is done in patients at risk of HIV infection.


Suspected platelet dysfunction

In patients with platelet dysfunction, a drug cause is suspected if symptoms began only after the patient started taking a potentially causative drug (eg, ticarcillin, prasugrel, clopidogrel, ticagrelor, abciximab). Platelet dysfunction caused by drugs may be severe, but specialized tests are rarely needed.

A hereditary cause is suspected if there is a lifelong history of easy bruising; bleeding after tooth extractions, surgery, childbirth, or circumcision; or heavy menstruation. In the case of a suspected hereditary cause, von Willebrand factor (VWF) antigen and VWF activity studies are routinely done.

In patients with suspected hereditary dysfunction, platelet aggregation tests may identify a defect in how the platelet responds to various platelet agonists (adenosine diphosphate [ADP], collagen, thrombin) and thereby demonstrate the type of platelet defect.

Platelet dysfunction caused by systemic disorders is typically mild and of minor clinical importance. In these patients, the causative systemic disorder is the clinical concern, and hematologic tests are unnecessary.

Diagnosis reference

  • Al-Samkari H, Rosovsky RP, Karp Leaf RS: A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv 14;4(1):9–18, 2020. doi: 10.1182/bloodadvances.2019000868.

Treatment of Platelet Disorders

  • Stopping drugs that impair platelet function

  • Rarely platelet transfusions

  • Rarely antifibrinolytic drugs

In patients with thrombocytopenia or platelet dysfunction, drugs that further impair platelet function, particularly aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), should not be given. Patients who are already taking such drugs should consider alternative drugs, such as acetaminophen, or simply stop using them.

Patients may require platelet transfusion Platelets Whole blood can provide improved oxygen-carrying capacity, volume expansion, and replacement of clotting factors and was previously recommended for rapid massive blood loss. However, because... read more , but transfusions are given only in limited situations. Prophylactic transfusions are used sparingly because they may lose their effectiveness with repeated use due to the development of platelet alloantibodies.

In platelet dysfunction or thrombocytopenia caused by decreased production, transfusions, thrombopoietin (TPO)-receptor agonists (eg, romiplostim, eltrombopag, avatrombopag), or antifibrinolytic drugs (eg, aminocaproic acid, tranexamic acid) are reserved for patients with

  • Active bleeding

  • Severe thrombocytopenia (eg, platelet count < 10,000/mcL)

  • A need for an invasive procedure

In thrombocytopenia caused by platelet destruction, transfusions are reserved for life-threatening or central nervous system bleeding.

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