Merck Manual

Please confirm that you are a health care professional

honeypot link

Overview of Platelet Disorders

By

David J. Kuter

, MD, DPhil, Harvard Medical School

Medically Reviewed Jun 2022 | Modified Sep 2022
View Patient Education
Topic Resources

Platelets are circulating 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 how much is bound to circulating platelets and possibly to bone marrow megakaryocytes and the extent to which circulating platelets are cleared. Platelets circulate for 7 to 10 days. About one third are always transiently sequestered in the spleen.

The platelet count is normally 140,000to 440,000/mcL (140 to 440 × 109/L). 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 markedly 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 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.

Table

Etiology of Platelet Disorders

Thrombocythemia and thrombocytosis

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... 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 is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... 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 is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... 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.

Thrombocytopenia

Causes of thrombocytopenia can be classified by mechanism (see table Classification of Thrombocytopenia Classification of Thrombocytopenia Classification of Thrombocytopenia ) and include

  • 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

Table

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

  • Extensive menstrual bleeding

Manifestations of Platelet Disorders

Heavy gastrointestinal bleeding and bleeding into the central nervous system are rare but 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, platelet-binding activity, and multimer 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.

Thrombocytopenia

Bone marrow aspiration is often 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 circulating 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 with or at risk of HIV infection, hepatitis B or C infection, or HIV and hepatitis coinfection.

Table

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

  • 1. Al-Samkari H, Rosovsky RP, Karp Leaf RS: A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv 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 [< 10 × 109/L)

  • A need for an invasive procedure

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

Drugs Mentioned In This Article

Drug Name Select Trade
Anacin Adult Low Strength, Aspergum, Aspir-Low, Aspirtab , Aspir-Trin , Bayer Advanced Aspirin, Bayer Aspirin, Bayer Aspirin Extra Strength, Bayer Aspirin Plus, Bayer Aspirin Regimen, Bayer Children's Aspirin, Bayer Extra Strength, Bayer Extra Strength Plus, Bayer Genuine Aspirin, Bayer Low Dose Aspirin Regimen, Bayer Womens Aspirin , BeneHealth Aspirin, Bufferin, Bufferin Extra Strength, Bufferin Low Dose, DURLAZA, Easprin , Ecotrin, Ecotrin Low Strength, Genacote, Halfprin, MiniPrin, St. Joseph Adult Low Strength, St. Joseph Aspirin, VAZALORE, Zero Order Release Aspirin, ZORprin
VONVENDI
Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin
Primsol, Proloprim, TRIMPEX
Qualaquin
ReoPro
Ablysinol
Effient
Plavix
BRILINTA
Recothrom, Thrombi-Gel , Thrombin-JMI, Thrombin-JMI Epistaxis, Thrombi-Pad, Thrombogen
7T Gummy ES, Acephen, Aceta, Actamin, Adult Pain Relief, Anacin Aspirin Free, Apra, Children's Acetaminophen, Children's Pain & Fever , Comtrex Sore Throat Relief, ED-APAP, ElixSure Fever/Pain, Feverall, Genapap, Genebs, Goody's Back & Body Pain, Infantaire, Infants' Acetaminophen, LIQUID PAIN RELIEF, Little Fevers, Little Remedies Infant Fever + Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Infants, Mapap Junior, M-PAP, Nortemp, Ofirmev, Pain & Fever , Pain and Fever , PAIN RELIEF , PAIN RELIEF Extra Strength, Panadol, PediaCare Children's Fever Reducer/Pain Reliever, PediaCare Children's Smooth Metls Fever Reducer/Pain Reliever, PediaCare Infant's Fever Reducer/Pain Reliever, Pediaphen, PHARBETOL, Plus PHARMA, Q-Pap, Q-Pap Extra Strength, Silapap, Triaminic Fever Reducer and Pain Reliever, Triaminic Infant Fever Reducer and Pain Reliever, Tylenol, Tylenol 8 Hour, Tylenol 8 Hour Arthritis Pain, Tylenol 8 Hour Muscle Aches & Pain, Tylenol Arthritis Pain, Tylenol Children's, Tylenol Children's Pain+Fever, Tylenol CrushableTablet, Tylenol Extra Strength, Tylenol Infants', Tylenol Infants Pain + Fever, Tylenol Junior Strength, Tylenol Pain + Fever, Tylenol Regular Strength, Tylenol Sore Throat, XS No Aspirin, XS Pain Reliever
Nplate
Promacta
DOPTELET
Amicar
Cyklokapron, Lysteda
View Patient Education
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz! 
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP