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
A decrease in platelets (thrombocytopenia)
Platelet dysfunction
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
Essential thrombocythemia
Essential Thrombocythemia Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased platelet count, megakaryocytic hyperplasia, and a hemorrhagic or microvascular vasospastic 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 called a
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 [> 1000 × 109/L]) develop bleeding due to loss of high molecular weight von Willebrand factor multimers (acquired type 2B
von Willebrand disease
Von Willebrand Disease Von Willebrand disease (VWD) is a hereditary quantitative deficiency or functional abnormality of von Willebrand factor (VWF), which causes platelet dysfunction. Bleeding tendency is usually... read more ).
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
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
Drugs that cause immune-mediated platelet destruction (commonly, heparin, trimethoprim/sulfamethoxazole, rarely quinine [cocktail purpura] or abciximab), and rarely vaccinations (eg, influenza, shingles, measles, mumps, and rubella, A COVID-19)
Drugs that cause dose-dependent bone marrow suppression (eg, chemotherapeutic agents, ethanol)
Systemic infection
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
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.
Peripheral smear examination is important in patients with thrombocytopenia because automated platelet counts sometimes show pseudothrombocytopenia due to platelet clumping caused by the ethylenediaminetetraacetic acid (EDTA) reagent present in some blood collection tubes. Also, schistocytes may be seen, which can indicate valvular hemolysis,
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
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.
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.
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
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.
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.
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