In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (μL) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/μL. Thrombocytopenia can be contrasted with the conditions associated with an abnormally high level of platelets in the blood – thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known).
Signs and symptoms
Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding, such as nosebleeds or bleeding gums. Some individuals may have heavier or longer periods or breakthrough bleeding. Bruising, particularly purpura in the forearms and petechiae in the feet, legs, and mucous membranes, may be caused by spontaneous bleeding under the skin. Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. Ensuring that the other blood cell types, such as red blood cells and white blood cells, are not also suppressed, is also important. Painless, round, and pinpoint (1 to 3 mm in diameter) petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue, or yellow-green areas of skin that vary in size and shape. They can occur anywhere on the body. A person with this disease may also complain of malaise, fatigue, and general weakness (with or without accompanying blood loss). Acquired thrombocytopenia may be associated with the use of certain drugs. Inspection typically reveals evidence of bleeding (petechiae or ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Adults may have large, blood-filled bullae in the mouth. If the person's platelet count is between 30,000 and 50,000/μL, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/μL, spontaneous bruising will be seen (mostly on the arms and legs).
Causes Thrombocytopenia can be inherited or acquired. There are many causes.
Decreased production Abnormally low platelet production may be caused by:
Dehydration, vitamin B12 or folic acid deficiency Leukemia, myelodysplastic syndrome, or aplastic anemia Decreased production of thrombopoietin by the liver in liver failure Sepsis, systemic viral or bacterial infection Leptospirosis Hereditary syndromes ACTN1-related thrombocytopenia Amegakaryocytic thrombocytopenia with radio-ulnar synostosis ANKRD26 related thrombocytopenia Autosomal dominant thrombocytopenia Bernard–Soulier syndrome (associated with giant platelet disorder) Congenital amegakaryocytic thrombocytopenia Congenital amegakaryocytic thrombocytopenia and radioulnar synostosis CYCS-related thrombocytopenia Epstein syndrome (associated with giant platelet disorder) ETV6 related thrombocytopenia Fanconi anemia Filaminopathies A FYB related thrombocytopenia Glanzmann's thrombasthenia GNE myopathy with congenital thrombocytopenia Gray platelet syndrome (associated with giant platelet disorder) Harris platelet syndrome (associated with giant platelet disorder) Macrothrombocytopenia and hearing loss May–Hegglin anomaly (associated with giant platelet disorder) MYH9-related disease (associated with giant platelet disorder) PRKACG-related thrombocytopenia Paris-Trousseau thrombocytopenia/Jacobsen syndrome Sebastian syndrome SLFN14-related thrombocytopenia Stormorken syndrome TRPM7-related thrombocytopenia Thrombocytopenia absent radius syndrome Tropomyosin 4-related thrombocytopenia TUBB1-related thrombocytopenia Upshaw–Schulman syndrome Wiskott–Aldrich syndrome X-linked thrombocytopenia X-linked thrombocytopenia with thalassemia
Increased destruction
Abnormally high rates of platelet destruction may be due to immune or nonimmune conditions, including:
Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Hemolytic–uremic syndrome Disseminated intravascular coagulation Paroxysmal nocturnal hemoglobinuria Antiphospholipid syndrome Systemic lupus erythematosus Post-transfusion purpura Neonatal alloimmune thrombocytopenia Hypersplenism Dengue fever Gaucher's disease Zika virus
Medication-induced These medications can induce thrombocytopenia through direct myelosuppression:
Valproic acid Methotrexate Carboplatin Interferon Isotretinoin Panobinostat H2 blockers and proton-pump inhibitors
Other causes Laboratory error, possibly due to the anticoagulant EDTA in CBC specimen tubes; a citrated platelet count is a useful follow-up study Snakebite Lyme disease Thrombocytapheresis (also called plateletpheresis) Niemann–Pick disease Cyclic thrombocytopenia, in which platelet counts vary in a cyclic pattern
Diagnosis Laboratory tests for thrombocytopenia might include full blood count, liver enzymes, kidney function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear. If the cause for the low platelet count remains unclear, a bone marrow biopsy is usually recommended to differentiate cases of decreased platelet production from cases of peripheral platelet destruction. Thrombocytopenia in hospitalized alcoholics may be caused by spleen enlargement, folate deficiency, and most frequently, the direct toxic effect of alcohol on production, survival time, and function of platelets. Platelet count begins to rise after 2 to 5 days' abstinence from alcohol. The condition is generally benign, and clinically significant hemorrhage is rare. In severe thrombocytopenia, a bone marrow study can determine the number, size, and maturity of the megakaryocytes. This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time.
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