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Thrombocytopenia

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Related Terms
  • Anticoagulant, blood cells, blood clot, blood disorder, blood transfusion, bone marrow, coagulation, coagulation abnormality, DIC, drug-induced immune thrombocytopenia, drug-induced non-immune thrombocytopenia, drug induced thrombocytopenia, enlarged spleen, HAT, hemolysis, hemorrhage, heparin, heparin-induced, heparin-induced immune-mediated thrombocytopenia, HIT, hypersplenism, immune thrombocytopenic purpura, internal bleeding, ITP, Intracranial hemorrhage, plasma, plasmapheresis, platelets, spleen, purpura, thrombosis, red blood cells, spleen, stroke, TTP.

Background
  • Thrombocytopenia is a general term for blood disorders that cause low levels of platelets in the blood. A platelet is a type of blood cell that helps the blood clot. These cells clump together at the site of a blood vessel injury in order to prevent blood loss. Therefore, thrombocytopenia is often associated with abnormal bleeding.
  • Healthy individuals have anywhere from 150,000 to 450,000 platelets per microliter of circulating blood in the body. The bone marrow continually produces new platelets because they only live about 10 days. Thrombocytopenia occurs when the platelet count falls below 20,000 per microliter of blood. The risk of bleeding increases as the number of platelets decreases. When there are less than 10,000 platelets per microliter of circulating blood, the condition is considered severe, and internal bleeding may occur.
  • Thrombocytopenia can occur by itself, or it can develop as a complication of another disease, such as cancer or a viral infection. Drug-induced thrombocytopenia may occur in response to medication (such as heparin). In some cases, thrombocytopenia is a chronic (long-lasting) condition that persists for years. However, it may develop suddenly and dramatically in some individuals.
  • Thrombocytopenia usually improves after treating the underlying cause. In some cases, medications or surgery can help treat chronic thrombocytopenia. If bleeding is severe, some patients may require a blood transfusion.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. MedlinePlus. . Accessed May 4, 2009.
  2. Moss RA. Drug-Induced Immune Thrombocytopenia. Am J Hematol. 1980;9(4):439-46.
  3. National Heart Lung and Blood Institute. . Accessed May 4, 2009.
  4. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2009. Accessed May 4, 2009.
  5. The Cleveland Clinic. . Accessed May 4, 2009.
  6. University of Virginia Health System. Thrombocytopenia. . Accessed May 4, 2009.

Causes
  • There are three major causes that lead to low platelet counts. The condition may be caused if the bone marrow does not produce enough platelets, there is an increased breakdown of platelets in the bloodstream (intravascular) or there is an increased breakdown of platelets in the spleen (extravascular).
  • Insufficient platelets produced: Several disorders, including aplastic anemia and bone marrow cancer may affect the bone marrow's ability to produce platelets. In rare cases, bone marrow infections or certain drugs (such as chemotherapy) may also inhibit the bone marrow from producing enough of the cells.
  • Increased platelets destroyed in bloodstream: There are also many disorders that lead to the destruction of platelets in the body. Examples include: Gram-negative sepsis, acute promyelocytic leukemia, anemia, malaria, tuberculosis or various connective tissue and inflammatory diseases. Certain medications, such as heparin, quinidine, quinine, sulfa-containing antibiotics, some oral hypoglycemia agents (drugs that treat diabetes) like diazoxide, gold salts and rifampin, may also destroy platelets. The drugs may destroy platelets directly or they may initiate an autoimmune response, causing the body to produce antibodies against platelets. Pregnancy may also cause mild thrombocytopenia.
  • Increased platelets destroyed in the spleen: Individuals who have an enlarged spleen are at risk for developing thrombocytopenia. In healthy individuals, the spleen works to fight infection and filters unwanted material from the blood. Normally, about one-third of the body's platelets are located in the spleen while the rest circulate in the blood. However, when the spleen becomes enlarged (which can be the result of many different disorders), the spleen may harbor too many platelets, which causes a decrease in the number of platelets in circulation.

Symptoms
  • Symptoms of thrombocytopenia can range from mild to severe. Individuals with mild cases may be asymptomatic. The duration and severity of symptoms depends on the cause. For instance, ITP is often a chronic condition that may last for years, while most drug-induced thrombocytopenic patients recover within seven to ten days after they stop taking the medication.
  • Symptoms of thrombocytopenia often include nosebleeds, bleeding in the mouth, easy or excessive bruising, prolonged bleeding from cuts, blood in stools, blood in urine, blood in vomit, purpura (purplish discolorations in the skin produced by small bleeding vessels near the surface of the skin), unusually heavy menstrual flows, profuse bleeding during surgery and superficial bleeding into the skin (that looks like a rash).
  • TTP may also cause fever, weakness, fatigue, pallor (pale skin), shortness of breath, increased heartbeat, bleeding into the skin or mucus membranes, confusion, speech changes, alterations in consciousness, jaundice (yellowing of the skin and eyes) and kidney failure.

Diagnosis
  • Mild thrombocytopenia often causes no signs or symptoms. A routine blood test may detect a low platelet count even if symptoms are not present. A fibrinogen test may also detect low levels of platelets. Once thrombocytopenia has been diagnosed, a bone marrow biopsy can be performed to determine whether the bone marrow is producing a sufficient number of platelets. Individuals who are at risk of developing thrombocytopenia (like pregnant women) should consult a qualified healthcare physician who can monitor their platelet count regularly.
  • CBC: A complete blood count (CBC) is usually conducted to determine how many and what types of cells are in the blood. This blood test can detect a low platelet count.
  • Bone marrow biopsy: A bone marrow biopsy may be performed to confirm a diagnosis. During the biopsy, the patient is given a local anesthetic, and a sample of bone marrow is removed with a needle. The sample is then analyzed in the laboratory to determine whether or not there is a deficiency of megakaryocytes (platelet-producing cells) or an infiltrating disease.
  • Fibrinogen test: A small sample of blood is taken from the patient in order to measure the amount of fibrinogen (a coagulation factor) in the blood.

Treatment
  • General: Thrombocytopenia usually improves after treating the underlying cause. In some cases, medications or surgery can help treat chronic thrombocytopenia. If bleeding is severe, some patients may require a blood transfusion. If the condition is drug-induced, the patient will be advised to stop taking the medication. Type II HIT requires immediate discontinuation of heparin and administration of an alternative anticoagulant (like lepirudin, bivalirudin, argatroban or danaparoid).
  • Blood transfusion and plasma exchange: If patients experience severe bleeding, they may receive blood transfusions with red blood cells. Platelet concentrates are given to treat severe thrombocytopenia (that causes severe bleeding), especially those related to cancer or chemotherapy. Thrombotic thrombocytopenic purpura often requires emergency treatment with plasma exchange therapy or therapeutic plasmapheresis. With the development of plasmapheresis about 80-90% of individuals with TTP are able to recover.
  • Medications: Individuals who have idiopathic thrombocytopenic purpura, have been treated with medications that block the antibodies that attack platelets, such as corticosteroids (like prednisone), or medications that suppress the immune system to reduce antibody formation, such as cyclophosphamide (Cytoxan®) or azathioprine (Imuran®).
  • Alternative anticoagulants: Type II HIT requires immediate discontinuation of heparin and administration of an alternative anticoagulant (like lepirudin, bivalirudin, argatroban or danaparoid). Lepirudin (Refludan®) is approved by the U.S. Food and Drug Administration (FDA) for anticoagulation for patients with heparin-induced thrombocytopenia and heparin-induced thrombosis. Bivalirudin (Angiomax®) is FDA-approved for use in patients undergoing coronary angioplasty with unstable angina and concomitant aspirin therapy. Argatroban (Argatroban®) is FDA-approved for the prevention or treatment of thrombosis in patients who have type II HIT. Danaparoid (Orgaran®) is FDA-approved for the prevention of deep vein thrombosis after hip surgery, although it is approved in some countries for the treatment of type II HIT.
  • Surgery: In severe cases a surgeon may remove the spleen (splenectomy) to relieve symptoms or to help improve chronic idiopathic thrombocytopenic purpura that does not respond to corticosteroids.

Integrative therapies
  • Unclear or conflicting scientific evidence:
  • Berberine: In limited available study, berberine has been shown to significantly increase platelet production in individuals with thrombocytopenia both as monotherapy and adjunctive therapy to prednisolone.
  • Avoid if allergic or hypersensitive to berberine, to plants that contain berberine (Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric)), or to members of the Berberidaceae family. Avoid in newborns due to potential for increase in free bilirubin, jaundice and development of kernicterus. Use cautiously with heart disease, gastrointestinal disorders, hematologic (blood) disorders, leucopenia, kidney disease, liver disease, respiratory disorders, cancer, hypertyraminemia, diabetes or hypotension (low blood pressure). Use cautiously in children due to lack of safety information. Use cautiously in individuals with high exposure to sunlight or artificial light. Use cautiously for longer than eight weeks due to theoretical changes in bacterial gut flora. Use cautiously if taking anticoagulants (blood thinners), antihypertensives (blood pressure lowering agents), sedatives, anti-inflammatories, medications metabolized by CYP P450 3A4 including cyclosporin, or any prescription medications. Avoid if pregnant or breastfeeding due to potential for crossing placenta, stimulating the uterus (based on historical use) or transferring to breast milk.
  • Dong quai: Poor-quality study has reported benefits of Dong quai in patients diagnosed with idiopathic thrombocytopenic purpura (ITP). However, these patients were not compared to individuals who were not receiving Dong quai, and therefore the results can only be considered preliminary.
  • Avoid if allergic to Angelica radix or members of the Aplaceae/Umbelliferae family (like anise, caraway, carrot, celery, dill or parsley). Dong quai's safety in medicinal doses is unknown. There are no reliable long-term studies of side effects. Most precautions are based on theory, laboratory research, tradition, or isolated case reports. Avoid if pregnant due to possible hormonal and anticoagulant/anti-platelet properties. Avoid if breastfeeding due to insufficient scientific evidence of safety.
  • Ginseng: Combination herbal products containing ginseng may help treat refractory idiopathic thrombocytopenic purpura, a blood disorder that does not respond well to treatment. Studies that use ginseng alone are needed.
  • Avoid if allergic to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.
  • Licorice: Early study has suggested that recombinant roasted licorice decoction combined with low-dose glucocorticoids may be more effective than glucocorticoids alone in treating idiopathic thrombocytopenic purpura. This combination has also shown a lower adverse effect rate than glucocorticoids alone.
  • Avoid with a known allergy to licorice, any component of licorice, or any member of the Fabaceae (Leguminosae) plant family. Avoid licorice with congestive heart failure, coronary heart disease, kidney or liver disease, fluid retention, high blood pressure, hormonal abnormalities, or if taking diuretics. Licorice can cause abnormally low testosterone levels in men or high prolactin or estrogen levels in women. This may make it difficult to become pregnant and may cause menstrual abnormalities.
  • Melatonin: Increased platelet counts after melatonin use has been observed in patients with thrombocytopenia. Stimulation of platelet production (thrombopoeisis) has been suggested but not clearly demonstrated. Additional research is necessary in this area.
  • Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. There are rare reports of allergic skin reactions after taking melatonin by mouth. Melatonin has been linked to a case of autoimmune hepatitis. Melatonin supplementation should be avoided in women who are pregnant or attempting to become pregnant, based on possible hormonal effects. High levels of melatonin during pregnancy may increase the risk of developmental disorders. In animal studies, melatonin is detected in breast milk and therefore should be avoided during breastfeeding. In men, decreased sperm motility and decreased sperm count are reported with the use of melatonin.

Prevention
  • Individuals who have already experienced drug-induced thrombocytopenia should avoid exposure to the medication again. Patients who experienced HIT or HAT may experience thrombocytopenia if they are exposed to trace amounts of heparin (such as heparin-coated plastics that are used in hospitals).
  • If a qualified healthcare provider has determined that a patient is at risk for developing thrombocytopenia, the patient may be advised not to take aspirin because it impairs platelet function.

Complications
  • The risk of bleeding increases as the number of platelets decreases. When there are less than 10,000 platelets per microliter of circulating blood, the condition is considered severe, and internal bleeding may occur.
  • Hemorrhage: Hemorrhage is possible throughout the body. Intracranial (bleeding in the head) is another possible complication of thrombocytopenia.
  • Gastrointestinal bleeding: In serious cases, blood may be present in vomit or stools.
  • Stroke: Individuals suffering from thrombocytopenia are at an increased risk of stroke.

Types of thrombocytopenia
  • Disseminated intravascular coagulation (DIC):
  • Disseminated intravascular coagulation (DIC) occurs when the blood coagulates through the entire body, which causes a depletion of platelets. This disorder has variable effects, and can result in either clotting symptoms or, more often, bleeding. Bleeding can be severe. DIC may be stimulated by many factors, including bacterial or fungal infections in the blood, severe tissue injury (like burns or head trauma), cancer, reactions to blood transfusions and obstetrical complications (like retained placenta after delivery).
  • Individuals suffering from this condition are at an increased risk of hemorrhage (internal bleeding). This disorder is most common among critically ill patients.
  • Drug-induced, non-immune thrombocytopenia:
  • Certain drugs can reduce the number of healthy platelets in the blood, resulting in drug-induced non-immune thrombocytopenia. Medications, such as heparin, quinidine, quinine, sulfa-containing antibiotics, some oral hypoglycemia agents (drugs that treat diabetes) like diazoxide, gold salts and rifampin, may destroy platelets. This is not an allergic reaction because the immune system is not involved. Instead, the drugs either destroy the platelets or damage the bone marrow where platelets are produced.
  • Type I Heparin-induced thrombocytopenia (HIT): Heparin is used to treat and prevent abnormal blood clotting. Heparin can induce thrombocytopenia in some patients. Type I Heparin-induced thrombocytopenia, also called heparin-associated thrombocytopenia (HAT), causes a transient decrease in platelet count without any further symptoms.
  • The cause of type I HIT may be mediated by a direct interaction between heparin and circulating platelets, which causes platelet clumping or sequestration. This type of thrombocytopenia may occur in patients who are receiving heparin in the presence of other comorbid factors, such as other medications or sepsis, which may complicate the diagnosis. Type I HIT usually occurs within the first 48 to 72 hours after initiation of heparin therapy. The platelet count usually rarely falls below 100 X 103/mm.3 Platelet levels often return to normal within four days, even if heparin is still administered. No laboratory tests are necessary to diagnose type I HIT, and it is not associated with an increased risk of thrombosis.
  • Type I HIT occurs in about 10-20% of all patients on heparin. It is not due to an immune reaction and antibodies are not present.
  • Drug-induced immune thrombocytopenia:
  • Certain medications may lead to the formation of antibodies against platelets. Some medications may cause the immune system to mistake the platelets for an invading substance, and the antibodies set out to destroy the cells. As a result of this autoimmune response, platelets are removed rapidly from the blood circulation. Quinidine and quinine have been most commonly implicated but, recently, both heparin and heroin have been indicated in an increasing number of reports.
  • Type II Heparin-induced thrombocytopenia (HIT): Heparin is used to treat and prevent abnormal blood clotting. Heparin can induce thrombocytopenia in some patients. Type II Heparin-induced thrombocytopenia, also called heparin-associated thrombocytopenia (HAT), is immune-mediated. This condition occurs when the antibodies also activate platelets and cause a hypercoagulable state. Type II Heparin-induced thrombocytopenia can range from mild to severe. In some cases, heparin-induced thrombocytopenia can cause excessive blood clotting instead of bleeding, which increases the risk of clot formation in a deep blood vessel in the leg. Such clots may also be transported to the lungs, which can be life threatening.
  • The condition may develop one to ten days after initiation of heparin therapy. Type II occurs in about 1-3% of patients receiving heparin.
  • Hypersplenism:
  • Hypersplenism, also called splenomegaly (enlarged spleen), occurs when the spleen, which fights infection and filters the blood, is overactive. When hypersplenism occurs, the spleen starts to automatically remove cells that may still be normal in function. This is often the result of tumors, anemia, malaria, tuberculosis or various connective tissue and inflammatory diseases. The spleen becomes enlarged, which often results in a low level of one or more types of blood cells. Individuals who have an enlarged spleen are at risk for developing thrombocytopenia because the spleen may harbor up to 90% of the body's platelets, causing a decrease in the number of platelets in circulation.
  • Idiopathic thrombocytopenic purpura (ITP):
  • When the immune system destroys platelets for an unknown reason, the condition is referred to as idiopathic thrombocytopenic purpura (or immune thrombocytopenic purpura). The lymphocytes (immune system cells) produce antibodies to fight off the platelets, which are then destroyed in the spleen. When the immune system mistakenly attacks part of a person's own body, the condition is called an autoimmune disease.
  • Acute ITP generally lasts less than six months. It mainly occurs in children, and it is the most common type of ITP. It typically occurs after a viral infection. This type of ITP often goes away on its own within a few weeks or months and does not return. Treatment may not be needed. Chronic ITP (lasting six months or longer) mainly affects adults. However, some teenagers and even younger children acquire this type of ITP. Chronic ITP affects women two to three times more often than men. Treatment depends on how severe the bleeding symptoms are and on the platelet count. In mild cases, treatment may not be needed.
  • Thrombotic thrombocytopenic purpura (TTP):
  • Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that is characterized by low levels of platelets, low levels of red blood cells, as well as abnormalities in the kidneys and nervous system. Most cases of TTP are the result of a deficiency of the ADAMTS13 enzymes, which are responsible for cleaving ultra large multimers of the von Willebrand factor. This result in hemolysis and organ damage. The condition is considered a medical emergency.
  • With the development of plasmapheresis, a process that involves removing plasma from blood, about 80-90% of individuals with TTP are able to recover. During plasmapheresis, plasma (which contains platelets) from a blood donor is transfused into the TTP patient's blood. Plasmapheresis is continued until the platelet count normalizes and there is minimal hemolysis.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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