Thrombocytopenia absent radius syndrome

• Thrombocytopenia absent radius (TAR) syndrome is a rare disorder that is congenital (present at birth). Thrombocytopenia is a general term for blood disorders that cause low levels of platelets. 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. TAR syndrome is characterized by very low levels of platelet-producing cells, called hypomegakaryocytic thrombocytopenia, associated with bilateral radial aplasia. This means that in addition to having dramatically low platelet levels, the bone that connects the elbow to the thumb side of the wrist (called the radius) fails to grow in both arms.
• TAR syndrome was first defined as a syndrome in 1969. TAR can have varied symptoms, which can include abnormalities in the digestive, bone, blood, and heart systems. Despite the absence of the radius bones, TAR patients usually have both of their thumbs, although thumb function is very limited.
• Bone defects are often present in individuals affected with TAR. In addition, TAR patients may be short for their age and are commonly intolerant of cow's milk.
• Although TAR syndrome is not completely understood, it is generally believed to be inherited because it has affected more than one member of some families. However, further research is needed to confirm this genetic link. Evidence has suggested that TAR syndrome may be the result of a more complex inheritance pattern; other theories also exist.
• The symptoms and complications of TAR syndrome are the most severe during infancy and almost all deaths occur before age two. Those that survive beyond age two may have normal life expectancies. There are a number of adults living with TAR syndrome, which suggests that there are few additional problems that develop during adulthood. Most adults with TAR syndrome are able to live independently and have productive jobs despite physical limitations from the disease. In addition, the Internet has become a valuable means of connection between people with TAR, who often feel isolated because the condition is so rare.

• Thrombocytopenia absent radius (TAR) syndrome is believed to be inherited in an autosomal recessive pattern. Autosomally inherited disorders are associated with abnormalities (mutations) in any of the first 22 non-sex chromosomes, which are the genetic structures that contain DNA. People inherit two copies of each autosomal gene (one from each parent). Recessive inheritance means that both copies of a gene must be defective to cause the disease. A person that has only one defective gene does not develop the disease, but is considered a carrier. Carriers can pass the abnormal gene to their children.
• Children born to parents who are both carriers of an autosomal recessive gene each have a 25% chance of inheriting two copies of the abnormal gene, one from each parent, and developing the disease. These children would also have a 50% chance of inheriting just one abnormal gene, which would make them carriers.
• If one parent has TAR and the other parent does not have TAR and is not a carrier of TAR, each of their children will be a carrier of TAR. Children who have one parent with TAR and one parent who is a carrier of TAR have a 50% chance of having TAR syndrome and a 50% chance of being a carrier of TAR. Many TAR patients have had children that did not develop the disease.
• Patients usually show symptoms of thrombocytopenia (low blood platelet production) in the first week of life. However, improved blood platelet counts during infancy and normalization of platelet levels with increasing age is common.
• TAR syndrome affects males and females equally, and the incidence is similar in most populations. For unknown reasons, TAR syndrome rarely occurs in the United States. The frequency is slightly higher in Spain, where TAR syndrome affects about four out of every one million babies.

• General: The development of thrombocytopenia absent radius (TAR) syndrome is poorly understood. Bone marrow samples from TAR patients show either decreased or absent megakaryocytopoiesis, the process of creating and specializing cells that make platelet cells (megakaryocytes). This indicates that thrombocytopenia in TAR syndrome is due to defective platelet production, which usually occurs when cells that have not yet developed to perform a specialized function are injured, or when the growth of these undeveloped cells is specifically prevented in bone marrow.
• Inheritance: The causes of TAR syndrome are not fully understood and genetic research is still underway. However, the general theory is that it is inherited as an autosomal recessive trait. This theory has been based, in part, on the observation that TAR syndrome has affected more than one member of some families with unaffected parents. However, further research is needed to confirm this genetic link, as evidence has suggested that TAR syndrome may be the result of a more complex inheritance pattern.
• Some have suggested that the inheritance pattern may be autosomal dominant with variable expressivity. This means that only one abnormal gene is needed to inherit the disorder, but symptoms and severity of the disease vary among patients.
• Other theories: Another theory suggests that TAR syndrome may be the result of allelic heterogeneity, a single disorder caused by different mutations within one gene. However, non-genetic or environmental factors cannot be ruled out.
• Some research has shown that a region of chromosome 1, which contains 11 genes, is mutated in TAR patients and in some percentage of their unaffected family members. This would indicate that this mutation is related to the development of TAR syndrome, but that the mutation alone cannot cause the disorder to be expressed. No specific mutation has been identified as the cause of disease in patients with TAR.
• Some researchers have proposed that TAR syndrome is the result of cellular injury to an unborn child during the period of development in which the systems affected by TAR syndrome are developing. Athough the bone and blood abnormalities present in TAR syndrome appear to be completely different, they may be related in that the heart, the radii, and the megakaryocytes (platelet forming cells) all begin to form between weeks six and eight of development. These malfunctions occurring together to cause TAR syndrome may be explained by cellular injury.
• Several genetic theories of inheritance have also been proposed because TAR syndrome has been observed to be very similar to congenital rubella and Robert's syndrome. However, a common genetic cause has not been identified. Further research is necessary to confirm these theories.

• General: Thrombocytopenia absent radius (TAR) patients typically have very low blood platelet levels associated with clotting problems. The other main feature of the condition is that the forearm bone that connects the elbow to the thumb-side of the wrist (called the radius) fails to grow in both arms. These main characteristics differentiate TAR syndrome from other conditions affecting blood platelet levels and the radius bone.
• Other conditions affecting the radius usually involve lack of growth or incomplete growth of thumbs as well as the radius, in one or both arms. This is not generally the case in TAR syndrome patients, most of whom have both of their thumbs.
• Most individuals with TAR syndrome are shorter than average for their age and gender. No important hormonal abnormalities or growth hormone deficiencies have been observed to be associated with TAR syndrome. Fifty percent of affected infants show symptoms during the first week of their lives. Ninety percent are symptomatic within the first four months of their lives. Most affected individuals have significant bruising at birth.
• Bone abnormalities: The most consistent skeletal abnormality observed in TAR syndrome patients is the absence of both radii but presence of the thumb. Other potential bone abnormalities include: the radius bone failing to grow in just one forearm (unilateral radial aplasia), other bones in the forearm failing to grow or fully develop, the wrist being permanently bent towards the radius bone (radial club hand), a flipper-like appearance caused by the hands being connected to shorter arms (phocomelia), and various conditions resulting in underdeveloped or abnormal upper arm, wrist, finger, and toe bones.
• Generally, the more severely affected the upper limbs are in TAR syndrome patients, the more likely it is that the lower limbs will be affected as well. Lower limb abnormalities have been observed in almost half of all cases of TAR syndrome and at least 20% of TAR patients experience significant lower limb involvement. These are usually less severe than those of the upper limbs and include hip dislocation, turning inward or outward of either the upper leg bone or the shin bone, absence of lower leg bones, abnormal toe positions, and deformities of the knee, which cause abnormal bending positions of the leg, loose kneecaps, or fused knee bones. Lower limb defects do not generally affect the structure of the toes or feet.
• Hematologic (blood-related) problems: Thrombocytopenia is a general term for any blood disorder resulting in low levels of blood platelets. Platelets are blood cells that cause the blood to clump together where a blood vessel injury occurs. Clotting helps to prevent blood loss. Therefore, thrombocytopenia is often associated with abnormal bleeding.
• Symptoms include bruising easily, purple-colored spots and patches, and small red or purple pinpoint spots on the skin (purpura and petechiae). Additional symptoms include bleeding in the mouth, bloody nose, coughing up blood, and blood in the urine. Bleeding in the stomach and intestines may cause a patient to vomit blood. In more serious cases, life-threatening bleeding into the brain (intracranial hemorrhage) may occur. Symptoms of severe intracranial hemorrhage in an infant are associated with poor feeding, lethargy, irritability, and variable levels of consciousness.
• Almost all patients with TAR syndrome begin to show symptoms of thrombocytopenia during the first year of life. Periods of very low platelets, called thrombocytopenic episodes, are common during the first two years of life. However, these episodes occur less frequently and platelet counts become more stable with age. The platelet counts may become normal in TAR patients by age four or five. Eventually, most affected individuals outgrow the risk of bleeding related to their low platelet levels.
• Facial irregularities: Facial anomalies occur in approximately half of TAR syndrome patients. These include an unusually prominent forehead, a very small lower jaw, increased distance between the eyes, lumps of built up blood vessels in the face, low set ears (often resulting in hearing loss), flattened cheek bones, cleft palate, and downward displacement of the tongue.
• In some cases, patients may be born with a neurological disorder in which the head is significantly smaller than average for the person's age and sex (microcephaly).
• Heart problems: Heart problems occur in about one-third of TAR syndrome patients. These can include conditions such as tetralogy of Fallot, a heart defect with four characterizing structural abnormalities that is present at birth. Other congenital heart defects that allow irregular blood flow between the right and left sides of the heart, or any structural defect causing this blood flow, may also occur.
• The most frequent other type of anomaly found in individuals with TAR syndrome is a hole in the heart. About 30% of affected individuals have some kind of structural abnormality of the heart.
• Other: Cow's milk intolerance is associated with almost half of all cases of TAR syndrome, and usually develops during infancy. Patients may experience vomiting and bloody diarrhea after consuming products made with cow's milk. Kidney defects are also a common occurrence in TAR patients.
• Other anomalies commonly associated with TAR syndrome include nuchal folds (excess skin on the back of the neck), excess fluid retained in the tissues of the feet, presence of skin moles, and excessive perspiration.
• Infants in particular may experience difficulty feeding due to small lower jaw structure and other gastrointestinal complications, especially underdevelopment of the esophagus.

• There are many disorders besides thrombocytopenia absent radius (TAR) syndrome that cause blood and bone problems. To accurately diagnose TAR syndrome, it is important to distinguish it from disorders with similar symptoms.
• TAR syndrome is characterized by very low levels of platelet-producing cells, called hypomegakaryocytic thrombocytopenia. In addition, TAR syndrome is marked by lack of growth of the forearm bone connecting to the thumb (bilateral radial aplasia) in both arms. Diagnosis is based on the observation of these features. Patients are almost always diagnosed at birth.
• Physical examination and imaging: X-rays and computed tomography (CT) scans are imaging techniques used to view the internal organ and bone structures. These techniques allow a medical professional to observe abnormalities in the physical development of a TAR syndrome patient. Characteristic skeletal abnormalities are detectable during prenatal ultrasound imaging, as early as thirteen weeks into the pregnancy. Ultrasound is another imaging technique that can also be used to examine kidneys, facial features, and extremities in developing fetuses that are suspected to have TAR syndrome.
• The most consistent skeletal abnormality observed in TAR syndrome patients is the absence of both radii but presence of the thumbs. Other potential bone abnormalities include growth of the radius bone in just one forearm (unilateral radial aplasia), other bones in the forearm failing to grow or fully develop, the wrist being permanently bent towards the radius bone (radial club hand), a flipper-like appearance caused by the hands being connected to shorter arms (phocomelia), and various conditions resulting in underdeveloped or abnormal upper arm, wrist, finger, and toe bones.
• Lower limb abnormalities have been observed in almost half of all cases of TAR syndrome, and at least 20% of TAR patients experience significant lower limb involvement. These are usually less severe than those of the upper limbs and include hip dislocation, turning inward or outward of either the upper leg bone or the shin bone, absence of lower leg bones, abnormal toe positions, and deformities of the knee, which cause abnormal bending positions of the leg, loose kneecaps, or fused knee bones. Lower limb defects do not generally affect the structure of the toes or feet.
• Other more visible characteristics of TAR syndrome include various facial abnormalities. These include an unusually prominent forehead, a very small lower jaw, increased distance between the eyes, lumps of built up blood vessels in the face, low set ears (often resulting in hearing loss), flattened cheek bones, cleft palate, and downward displacement of the tongue. Patients may also show signs of a neurological disorder in which the head is significantly smaller than average (microcephaly).
• Red and purple pinpoint spots called petechiae may be visible. These sometimes group together to form larger bruises and can occur anywhere on the body following a traumatic injury.
• A thorough physical examination should also include observations of the size of the spleen, as many TAR syndrome patients have an enlarged spleen due to thrombocytopenia.
• Lab studies: The most common finding in lab studies of TAR syndrome patients is that platelet count may be very low, indicating thrombocytopenia. However, thrombocytopenia can fluctuate over time. If TAR syndrome is strongly suspected on the basis of one platelet count, repeating the blood work is recommended.
• Levels of certain white blood cells are elevated in about 50% of patients. Anemia may be present after an episode of bleeding.
• Thrombocytopenia can occur as a separate condition and may be the result of causes other than TAR syndrome. A thorough medical history must be taken to rule out these possibilities. A person with thrombocytopenia may complain of general discomfort (malaise), fatigue, and weakness.
• Platelet defects can be diagnosed using a bone marrow sample or biopsy. These samples are examined for the number, size, and maturity of platelet-producing cells, called megakaryocytes. Thrombocytopenia is generally characterized by low levels of small, immaturely developed megakaryocytes.
• Genetic testing: Cordocentesis is a type of genetic testing that analyzes blood from the umbilical cord before a baby is born. This test can be used to confirm known genetic conditions. However, cordocentesis poses a 1-2% risk of miscarriage as well as a risk of prolonged bleeding from the umbilical cord at the test site.
• It is useful for prenatal diagnostic methods to be performed, which can examine cells for genetic abnormalities before birth, to determine whether or not a child is affected. TAR syndrome infants should be delivered by cesarean section to avoid bleeding, bruising, and intracranial bleeding.

• General: The most serious complications of thrombocytopenic absent radius (TAR) syndrome occur during the first two years of a patient's life. This is also when mortality rates are highest. If a patient survives the initial two years of life, life expectancy is generally normal.
• Hemorrhage: The major cause of death in TAR syndrome patients is hemorrhage due to an episode of dramatically low blood platelet levels. The incidence of death as a result of hemorrhage is almost completely limited to patients in their first year of life.
• Children with TAR syndrome who are not delivered by cesarean section have an increased incidence of death due to bleeding, severe bruising, and intracranial hemorrhage (bleeding into the brain).
• Bleeding and hemorrhage, especially intracranial hemorrhage, can also result in other serious complications, including brain damage.
• Thrombocytopenic episode: Episodes of low platelets occur most often before age one, greatly increasing the risk of severe bleeding. Bleeding into the brain (intracranial hemorrhage) is the most common complication of these episodes.
• The frequency of thrombocytopenic episodes decreases with age. By school age, patients can be expected to have near-normal platelet counts.
• Thrombocytopenia may be accompanied by varying degrees of anemia or a decrease in hemoglobin in red blood cells. Since hemoglobin carries oxygen from the lungs to the tissues and organs of the body, individuals with anemia experience weakness, general fatigue, exercise-induced fatigue, shortness of breath, general discomfort, and poor concentration. Anemia in TAR syndrome patients is generally associated with severe bleeding caused by thrombocytopenic episodes. Affected individuals tend to outgrow anemia.
• Episodes can be triggered by nonspecific stress, diarrheal illness (which is common during infancy), infection, or elements of an individual's diet, especially since a number of TAR syndrome patients have intolerance to cow's milk.
• Gastrointestinal problems: Several severe gastrointestinal problems may occur in TAR syndrome patients. During episodes of thrombocytopenia, individuals may experience blood in the stool and/or urine or may vomit blood due to gastrointestinal tract bleeding.
• TAR syndrome patients may also experience congenital (present at birth) gastrointestinal complications. Esophageal atresia is a disorder in which the esophagus does not develop properly. This causes bluish skin color when feeding, as well as choking, coughing or gagging, and drooling. Esophageal atresia may lead to serious feeding problems, especially in infants, which can affect nutrition.
• Tracheoesophageal fistula is a disorder in which the trachea (or windpipe) is connected to the esophagus, often leading to fatal pulmonary complications. Anal atresia is the absence of an opening at the bottom of the intestinal tract, which can be fatal without corrective surgery.
• Leukemia and leukemoid reaction: In addition to platelet problems, individuals with TAR syndrome may experience what is called a leukemoid reaction. This consists of the production of too many white blood cells. White blood cells help to protect the body from infection and other foreign materials. Leukemoid reactions alone are not generally dangerous. However, they are usually the result of a more serious disease state. Leukemoid reaction, not to be confused with leukemia, most often occurs in response to stress or infection during early infancy along with thrombocytopenic episodes in more severe cases of TAR syndrome. It can also be the result of bleeding into the brain caused by an episode of thrombocytopenia.
• A leukemoid reaction may also be associated with cow's milk intolerance. TAR syndrome patients tend to have elevated levels of eosinophils, which are white blood cells usually associated with allergies and asthma.
• In some cases, acute leukemia has been observed in both pediatric and adult patients with TAR syndrome. However, is not yet clear whether patients with TAR syndrome are at an increased risk of developing cancer.
• Functional and developmental problems: Individuals with TAR often have delayed motor skill development because of their short arms. Hand and arm function is usually good if radial aplasia is the only skeletal abnormality.
• Learning disabilities have been observed in TAR syndrome patients. However, they appear to occur only in individuals who have had an intracranial hemorrhage (bleeding into the brain). Intellectual disability (formerly called mental retardation) is associated with about seven percent of all cases of TAR syndrome. The association of TAR with intellectual disability is believed to be due to complications from intracranial hemorrhage caused by thrombocytopenia. Some patients may be at risk for intellectual disability and other neuropsychiatric disorders (psychosis) because of structural defects, although research on this theory is unclear.
• Musculoskeletal symptoms of TAR syndrome may cause significant functional disabilities and cosmetic concerns for patients with the disorder.
• Other: Women with TAR syndrome often have very heavy menstrual periods. This lowers platelet levels and may bring on an episode of thrombocytopenia or conditions of anemia.
• The spleen works to filter unwanted materials from the blood. In TAR syndrome patients, the spleen collects platelet cells, becomes enlarged, and may be at risk for bursting. This may result in low blood platelet levels and cause a thrombocytopenic episode.
• TAR syndrome patients may have large, horseshoe-shaped kidneys, which function abnormally in almost 25% of patients. They may also have a ring of pancreatic tissue that constricts or blocks blood flow to the lower intestines (annular pancreas). In addition, TAR syndrome patients may have a small bulge in the small intestine (Meckel's diverticulum). Patients may also develop urinary tract or uterine disorders.
• Patients with TAR syndrome may have abnormalities in the structure of the ribs, including asymmetrical first rib or cervical (extra) rib. They may also have abnormalities of the spine, including spina bifida ("split" spine), scoliosis, and cervical spinal fusion. Depending on the severity of these abnormalities, they may create functional disabilities for the patient or require serious medical attention.
• About 30% of individuals with TAR syndrome have some kind of structural abnormality of the heart, in some cases, a hole in the wall between the right and left sides of the heart. These abnormalities often require surgery. Due to the low platelet levels in TAR syndrome patients, however, individuals are at higher risk for complications during any type of heart surgery.

• General: Patients with thrombocytopenic absent radius (TAR) syndrome should be examined by hematologists, orthopedic surgeons, plastic surgeons, and cardiologists. Treatments may range from platelet transfusions to surgery to improve the functioning and appearance of the arms.
• TAR patients may have a wide range of lower body deformities. Treatment must therefore be planned on an individual basis. There may be no treatment necessary if the deformity is mild and does not affect function. However, some patients may require the use of a power wheelchair or other mobilization aid if the defect is severe and limits the ability to walk.
• While some short-term treatments may be necessary to treat thrombocytopenic episodes and other complications, the overall goal of treatment is to improve long-term functioning and increase independence.
• It is useful for prenatal diagnostic methods to be performed in cases in which a fetus is at risk for inheriting TAR syndrome. TAR syndrome babies should be delivered by cesarean section to avoid bleeding, bruising, and intracranial bleeding.
• Medication: Corticosteroids may be used to increase platelet production and reduce the risk of thrombocytopenic episodes. Lithium carbonate or folate~ may also be used to stimulate bone marrow production of platelets for this same purpose.
• Antifibrinolytic agents may also be administered to decrease bleeding and the need for platelet transfusion.
• Aminocaproic acid (Amicar®) or tranexamic acid (Cyklokapron®) are both medications that may be given to inhibit the action of certain enzymes that prevent blood clots from forming at the site of bleeding.
• Platelet transfusion: Platelet transfusions are used to treat patients with severely low platelet levels who are at high risk of hemorrhage, especially infants. The goal is to maintain healthy platelet levels and prevent bleeding without further complications. Transfusions involve the addition of platelets from other people (donors) into the patient's blood and are performed using a small tube connected to a vein in the patient's arm or hand. Platelet transfusions may be used to stop abnormal bleeding during a thrombocytopenic episode and must be performed based on the patient's individual needs. The most critical period of thrombocytopenic episodes is during the first year of life, and platelet levels eventually become stable with age.
• Potential risks of platelet transfusion include infection, anaphylaxis, and hemolytic reactions. Hepatitis viruses (B, C, other) and HIV are the most common infective pathogens that may be transmitted with the transfusion of blood products.
• Surgery: About 30% of individuals with TAR syndrome have some kind of structural abnormality of the heart, in some cases, a hole. These abnormalities often require surgery. Due to low platelet levels in TAR syndrome patients, however, individuals are at higher risk for complications during any type of heart surgery. However, even complicated heart surgery has been successful in TAR syndrome patients with the aid of platelet transfusions.
• If the absence of the radius bone is the only skeletal abnormality in a TAR syndrome patient, hand and arm function are generally good. However, in many cases patients will require orthopedic or plastic surgery to correct the functional and cosmetic aspects of their musculoskeletal abnormalities.
• When orthopedic surgery is necessary, it is ideal to delay it as long as possible until the patient is in less danger of thrombocytopenia and severe bleeding. It is recommended that any surgery performed during the first few years of life be limited to life-saving surgeries. Splinting of the hands (and legs, if indicated) during infancy improves future function as a good alternative to surgery. Another alternative to surgery is the use of adaptive devices to assist with activities of daily living. Prostheses (artificial limbs) are also an option but are generally less useful than adaptive devices.
• Removal of the spleen (splenectomy) may be necessary to correct thrombocytopenia caused by platelet destruction and to ultimately increase platelet count. A splenectomy may significantly reduce platelet destruction and increase platelet count by up to 30% because the spleen acts as the primary site of platelet removal and antibody production.
• Bone marrow transplantation (BMT) is an option for patients who remain thrombocytopenic with bleeding despite platelet transfusion. This treatment is generally used only in very severe cases.
• Physical/occupational therapy: TAR syndrome patients may also benefit from occupational therapy and physical therapy. These therapies may help TAR syndrome patients improve their physical abilities and perform daily functions in order to increase their independence.
• Diet: Patients should avoid ingesting cow's milk, especially during the first year of life because of the high incidence of cow's milk intolerance associated with TAR syndrome. Reactions to cow's milk may precipitate thrombocytopenic episodes.

C

Unclear or conflicting scientific evidence

• Berberine
  : Berberine is a bitter-tasting, yellow plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. In one low-quality study, berberine was shown to significantly increase platelet production in individuals with thrombocytopenia both alone and in combination with a medication called prednisolone.
• Avoid if allergic or hypersensitive to berberine, to plants that contain berberine, or goldenseal (Hydrastis canadensis), 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 the potential for an increase in free bilirubin, jaundice, and the development of kernicterus. Use cautiously with heart disease, gastrointestinal disorders, hematologic (blood) disorders, leukopenia, 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 the potential for crossing the placenta, stimulating the uterus (based on historical use), or transferring to breast milk.
• Bupleurum
  : Bupleurum is an herb that is typically found in East Asia. Bupleurum has long thin leaves that look like fennel. Thrombocytopenia may respond in some cases to treatment with bupleurum-containing herbal formulas. However, currently there is not enough available evidence for or against the use of bupleurum for this indication.
• Avoid if allergic or hypersensitive to bupleurum or any members of the Apiaceae or Umbelliferae (carrot) families. Use cautiously if driving or operating heavy machinery because bupleurum may cause drowsiness. Use cautiously with diabetes, high blood pressure, or edema. Use cautiously if taking drugs that increase the risk of bleeding (anticoagulants).
• Dong quai
  : Dong quai (Angelica sinensis), also known as Chinese Angelica, has been used for thousands of years in traditional Chinese, Korean, and Japanese medicine. It remains one of the most popular plants in Chinese medicine and is used primarily for health conditions in women. A poor-quality study reports 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 Apiaceae/Umbelliferae family (such as anise, caraway, carrot, celery, dill, or parsley). Dong quai's safety in medicinal doses is unknown. Long-term clinical studies investigating side effects of dong quai are currently lacking in the available literature. 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.
• Melatonin
  : Increased platelet counts after melatonin use have been observed in patients with decreased platelets due to cancer therapies (several studies reported by the same author). Stimulation of platelet production (thrombopoeisis) has been suggested but not clearly demonstrated. Additional research is necessary in this area before a clear conclusion can be drawn.
• There are rare reports of allergic skin reactions after taking melatonin by mouth. Melatonin has been linked to a case of autoimmune hepatitis. Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. Melatonin supplementation should be avoided in women who are pregnant or attempting to become pregnant, based on the possibility of 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 have been reported with the use of melatonin.

• Thrombocytopenia absent radius (TAR) syndrome is an inherited condition and currently has no known method of prevention. Genetic screening is available for parents who may have an increased likelihood of having a child with TAR syndrome. However, the genetic screening process increases the risk of miscarriage and, in most cases, is not recommended unless the parents have previously had a child with the disorder.
• Diagnosis of TAR syndrome can be made before a child is born, using methods that examine cells for genetic abnormalities. The benefit of discovering that a child has TAR syndrome during pregnancy is that the child may be delivered through cesarean section. It is recommended that babies with TAR syndrome be delivered by cesarean section to avoid bleeding, bruising, and intracranial bleeding.
• Patients with TAR syndrome should avoid ingesting cow's milk for the first year of life because cow's milk intolerance may cause thrombocytopenic episodes.
• It is also especially important to take precautions to avoid viral illnesses during the first two years of life.
• During periods of low platelet counts, TAR syndrome patients should avoid trauma and any drug with antiplatelet effects to reduce the risk of hemorrhage. Special precautions should be taken for infants with TAR syndrome, including padding the inside of the child's crib and the use of a soft helmet.
• All platelet and white blood cell counts and musculoskeletal conditions should be followed closely by a physician to prevent further complications.