blood gas determination. bubble contrast echocardiography (bubble echo) may be used as a screening tool to identify abnormal connections between the lung arteries and veins. this involves the injection of agitated saline into a vein, followed by ultrasound-based imaging of the heart. normally, the lungs remove small air bubbles from the circulation, and they are therefore only seen in the right atrium and the right ventricle. if an avm is present, bubbles appear in the left atrium and left ventricle, usually 3–10 cardiac cycles after the right side; this is slower than in heart defects, in which there are direct connections between the right and left side of the heart. a larger number of bubbles is more likely to indicate the presence of an avm. bubble echo is not a perfect screening tool as it can miss smaller avms and does not identify the site of avms. often contrast-enhanced computed tomography (ct angiography) is used to identify lung lesions; this modality has a sensitivity of over 90%. it may be possible to omit contrast administration on modern ct scanners. echocardiography is also used if there is a suspicion of pulmonary hypertension or high-output cardiac failure due to large liver lesions, sometimes followed by cardiac catheterization to measure the pressures inside the various chambers of the heart. ct-scan of vascular malformations in the liver in a patient with hereditary hemorrhagic telangiectasia causing an inhomogeneous perfusion pattern. liver avms may be suspected because of abnormal liver function tests in the blood, because the symptoms of heart failure develop, or because of jaundice or other symptoms of liver dysfunction. the most reliable initial screening test is doppler ultrasonography of the liver; this has a very high sensitivity for identifying vascular lesions in the liver. if necessary, contrast-enhanced ct may be used to further characterize avms. it is extremely common to find incidental nodules on liver scans, most commonly due to focal nodular hyperplasia (fnh), as these are a hundredfold times more common in hht compared to the general population. fnh is regarded as harmless. generally, tumor markers and additional imaging modalities are used to differentiate between fnh and malignant tumors of the liver. liver biopsy is discouraged in people with hht as the risk of hemorrhage from liver avms may be significant. liver scans may be useful if someone is suspected of hht, but does not meet the criteria (see below) unless liver lesions can be demonstrated. brain avms may be detected on computed tomography angiography (cta or ct angio) or magnetic resonance angiography (mra); cta is better in showing the vessels themselves, and mra provides more detail about the relationship between an avm and surrounding brain tissue. in general, mri is recommended. various types of vascular malformations may be encountered: avms, micro-avms, telangiectasias and arteriovenous fistulas. if surgery, embolization, or other treatment is contemplated (see below), cerebral angiography may be required to get sufficient detail of the vessels. this procedure carries a small risk of stroke (0.5%) and is therefore limited to specific circumstances. recent professional guidelines recommend that all children with suspected or definite hht undergo a brain mri early in life to identify avms that can cause major complications. others suggest that screening for cerebral avms is probably unnecessary in those who are not experiencing any neurological symptoms, because most lesions discovered on screening scans would not require treatment, creating undesirable conundrums. genetic testing genetic tests are available for the eng, acvrl1 and madh4 mutations. testing is not always needed for diagnosis, because the symptoms are sufficient to distinguish the disease from other diagnoses. there are situations in which testing can be particularly useful. firstly, children and young adults with a parent with definite hht may have limited symptoms, yet be at risk from some of the complications mentioned above; if the mutation is known in the affected parent, absence of this mutation in the child would prevent the need for screening tests. furthermore, genetic testing may confirm the diagnosis in those with limited symptoms who otherwise would have been labeled "possible hht" (see below). genetic diagnosis in hht is difficult, as mutations occur in numerous different locations in the linked genes, without particular mutations being highly frequent (as opposed to, for instance, the δf508 mutation in cystic fibrosis). sequence analysis of the involved genes is therefore the most useful approach (sensitivity 75%), followed by additional testing to detect large deletions and duplications (additional 10%). not all mutations in these genes have been linked with disease. mutations in the madh4 gene is usually associated with juvenile polyposis, and detection of such a mutation would indicate a need to screen the patient and affected relatives for polyps and tumors of the large intestine. criteria the diagnosis can be made depending on the presence of four criteria, known as the "curaçao criteria". if three or four are met, a patient has "definite hht", while two gives "possible hht": spontaneous recurrent epistaxis multiple telangiectasias in typical locations (see above) proven visceral avm (lung, liver, brain, spine) first-degree family member with hht despite the designation "possible", someone with a visceral avm and a family history but no nosebleeds or telangiectasias is still extremely likely to have hht, because these avms are very uncommon in the general population. at the same time, the same cannot be said of nosebleeds and sparse telangiectasias, both of which occur in people without hht, in the absence of avms. someone's diagnostic status may change in the course of life, as young children may not yet exhibit all the symptoms; at age 16, thirteen percent are still indeterminate, while at age 60 the vast majority (99%) have a definite diagnostic classification. the children of established hht patients may therefore be labeled as "possible hht", as 50% may turn out to have hht in the course of their life. treatment treatment of hht is symptomatic (it deals with the symptoms rather than the disease itself), as there is no therapy that stops the development of telangiectasias and avms directly. furthermore, some treatments are applied to prevent the development of common complications. chronic nosebleeds and digestive tract bleeding can both lead to anemia; if the bleeding itself cannot be completely stopped, the anemia requires treatment with iron supplements. those who cannot tolerate iron tablets or solutions may require administration of intravenous iron, and blood transfusion if the anemia is causing severe symptoms that warrant rapid improvement of the blood count. most treatments used in hht have been described in adults, and the experience in treating children is more limited. women with hht who get pregnant are at an increased risk of complications, and are observed closely, although the absolute risk is still low (1%). nosebleeds an acute nosebleed may be managed with a variety of measures, such as packing of the nasal cavity with absorbent swabs or gels. removal of the packs after the bleeding may lead to reopening of the fragile vessels, and therefore lubricated or atraumatic packing is recommended. some patients may wish to learn packing themselves to deal with nosebleeds without having to resort to medical help. frequent nosebleeds can be prevented in part by keeping the nostrils moist, and by applying saline solution, estrogen-containing creams or tranexamic acid; these have few side effects and may have a small degree of benefit. a number of additional modalities has been used to prevent recurrent bleeding if simple measures are unsuccessful. medical therapies include oral tranexamic acid and estrogen; the evidence for these is relatively limited, and estrogen is poorly tolerated by men and possibly carries risks of cancer and heart disease in women past the menopause. nasal coagulation and cauterization may reduce the bleeding from telangiectasias, and is recommended before surgery is considered. however, it is highly recommended to use the least heat and time to prevent septal perforations and excessive trauma to the nasal mucosa that are already susceptible to bleeding. sclerotherapy is another option to manage the bleeding. this process involves injecting a small amount of an aerated irritant (detergent such as sodium tetradecyl sulfate) directly into the telangiectasias. the detergent causes the vessel to collapse and harden, resulting in scar tissue residue. this is the same procedure used to treat varicose veins and similar disorders. it may be possible to embolize vascular lesions through interventional radiology; this requires passing a catheter through a large artery and locating the maxillary artery under x-ray guidance, followed by the injection into the vessel of particles that occlude the blood vessels. the benefit from the procedure tends to be short-lived, and it may be most appropriate in episodes of severe bleeding. to more effectively minimize recurrence and severity of epistaxis, other options may be used in conjunction with therapies listed above. intravenously administered anti-vegf substances such as bevacizumab (brand name avastin), pazopinab and thalidomide or its derivatives interfere with the production of new blood vessels that are weak and therefore prone to bleeding. due to the past experiences with prescribing thalidomide to pregnant women to alleviate symptoms of nausea and the terrible birth defects that followed, thalidomide is a last resort therapy. additionally, thalidomide can cause neuropathy. though this can be mitigated by tinkering with dosages and prescribing its derivatives such as lenolidomide and pomalidomide, many doctors prefer alternative vegf inhibitors. bevacizumab has been shown to significantly reduce the severity of epistaxis without side effects. if other interventions have failed, several operations have been reported to provide benefit. one is septal dermoplasty or saunders' procedure, in which skin is transplanted into the nostrils, and the other is young's procedure, in which the nostrils are sealed off completely. skin and digestive tract the skin lesions of hht can be disfiguring, and may respond to treatment with long-pulsed nd:yag laser. skin lesions in the fingertips may sometimes bleed and cause pain. skin grafting is occasionally needed to treat this problem. with regards to digestive tract lesions, mild bleeding and mild resultant anemia is treated with iron supplementation, and no specific treatment is administered. there is limited data on hormone treatment and tranexamic acid to reduce bleeding and anemia. severe anemia or episodes of severe bleeding are treated with endoscopic argon plasma coagulation (apc) or laser treatment of any lesions identified; this may reduce the need for supportive treatment. the expected benefits are not such that repeated attempts at treating lesions are advocated. sudden, very severe bleeding is unusual—if encountered, alternative causes (such as a peptic ulcer) need to be considered—but embolization may be used in such instances. lung avms lung lesions, once identified, are usually treated to prevent episodes of bleeding and more importantly embolism to the brain. this is particularly done in lesions with a feeding blood vessel of 3 mm or larger, as these are the most likely to cause long-term complications unless treated. the most effective current therapy is embolization with detachable metal coils or plugs. the procedure involves puncture of a large vein (usually under a general anesthetic), followed by advancing of a catheter through the right ventricle and into the pulmonary artery, after which radiocontrast is injected to visualize the avms (pulmonary angiography). once the lesion has been identified, coils are deployed that obstruct the blood flow and allow the lesion to regress. in experienced hands, the procedure tends to be very effective and with limited side effects, but lesions may recur and further attempts may be required. cta scans are repeated to monitor for recurrence. surgical excision has now essentially been abandoned due to the success of embolotherapy. those with either definite pulmonary avms or an abnormal contrast echocardiogram with no clearly visible lesions are deemed to be at risk from brain emboli. they are therefore counselled to avoid scuba diving, during which small air bubbles may form in the bloodstream that may migrate to the brain and cause stroke. similarly, antimicrobial prophylaxis is advised during procedures in which bacteria may enter the bloodstream, such as dental work, and avoidance of air bubbles during intravenous therapy. liver avms given that liver avms generally cause high-output cardiac failure, the emphasis is on treating this with diuretics to reduce the circulating blood volume, restriction of salt and fluid intake, and antiarrhythmic agents in case of irregular heart beat. this may be sufficient in treating the symptoms of swelling and breathlessness. if this treatment is not effective or