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HHT for the hematologist
mia and iron deficiency that result from this blood loss is addressed below.
Management of pulmonary, hepatic, and CNS AVMs
Collaboration with a pulmonologist, hepatologist, gas- troenterologist, neurologist, neurosurgeon, and interven- tional radiologist with experience in treating HHT patients is crucial to the management of AVMs found in the lungs, liver or brain. Screening is, therefore, important early in the diagnosis of these patients. Management will depend on the size of the AVMs, symptoms and location, and may include embolization of a pulmonary AVMs, sur- gical intervention for a CNS AVM and/or continued sur- veillance. Angiographic treatment of hepatic AVMs may be helpful in some patients but is often considered a high- er risk by interventional radiologists.
Management of iron deficiency anemia
The development of anemia can have significant conse- quences for the patient with HHT. Although oral iron [e.g. ferrous sulfate 325 mg 3 times daily, ferrous asparto glyci- nate-polysaccharide iron complex 150 mg capsules 1-3 times daily] may be adequate for mildly affected HHT patients, many require intravenous iron such as ferumoxy- tol, iron sucrose or ferric carboxymaltose. Some patients may require 500-1000 mg of iron a month. Sometimes red blood cell (RBC) transfusion support is needed, but chron- ic RBC transfusion carries risk of infections and can lead to transfusion reactions and alloimmunization. In some patients, supplementation with erythroid stimulating agents (e.g. epoetin alfa, darbepoetin alfa) may be helpful. A suggested approach to the anemic HHT patient is pre- sented in Figure 3.
Use of hormonal agents
Estrogen and progestins (e.g. ethinyl estradiol, norethin- drone or mestranol) have been used in HHT patients to
reduce bleeding complications. Mestranol or norethyn- odrel may help increase nasal squamous epithelium and protect nasal lesions from injury. This hormonal therapy, however, can result in gynecomastia and/or loss of libido in men, weight gain, coronary events, and venous throm- boembolism (VTE). Given the age of some patients and the potential side effects of this treatment, it has not been widely used. The overall improvement in hematologic parameters is also questionable.
Other hormonal treatment options include danazol 200 mg 3-4 times oral daily, tamoxifen 20 mg oral daily or raloxifene 60 mg oral daily.67 But these are not widely used.
Use of novel systemic anti-angiogenic therapies
Anti-VEGF therapies are relatively new for patients with HHT, and their use has been increasing. Thalidomide, used commonly in the management of mul- tiple myeloma, is thought to have both vascular and immunomodulatory effects. Its antiangiogenic activity may be due to the suppression of production of VEGF and basic fibroblast growth factor (bFGF).68 Serum levels of VEGF were found to be decreased after thalidomide treat- ment in patients with GI bleeding.69 Nasal mucosal biop- sies in HHT patients with epistaxis treated with thalido- mide demonstrated vessel maturation and improved ves- sel wall defects.70
Bevacizumab, an anti-VEGF antibody, is a rational ther- apeutic for HHT as it may reduce excessive angiogenesis (Figure 4). To date, all of the studies describing the use of systemic bevacizumab for the management of HHT have been retrospective cohorts, small case series, or single patient case reports (Table 3). A very recent retrospective study by Iyer et al. describes a large cohort of HHT patients receiving bevacizumab to treat GI bleeding and epistaxis.8 Thirty-four patients were given intravenous bevacizumab according to a standardized protocol, result- ing in a statistically significant reduction in epistaxis sever-
Figure 3. Treatment algorithm for iron deficiency anemia in hereditary hemorrhagic telang- iectasia (HHT). Oral iron may be attempted first but is typically insufficient in HHT patients with moderate or severe chronic bleeding. In this case, intra- venous (IV) iron should be given at regular intervals unless bleed- ing ceases. When bleeding is so severe that IV iron is insufficient, consideration of antifibinolytics, such as tranexamic acid, is the next step. If this is unsuccessful, a trial of bevacizumab therapy is
reasonable. CBC:
blood count; IV: intravenous; PO: oral administration; TID: 3 times / day; q: every.
complete
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