Abstract: Macrocytosis occurs with HIV therapies containing zidovudine (AZT) and stavudine (d4T) and may help assess adherence. Occurrence in antiretroviral therapy regimens without these agents or when they are added to multidrug antiretroviral therapy is unknown.
Full Answer
Can macrocytosis be used as a clinical indicator of zidovudine adherence?
Macrocytosis as an indicator of medication (zidovudine) adherence in patients with HIV infection This retrospective chart review was conducted in an outpatient human immunodeficiency virus (HIV) clinic to determine if macrocytosis can be used as a clinical indicator of zidovudine adherence in HIV-infected outpatients.
What is the pathophysiology of macrocytosis?
Macrocytosis can occur when there is increased RBC production secondary to peripheral blood cell destruction (i.e., hemolysis) or loss (i.e., hemorrhage), leading to a reticulocytosis. Reticulocytes are incompletely processed RBCs and, therefore, are slightly larger than the average RBC.
Does zidovudine cause anemia?
More recent studies of combination antiretroviral therapy have confirmed the relative low incidence of severe anemia at lower doses of zidovudine. Despite these findings, many patients receiving the drug in clinical practice will require occasional transfusion or change in drug therapy to ameliorate this toxicity.
What causes macrocytosis and macrocytic anemia?
It may be caused by abnormalities of RBC production in the bone marrow, altered RBC membrane composition, or an increase in the percentage of reticulocytes, which are larger than mature RBCs. This topic discusses causes of macrocytosis and macrocytic anemia.
Does zidovudine cause macrocytosis?
Abstract. Objective: Zidovudine is a well known cause of macrocytosis. However, many HIV-infected patients develop macrocytosis even though they do not receive zidovudine. The aim of this case-control study was to evaluate other causes of high mean corpuscular volumes (MCV) in HIV infected patients.
Why does zidovudine cause anaemia?
The exact mechanism of anemia is still unknown. It was hypothesized that AZT may suppress erythropoesis or inhibit erythroid stem cells, thus ensuring pure red-cell aplasia (i.e; decreased reticulocyte counts and hemoglobin levels without hemolysis or blood loss), increasing MCV and elevating erythropoietin level.
What is the pathophysiology of macrocytic anemia?
The most common cause of macrocytic anemia is megaloblastic anemia, which is the result of impaired DNA synthesis. Although DNA synthesis is impaired, RNA synthesis is unaffected, leading to a buildup of cytoplasmic components in a slowly dividing cell. This results in a larger-than-normal cell.
Does AZT cause macrocytic anemia?
A review of the literature confirms that AZT is the NRTI most likely to induce a macrocytosis, and is the only member of the class that has also been associated with macrocytic anemia.
What is the mechanism of action of zidovudine?
Mechanism of Action: Zidovudine is phosphorylated to zidovudine-triphosphate, which competes with endogenous nucleotides for incorporation into the viral DNA and once incorporated causes chain termination due to the lack of a 3' OH group.
What are the common adverse effects of zidovudine?
Zidovudine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:stomach pain or cramps.heartburn.diarrhea (especially in children)constipation.headache.difficulty falling asleep or staying asleep.
What drugs cause macrocytosis?
Common drugs that cause macrocytosis are hydroxyurea, methotrexate, zidovudine, azathioprine, antiretroviral agents, valproic acid, and phenytoin (Table 1).
Why does macrocytosis occur?
Macrocytosis can occur when there is increased RBC production secondary to peripheral blood cell destruction (i.e., hemolysis) or loss (i.e., hemorrhage), leading to a reticulocytosis. Reticulocytes are incompletely processed RBCs and, therefore, are slightly larger than the average RBC.
What is the treatment for macrocytic anemia?
Management of macrocytosis consists of finding and treating the underlying cause. In the case of vitamin B-12 or folate deficiency, treatment may include diet modification and dietary supplements or injections. If the underlying cause is resulting in severe anemia, you might need a blood transfusion.
What are the two most common causes of macrocytic anemia?
Most often, macrocytic anemias are caused by a lack of vitamin B-12 and folate. Macrocytic anemia can also signal an underlying condition.
What is macrocytosis anemia?
Macrocytosis is a condition in which your red blood cells are larger than they should be. While it isn't a condition of its own, macrocytosis is a sign that you have an underlying health condition and may lead to a severe form of anemia called macrocytic normochromic anemia.
What is the cause of enlarged red blood cells?
It is associated with anemia, when you also have insufficient numbers of properly functioning red blood cells. Macrocytosis is usually caused by low vitamin B12 or folate levels, but there are other reasons it develops, including from liver disease, alcoholism, and from taking certain medications.
Which ARV drug causes anemia?
However, Zidovudine (ZDV), an element of some ART regimens and one of the first-line antiretroviral drugs for treating HIV infected adults in low resource countries (11), is identified as the commonest cause of drug associated anemia (12,13).
What is zidovudine used for?
Zidovudine is used to slow the progression of disease in patients infected with HIV who have advanced symptoms, early symptoms, or no symptoms at all. This medicine is also used to help prevent pregnant women who have HIV from passing the virus to their babies during pregnancy and at birth.
When is zidovudine initiated?
The women were given either zidovudine starting at 28 weeks' gestation (the long maternal regimen) or placebo from 28 to 35 weeks' gestation followed by zidovudine (the short maternal regimen).
What causes macrocytosis?
Megaloblastic anemia is caused by deficiency or impairment of utilization of vitamin B12 or folate. Nonmegaloblastic anemia may be the result of liver dysfunction, alcoholism, myelodysplastic syndrome (MDS), or hypothyroidism. Common causes of macrocytosis are different by region and setting.
What is macrocytosis in adults?
Abstract. Anemia is one of the most common health problems in the primary care setting. Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) >100 femtoliter (fL). Macrocytic anemias are generally classified into megaloblastic or nonmegaloblastic anemia.
Does B12 affect DNA synthesis?
As a result, the intracellular reaction involving the coenzyme form of folic acid is affected. Thus, not only vitamin B 12 but also folate defici encies impair DNA synthesis.
Abstract
Macrocytosis occurs with HIV therapies containing zidovudine (AZT) and stavudine (d4T) and may help assess adherence. Occurrence in antiretroviral therapy regimens without these agents or when they are added to multidrug antiretroviral therapy is unknown.
REFERENCES
1. Richman DD, Fischl MA, Grieco MH, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double blind, placebo-controlled trial. N Engl J Med. 1987;317 (4):192-197.