Download Management of the Hematological Manifestations of HIV Infection

Management of the Hematological Manifestations of
HIV Infection and AIDS
Kristin Kane Ownby, MPH, MSN, RN-CS, OCN
Hematological abnormalities, characterized by
Kristin Kane Ownby, MPH, MSN, RN-CS, OCN, is a
doctoral student, Texas Women's University,Houston, TX.
cytopenias, are a problem commonly encountered
by persons with HIV or AIDS. Cytopenias can be
multifactorial in their causation and potentially
life threatening to this population. An
understanding of the various causes of these
cytopenias and the appropriate nursing care are
tantamount to nursing practice and to ensure
quality of life. Goals of medical and nursing care
are directed at assessment, interventions, and
S e v e n t y percent to 95% of persons with AIDS (PWAs)
will experience some degree of anemia during the course
of their disease (Brogan & Zell, 1990). Thrombocytopenia
occurs in 3%-9% of p e r s o n s infected w i t h HIV
(Glassman, 1989), and as the CD4+ count falls below 100
cells/mm 3, the risk of developing granulocytopenia is
increased. The differential diagnosis of hematological
abnormalities can be multifactorial, including direct
effects of the HIV virus on the hematological system,
malignancies, opportunistic infections (OIs), and side
effects of the various medications prescribed to treat the
virus and OIs. Hematological abnormalities occur by
three mechanisms: (a) decreased production of precursor
cells in the bone marrow; (b) increased peripheral
destruction of the differentiated cells; and (c) ineffective
hematopoiesis.
patient education to prevent or minimize the
Direct Effects of HIV on the Hematological System
complications of hematological abnormalities.
This article reviews current knowledge regarding
the causes, pathophysiology, treatments, and
nursing care of HIV/AIDS-related hematological
abnormalities.
Key words:
Hematological abnormalities,
HIV/AIDS, medical~nursing management
JANAC Vol.6, No. 4, July-August1995
HIV infection is associated with cytopenias. In vitro,
the virus has been identified in myelomonocytic bone
marrow precursor cells (CD34). This phenomenon suggests direct bone marrow invasion, resulting in abnormal
growth of various progenitor cells (Folks et al., 1988).
Defects in helper lymphocytic function may be associated with HIV-induced myelosuppression (Mitsuyasu,
1994). Mitsuyasu states that defects in mature granulocytes, monocytes, and lymphocytes have been identified.
These defects may contribute to the increased incidence
of infections and malignancies in HIV disease.
Cytokine production can be altered by the virus. For
example, the cytokine tumor necrosis factor (TNF) can be
stimulated by the virus, which can result in inhibition of
erythrocyte production (Groopman, 1990). Hypergammaglobulinemia, associated with abnormal B-lymphocyte regulation and the development of autoantibodies
that bind specifically to the membranes of myeloid cells,
can induce cytopenias (Israel & Plaisance, 1991).
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M a n a g e m e n t of the H e m a t o l o g i c a l M a n i f e s t a t i o n s of H I V I n f e c t i o n a n d A I D S
d y s f u n c t i o n a l , the PWA is at risk for
infections; these infections can induce or exacerbate
existing cytopenias. Direct invasion of the bone marrow
is the mechanism by which certain obligate intracellular
parasites cause suppression of marrow.
Mycobacterial infections--such as Mycobacterium
avium complex and Mycobacteriumtuberculosis--and fungal infections--including cryptococcus, histoplasmosis,
and coccidiomycosis--have been implicated in cytopenias. Viruses, including varicella and cytomegalovirus,
have been implicated in cytopenia induction, both by
direct marrow invasion and by infecting peripheral
monocytes (Baranski & Young, 1987).
The cytomegalovirus (CMV) also is capable of suppressing antigen presentation. Antigen presentation is
necessary in the activation of specific immunity (Causey,
1991). Splenomegaly, caused by mycobacterial infections,
also may lead to peripheral destruction of erythrocytes.
The protozoal infection, toxoplasmosis, has been associated with thrombocytopenia. Salmonellosis can result in
granulocytopenia.
developing numerous opportunistic
Malignancies That Affect the Hematological System
infections.
Lymphoproliferative malignancies, particularly nonHodgkin's lymphoma, are diagnosed in 3% of PWAs
(Pluda, Yarchoan, & Broder, 1991). These malignancies
invade the bone m a r r o w and cause suppression of
myeloid progenitors. Antineoplastic agents prescribed to
treat neoplasms such as lymphomas and Kaposi's sarcoma (KS) cause myelosuppression. These chemotherapeutic agents include ectoposide, doxorubicin, and
cyclophosphamide. KS lesions, treated with radiation
therapy, can result in myelosuppression if the radiation
fields include significant marrow sites (e.g., long bones).
HIV-associated immune thrombocytopenia purpura
(ITP), a syndrome characterized by increased peripheral
platelet destruction, is an example of autoantibodies
affecting platelets. Antibodies, primarily IgG, are
deposited on the membrane surface of platelets, forming
circulating immune complexes (Murphy et al., 1987). As
the platelets travel through the spleen, phagocytic cells of
the reticuloendothelial system recognize the Fc receptor
of the i m m u n o g l o b u l i n and d e s t r o y the platelets.
Researchers hypothesize that antiplatelet antibodies recognize a specific antigen on the membrane of infected
platelets. These antiplatelet antibodies will stimulate the
complement to destroy platelets (Klaassen et al., 1990),
thus resulting in a diminished number of platelets.
As the i m m u n e s y s t e m b e c o m e s
Since HIV disease is a chronic infectious process, the
anemia associated with the virus itself is categorized as
an anemia of chronic disease. It is characterized by a normochromic, norrnocytic anemia, with hemoglobin concentrations ranging from 8 - 1 0 g / d L . This anemia
includes a m o d e s t r e d u c t i o n in red cell survival,
decreased iron reutilization, and reduced levels of erythropoietin--an endogenous hormone that stimulates
the production of erythrocytes.
Opportunistic Infections That Affect the
Hematological System
As the immune system becomes dysfunctional, the
PWA is at risk for developing numerous opportunistic
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Medications That Affect the Hematological System
Many of the agents used for prophylaxis and treatment of OIs cause a drug-induced cytopenia. For example, sulfanamides such as sulfamethoxazole, sulfadiazine, and dapsone have a direct cytotoxic effect on
precursor cells in the bone marrow.
JANAC Vol.6, No. 4,July-August1995
Sulfonamide-induced cytopenias appear to be associated with hapten formation (Israel & Plaisance, 1991).
Haptens are specific nonprotein substances that do not
elicit antibody formation by themselves. However, when
haptens are coupled with a carrier protein, they can elicit
an immune response.
Folate antagonists--including trimetrexate, trimethoprim, and p y r i m e t h a m i n e - - a c t as inhibitors of an
enzyme needed for folate metabolism and block marrow maturation, resulting in ineffective hematopoiesis.
Many OIs are treated with combination therapy using
both a folate antagonist and a sulfonamide, thus comp o u n d i n g the problem of marrow suppression and
hematopoiesis.
Combination therapy includes trimethoprimsulfamethaxazole, used for prevention and treatment of
Pneumocystis carinii pneumonia (PCP), and pyrimethamine-sulfadiazine, used for the treatment of toxoplasmosis. This combination of two cytopenic agents may
result in the additive effect of bone marrow suppression.
Pentamidine, also used to treat PCP, can cause granulocytopenia. Although its direct mechanism of action is
unknown, pentamidine is thought to be a folate antagonist.
Ganciclovir, effective in the treatment of CMV infections, can inhibit the maturation of progenitor cells and
can lead to granulocytopenia and thrombocytopenia.
Flucytosine, used in c o m b i n a t i o n t h e r a p y w i t h
Amphotericin B for the treatment of fungal infections,
can be deaminated by intestinal bacteria and converted
to fluorouracil, a chemotherapeutic agent that causes
suppression of bone marrow.
Alpha interferon, used to treat KS, can induce granulocytopenia.
Z i d o v u d i n e (ZVD), until recently the only d r u g
a p p r o v e d by the U n i t e d States Food and D r u g
Administration (FDA) to inhibit the proliferation of HIV,
causes cytopenias - - especially anemia. Zidovudine has
been associated with a greater than 50% reduction of
neutrophils in more than one-half of patients treated
with this antiretroviral agent (Brogan & Zell, 1990).
Researchers propose that the ZDV causes cytopenias
through the suppression of bone marrow precursor cells.
JANAC Vol.6, No.4,July-August1995
Additional Factors
Poor nutritional intake and decreased, abnormal
absorption of the GI tract can result in folate and vitamin
B12 deficiencies. Although not solely implicated in the
occurrence of certain cytopenias, these folate and B12
deficiencies can exacerbate an existing problem.
M a n y OIs are treated w i t h c o m b i n a t i o n
therapy, thus c o m p o u n d i n g the p r o b l e m of
marrow s u p p r e s s i o n and h e m a t o p o i e s i s .
In addition, blood loss can cause or worsen preexistent anemia. Blood loss in the PWA may occur because
of one or more of the f o l l o w i n g problems: (a)
Cytomegalovirus colitis can compromise the integrity of
and erode the GI tract; (b) KS lesions in the GI tract can
perforate; (c) frequent phlebotomy of hospitalized PWAs
can have a cumulative and significant effect; and (d)
coexistent marrow suppression can blunt the body's ability to compensate for GI tract blood loss.
Management of Cytopenias
Identifying the underlying cause of the cytopenia is
the first step in the medical management of myelosuppression. If the cytopenia is drug induced, the physician
reduces the dose of the offending agent. If the cytopenia
does not resolve, the therapy may have to be stopped in
favor of an alternative therapy less likely to cause myelosuppression.
Red blood cell indices are used to diagnose the type of
anemia the patient may be experiencing. When the absolute neutrophil count falls below 1000/mm 3, the patient
is at high risk for developing an infection (Brager &
Yasko, 1984). Platelet counts of less than 50,000/mm 3
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Management
of the Hematological
Manifestations
places the patient at increased risk for bleeding and
requires f r e q u e n t platelet c o u n t s (Brager & Yasko).
Hemoglobin levels of 8 g / d L or less or hematocrit levels
of 23% or less n e e d to be r e p o r t e d to a p h y s i c i a n .
Vitamin B12 and folate levels are drawn when deficiencies are suspected.
Epoetin (see Table 1) is a medication that stimulates
the p r o d u c t i o n of e r y t h r o i d precursors. Epoetin is a
genetically engineered derivative of an endogenous hormone, erythropoietin. It is effective in patients w h o s e
e n d o g e n o u s e r y t h r o p o i e t i n l e v e l s are less t h a n
500mu/mL. However, the drug is not efficacious if the
erythropoietin level is above 5 0 0 m u / m L (Adamson &
Eschbach, 1990). Epoetin is admu-fistered subcutaneously
at doses of 300iu/kg, 3 times a week. Dose changes are
dependent on the individual's hematocrit. If the hematocrit rises more than four points over a 2-week period, or
exceeds 36%, the dose should be reduced (Adamson &
Eschbach).
Treatment of anemia may involve the transfusion of
packed red blood cells. Transfusions generally are indicated if the h e m o g l o b i n falls b e l o w 8 g / d L or if the
hematocrit falls below 23%.
Supplemental vitamin B12 can be administered to correct a nutritional deficiency, a possible cofactor in cytopenias. Injections of B12 are administered on a m o n t h l y
schedule.
The appropriate intervention for thrombocytopenia is
to prevent bleeding by maintaining the integrity of the
skin and m u c o u s membranes and to prevent injury to
the patient. Thrombocytopenia m a y present with easy
bruisability, petechiae, epistaxis, gingival and rectal
b l e e d i n g , b l o o d in the e j a c u l a t e , a n d m i l d
splenomegaly--specifically se~n in persons with idiopathic thrombocytopenia purpura (ITP).
T h r o m b o c y t o p e n i a d u e to ITP generally does not
result in excessive bleeding. Platelet transfusions are
indicated rarely. Corticosteroids have been found to be
effective for some patients with ITP. Prednisone is started
at doses of 30mg-40mg dally for 1-2 weeks, then rapidly
tapered to a m a i n t e n a n c e d o s e of 1 0 m g - 1 5 m g daily
(Karpatkin, 1990). Researchers hypothesize that pred-
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of HIV Infection and AIDS
Table 1. Managing the Patient on Epoetin Therapy
1. Obtain an endogenous serum erythropoietin level before
initiating therapy. Epoetin is indicated for patients whose
levels are < 500 mU/mL.
2. Evaluate iron stores, including transferrin saturation (at
least 20%) and serum ferritin levels (at least 100ng/mL),
before initiating therapy.
3. Obtain and record a baseline blood pressure. Hypertension
should be controlled before the therapy is initiated.
4. Start Epoetin at an initial dose of 100U/kg by SC or IV
injection 3 times a week. Maintain this initial dose for at
least 8 weeks.
5. Evaluate the efficacy of the therapy every 4 - 8 weeks by
monitoring the patient's hematocrit.
6. Increase the initial dose by 50 to 100U/kg if the hematocrit
has not increased after 8 weeks. Titrate to a maxinaum dose
of 300U/kg 3 times a week.
7, Discontinue tee drug ff the Eematocfit exceeds 40%. Restart
the drug when the hematocrit falls to 36%. Decrease the
dose by 25% when the hematocrit drops below 36%,
8. Teach the patient the elements of proper drug administration: drawing up the correct close from a vial into a syringe;
prepanng the skin; injecting the drug subcutaneously; storing the drug; and disposing of syringes and needles.
nisone modulates the roticuloendothelial system to clear
circulating immune complexes. The potential side effects
of steroid therapy, including hyperglycemia and fluid
retention, should be monitored. The use of steroids in
PWAs is a controversial treatment choice. Steroids are
thought possibly to make the patient susceptible to the
d e v e l o p m e n t of esophageal candidiasis or to p r o m o t e
herpes outbreaks.
A s p l e n e c t o m y is a treatment option for ITP (Karpatkin, 1990). However, this procedure is associated with
adverse effects, which include an increased incidence of
infections by encapsulated organisms, such as pneumococci, and coagulopathies, which can be potentially lifethreatening to hemophiliacs.
JANAC VoL6, No. 4, July-August1995
Another treatment is immune gamma globulin (IgG),
which has been demonstrated to provide transient relief of
ITP by binding with the Fc portion of immunoglobulins
(Glassman, 1989).
The risk of developing a bacterial infection is greatly
increased as the person's absolute neutrophil count falls
below 1000/mm 3. Infection is the most serious complication of granulocytopenia.
Colony-stimulating factors are drugs found to be
effective in reversing granulocytopenia. Granulocytecolony stimulating factor (G-CSF) is the first drug in
this classification to be approved for the treatment of
neutropenia. This drug enhances the migration of circulating neutrophils toward a site of infection or inflammation, increases phagocytic activity, and increases
antibody-dependent cellular cytotoxicity (Scarffe &
Kamthan, 1990). It is administered either intravenously
or s u b c u t a n e o u s l y and is associated with mild-tomoderate bone pain.
Granulocyte macrophage-colony stimulating factor
(GM-CSF) is another genetically engineered cytokine
found to stimulate the proliferation and differentiation
of granulocytes and macrophages. It enhances neutrophil chemotaxis and phagocytic and cytocidal activity against bacteria and yeasts (Hardy, 1991). GM-CSF
increases the survival of neutrophils and eosinophils.
The side effects of GM-CSF include fever, myalgias,
fatigue, gastrointestinal distress, rash, and bone pain.
Leucovorin may be prescribed with pyrimethamine
and sulfadiazine and with trimetrexate to reduce the
granulocytopenia caused by these agents. Its mechanism
of action is to compete with tile re/late antagonist for the
folate receptors Qf the cells.
The Nurse's Role
The nurse serves a vital role in the team approach
when caring for the PWA. This role includes assessing
for the manifestations of cytopenias, administering and
monitoring the progress and effectiveness of prescribed
medical treatments, and planning and implementing
appropriate nursing interventions.
JANAC
Vol. 6, No. 4, July-August 1995
Assessment for cytopenias involves monitoring the
patient's complete blood count (CBC) for decreases in
the w h i t e b l o o d cell c o u n t and its differential,
hemoglobin, hematocrit, and platelets. The nurse should
observe for the clinical presentation of anemia, which
includes fatigue, malaise, tachycardia, decrease in activities of daily living, diminished sexual function, shortness
of breath, and/or pallor.
T h e u s e o f s t e r o i d s i n P W A s is a
controversial treatment choice.
Nursing interventions for anemia include minimizing
fatigue through planned periods of rest and activity,
instituting measures to reduce shortness of breath, and
administering blood transfusions or Epoefin as ordered.
When a transfusion is medically indicated, the nurse
should insure that the ABO blood type and Rh factor of
the transfusion are compatible with the patient and monitor the patient for possible hemolytic reactions.
Because the possibility of multiple bleeding sites exists,
the urine, stool, and emesis of thrombocytopenic patients
should be tested for occult blood. In the menstruating patient, pad and/or tampon counts, along with the amount
of saturation, need to be monitored and documented. Also,
the assessment for blood loss requires examining the
patient for tachycardia, hypotension, and tachypnea.
Intracranial bleeding is an emergency situation that
can occur in the thrombocytopenic patient. The nurse
should evaluate the patient for complaints of headaches
and blurred vision, changes in personality, such as restlessness, and changes in the level of consciousness.
To prevent trauma to rectal tissue, the use of rectal thermometers should be avoided. Intramuscular injections are
contraindicated; and all venipuncture sites require firm
pressure for a least 5 minutes. Extending the patient's arm
above the head after venipuncture helps to stop bleeding.
13
Management of the Hematological Manifestations of HIV Infection and AIDS
The nurse should monitor the patient for signs and
symptoms of infection. Problems of the respiratory tract signaling infection include changes in breath sounds, cough,
and dyspnea. In the genitourinary tract, these problems
include dysuria; cloud3r odorous urine; hema~ria; and urinary frequency. Other potential sources of infection need to
be assessed, such as intravenous infusion sites, indwelling
catheters, body cavities, and skin folds. However, the nurse
must be aware that the neutropenic patient may not have
the usual signs and symptoms of inflammation--redness,
swelling, heat, and discl~rge (pus).
The nurse must be aware that the
neutropenic patient may not have the usual
signs and symptoms of inflammation.
Patient Education
Patients need to learn about the potential and actual
signs and symptoms of cytopenias, as well as the interventions that may prevent and/or alleviate the problems.
Fatigue is a common symptom of anemia. To preserve
energy levels, the PWA should be taught to rest at intervals, pace activities, and ~eek assistance when physical
tasks become difficult. Because sleep is vital to alleviating fatigue, the nurse should instruct the patient to follow usual bedtime habits, use relaxation techniques, and
minimize distractions in the*environment (Brager &
Yasko, 1984)
Optimal nutritional intake is important to the PWA
with hematological disorders; therefore, dietary counseling
cannot be overlooked during educational interventions.
The patient needs to know the key to proper nutrition is a
diet high in carbohydrates and protein and low in fat.
Thrombocytopenia can result in life-threatening hemorrhage. Consequently, several strategies designed to
14
decrease the possibility of bleeding should be taught to
the PWA. For example, medications that might alter
platelet production and function are harmful and should
not be taken. These treatments include the familiar overthe-counter medicines--aspirin and nonsteroidal antiinflammatory drugs. Alcohol can inhibit platelet function
and must be avoided. The mucous membranes in the oral
cavity may be maintained by using a soft bristle toothbrush or sponge-tipped applicator. Gastrointestinal
integrity may be preserved by promoting mobility and
good fluid intake, as well as taking stool softeners, to prevent constipation. Enemas, harsh laxatives, and anal intercourse should be avoided. Prevention of physical injury is
a priority; strenuous activity and bending from the waist
is not recommended. For sha~ng, electric razors are safe.
The greatest risk to a neutropenic patient is infection.
The PWA needs to be educated about exposure to potential sources of infection (see Table 2.) Vigorous handwashing using friction is an important preventive measure for the individual when preparing or eating food, or
after using the toilet. In addition, the patient should be
taught to take his or her temperature twice daily at the
same time each day and report to the physician any
elevations (usually readings greater than 101~
The patient's first line of defense against invading
pathogens is good personal hygiene, which maintains
the integrity of the skin. A mild soap should be used to
prevent skin drying and cracking. Consistent and thorough oral hygiene is necessary to prevent infections. The
female patient should be taught the importance of perianal care, including front-to-back cleansing.
Finally, the nurse needs to shore up the patient's
knowledge about the spread of diseases, placing emphasis on sexual hygiene, the use of condoms, and routine
infection-control practices.
Summary
The causes of hematological abnormalities and myelosuppression in persons with AIDS are multifaceted and
include treatment-induced cytopenias, malignancies,
opportunistic infections, and the virus itself. Diligent
JANAC
Vol. 6, No. 4, July-August 1995
Table 2. Potential Sources of Infection
9 Persons with transmittable diseases:
Herpes zoster
Colds
9 Excrement
Israel, D., & Plaisealce, K. (1991). Neutropenia in patients infected with
the human immunodeficiency virus. ClinicalPharma~, 10, 268 - 279.
Karpatkin, S. (1990). HIV-l-related thrombocytopenia. Hematology/
Oncology Clinics of North America, 4, 193 - 218.
Influenza
Chicken pox
Measles
9 Persons recently
microbes
Hardy, D. (1991) Combined ganciclovir and recombinant h u m a n granulocyte-macrophage CSF in the treatment of CMV retinitis in AIDS
patients. Journal of Acquired ImmunodeficiencySyndrome, 4S, 522 - 528.
vaccinated
with live or attenuated
from animals such as birds, cats, and dogs
9 Fresh fruits, raw vegetables, raw eggs
9 House plants, cut flowers, and stagnant water
assessment is required to diagnose the problem and to
identify the underlying causes of the cytopenias. The
appropriate medical treatments, nursing interventions,
and patient education may prevent the potentially lifethreatening consequences of such abnormalities.
Klaassen, R., Mutder, J., Viekke, A., Eefftinck-Schattenkirk, J., Weigels,
H., Lange, J., & Von Dem Barne, A. (1990). Autoantibodies against
peripheral blood cells appear early in h u m a n immunodeficiency
virus infection and their prevalence increases with disease progression. Clinical ExperimentalImmunology, 81(1), 11 - 17.
Mitsuyasu, R. (1994). Clinical uses of hematopoietic growth hormones
in HIV-related illnesses. In P. Volberding & M. Jacobson (Eds.),
AIDS Clinical Review 1993/1994 (pp. 189 - 212). N e w York: Marcel
Dekker, Inc.
Murphy, M., Metcalf, P., Waters, A., Carne, C., Weller, V., Linch, D., &
Smith, A. (1987). Incidence and m e c h a n i s m of neutropenia and
thrombocytopenia in patients with HIV infections. British Journal of
Haematology, 66, 337 340.
Pluda, j., Yarchoan, R., & Broder, S. (1991). The occurrence of opportunistic non-Hodgkin's l y m p h o m a in the settings of infection with the
human immunodeficiency virus. Annals of Oncology, 2S, 191 -200.
Scarffe, J., & Kamthan, A. (1990). Clinical studies of granulocyte colony
stinlulating factor (G-CSF). Canc~,"Survc~js,9, 115 - 130.
References
Adamson, J., & Eschbach, J. (1990). The use of recombinant h u m a n eryttzropoietin (rHuEPO) in humans. Cancer Surveys, 9, 157 - 167.
Baranski, B., & Young, N. (1987). Hematological consequences of viral
infections. Hematolo~j/Oncology Clinics of North America, 1,167 - 183.
Brager, B., & Yasko, J. (1984). Care of the client receiving chemotherapy.
Reston, VA: Reston Publishing.
Brogan K., & Zell, S. (1990). Hematologic toxicity of zidovudine in HIVinfected patients. American Family Physician, 41, 1521 - 1528.
Causey, D. (1991). Concomitant ganciclovir and zidovudine treatment
for CMV retinitis in patients with HIV infection. Journal of Acquired
Immunodeficiency Virus Syndrome, 4S, 516 -521.
Folks, T., Kessler, S., Orenstein, J., Justement, J., Jaffe, E., & Fauci, A.
(1988). Infection and replication of H1V-1 in purified progenitor cells
of normal h u m a n bone marrow. Science,242, 919 - 922.
Glassman, A. (1989). Thrombocytopenia: Proposed mechanisms and
treatment in HIV infection. Annals of Clinical and Laboratory Science,
1,319 - 322.
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ANAC's
8th Annual
Conference
S e p t e m b e r 16-20, 1995
Boston, M A
For m o r e information:
202/462-1038
Groopman, J. (1990) Management of the hematological complications
of H W infection. Reviews of Infectious Diseases, 12, 931 - 937.
JANAC
Vol. 6, No. 4, July-August 1995
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