Pure Red Cell Aplasia
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Pure Red Cell Aplasia

Synonyms, Key Words, and Related Terms: erythroblastic hypoplasia, erythroblastopenia, erythroid hypoplasia, red cell agenesis

AUTHOR INFORMATION Section 1 of 9    Click here to go to the top of this page Click here to go to the next section in this topic

Authored by Paul Schick, MD, Professor, Department of Internal Medicine, Thomas Jefferson University Medical College

Paul Schick, MD, is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences

Edited by Rodger L Bick, MD, PhD, Director of Dallas Thrombosis Hemostasis and Difficult Hematology Center, Clinical Professor, Departments of Internal Medicine and Pathology, University of Texas Southwestern School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Troy H Guthrie, Jr, MD, Chief, Professor, Department of Medicine, Division of Hematology/Oncology, University of Florida School of Medicine; Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC and Department of Medicine, Good Samaritan Hospital, Advocate Health Systems; and Emmanuel C Besa, MD, Professor, Department of Internal Medicine, Division of Hematology and Oncology, Medical College of Pennsylvania Hahnemann University

Author's Email: Paul Schick, MDClick here to view conflict-of-interest information on the author of this topic
Editor's Email:Rodger L Bick, MD, PhD

eMedicine Journal, September 13 2001, Volume 2, Number 9
INTRODUCTION Section 2 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

Background: Pure red cell aplasia (PRCA) describes a condition in which there is a near absence of red blood cell precursors in bone marrow, while megakaryocytes and white blood cell precursors usually are present at normal levels. In 1922, Kaznelson recognized that this condition was a different entity than aplastic anemia. PRCA exists in several forms, and the most common form is an acute self-limiting condition. Acquired PRCA often is chronic and is associated with underlying disorders such as thymomas and autoimmune diseases. A congenital form of PRCA initially was described by Joseph in 1936 and by Diamond-Blackfan in 1938. Congenital PRCA is a lifelong disorder, and it is associated with physical abnormalities. Both acquired and congenital PRCA occasionally can be refractory to therapy.

Pathophysiology: Erythroid precursors in bone marrow are the primary targets in PRCA. As a result, patient can develop a normoblastic normochromic anemia and a virtual absence of reticulocytes.

Injury of stem cells in utero is believed to be the etiology of approximately 90% of cases of congenital PRCA (ie, Diamond-Blackfan syndrome). This therapy is based on evidence that congenital PRCA frequently is associated with random physical abnormalities, while it rarely is familial or associated with significant chromosomal abnormalities. However, a familial history of PRCA has been detected in approximately 10% of patients with the congenital form of PRCA.

The acute self-limited form is secondary to viral and drug-induced impairment of erythroid progenitor cells. The acquired chronic form of PRCA is associated with thymomas and autoimmune disorders. Damage to erythroid progenitors or precursor cells appears to be immune and T-cell mediated. In both the acute and acquired chronic forms of PRCA, the affected cells are progenitors that have differentiated from stem cells and can express erythropoietin receptors. Thus, unlike in congenital PRCA, stem cells usually are not the targets in the acute and acquired forms of PRCA.


Mortality/Morbidity: Since most cases of PRCA are the acute self-limiting form of PRCA, the incidence of morbidity and mortality in PRCA is not significant. The mortality rate in acquired chronic PRCA and in congenital PRCA is expected to be slightly greater than in the acute form of PRCA. Most individuals with congenital PRCA survive to early adulthood.

When acquired PRCA is associated with thymomas and autoimmune disorders, morbidity can be due to these underlying conditions. Patients with the congenital form of PRCA also can have physical abnormalities.

Profound transfusion-dependent anemia is the most common morbidity of acquired chronic PRCA and congenital PRCA. However, the treatment of anemia in PRCA can contribute to significant morbidity, as follows:

  • Transfusion therapy can lead to hemosiderosis, and the consequences of iron overload are growth retardation, delay in sexual maturity, cardiac arrhythmias, and cardiac failure. Transfusions also can transmit infections.
  • Corticosteroid therapy can lead to growth retardation, osteopenia, diabetes, and other complications.
  • Because of immunotherapy, a small percentage of patients can develop aplastic anemia or acute myelogenous leukemia, and both conditions have high morbidity and mortality rates.

Race: No racial preponderance is observed.

Sex: Females are more likely to be affected in immunologically related PRCA. However, the male-to-female ratio is 2:1 for PRCA associated with thymoma.
CLINICAL Section 3 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

History: Anemia is the primary problem in PRCA. The degree of anemia can range from subclinical to severe. Anemia in acute self-limiting PRCA is barely noticeable. Profound anemias also can occur in chronic acquired PRCA and in congenital PRCA. Patients with severe anemias have symptoms and signs of uncompensated anemia and present with weakness, tachycardia, and dyspnea.

Physical: The signs of anemia and its severity are the major physical findings in PRCA. Pallor and weakness are early manifestations. Evidence of a decompensated anemia (eg, dyspnea, tachycardia, incipient heart failure) occurs in more severe anemias. Severe anemias can be observed in patients with acute PRCA and hemolytic disorders who develop an aplastic crisis. Specific physical findings in acute, acquired chronic, and congenital PRCA are described below:

Causes: The etiology of PRCA is diverse and differs in acute self-limited, acquired chronic (sustained), and congenital chronic forms of PRCA.

WORKUP Section 4 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

Lab Studies:

  • Basic studies
    • CBC

    • Platelet count

    • Differential count
  • RBC indices

  • Reticulocyte count
  • Studies to rule out hemolysis
    • Lactate dehydrogenase (LDH)

    • Indirect bilirubin

    • Serum haptoglobin
  • Studies to rule out iron overload
    • Serum iron

    • Total iron-binding capacity (TIBC)

    • Serum ferritin levels

      In some cases, liver biopsy with quantitation of iron levels may be indicated.

  • In acute PRCA, rule out the following:
    • Parvovirus B19

    • Infectious mononucleosis

    • Atypical mycoplasmic pneumonia

    • Mumps

    • Viral hepatitis
  • In acquired chronic PRCA, rule out the following:
    • Human immunodeficiency virus

    • Thymoma

      Chronic active hepatitis

    • Systemic lupus erythematosus

    • Autoimmune disorders (direct Coombs test)

    • Collagen vascular disorders

    • Pregnancy
  • Congenital PRCA
    • Fetal Hgb and erythrocyte adenine deaminase (ADA)

    • Serum folate and vitamin B-12

    • Genetic testing

    • Megaloblastic changes can be observed on peripheral smears.

Imaging Studies:

  • Chest x-ray (posteroanterior and lateral)
  • Computerized tomography to rule out a thymoma
  • Magnetic resonance imaging to rule out thymoma


  • Bone marrow aspiration and biopsy are indicated to confirm the diagnosis. This procedure may not be indicated in acute PRCA. Bone marrow biopsy may be useful to assess iron overload. A bone marrow biopsy is indicated to diagnose an acute myelogenous leukemia, which can be a complication of immunotherapy.
  • Obtaining tissue samples to rule out thymoma - Thoracotomy or mediastinoscopy
Histologic Findings: Bone marrow aspirates and biopsy usually reveal a selective depletion in RBC precursors. In congential PRCA, megaloblastosis of RBC precursors may be observed, and, occasionally, there is a depression in the level of megakaryocyte and WBC precursors.

In acute PRCA, a bone marrow aspiration and biopsy performed during the recovery phase may be misleading and may suggest active erythropoiesis.

Biopsy of a thymoma usually reveals that the tumor is encapsulated and contains primarily spindle cells, with or without small lymphocytes.

TREATMENT Section 5 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

Medical Care: Specific aspects of the treatment of acute, chronic acquired, and congenital forms of PRCA are mentioned below. Common to all forms is the treatment of anemia. Adequate Hgb levels should be maintained by transfusion therapy. Folic acid and multivitamins have been recommended, but their value has not been established. High-dose immunoglobin can be used to transiently restore Hgb levels in parvovirus B19 infections and other forms of acquired PRCA.

The decision to hospitalize patients with PRCA or to treat them in an outpatient setting depends on their clinical status and the ability to evaluate, treat, and transfuse patients outside the hospital setting.

  • Acute self-limiting PRCA
    • Discontinue offending drugs and treatment of associated infections or other illness.

    • Transfusion therapy usually is not indicated because of the self-limiting nature of acute PRCA.

    • Transfusions may be indicated in patients with hemolytic anemias who develop PRCA.
  • Acquired chronic (sustained) PRCA
    • A strategy needs to be developed.

    • An underlying disorder (eg, thymoma, SLE, collagen vascular disease, lymphoproliferative disorder) should be treated.

    • Corticosteroids can be effective, but a high dosage often is required, and the adverse effects frequently preclude using these agents. However, some patients respond to low doses of corticosteroids. Prednisone can induce remission in approximately 45% of cases.

    • If the underlying cause of PRCA is immunological and the response to corticosteroids has been inadequate, the next level of treatment is with cytotoxic or immunosuppressive drugs. The following agents have been used: (1) cyclophosphamide, (2) 6-mercaptopurine, (3) azathioprine, or (4) cyclosporine, at sufficient dosage to induce leukopenia, have been effective. Some immunogenic agents can be leukemogenic.

    • Antithymic or antilymphocyte serum has been effective. Several patients have responded to plasmapheresis or lymphocytapheresis.

    • Patients who are refractory to immunosuppressive therapy may respond to Danazol.

    • Transfusions most likely have to be performed on a weekly basis to maintain an adequate Hgb level as long as patients do not respond to any of the above measures. Two units of blood every 2 weeks usually are sufficient, unless patients have hypersplenism, blood loss, or hemolysis. Consider iron chelation in patients with a prolonged transfusion requirement to avoid hemosiderosis.
  • Congenital PRCA
    • Treatment is complicated because this condition is a lifelong disorder, and the consequences of treatment can have devastating effects on growth and sexual maturity.

    • Transfusion is an integral modality in treating congential PRCA. The severity of anemia varies from patient to patient. With severe anemia, patients can have a lifelong dependency on transfusions. Two units of blood every 2 weeks usually are sufficient. Aggressive chelation using deferrioxamine (ie, desferrioxamine) infusions are critical to avoid hemosiderosis because transfusion therapy usually is started at a young age.

    • Corticosteroids also are a principal therapeutic option, and this therapy is believed to allow the abnormal stem cells in congenital PRCA to become more sensitive to growth factors. High doses of prednisone (1-2 mg/kg) are needed but should not be continued for more than 4-6 weeks. Following a failure in prednisone therapy, a trial of high-dose methylprednisolone can be tried. Some patients respond to high-dose corticosteroid therapy and can be maintained on low doses of these agents. The major complications of corticosteroid therapy in these patients are growth retardation, muscle weakness, and osteopenia.

    • Cyclosporine has been used but has not been effective. Danazol and other androgens can be used in refractory cases, but these agents may be contraindicated in prepubertal children.

    • Bone marrow transplantation has been used and could be considered in patients who are refractory and who have human leukocyte antigen (HLA)-identical siblings.

Surgical Care: Surgical are may be indicated if a thymoma is suspected or if the patient has significant hypersplenism.

  • Thymectomy
    • This procedure may be indicated for the treatment of acquired chronic PRCA. However, the incidence of thymoma-induced PRCA is not as common as it had been reported in the past.
    • Recent evidence indicates that only 30% of patients with acquired PRCA responded to thymectomy, and that only 2 of 37 patients with PRCA had thymic enlargement.
    • While the removal of a thymoma may be helpful, the removal of a normal thymus has not been effective in treating PRCA.
  • Splenectomy is not indicated unless hypersplenism can be documented to interfere with the treatment of PRCA.

Consultations: Consulting a hematologist and rheumatologist may be indicated.

  • Consult a hematologist to assist with the treatment of patients with hypersplenism, underlying hemolytic anemia, and the underlying lymphoproliferative disorders. A hematologist should be consulted to monitor therapy, especially immunotherapy, intravenous IgG and ATG therapy.
  • Consult a rheumatologist or a specialist in collagen vascular diseases if rheumatoid or collagen vascular disorders may be responsible for PRCA.

Activity: Activity should be monitored and, at times, curtailed in patients with significant anemia.
MEDICATION Section 6 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

The goal of therapy is to restore erythroid production, to maintain the Hgb at an adequate level, and to treat underlying disorders. Therapy also is designed to prevent and treat complications of therapy.

Drug Category: Corticosteroids -- Mainstay of therapy for PRCA. Approximately 45% of patients with PRCA respond to corticosteroids.
Drug Name
Prednisone (Deltasone, Orasone, Meticorten) -- These agents are useful in acquired PRCA because they can modify the body's immune response. In congenital PRCA, corticosteroids are believed to allow the abnormal stem cells to become more sensitive to growth factors. These agents have an anti-inflammatory effect, have a profound effect on metabolism, and have a number of potentially serious adverse effects.
Refer to references listed in bibliography for a complete list of potential contraindications. The benefits and risks of corticosteroids should be individualized in treating PRCA.
Adult Dose1-2 mg/kg PO qd for 4-6 wk; discontinue if not successful after 4 wk; taper gradually when no longer indicated
Pediatric Dose1-2 mg/kg PO qd; taper gradually when no longer indicated
ContraindicationsDocumented hypersensitivity; viral, fungal and bacterial infections; relative contraindications include peptic ulcer disease, hepatic dysfunction, connective tissue infections, diabetes, and fungal or tubercular skin infections; osteoporosis and GI disease
InteractionsCoadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin, may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsAbrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; abrupt discontinuation of glucocorticoids may cause adrenal crisis and depression as well as relapse of PRCA
Drug Name
Prednisolone (Delta-Cortef, Econopred) -- Treatment with high-dose prednisolone is an option if there is no response to prednisone.
Adult Dose1 g/d IV push for 3 d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; viral, fungal, or tubercular skin lesions
InteractionsDecreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis
Drug Category: Immunosuppressive agents -- Important agents for the treatment of PRCA. Cytoxan, 6-mercaptopurine and azathioprine are used most often. Has been reported that cyclosporine has not been effective. These agents increase the remission rate and may reduce the dose of corticosteroids needed to manage PRCA. Typical doses for immunosuppressive agents are listed below. A hematologist should be consulted to individualize the doses of immunosuppressive agents to arrive at the appropriate dosage.

Antilymphocytic serum and high-dose IVIG. These therapies need to be administered by physicians with extensive experience with these agents since there are a number of complications that should be anticipated and monitored.

Androgens (danazol) may be effective in some cases of refractory PRCA
Drug Name
Cyclophosphamide (Cytoxan, Neosar) -- Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult Dose50-100 mg/m2/d PO or 400-1000 mg/m2 PO in divided doses 4-5 d
Alternatively, 400-1800 mg/m2 (30-40 mg/kg), IV in divided doses over 2-5 d; may repeat at 2-4 wk intervals; alternatively, administer 10-15 mg/kg IV q7-10d or 3-5 mg/kg bid
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; severely depressed bone marrow function
InteractionsAllopurinol, may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy D - Unsafe in pregnancy
PrecautionsRegularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; nausea and vomiting may occur; reversible hair loss may occur; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; hydration (2-3 quarts of fluid daily) may prevent development of hemorrhagic cystitis; patients should be monitored for the development of Cytoxan-related acute leukemia and myelodysplastic syndromes
Drug Name
6-Mercaptopurine; 6-MP (Purinethol) -- Purine analog that inhibits DNA and RNA synthesis, causing cell proliferation to arrest.
Adult Dose1.2-2.5 mg/kg/d PO or 80-100 mg/m2/d qd
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; severe leukopenia, thrombocytopenia, and pancytopenia
InteractionsToxicity increases when administered with allopurinol; hepatic toxicity increases when used in combination with doxorubicin
Pregnancy D - Unsafe in pregnancy
PrecautionsExercise caution in patients diagnosed with renal or hepatic impairment; patients on this medication have a high risk of developing pancreatitis, monitor for myelosuppression
Drug Name
Azathioprine (Imuran) -- Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult Dose1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d
Pediatric DoseInitial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV
ContraindicationsDocumented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT); severe leukopenia or pancytopenia
InteractionsToxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Pregnancy D - Unsafe in pregnancy
PrecautionsIncreases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated
Drug Name
Cyclosporine (Sandimmune, Neoral) -- Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft vs host disease for a variety of organs.
For children and adults, base dosing on ideal body weight.
Adult DoseInitial PO dose: 14-18 mg/kg/d 4-12 h
Maintenance PO dose: 5-15 mg/kg/d qd or divided bid
Initial IV dose: 5-6 mg/kg qd 4-12 h
Maintenance IV dose: 2-10 mg/kg/d divided q8-12h
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because it may increase risk of cancer
InteractionsCarbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsEvaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO
Drug Name
Antithymocyte globulin (Thymoglobulin) -- Purified concentrated gamma-globulin (primarily monomeric IgG) from hyperimmune horses immunized with human thymic lymphocytes. Mechanism of action is thought to be its effect on lymphocytes responsible in part on for cell-mediated immunity and lymphocytes involved in cell immunity.
A hematologist or another physician with extensive experience must be involved in the administration and monitoring of antilymphocyte serum because of the many complications and side effects of this therapy.
Adult Dose10-20 mg/kg/d IV for 8-14 d; a test dose of 5 mcg IM should be given and anaphylaxis monitored
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; severe thrombocytopenia, leukopenia, or aplastic anemia; anaphylaxis; should not be given to a patient who has received varicella vaccine or another live vaccine within 3 mo
InteractionsUnstable in acidic solutions and will precipitate when in dextrose solutions (package inserts describe optimal)
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsComplications include thrombocytopenia, leukopenia, pancytopenia, eosinophilia, anemia, hemolysis, deep vein thrombosis, lymphadenopathy, CNS signs (eg, seizures, paresthesias, confusion, headache), chills and fevers, hyperglycemia, GI symptoms and signs (eg, diarrhea, nausea, vomiting), nephrotoxicity, GYN malignancies (eg, vaginal, cervical and endometrial), hepatotoxicity, respiratory failure, dermatological reactions, musculoskeletal symptoms (eg, back pain, arthralgias, myalgia, tremors), anaphylaxis and serum sickness, transmission of infections (herpes simplex)
Drug Name
Intravenous immune globulin (Gammaimmune, Gammagard, Sandoglobulin, Gammar-P) -- A hematologist or a physician experienced in administering this agent should be consulted because anaphylaxis, renal failure, transmission of infections, and aseptic meningitis are potential complications of this therapy. Experience in selecting patients that can tolerate IVIG, dosage, monitoring for adverse effects and managing complication of therapy are mandatory. One has also to consider the expense of this therapy.
Mechanism is not fully established. Has been reported that IVIG neutralizes autoantibodies. Down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade.
Total dose is given IV but is graduated with low doses initially to monitor for anaphylaxis and other complications. Therefore, doses mentioned in package insert should be followed. Lower dosages per day but extended over 4 days are indicated in patients with fluid overload.
Adult DoseNot to exceed 2 g/kg IV over 4 d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies, renal insufficiency and >85% volume depletion; benefits versus risks of administering IVIG to patients with preexisting renal disease and minimal volume depletion must be considered
InteractionsIncreases toxicity of live virus vaccine (MMR); do not administer within 3 mo of vaccine
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCheck serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
Drug Name
Danazol (Danocrine) -- Increases levels of C4 component of complement and reduces attacks associated with angioedema. In hereditary angioedema, danazol increases level of deficient C1 esterase inhibitor.
Adult Dose200 mg PO bid/tid initially; if efficacious, taper dosage by 50% over following 2-3 mo
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; seizure disorders; hepatic, renal, or hepatic insufficiency; lactation; conditions influenced by edema; undiagnosed genital bleeding; porphyria
InteractionsDecreases insulin requirements and increases effects of anticoagulants; may increase carbamazepine levels
Pregnancy X - Contraindicated in pregnancy
PrecautionsCaution in renal, hepatic or cardiac insufficiency, and seizure disorders
FOLLOW-UP Section 7 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

Further Inpatient Care:

Further Outpatient Care:

In/Out Patient Meds:


  • When medication has been implicated in causing acute PRCA, medications that potentially can cause PRCA should be avoided.


  • Effects of severe uncompensated anemia can cause myocardial dysfunction, heart failure, and failure of other organs.
  • Repeated transfusions can cause hemosiderosis, cardiac failure and arrhythmias, failure of growth, and retardation of sexual maturity.
  • Patients who are on immunotherapy can develop an acute leukemia and aplastic anemia.


  • Prognosis varies widely depending the etiology of PRCA, underlying disorders, and the clinical course.
    • Acute self-limiting PRCA usually has an excellent prognosis.
    • Acquired chronic PRCA is associated with a number of complications. The morbidity depends on the underlying conditions, the response to therapy, and the complications of therapy. Mortality is low.
    • Congenital PRCA usually is a lifelong disorder and is associated with a high morbidity rate due to the disorder and the treatment of the condition. Most patients survive through early adulthood, and estimating the mortality in this disorder has been difficult.

Patient Education:

  • The consequences of iron overload due to repeated transfusions should be explained to patients and to responsible parents if the patient is a child. This is important because hemosiderosis may cause growth failure and the retardation of sexual development.
  • The possibility of the transmission of infections by transfusion therapy, intravenous IgG and antilymphocytic serum should be explained.
  • The diverse adverse effects of corticosteroids, immunotherapy, and other aspects of managements should be explained.
MISCELLANEOUS Section 8 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

Medical/Legal Pitfalls:

  • Missing the diagnosis or instituting inappropriate care is subject to lawsuits. However, a few points should be considered, as follows:
    • Failure to explain the consequences of iron overload due to transfusions
    • Failure to explain the possibility of transmission of infections by transfusion, intravenous IgG, and antilymphocytic therapy.
    • Failure to explain the adverse effects of corticosteroids, immunotherapy, and other aspects of treatment
    • The administration of immunotherapy, intravenous IgG and antilymphocytic therapy without consultation and significant involvement of a physician with extensive experience with these agents.
BIBLIOGRAPHY Section 9 of 9   Click here to go to the previous section in this topic Click here to go to the top of this page

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eMedicine Journal, September 13 2001, Volume 2, Number 9
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