pure red cell aplasia by assistant lecture: waleed fouad
TRANSCRIPT
![Page 1: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/1.jpg)
PURE RED CELL APLASIA
By assistant lecture: Waleed fouad
![Page 2: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/2.jpg)
Definition
• Erythropoietic hypoplasia occurring in the absence of abnormalities in the leukopoietic or thrombocytopoietic systems.
• The marrow is normally cellular but devoid of erythroblasts.
![Page 3: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/3.jpg)
Classification
Congenital (Diamond-Blackfan syndrome)
Acquired:• Acute• Chronic
![Page 4: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/4.jpg)
Acquired forms
Hemolytic Disorders (aplastic crisis)
Infection parvovirus B19 and others
Malnutrition
Drug therapy
Thymoma
Immunoglobulin inhibitors (cytotoxic for erythroid precursors, inhibitor of erythropoietin)
Idiopathic or unknown orgin
Congenital (diamond-Blackfan syndrome)
![Page 5: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/5.jpg)
Acute Acquired Pure Red Cell Aplasia
![Page 6: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/6.jpg)
Hemolytic Disorders• In chronic hemolytic anemias,
erythroblasts may suddenly disappear from the marrow for a short time.
• Transient aplastic crisis occurs when reticulocytes disappear from the peripheral blood and progressive anemia follows.
• These episodes often are accompanied by a prodromal illness and usually are followed by recovery, with return of reticulocytes in 7 to 10 days.
![Page 7: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/7.jpg)
Transient erythroblastopenia of
childhood • Reported in children in the course of various
infections or in association with malnutrition.• It occurs most commonly in children between
1 and 4 years of age.• Often associated with prodromal symptoms,
and is almost always self–limited, with complete recovery in a few weeks.
• The presence of serum inhibitors of erythropoiesis has been demonstrated.
![Page 8: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/8.jpg)
Infections • Acute arrest of erythropoiesis also has
been reported in adults during the course of: Respiratory infections. Gastroenteritis. Primary atypical pneumonia. Infectious mononucleosis. Mumps. Viral hepatitis. Parvovirus B19 infection.
![Page 9: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/9.jpg)
DrugsAminosalicylic
acidPhenylbutazone Aspirin
co–trimoxazole Sulfonamide Isoniazid
Colchicines Azathioprine Heparin
Butabarbital Diphenylhydantoin Halothane
Tolbutamide Chlorpropamide Aminopyrine
Complete recovery follows withdrawal of the drug.
![Page 10: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/10.jpg)
Chronic Acquired Pure Red Cell Aplasia
![Page 11: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/11.jpg)
• It occurs in adults. • A rare disease and only a few
hundred cases have been reported. • It has been suggested that two
forms may exist:
Those associated with benign thymoma.Those unassociated with thymic abnormality.
![Page 12: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/12.jpg)
Benign thymoma associated cases
• More than 50% of the patients are females.
• Myasthenia gravis was noted in 14% of the patients in one series.
• Thymectomy may provide immediate hematologic improvement in some patients.
![Page 13: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/13.jpg)
Non Benign thymoma associated cases
• Noted more often in male patients than in females (2:1).
• Has been associated with immunologic, lymphoproliferative, and neoplastic disorders as well as drug and toxic exposures.
• An etiology cannot be established in many patients.
• Noted most often in the fifth to seventh decades of life.
![Page 14: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/14.jpg)
• Antibody-mediated pure red-cell aplasia is a rare syndrome of anemia associated with a low reticulocyte count, an absence of erythroblasts in the bone marrow, resistance to recombinant human erythropoietin (epoetin) therapy, and neutralizing antibodies against erythropoietin.
• This syndrome was reported in patients who had been receiving epoetin administered subcutaneously.
![Page 15: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/15.jpg)
Pathogenesis of acquired form
Two proposed theories:
• The first is called the "seed or stem cell-deficiency theory". It proposes that a common stem cell population is irreversibly altered, rendering it incapable of proliferation and differentiation.
• The second theory is the "microenvironmental deficiency theory", which proposes that the stem cell environment (the marrow) is altered so as to inhibit erythropoiesis.
![Page 16: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/16.jpg)
Congenital Erythroid Hypoplasia of
Diamond–Blackfan
![Page 17: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/17.jpg)
• In 1938, Diamond and Blackfan described a syndrome that they characterized as a slowly developing and progressive anemia, beginning early in infancy, in which the white blood cells and platelets were normal and only red cell precursors in bone marrow were deficient.
• 90% of cases are sporadic and are caused by in utero damage to erythroid stem cells while 10% of patients have a dominant, or more rarely recessive, familial pattern.
![Page 18: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/18.jpg)
Manifestations
Anemia is the primary problem in PRCA.The degree of anemia can range fromsubclinical to severe according to type:
![Page 19: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/19.jpg)
In acquired acute PRCA:
• Anemia is barely noticeable because the decrease in the hemoglobin level is gradual and self-limited.
• Evidence of a recent viral infection:
Rash, jaundice in viral hepatitis.Splenomegaly in infectious mononucleosis.Enlarged parotid glands in mumps.
![Page 20: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/20.jpg)
In acquired chronic PRCA:
• Evidence of anemia.
• Physical findings of underlying thymomas, however, thymomas are rarely large enough to be detected during the physical examination.
• Lymphadenopathy and splenomegaly may indicate the presence of an underlying lymphoproliferative disorder.
![Page 21: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/21.jpg)
In congenital PRCA:
• Some, but not all cases are associated with severe anemias.
• Anemia is often not observed during the early neonatal period, but pallor, weakness, and dyspnea develop during the first year of life.
• Physical abnormalities involving the head, upper limbs, thumbs, urogenital system or cardiovascular system may be detected.
![Page 22: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/22.jpg)
Work up for a case of PRCA
Basic studies include:
• CBC counts. • Reticulocyte count.
Studies to rule out hemolysis include:• Lactate dehydrogenase.• Indirect bilirubin.• Serum haptoglobin.
![Page 23: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/23.jpg)
• Parvovirus B19 infection.• Infectious mononucleosis.• Atypical mycoplasmic pneumonia.• Mumps.• Viral hepatitis.
In acute PRCA, rule out the following:
![Page 24: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/24.jpg)
• HIV infection. • Thymoma. • Chronic active hepatitis. • Systemic lupus erythematosus. • Autoimmune disorders (direct Coombs test).• Collagenvascular disorders.
In acquired chronic PRCA, rule out the following:
![Page 25: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/25.jpg)
• Fetal Hgb and erythrocyte adenine deaminase levels.
• Serum folate and vitamin B12 levels.• Genetic testing.• Peripheral smear results Can show
megaloblastic changes.
For congenital PRCA
![Page 26: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/26.jpg)
• Bone marrow aspiration and biopsy are indicated to confirm the diagnosis.
• It usually reveals a selective depletion in RBC precursors.
• In acute PRCA, bone marrow aspiration and biopsy performed during the recovery phase may yield misleading findings that suggest active erythropoiesis.
Bone marrow
![Page 27: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/27.jpg)
• In congenital PRCA, megaloblastosis of RBC precursors may be observed and occasionally, a depression in the level of megakaryocyte and WBC precursors occurs.
• Findings from biopsy of a thymoma usually reveal that the tumor is encapsulated and contains primarily spindle cells, with or without small lymphocytes.
![Page 28: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/28.jpg)
TREATMENT
Acute self-limited PRCA:• Discontinue offending drugs and treatment
of associated infections or other illness. • Transfusion therapy is not usually indicated
because of the self-limited nature of acute PRCA.
• Transfusions may be indicated in patients with hemolytic anemias who develop PRCA.
![Page 29: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/29.jpg)
Acquired chronic PRCA:
• The underlying disorder should be treated.
• Corticosteroids can be effective, but a high dosage is often 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.
![Page 30: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/30.jpg)
• 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.
• Cyclophosphamide, 6-mercaptopurine, azathioprine, and cyclosporine have all been used.
• These drugs have been effective at dosages sufficient to induce leukopenia.
![Page 31: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/31.jpg)
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 congenital PRCA.
• With severe anemia, patients can have a lifelong dependency on transfusions.
• Two units of blood every 2 weeks is usually sufficient.
![Page 32: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/32.jpg)
• Aggressive chelation using deferrioxamine infusions are critical to avoid hemosiderosis because transfusion therapy is usually started at a young age.
• Corticosteroids are also a principal therapeutic option, and this therapy is believed to allow the abnormal stem cells in patients with congenital PRCA to become more sensitive to growth factors.
![Page 33: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/33.jpg)
• High doses of prednisone (1-2 mg/kg) are needed but should not be continued for more than 4-6 weeks.
• If prednisone therapy fails, a high-dose methylprednisolone can be tried.
• The major complications of corticosteroid therapy in these patients are growth retardation, muscle weakness, and osteopenia.
![Page 34: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/34.jpg)
• Danazol and other androgens can be used in refractory cases, but these agents may be contraindicated in prepubertal children.
• Surgical Care: Surgical care may be indicated if a thymoma is suspected or if the patient has significant hypersplenism.
![Page 35: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/35.jpg)
Prognosis• Prognosis varies widely, depending on:
Etiology.Underlying disorders.Clinical course.
• Acute self-limited PRCA usually has an excellent prognosis.
• Acquired chronic PRCA is associated with a number of complications.
![Page 36: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/36.jpg)
• Congenital PRCA is usually a lifelong disorder and is associated with a high morbidity rate due to the disorder and the treatment adverse effects.
• Most patients survive through early adulthood.
![Page 37: PURE RED CELL APLASIA By assistant lecture: Waleed fouad](https://reader035.vdocument.in/reader035/viewer/2022062300/56649de45503460f94adb2a5/html5/thumbnails/37.jpg)
THANK YOU