Aplastic anamia & Sideroblastic anemia

Transcription

1 Hematology Lecture 7 كلية التقنيات الصحية والطبية قسم التحليالت المرضية Aplastic anamia & Sideroblastic anemia اإلعداد: ظفر جبار دهاق فؤاد

2 APLASTIC ANEMIA

3 What is Aplastic anemia? Aplastic anemia is a disease caused by the failure of the bone marrow (hypoactive bone marrow)in the production of blood cells, leading to poverty in all types of blood cells )pancytopenia( Atypical anemia affects all ages but is common among adolescents and in the twenties. An aplastic anemia occurs abruptly or gradually and increases over time.

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5 Pancytopenia is a reduction in the blood count of all the major cell Inesred, white cells and platelets. Causes Decrease bone marrow function : - Aplasia - Acute leukemia,myelody splasia,myeloma. - Infiltration with lymphoma, solid tumor, tuberculosis. - Megaloblastic anemia. - Paroxysmal nocturnal hemoglobinurea (PNH ) - Myelofibrosis. Increase peripheral destruction: -Splenomegaly.

6 Clasification of Aplastic anemia primary Aplastic anemia Secondary Aplastic anemia Primary aplastic anemia - -Congenital ( Fanconi Syndrome ( -Acquired

7 Congenital( Fanconi syndrome( : is an autosomal recessive often associated with : -growth retardation -mental retardation -congenital defects of the skeleton (e.g microcephaly, absent radii or thumbs) or the renal tract (e.g. pelvic or horse shoe kidney) or skin( areas of hypo and hyper pigmentation( usual age of presentation is 5-10 years approximately 10 %of patients develops myeloid leukemia.

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9 Idiopathic acquired aplastic anemia : Is the most common type of aplastic anemia caused by immune process directed against the cytotoxic T cells which secrets alpha interferon and tumor necrosis factor (TNF).The favorable response to anti lymphocyte globulin (ALG) and cyclosporine support he concept of the auto immune T cell mediated damage.

10 2-Secondary Aplastic anemia : is a failure of the bone marrow to make enough blood cells. All blood cell types are affected. Caused by direct damage to the hemopoitic marrow by : a- Radiation. b- cytotoxic drugs. c- Viral hepatitis more frequently A,B or C. d- toxin such as benzene. e- rarely aplastic anemia is the presenting feature of acute lymphoblastic or myeloid leukemia

11 Relapse sometimes severe or even fatal. Disease might transform into myelodysplasia or acute leukemia Clinical Features onset at any age, peak incidence around age of 30 years Slight male predominance. Onset is insidious or acute. Severe cases have high mortality within 6-12 months. Less severe cases might have transient or chronic course with ultimate recovery.

12 Signs and symptoms : -Fatigue. -Shortness of breath with exertion. -Rapid or irregular heart rate. -Pale skin. -Frequent or prolonged infections. -Unexplained or easy bruising. -Nosebleeds and bleeding gums. -Prolonged bleeding from cuts. -Skin rash. -Dizziness. -Headache.

13 signs and symptoms result from : A- Reduced red cells B- Reduced white cells C- Reduced platelet count

14 Signs and symptoms

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16 Diagnosis of aplastic anemia : 1- Complete blood count (CBC( 2- Reticulocyte count 3- Bone marrow biopsy tests.

17 Diagnosis of aplastic anemia : 4- other tests: X ray, ultrasound imaging test. These tests can show enlarged lymph nodes in your abdomen. Enlarged lymph nodes may be a sign of blood cancer. Liver tests and viral tests, used to check for liver diseases and viruses infection. Tests that check vitamin B 12 and folate levels in the blood. These tests can help rule out anemia caused by vitamin deficiency.

18 Laboratory Findings : Anemia: normochromic, normocytic or macrocytic )MCV fl ) low Reticulocyte count. Leucopenia: fall in granulocytes,lymphocytes are reduced in sever cases, neutrophils appears normal in morphology Thrombocytopenia: present in sever cases, platelets less than 20,000 c/l. No abnormal cells in blood film. Bone marrow: hypoplastic with loss of hemopoietic tissue and replacement by fat which involve over 75%of the marrow

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20 Treatment General treatment which include removal of the causes ; e.g stop the cytotoxic drug and avoiding radiation exposure. Blood transfusion for alleviate symptoms and compensation blood lost (red blood cell and platelets transfusion ( stem cell transplantation specific drugs such as Androgen antilymphocyte globulin, cyclosporin.

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22 SIDEROBLASTIC ANEMIA

23 Sideroblastic anemia characterized by an impaired ability of the bone marrow to produce normal red blood cells. In this condition, the iron inside red blood cells is inadequately used to make hemoglobin, despite normal amounts of iron. As a result, iron accumulates in the red blood cells, giving a ringed appearance to the nucleus (ringed sideroblast) in bone marrow because impaired heme biosynthesis. )abnormal erythroblasts with excessive iron accumulation in the mitochondria(

24 Sideroblastic anemia Hemoglobin contains nearly 80% of the body heme and there in more than two-thirds of the body iron Heme is assembled from iron and protoporphyrin Heme biosynthesis begins in the mitochondria with the condensation of succinyl-coa and glycine to form 5- aminolevulinic acid (delta-aminolevulinic acid). Biosynthesis moves to the cytosol where multiple enzymatic steps produce coproporphyrinogen III. This molecule enters the mitochondria for the final steps of heme biosynthesis.

25 HEME SYNTHESIS

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27 Sideroblastic anemia Under normal circumstances, this iron would have been used to make heme. The process only occurs in the bone marrow, because mature erythrocytes lack mitochondria. In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome

28 TYPE OF SIDEROBLASTIC ANEMIA 1- Congenital 2- Acquired

29 Congenital sideroblastic anemia X-linked SA (XLSA) is the most common SA, constituting about 40% of cases. It is often mild or asymptomatic and may be discovered only in young adulthood or even in later life occasional severe cases have presented in infancy or childhood

30 Congenital sideroblastic anemias : X-linked sideroblastic anemia (XLSA) due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase (ALAS2), has linked heme deficiency causes accumulation iron in mitochondrial - pyrioxal-6-phosphate is a coenzyme for ALAS2

31 Acquired sideroblastic anemia Primary (myelodysplastic syndrome) : The myelodysplastic are a group of disorders whose emblematic feature is haematopoietic stem cell dysfunction

32 Secondary : Sideroblastic anemia associated with -Leukemia -Lymphoma ( cancer of the lymph glands( -Myeloma (cancer of the bone marrow( - Drugs and toxins are important causes of sideroblastic anemia. The compounds most commonly implicated inhibit steps in the heme -Chronic alcoholism -Nutritional deficiencies - eg, copper,vitamin B 6 -which can develope into hematological malignancies

33 Sign and Symptom -Weakness - Fatigue - Anorexia - Skin paleness - Enlanged spleen and liver - Heart disease - Liver damage failure can result from iron buildup in these organs Causes failure to completely form heme molecules in the mitochondria lead to deposits of iron in the organ

34 Diagnosis : Complete blood count (CBC( : - Hb : low - pcv : low - HCV : normal - Leukocytes and platelets are normal The anemia is moderate to severe blood film ( Microscopic viewing of the red blood) : - unequal cell size and abnormal cell shape ( dimorphic) -Pappenheimer bodies are present in the red blood cells

35 Diagnosis : Bone marrow aspirate : Ringed sideroblasts are seen in the bone marrow. by using Specific test: Prussian blue stain of RBC in marrow shows ringed sideroblasts. Normally, sideroblasts are present in the bone marrow, and enter the circulation after maturing into a normal erythrocyte.

36 Blood smear: Red cell accumulation :iron around nuclius Sideroblastic cell

37 Laboratory findings : - Serum Iron : High - ferritin levels : increased - Normal total iron-binding capacity - High transferrin saturation - Hematocrit of about 20-30% -MCV is normal or low for congenital causes of sideroblastic anemia but normal or high for acquired forms.

38 Peripheral blood picture

39 Ring sideroblastic cell

40 Treatment 1- erythropoietin therapy. 2- blood transfusion with medications are prescribed to stimulate excretion or excess iron that accumulates as a result of these transfusions. 3- pyrodoxine (vitamin B6) to improved heme level in severe cases. Treatment with oral pyridoxine usually benefits patients whose sideroblastic anemia was present at birth. This treatment improves the condition of some patients. 4-bone marrow transplant.

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