Documente Academic
Documente Profesional
Documente Cultură
Dr . Yenny Dian Andayani SpPD -KHOM Divition Hematologic Oncologi Medic Dept Internal Medicine Moh HoesinGeneral Hospital Palembang Faculty of Medicine Sriwijaya University Palembang
09/10/2012
dr.Yenny
09/10/2012
dr.Yenny
09/10/2012
dr.Yenny
09/10/2012
dr.Yenny
MACROCYTIC anemia
MCV MCH MCHC
09/10/2012
dr.Yenny
BMP
Normal Perdarahan ?
Tidak Ya
Tinggi
Anemia Hemolitik Periksa urin
Negatif
Hemolisis Intravaskular
09/10/2012
Elektroforesis hemoglobin
Normal/Tinggi
Defisiensi Fe
Normal
Dalam terapi Fe ?
BMP
Pasokan, Absorpsi ? Hemolitik ? Gangguan metabolisme Fe Mielodisplasia (MDS) Anemia of Chronic Diseases (ACD)
09/10/2012
dr.Yenny
HEMOLYTIC ANEMIAS
Yenny Dian Andayani Hematology Oncology Medic Division Dept.Internal Medicine Moh Hoesin General Hospital Faculty of Medicine /Sriwijaya University Palembang
09/10/2012
dr.Yenny
HEMOLYTIC ANEMIA
Anemia of increased destruction
Normochromic, normochromic anemia Shortened RBC survival Reticulocytosis - Response to increased RBC destruction Increased indirect bilirubin Increased LDH
09/10/2012
dr.Yenny
09/10/2012
dr.Yenny
10
1. Intracorpuscular factor
Red cell abnormality A. Hereditary 1. Membrane defect (spherocytosis, elliptocytosis) 2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency, Pyruvate kinase (PK) deficiency) 3. Hemoglobinopathies (unstable hemoglobins, thalassemias, sickle cell anemia ) B. Acquired 1. Membrane abnormality-paroxysmal nocturnal hemoglobinuria (PNH)
09/10/2012
dr.Yenny
11
09/10/2012
dr.Yenny
12
Intravascular Hemolysis
Hgb liberated in blood vessel Hgb + haptoglobin Serum haptoglobin + hemalbumin & plasma Hgb + hemoglobinuria & hemosidenuria
13
Iron
Reutilized Protoporphyrin
Hgb + albumin
Hgb excreted in urine
dr.Yenny
Reutilized
09/10/2012
bilirubin
09/10/2012
dr.Yenny
14
Inravascular hemolysis :
- Red cells destruction occurs in vascular space - Clinical states associated with Intravascular hemolysis: Acute hemolytic transfusion reactions Severe and extensive burns Paroxysmal nocturnal hemoglobinuria (PNH) Severe microangiopathic hemolysis Physical trauma Bacterial infections and parasitic infections (sepsis)
09/10/2012
dr.Yenny
15
- Laboratory
Indirect hyperbilirubinemia Erythroid hyperplasia Hemoglobinemia Methemoalbuminemia Hemoglobinuria Absence or reduced of free serum haptoglobin Hemosiderynuria
09/10/2012
dr.Yenny
16
Extravascular hemolysis :
- Red cells destruction occurs in reticuloendothelial system (RES) - Clinical states associated with extravascular hemolysis : Autoimmune hemolysis Delayed hemolytic transfusion reactions Hemoglobinopathies Hereditary spherocytosis Hypersplenism Hemolysis with liver disease - Laboratory signs of extravascular hemolysis: Indirect hyperbilirubinemia Increased excretion of bilirubin by bile Erythroid hyperplasia Hemosiderosis
09/10/2012
dr.Yenny
17
Anamnesa
Fatigue Pallor Shortness of Breath Bleeding/petechiae Joint symptoms Rash-eg malar Family History Medications
dr.Yenny 18
09/10/2012
09/10/2012
dr.Yenny
19
Laboratory features:
Hematology test
1. Laboratory features - Normocytic/macrocytic, hyperchromic anemia - Reticulocytosis - Increased serum iron - Antiglobulin Coombs test is positive
2. Blood smear - Anisopoikilocytosis, spherocytes - Erythroblasts - Schistocytes 3. Bone marrow smear - Erythroid hyperplasia
09/10/2012
dr.Yenny
20
09/10/2012
dr.Yenny
21
* cold-reactive antibodies:
I. Primary cold agglutinin disease II. Secondary hemolysis: - Mycoplasma infections - Viral infections - Lymphoproliferative disorders III. Paroxysmal cold hemoglobinuria
09/10/2012
dr.Yenny
22
Diagnosis
- positive Coombs test (DAT)
Treatment:
- steroids - splenectomy - immunosupressive agents - transfusion
09/10/2012
dr.Yenny
23
09/10/2012
dr.Yenny
24
3. PNH laboratory features: - pancytopenia - chronic urinary iron loss - serum iron concentration decreased - hemoglobinuria - hemosiderinuria - positive Hams test (acid hemolysis test) - positive sugar-water test - specific immunophenotype of erytrocytes (CD59, CD55) 4. Treatment : - washed RBC transfusion - iron therapy - allogenic bone marrow transplantation
09/10/2012
dr.Yenny
25
Metabolic Machinery
G6PD deficiency Pyruvate kinase deficiency
09/10/2012
dr.Yenny
26
G6PD deficiency
Most frequently encountered abnormality of red cell metabolism Over 200 million people worldwide ? Survival advantage with malaria infection X chromosome Extensive polymorphism
09/10/2012
dr.Yenny
27
Macrocytic Anemia
Yenny Dian Andayani Hematology Oncology Medic Division Dept.Internal Medicine Moh.Hoesin General Hospital /Faculty of Medicine Sriwijaya University Palembang
09/10/2012
dr.Yenny
28
09/10/2012
dr.Yenny
29
09/10/2012
dr.Yenny
30
Folate deficiency
Reduced intake ( nutritional & malabsorpsi) increased utilisation (pregnancy, malignancy, hyperthytoidsm) Defective utilisation : drugs (anticonvulsant, oral contraceptive), alcoholism. Reduced hepatic stores alcohosm, hepatoma
09/10/2012
dr.Yenny
31
Clinical Feature
Sympton and sign Vit B12 Def : Severe : anemia, neuropathy Other symptom : sore mouth,loss of taste, atropy mucosa of the tongue. Disorder of the central nervous system : paresthesias of the hands & feet, unsteadiness of gait, memory loss etc.
09/10/2012
dr.Yenny
32
09/10/2012
dr.Yenny
33
09/10/2012
dr.Yenny
34
09/10/2012
Biochemical findings in MA
serum indirect (unconjugated) bilirubin serum LDH (principally LDH-1) serum iron
(unless the anemia is complicated with iron deficiency)
09/10/2012
dr.Yenny
36
09/10/2012
dr.Yenny
37
Diagnosis
Establised based on laboratory test. DD : Macrocytosis in patients : dysplastic anemias, liver disease, hemolysis, exposure to the chemotherapeutic agents.
09/10/2012
dr.Yenny
38
Treatment
Folic Acid and Vit B12 ( etiology must known well) Severe with anemias : PRC transfusion
09/10/2012
dr.Yenny
39
Yenny Dian Andayani Hematologic Oncology Medic Division Dept Internal Medicine Moh.Hoesin General Hospital Faculty of medicine Sriwijaya University Palembang
09/10/2012
dr.Yenny
40
Aplastic anemia
Aplastic anemia is a severe, life threatening syndrome in which production of erythrocytes, WBCs, and platelets has failed. Aplastic anemia may occur in all age groups and both genders. The disease is characterized by peripheral pancytopenia and accompanied by a hypocellular bone marrow.
09/10/2012
dr.Yenny
41
09/10/2012
dr.Yenny
42
Aplastic anemia
Etiology
Acquired Most cases of aplastic anemia are idiopathic and there is no history of exposure to substances known to be causative agents of the disease Exposure to ionizing radiation hematopoietic cells are especially susceptible to ionizing radiation. Whole body radiation of 300-500 rads can completely wipe out the bone marrow. With sublethal doses, the bone marrow eventually recovers. Chemical agents include chemical agents with a benzene ring, chemotherapeutic agents, and certain insecticides. Idiosyncratic reactions to some commonly used drugs such as chloramphenicol or quinacrine.
09/10/2012
dr.Yenny
43
Aplastic anemia
Infections viral and bacterial infections such as infectious mononucleosis, infectious hepatitis, cytomegalovirus infections, and miliary tuberculosis occasionally lead to aplastic anemia Pregnancy (rare) Paroxysmal nocturnal hemoglobinuria this is a stem cell disease in which the membranes of RBCs, WBCs and platlets have an abnormality making them susceptible to complement mediated lysis. Other diseases preleukemia and carcinoma
09/10/2012
dr.Yenny
44
Aplastic anemia
Congenital disorders
Fanconis anemia the disorder usually becomes symptomatic ~ 5 years of age and is associated with progressive bone marrow hypoplasia. Congenital defects such as skin hyperpigmentation and small stature are also seen in affected individuals. Familial aplastic anemia a subset of Fanconis anemia in which the congenital defects are absent.
09/10/2012
dr.Yenny
45
Clinical features
Fatique Heart palpitation Palor Infections Ptchiae Mucosal bleeding/gum bleeding
09/10/2012
dr.Yenny
46
Aplastic anemia
Pathophysiology:
The primary defect is a reduction in or depletion of hematopoietic precursor stem cells with decreased production of all cell lines. This is what leads to the peripheral pancytopenia.
This may be due to quantitative or qualitative damage to the pluripotential stem cell. In rare instances it is the result of abnormal hormonal stimulation of stem cell proliferation or the result of a defective bone marrow microenvironment or from cellular or humoral immunosuppression of hematopoiesis.
09/10/2012
dr.Yenny
47
Aplastic anemia
Lab findings Severe pancytopenia with relative lymphocytosis (lymphocytes live a long time) Normochromic, normocytic RBCs (may be slightly macrocytic) Mild to moderate anisocytosis and poikilocytosis Decreased reticulocyte count Hypocellular bone marrow with > 70% yellow marrow
09/10/2012
dr.Yenny
48
Differential Diagnosis of pancytopenia and hypoplastic marrow 1. Aplastic anemia 2. Hypoplastic myelodysplastic syndrome or hypoplastis AML 3. PNH 4. Hypoplastic antecedent phase of acute lymphocytic leukemia 5.Hypoplastic antecedent of hairy cell leukemia 6. Idiopathic myelofibrosis 7. Pure red cell aplasia 8. Agranulocytosis.
dr.Yenny 49
09/10/2012
Treatment
Marrow tranplantation isI curative for < 40 years. Only one third of patients have suitable donor. Immunosuppressive therapy : not curative -ATG -Cyclosporin -Androgen - Corticosteroids
09/10/2012
dr.Yenny
51
09/10/2012
dr.Yenny
52
Definition
ACD is a common type of anemia that occurs in patients with infectious, inflammatory, or neoplastic diseases that persist for more than 1 or 2 months. It does not include anemias caused by marrow replacement, blood loss, hemolysis, renal insufficiency, hepatic disease, or endocrinopathy, even when these disorders are chronic.
09/10/2012 dr.Yenny 53
Epidemiology
ACD is more common that any anemia syndrome other than blood loss with consequent iron deficiency ACD is the most common cause of anemia in hospitalized patients After patients with bleeding, hemolysis, or known hematologic malignancy were excluded, 52% of anemic patients met laboratory criteria for the anemia of chronic disorders ACD is observed in 27% of outpatients with rheumatoid arthritis .
09/10/2012
dr.Yenny
54
Malignant diseases
- Cancer - Hodgkins disease and Non-Hodgkins Lympmhomas - Leukemias - Multiple myeloma
Miscellanous
- Alcoholic liver disease - Thrombophlebitis - Ischemic heart disease
Idiopathic ACD
09/10/2012 dr.Yenny 56
Pathogenesis
Shortened red cell life span, moderately 20-30% (from 120 to 60-90 days) Relative bone marrow (erythropoiesis) failure - Cytokines released from inflammatory cells (TNF-, IL-1, IFN-) affects erythropoiesis by inhibiting the growth of erythroid progenitors - Serum erythropoietin levels in patiens with ACD are normal when compared to healthy subjects but much lower than levels in non-ACD anemic patients
09/10/2012
dr.Yenny
57
Pathogenesis
ABNORMAL IRON METABOLISM Activation of the reticuloendothelial system with increased iron retention and storage within it impaired release of iron from macrophages to circulating transferrin (impaired reutilization of iron) Reduced concentration of transferrin (decreased production, increase sequestration in the spleen and in the foci of inflammation, increase loss )
09/10/2012
dr.Yenny
58
ACD
Infection and inflammation Interleukin-1 (IL-1) Other Cytokines
[Leukocytes (granulocytes)]
Lactoferrin iron
Increased phagocytosis - Decreased RBC survival Reticulo endothelial system Increased ferritin synthesis - Increased stored iron Increased membrane receptors - Increased avidity for RBCs and iron-binding proteins
IL-1
Lactoferrin
60
09/10/2012
dr.Yenny
61
Laboratory features
The anemia is usually mild or moderate ( Hb 7-11g/dl) - lower values are observed in 20-30% of patients The anemia is most often normochromic and normocytic (MCHC and MCV are normal) - MCV 70-80 fl in 5-40% of patients with ACD - MCHC 26-32 g/dl in 40-70% Erythrocyte sedimentation rate (ESR) - usually rapid Retikulocytes - most often normal or slightly decreased number, increased count is rarely
09/10/2012
dr.Yenny
62
Laboratory features
Iron metabolism 1. Serum Iron - decreased (it is necessary for the diagnosis of ACD) 2. TIBC - reduced or low-normal (N) 3. Saturation index is decreased and is often < 15 %. 4. Serum Ferritin-increased or normal 5. Serum Transferrin Receptor (sTR)-Normal 6. Sideroblasts in the bone marrow-reduced (5-20%)
09/10/2012
dr.Yenny
63
Differential diagnosis
Laboratory features sFe TS TIBC sFerritin Sideroblasts sTR
09/10/2012
Iron deficiency without iron deficiency <10% <10g/L <10% >10% , N >200g/L, N 10-20% N
dr.Yenny
64
Therapy
1. Treatment of the underlying disorder 2. Iron supplementation (IS) - for patients with ACD with chronic infection or malignancy IS should be strictly avoided - IS benefit patients with ACD associated with auto-immune or rheumatic disorders. - when ACD is complicated by iron deficiency (about 27% patients).
09/10/2012 dr.Yenny 65
3. Transfusion demand (about 30% ) patients who have low Hb and are symptomatic 4. Recombinant erythropoietin 10.000 units 3 times a week i.v. or s.c. 2-3tg, in the absence of response 20000j, If there is still no respose, the treatment should be discontinued. (in 40% of patients it reduces number of transfusions) 5. Sequential administration of erythropoietin and iron (48h later) 5. Iron chelation with deferoxamine - in some patients therapy was associated with a rise in hemoglobin level 6. In future anti-TNF-antibodies
09/10/2012
dr.Yenny
66
POYCYTHEMIA
Yenny Dian Andayani Hematology Oncology Medic Dept.of Internal Medicine Moh Hoesin General Hospital /Faculty of Medicine University Sriwijaya Palembang.
09/10/2012
dr.Yenny
67
Myeloproliferative disease
arise from precursors of the "myeloid" lineage in the bone marrow
1.
Polycythemia vera
(PV) (ET)
2. Essential thombocytosis 3. 4.
09/10/2012
dr.Yenny
68
Polycythemia vera
1892 : 1st described by Vaquez 1900 : Phlebotomy as treatment by Osler 1951 : Dameshek classified PV as a MPD 1967 : Wesserman defined of PV and treatment
: : :
09/10/2012
dr.Yenny
69
Classfication of Polycythemia
I. Primary (autonomous) Polycythemia Vera II. Secondary Polycythemia A. Physiologically appropriate ( decreased tissue oxygenation) B. Physiologycally in appropriate (normal tissue oxygenation ).
09/10/2012 dr.Yenny 70
Renal artery stenosis Adrenal cortical hypersecretion Exogenous androgens NS Bartters syndrome Renal cyst , hydronephrosis
dr.Yenny 71
09/10/2012
Smoking
Cyanotic Heart disease Methemoglobinemia High O2 affinity hemoglobin Cobalt
dr.Yenny 72
Clinical Features
- Head ache
Thrombosis common cause of death Pruritis ( aggravated by bathing ) 50% Erythromelagia Digital ischemia ( palpable pulse ) Joint pain Weight loss Headache , vertigo Visual disturbance Conjunctival plethora Palpable splenomegaly 70%
dr.Yenny 73
09/10/2012
Clinical Features
- Lab : elevated leukocyte alkaline phosphatase ( LAP ) 70% elevated serum B12 - Risk to transform to acute leukemia spent phase ( Spent phase 40% 1.5 % 10-25%
Absence of familial erythrocytosis No elevation of EPO from - hypoxia ( PaO2 92 % ) - high O2 affinity Hb. - truncated EPO receptor - inappropiated EPO production by tumor A3. Splenomegaly
B1. Thrombocytosis
> 400,000
B2. WBC > 12,000 B3. BM Biopsy showing panmyelosis with prominent erythroid & megakaryocytic proliferation
B4.
Diagnosis : A1+A2 and any other of cathegory. A or A1+A2 and any 2 of cathegory. B or > 99th percentile of method specific reference range of age ,gender,altitude of residence
09/10/2012 dr.Yenny 76
09/10/2012
dr.Yenny
77
2. Leukocytosis 12x 103/ul 3. Increased leukocyte alkaline phosphatase (LAP) 4. Serum B12 > 900 pg/ml or B12 binding capacity > 2200 pg/ml
Pv Diagnosis : when A1+A+2+A3 and any 2 from category B are present.
09/10/2012
dr.Yenny
78
PV
+ + + increased normal increased increased
Panhyperplasia decreased +
dr.Yenny
2nd Polycythemia
normal normal normal normal normal normal 79
09/10/2012
dr.Yenny
80
Treatment
aim ; - reduce thrombotic risk & slow leukemic transformation - based on risk of thrombosis
Low risk -age < 60yr. -no Hx thrombosis -Plt. < 1,500,000 -no CVD risk Intermediate risk
High risk
-age > 60yr. -Previous Hx. thrombosis -CVD risk(smoking, )
09/10/2012
dr.Yenny
81
Treatment
Treatment of choice is Phlebotomy
Hydroxyurea
IFN alfa use for cytoreduction in younger ( decreased risk to leukemic transformation of hydroxyurea )
09/10/2012
dr.Yenny
82
Treatment
Busulfan or P-32 in elderly pt. with hydroxyurea intolerated
Low dose ASA ( 40 mg ) ; alleviate of microvascular sequelae ( headache, vertigo,visual disturbance , erythromelalgia )
09/10/2012
dr.Yenny
83