Anaemia
Definition Reduction of Hb below normal conc. i.e. < 13 g. / dl for males (P.C.V. < 0.40 L/L) <12 g. /dl for females (P.C.V. < 0.37 L/L)Types of anaemia
(1) Excessive loss or destruction of red cells (a) loss – post haemorrhagic anaemia (b) destruction – haemolytic anaemias(2) Failure of production of red cells (a) diminished production with marrow hyperplasia – dyserythropoietic anaemias e.g. iron deficiency anaemia & megaloblastic anaemia (b) diminished production with marrow hypoplasia --- hypoplastic or aplastic anaemiasMorphological classification
I Hypochromic microcytic anaemia A-iron deficiency anaema B-B -Thalassaemia C-Sideroblastic anaemia D-Anaemia of chronic disease II Normochromic macrocytic anaemia (Megaloblastic anaemia) III Normochromic normocytic anaemia A-acute blood loss anaemia B-all haemolytic anaemias except Thalassaemia C-secondary anaemias.. Leukaemia , malignancies in general , collagen and autoimmune diseases , uraemia , chronic liver diseasesCauses of IDA
Dietary deficiency of Iron (important only when associated with other causes) may arise due to poverty, religious trends and among vegetarians. Malabsorption of iron : this occurs in gluten enteropathy and after gastrectomy. Increased demands: Infancy aggravated by prematurity, infections and delayed mixed feeding. Adolescence Pregnancy : fetal requirements is around 300 mg + 500 mg needed for maternal circulation expansion. Blood loss: this is the most important cause of IDA, in females it is most commonly from the genital tract while in males from GIT usually.Haematological features:
Peripheral blood: Hypochromia + microcytosis with mild to moderate anisopoikilocytosis Platelets are usually increased but may be normal, WBCs are normal though few hyper segmented neutrophils may be seen.Diagnosis of IDA
In most cases: Clinical data. Typical red cell morphology Reduced transferrin saturation In more complicated cases: S. Ferritin B.M iron assessment (reduced bone marrow iron when stained by special stain for iron ; Prussian blue ((Pearls)) stain)Megaloblastic Anaemia
Definition:A group of haematological disorders characterized by distinctive morphological appearance of the developing erythroid cells in the marrow. Causes include: B12 or folate deficiency ( in the vast majority ). Abnormalities of B12 and folate metabolism. Abnormalities of DNA synthesis.
Haematological features
Peripheral blood: Pancytopenia ( usual ). RBCs: macrocytosis, characteristically oval in shape with marked red cell distortion ( anisopoikilocytosis ). WBCs: usually reduced in number with a neutrophil shift to right.鰃б(鰀ĥ鰂ȠăxǯЂꅀ֚煼П᠌Yྟྨ Haemolytic Anaemias
Haemolysis: Shortening of red cell survival with premature red cell death. When the life span of the red cells is shortened to less than 20 days, Hb drops and anaemia develops (Haemolytic anaemia ), with longer life spans the marrow can compensate by hyperactivity &/or expansion keeping Hb within normal limits (Compensated haemolysis )
General Features of Haemolysis
Features due to Hb degradation: Indirect hyperbilirubinaemia ( clinically; Jaundice, gall stones ) Hyperurobilinogenuria RES hyperplasia ( clinically; splenomegaly ) Iron overload Featurs due to marrow compensation: Reticulocytosis Skeletal abnormalities due to marrow expansion. Folate deficiency. Features specific of intravascular haemolysis: Haemoglobinaemia & hypohaptoglobinaemia. Haemoglobin & haemosiderinuria.Classification
H. Anaemias due to intrinsic red cell defects ( usually inherited ) Red cell membrane defects ( e.g H.Spherocytosis) Metabolic defects ( Enzymopathies, e.g G6PD deficiency) Hb synthesis defects ( haemoglobinopathies ) H. Anaemias due to extrinsic defects: Immune H. Anaemias Mechanical H. Anaemias. H. Anaemias due to Infections, Chemical toxins and Physical agents. Haemolysis is called intravascular when RBCs are destroyed in the circulation, while it is called extravascular when destruction occurs by the cells of the RES in the spleen, liver & B.MHaemoglobinopathies
A group of genetic disorders of Hb synthesis characterized by either a reduction of the rate of synthesis of globin chains ( Thalassaemias ) or the production of abnormal globin chains ( Hb-variants ).
The Thalassaemia Syndromes
A heterogeneous group of genetic disorders of Hb synthesis characterized by reduction in the rate of synthesis ( or total absence ) of one or more of the globin chains; according to the chain involved they are pathologically subdivided into:β -thalassaemias ( the commonest type in Iraq )α -thalassaemiasδ- thalassaemiaCompound inheritance of more than one thalassaemic gene ( δβ, αβ) or Hb-variant ( sickle cell-thalassaemia ) Original cases described were all of Mediterranean origin hence the name thalassaemia (thalos=sea, aemia=blood)Clinical classification
Regardless of the underlying pathology, thalassaemias are classified into 3 types according to the clinical severity: Thalassaemia major: transfusion dependent, anaemia is severe ( Hb about 5 g/dl ), starts within the 1st year of life, rarely live beyound the 2nd decade of life. Thalassaemia intermedia: moderate anaemia ( Hb>7 g/dl), infrequent or no need for transfusions, late presentation and long survival. Thalassaemia minor: Mild or no anaemia, minimal red cell morphological changes, increased Hb-A2, also called thalassaemia trait or carrier.Clinical Presentation
Anaemia with splenomegaly starting in the 1st 6 months of life Inadequately transfused patients suffer intercurrent infections, progressive abdominal distension and severe growth retardation with skeletal deformities. Adequately transfused patients have little anaemia & splenomegaly & normal growth. During the 2nd decade organ failure develop due to iron over load & most die for this reason.Haematological features
Hypochromic microcytic anaemia with marked red cell distortion, target forms and normoblastaemia. Raised Hb-F level(10->90%) BM shows erythroid hyperplasia with increased marrow iron. Increased body iron contents Increased S.ferritin Increased transferrin saturation Increased marrow ironHb – Variants ; Sickle cell disease(SCD) SCD is the homozygous state of Hb-S, the disease is common in central Africa, middle east and in Black Americans of African origin. Molecular defect & pathogenesis SCD results from a point mutation in the B-globin gene that causes substitution of valine instead of glutamic acid at the 6th amino position of the globin chain, this markedly reduces Hb solubility which under reduced O2 tention forms crystals ( tactoids ) that gives a sickle form to the cells, these cells are rigid and will occlude microcirculations ( vas-occlusive phenomena ) leading to multiple infarcts in the spleen, bones and elsewhere. Sickle cells are abnormal that have a shortened life span and this lead to chronic haemolytic anaemia .
Haematological features.
Normochromic normocytic RBCs with frequent target forms and occasional sickle cells. Reticulocytosis Erythroid hyperplasia with increased marrow iron.