DEFINITION: anemia refers to a state in which the level of haemoglobin in the blood is below the reference range appropriate for age and sex . reference range: adult male 13-18 g\dl adult female 11.5- 16.5 g\dl
04
Physical EXAMINATION
HISTORYINVESTIGATION
HOW to approach to anemic patient?
TREATMENT
HISTORY:-
Presenting symptoms:-Tiredness\ easy fatigabilityLightheadednessBreathlessness( Exertional dyspnoea) Pallor Palpitation Dizziness Development\worsening of ischemic symptoms, e.g. angina or claudicationDysphagia ( IDA)PICA Neurological symptoms (paraesthesia, poor memory, depression ,visual disturbance…) ( B12 deficiency )Is there a recent history of loss of appetite, weight loss, fever and\or night sweats that might indicate infection or malignancy? Symptoms of medical conditions that result in anemia,e.g. upper GI bleeding , significant blood loss from other sites , changes in bowel habit , abnormal urine color ,renal failure …)Past medical history of chronic diseases, e.g. rheumatoid arthritis ,SLE or malabsorption …)Past surgical history e.g. resection of stomach or small bowel.Family history and ethnic background may raise suspicion of hemolytic anemias. Drug history nutritional historyIn female ask about pregnancies, abortions, menstrual loss
Physical Examination:-
Tachypnea Pallor ( conjunctiva , palmer creases & mucus membranes) Jaundice? mouth :Angular cheilosis, atrophy of tongue papillae, stomatitis (IDA) Glossitis, beefy red, smooth tongue ( B12 deficiency )LymphadenopathyRaised JVP Nail :thinning of nail , brittle , spoon-shaped ( Koilonychia) in IDA Bruises, petechiae ( bleeding tendency ) vital sign: pulse( tachycardia ,bounding ) , postural hypotension Abdominal examination for any superficial mass or organomegally cardiovascular examination may find flow murmur Evidence of the underlying disease ( features of renal disease , liver disease , malignancy , rheumatoid arthritis , SLE …..) neurological findings in B12 deficiencyInvestigations:-
1_Complete Blood Count :(Hemoglobin, hematocrit , RBC count , MCV , ,MCH ,MCHC , RDW ,WBC and differential &platelet count) .MCV(mean cell volume ) is a measure of the size of RBC.N.R.(76 fl – 100 fl)2- Reticulocyte count is used to estimate the degree of effective erythropoiesis. N.R.(1%-2%).3-Blood film examination :although technical advances in CBC have resulted in fewer blood sampling require manual examination , blood film can often yield valuable information :anisocytosis ,poikilocytosis.
Target cells spherocytes
.Red cell fragments Elliptocytes (Schistocytes)
Howell-Jolly bodies Tear drop cellsSickle cells Hypersegmented neutrophils
Bite cells
4- Iron study (s.iron ,s.ferritin, TIBC), s.vitamin B12, RBC folate in megaloblastic anemia .5- serum lactate dehydrogenase (LDH), indirect bilirubin , serum haptoglobin and Coomb’s test in hemolytic anemia & other investigations according to the case ! .6- bone marrow examination :used to assess the composition and morphology of hematopoietic cells; bone marrow aspiration and trephine biopsy are indicated in;1_Atypical cells in peripheral blood.2_Unexplained depression of more than one peripheral blood element(cytopenias). ANC (absolute neutrophil count) <500/microL ,Hb< 8g/dL or platelet count <150,000/microL.3_Uneplained lymphadenopathy or hepatosplenomegaly associated with cytopenias.MCV(mean cell volume ) is a measure of the size of RBC.N.R.(76 fl – 100 fl) Reticulocyte count is used to estimate the degree of effective erythropoiesis. N.R.(1%-2%)
IRON
Iron in the body is used primarily for the synthesis of Hemoglobin and normal erythropoiesis requires 20-25 mg of iron per day.IRON STORAGE Two different configurations : Ferritin : water soluble, hydroxyl iron, & protein (Apoprotein). Hemosiderin : insoluble Aggregate of ferritin molecules that have been stripped of apoprotein.
Metabolic pathway of IRON
Phagocytic macrophages in the liver, spleen, BM take RBC that have complete their 120-day life span. Hemoglobin is broken down into its constituents and iron is stored as ferritin or hemosiderin. Erythroid precursors in the marrow develop around the macrophages and take up the ferritin. Macrophages in the marrow and spleen remove excess ferritin and hemosiderin. Transferrin mediate iron transport from macrophages and gastro-intestinal mucosa to the immature RBC and for storage in the liver.Iron transport
Transferrin is the principle means for moving iron and is a transport protein with two iron binding site. transferrin picks up iron from the mucosal cells of the intestine then deliver iron to receptors on surface of nucleated RBCs and reticulocytes The macrophages then transport the iron-free transferrin back to the place . The amount of transferrin in the serum is measured directly as the total iron binding capacity(TIBC).Absorption sites : maximal absorption occur in the duodenum and upper jejunum. The acidic gastric juice reduces insoluble ferric iron to its soluble ferrous state.
Factors influence iron absorption
Increase Fe absorption Decrease Fe absorption - Acids : HCl ,vit.C -Alkalis, antacids - ferrous iron (Fe+2) pancreatic secretion - Agents that solubilize iron organic iron, Ferric iron as(sugars, amino acids) Agents precipitate Iron as - Iron deficiency (Phytate in the tea and - -Increased demand as in phosphate in the bran) pregnancy, infancy , excess iron utilization adolescence,Hemolysis (infection&inflammation) or bleeding disorder -primary hemochromatosisa. Depletion of tissue iron. in negative iron balance, and to preserve the level of iron in the serum and RBC, results in Depleting the tissue iron stores and this results in:
IRON DEFICIENCY ANAEMIA (IDA) Stages of iron deficiency
Reduced levels of Ferritin and hemosiderin
Reduced levels of serum ferritin
In tissue macrophage
IDA
b. Changes in serum iron are indicative of depletion of the iron stores : Serum iron are usually low. TIBC increase. c. Progressive anaemia : initially normochronic, normocytic eventually hypochromic, microcytic tissue changes occur.
CAUSES OF IRON DEFICIENCY
Chronic blood loss: uterine blood loss. GIT blood loss. * Benign conditions: peptic ulcer. esophageal varicies. hiatus hernia. colonic diverticula or polyp. hemorrhoids. chronic aspirin use. Parasites (hook worm). *Malignancy: colonic ;colorectal Ca. Gastric Ca. Esophageal Ca. small intestinal Ca
Causes of IDA cont.
pulmonary accumulation lead to hemosiderosis. Hypernephroma. urinary tract Bladder Ca. paroxysmal nocturnal hemoglobinuria (PNH). Increase iron requirement Iron malabsorption Poor dietSYMPTOMS OF IRON DEFICIENCY
symptoms and signs pertaining to anaemia : 1. Non-specific symptoms :fatigue, weakness , dyspnoea, symptoms of CHF 2. Signs : Pallor, tachycardia, splenomegaly (minority of cases) b. Symptoms and signs specific to iron deficiency : 1. atrophic changes in the epithelium results from levels of heme-containing enzymes (cytochrome, succinate dehydrogenase, catalase, peroxidase, xanthine oxidase) : a. oral lesions : angular cheilosis Atrophy of the tongue papilla with intermittent glossitis, and stomatitis. Dysphagia : post-cricoid esophageal webbing (Plummer Vinson syndrome). Nail lesions : (Koilonychias) Flattening , thinning lead to brittle, spoon- shaped nail. 2. Pica : Compulsive ingestion of non nutritive substances. Children : craving for & ingestion of clay, dirt, paint Adult : to eat ice (pagophagia) clay.Nutritional deficiency anaemia clinical application
Angular CheilosisKoilonychia
Glossitis
Marrow iron stores
Plummer-Vinson syndrome
DIAGNOSIS:
Laboratory studies : A. peripheral blood : 1. RBC indices : MCV (55-74 fl) MCH (25-30 pg/cell) RDW > 16 2. Peripheral blood smears : microcytic hypochromic poikilocyte = abnormally shaped RBCs. Anisocyte = vary in size of RBCs. 3. Blood count : normal or low reticulocytes occasionally high platelet count.Microcytic hypochromic anemia
Sideroblastic anaemiaThalassaemia trait
Anaemia of chronic disorderes
IRON Deficiency anaemia
Transpart iron
N or high N or high
N N
Low NR or low
Low low
*plasma iron *saturation of TIBC
Storage iron
N or high
N
N or high
low
Plasma ferritin
N or low
N
N or low
high
Plasma TIBC
N or high
N
N or high
low
Marrow iron
Differntial diagnosis of microcytic anaemia
DISEASES
Investigation-cont.
TREATMENT1- Determine the cause of iron deficiency. In men and in post-menopausal women with a normal diet, the upper and lower gastrointestinal tract should be investigated by endoscopy or radiological studies stool for occult blood loss from GIT bleeding. radiological analysis of upper & lower GIT for occult malignancy. urine analysis for hematuria. CXR for pulmonary Hemosiderosis. Pelvic exam. In woman *Serum antiendomysial antibody or anti-transglutaminase antibodies and possibly a duodenal biopsy are indicated to detect coeliac disease . .
TREATMENT:- 1. Determine the cause of iron deficiency ( most important). 2. Treat the underlying causes. 3. Initiaite iron replacement therapy: Oral iron therapy Ferrous sulfate , fumarate and gluconate. Dosage .. Adult dose 300mg\day gradually increased to 900mg\day but adverse effect of it....
Parental iron therapy Indications: Can not tolerate the side effect of oral iron . Suffer from IBD and peptic ulcer Iron malabsorption Suffer from HHT Does not comply with prescribed dosage.
Preparations: Iron dextrane ( im injection) may lead to hypersensitivity reaction and anaphylaxsis and discoloration at injection site. Iron Sorbitol and iron sucrose. New preparation of iron isomaltose and iron caboxymaltose have fewer allergic effect and are preferred.
Unless the patient has angina, heart failure or evidence of cerebral hypoxia, transfusion is not necessary and oral iron replacement is appropriate.
PREPARATIONS
1- Iron dextran (imferon) Intramuscular injection. it may lead to hypersensitivity reaction and anaphylaxis to the dextran and permanent stain with discoloration at the injection site. The later can be avoided by using the Z technique of IM injection. 2- Iron sorbitol (Jectofer) IV .A small test dose 0.25 ml of the drug should be administered before IM or IV to determine hypersensitivity to the agent Dose in ml = 0.0476 x weight (kg) x (Hb. deficit) + 1 ml/5kg to a maximum of 14 ml to replete iron stores.The total dose can be diluted in normal saline at 1:20 dilution and infused slowly over several hours. 3- Iron sucrose IV in patient who are allergic to dextran. . 4-new preparations of iron isomaltose and iron carboxymaltose have fewer allergic effects and are preferred.Treatment-cont.
*Maintain iron replacement therapy : the treatment should be extended to beyond the point where the anaemia is corrected for a period of usually 3-6 months in order to replenish depleted iron stores.**The haemoglobin should rise by around 10 g/L every 7–10 days and a reticulocyte response will be evident within a week. ****- A failure to respond to iron therapy should suggest the following : incorrect diagnosiscontinued loss of iron.Presence of chronic infection or inflammation will suppress BM activity .Lack of pt compliance.Ineffective release of iron.Malabsorption of iron.LOW HB LOW HCT LOW MCV LOW MCH MCHC LOW / N LOW FERRITIN LOW FE HIGH TIBC HIGH RDW Increase Soluble Transferrin receptor
IDA CRITERIA
Anaemia of chronic disease
Anaemia of chronic disease (ACD) is a common type of anaemia, particularly in hospital populations. It occurs in the setting of chronic infection, chronic inflammation or neoplasia. The anaemia is not related to bleeding, haemolysis or marrow infiltration