Approach to Anemia disorders in Pediatrics.pptx

Anemia in Pediatrics Clinical Approach

1. APPROACH TO ANEMIA

2. DEFINITION OF ANEMIA Anemia is defined as a reduction of the hemoglobin concentration or red blood cell (RBC) volume below the range of values occurring in healthy persons . Cut-off values to define anemia as proposed by WHO- AGE Hemoglobin Hematocrit 6 month – 5 years <11 <33 5 years – 11 years <11.5 <34 12 years – 13 years <12 <36

3. CLINICAL FEATURES IN ANEMIA Symptoms- Tiredness and lasitude Easy fatigability and generalized weakness Poor feeding Irritability Poor school performance CNS symptoms like headache, tinnitus, lack of concentration, dizziness etc Severe anemia- dyspnea on exertion, palpitations, drowsiness and clouding of consciousness

4. CLINICAL FEATURES IN ANEMIA Signs- Pallor is the most important sign (seen in nail bed, palms, mucous membranes, conjunctiva) Elevated pulse pressure and collapsing pulse Hemic (systolic) murmur predominantly heard in pulmonary area Severe anemia may present with signs of CCF like tachycardia, S3 gallop, pulmonary crepts , hepatomegaly and pedal e dema

5. CLUES TO DIAGNOSIS FROM HISTORY HISTORY PROBABLE ETIOLOGY RACE PARSEES SINDHIS, PUNJABIS TRIBALS G6PD DEFICIENCY THALASSEMIA SICKLE CELL ANEMIA DIETARY HISTORY PICA, PAGOPHAGIA , COW MILK DIET VEGETARIAN DIET IRON DEFICIENCY ANEMIA VITAMIN B12 DEFICIENCY ANEMIA HISTORY OF BLEEDING PETECHIAE, MALENA, HEMATEMESIS APLASTIC ANEMIA, LEUKEMIA, ITP, DIC HISTORY OF FEVER MALARIA, TYPHOID FEVER, LEUKEMIA, LYMPHOMA

6. CLUES TO DIAGNOSIS FROM HISTORY HISTORY PROBABLE ETIOLOGY SYSTEMIC SYMPTOMS CHRONIC DIARRHEA MEGALOBLASTIC ANEMIA, PELLAGRA, CELIAC DISEASE WORM INFESTATION IRON DEFICIENCY ANEMIA JAUNDICE HEMOLYTIC ANEMIA HIGH COLORED URINE (HEMOGLOBINURIA) HEMOLYTIC ANEMIA, G6PD DEFICIENCY, MALARIA NODULAR SWELLING, BONE PAINS, WEIGHT LOSS LEUKEMIA, LYMPHOMA NEUROLOGICAL SYMPTOMS LIKE COGNITIVE IMPAIRMENT, LOSS OF JOINT POSITION & VIBRATION VITAMIN B12 DEFICIENCY FAILURE TO THRIVE CELIAC DISEASE, CHRONIC RENAL DISEASE ABNORMAL FACIES OR OTHER SKELETAL ANOMALIES FANCONI ANEMIA, DIAMOND- BLACKFAN ANEMIA

7. CLUES TO DIAGNOSIS FROM HISTORY HISTORY PROBABLE ETIOLOGY PAST INFECTIONS VIRAL HEPATITIS PARVOVIRUS B19 INFECTION APLASTIC ANEMIA, RED CELL APLASIA FAMILY HISTORY HISTORY OF ANEMIA, JAUNDICE, GALL STONES, SPLENECTOMY IN FAMILY THALASSEMIA, SICKLE CELL ANEMIA, HEREDITARY SPHEROCYTOSIS HISTORY OF DRUG INTAKE PHENYTOIN, PHENOBARBITONE, ANTI-CANCER DRUGS MEGALOBLASTIC ANEMIA PRIMAQUINE, SULPHAMETHOXAZOLE, CHLORAMPHENICOL, DAPSONE, PAS, NALIDIXIC ACID, NITROFURANTOIN G6PD DEFICIENCY INDUCED ANEMIA

8. CLUES TO DIAGNOSIS FROM EXAMINATION SYSTEM CLINICAL FINDING PROBABLE ETIOLOGY SKIN Generalized hyperpigmentation with hypopigmented patches Fanconi anemia Hyperpigmentation of the knuckles Petechiae , purpura Megaloblastic anemia Aplastic anemia , leukemia , autoimmune hemolytic anemia with thrombocytopenia, thrombocytopenia with excessive blood loss Jaundice (mild) Acute and chronic hemolytic anemia , aplastic anemia Cavernous hemangioma Leg ulcers Microangiopathic hemolytic anemia Sickle cell anemia , thalassemia intermedia

9. CLUES TO DIAGNOSIS FROM EXAMINATION SYSTEM CLINICAL FINDING PROBABLE ETIOLOGY General physical examination Edema Congestive heart failure due to severe anemia Clubbing Malabsorption disorder Lymphadenopathy Leukemia , lymphoma, infectious mononucleosis, collagen vascular/infiltrative disorder, malignancy Presence of significant lymphadenopathy rules out aplastic anemia Marked wasting Anemia of malnutrition because of multiple micronutrient deficiency Tongue- glossitis Megaloblastic anemia Bald tongue Iron deficiency anemia Mouth- angular cheilosis Iron deficiency anemia

10. CLUES TO DIAGNOSIS FROM EXAMINATION SYSTEM CLINICAL FINDING PROBABLE ETIOLOGY Facies Hemolytic facies —large head, depressed nasal bridge, frontal and parietal bossing, malar prominence, anterior over-riding of maxillary teeth Chronic hemolytic anemia (thalassemia major, sickle cell anemia , hereditary spherocytosis) Eyes Microcornea Fanconi anemia Microaneurysms of retinal vessels Sickle cell anemia Blindness Osteopetrosis Hands Triphalangeal thumb Red cell aplasia (Diamond- Blackfan syndrome) Hypoplasia of thenar eminences, absent/abnormal thumb Fanconi anemia Koilonychia , platynychia Iron deficiency anemia

11. CLUES TO DIAGNOSIS FROM EXAMINATION SYSTEM CLINICAL FINDING PROBABLE ETIOLOGY Chest Shield chest Diamond- Blackfan syndrome Basal crepts Congestive cardiac failure due to severe anemia Abdomen Hepatosplenomegaly Hemolytic anemia (thalassemia,(36PD) deficiency, hereditary spherocytosis lnfiltrative disorder: Leukemia , lymphoma Presence of hepatosplenomegaly usually rules out aplastic anemia CVS S3, gallop rhythm, ejection systolic murmur Congestive cardiac failure due to severe anemia

12. BASIC INVESTIGATIONS IN A CASE OF ANEMIA Complete Blood Counts RBC indices Peripheral smear examination Packed Cell Volume Reticulocyte counts

13. PACKED CELL VOLUME PCV is defined as the   volume percentage   of RBCs in   blood, expressed in percentage values. The packed cell volume (PCV) can be determined by centrifuging EDTA-treated or heparinized blood in a capillary tube  at 10,000 RPM for five minutes, or by an automated analyser . It can be elevated in conditions like polycythemia, high altitudes, dehydration and severe dengue fever. It is decreased in anemia.

14. RETICULOCYTE COUNTS Reticulocyte count is the test for determining bone marrow function and evaluating erythropoietic activity. Reticulocyte number increases when there is an increase in erythropoietic activity in conditions like hemolytic anemia, hemorrhage, after treatment of anemia. Reticulocyte count decreases in conditions like i ron deficiency anemia, aplastic anemia etc.

15. PERIPHERAL SMEAR EXAMINATION It is useful in- Evaluation of anemia Evaluation of thrombocytopenia Evaluation of abnormal cells(blast cells/ atypical lymphoid cells) Evaluation of malaria

16. High power view of a normal peripheral blood smear. Several platelets (black arrows) and a normal lymphocyte (blue arrow) can also be seen. The red cells are of relatively uniform size and shape. The diameter of the normal red cell should a pproximate that of the nucleus of the small lymphocyte; central pallor (red arrow ) should equal one-third of its diameter . Peripheral blood smear taken from a patient with increased reticulocytes. Unlike mature red cells (thin black arrows), which have central pallor and are the same size as the nucleus of a small lymphocyte (thick arrow ), reticulocytes (blue arrows) are larger, have a blue tint, and lack central pallor because they are not biconcave discs. (Wright- Giemsa stain ).

17. Peripheral smear from a patient with iron deficiency shows pale small red cells with just a scant rim of pink hemoglobin ; occasional "pencil" shaped cells are also present. Normal red cells are similar in size to the nucleus of a small lymphocyte (arrow); thus, many microcytic cells are present in this smear. T halassemia can produce similar findings. Peripheral smear shows marked macro- ovalocytosis in a patient with vitamin B12 deficiency.

18. Peripheral smear from a patient with beta thalassemia trait . The field shows numerous hypochromic and microcytic red cells (thin arrows), some of which are also target cells (blue arrows). Peripheral blood smear from a patient with a microangiopathic hemolytic anemia with marked red cell fragmentation. The smear shows multiple helmet cells (small black arrows), other fragmented red cells (large black arrow); microspherocytes are also seen (blue arrows). The platelet number is reduced; the large platelet in the center (red arrow) suggests that the thrombocytopenia is due to enhanced destruction

19. Peripheral smear from a patient with sickle cell anemia shows multiple sickle cells (blue arrows), a nucleated red blood cell in the upper left, and a Howell-Jolly body (black arrow), which is a nuclear fragment normally removed by the spleen. Target cells are also present (red arrow). Peripheral smear from a patient with infectious mononucleosis shows three atypical lymphocytes with generous cytoplasm.

20. Blood smear showing small lymphoblasts with rare nucleoli and vacuoles, as seen in acute lymphocytic leukemia (ALL) of the L-1 morphologic type.

21. BASIC APPROACH TO DIAGNOSIS OF ANEMIA

22. APPROACH TO MICROCYTIC ANAEMIA

23. APPROACH TO MACROCYTIC ANEMIA

24. APPROACH TO NORMOCYTIC ANEMIA

25. APPROACH TO HEMOLYTIC ANEMIA

26. THALASSEMIA

27. INDICATIONS OF TRANSFUSION IN THALASSEMIA Haemoglobin level ( Hb ) <7 g/dl on 2 occasions, > 2 weeks apart (excluding all other contributory causes such as infections) OR Haemoglobin > 7 g/dl with any of the following: Facial changes Poor growth Fractures Clinically significant extramedullary haematopoiesis

28. MANAGEMENT OF THALASSEMIA Chelation therapy Iron-chelation therapy should start as soon as the patient becomes significantly iron-overloaded. In general, this occurs after 1 yr of transfusion therapy and correlates with the serum ferritin >1,000 ng /mL and/or a liver iron concentration of >5,000 µg/g dry weight. Deferoxamine : it has an excellent safety and efficacy profile. It requires subcutaneous or IV administration as a continuous infusion over at least 8 hr daily, 5-7 days/wk. Deferasirox : it has a half-life of >16 hr and requires once-daily administration. T he initial dose typically is 20 mg/kg/day and can be escalated to as high as 40 mg/kg/day based on the iron burden. The most common side effects are gastrointestinal (GI) symptoms The most serious side effect is potential kidney damage. Deferiprone : Deferiprone requires dosing 3 times daily. The starting dose is 75 mg/kg/day and can be escalated to 99 mg/kg/day based on the degree of iron overload. The most serious side effect i s transient agranulocytosis , which occurs in 1% of patients.

29. MANAGEMENT OF THALASSEMIA Routine monitoring recommended- EVERY 3 MONTHS- Clinical examination, CBC, LFT, RFT, Urine for proteinuria, S. ferritin (if possible) EVERY YEAR- HIV, HbsAg , anti-HCV AFTER 10 YEARS OF AGE- Calcium, phosphorous, Thyroid profile, Echo, Pulmonary function tests Immunizations- Routine childhood immunizations, as well as administration of influenza vaccine, typhoid, pneumococcal and meningococcal vaccinations are recommended .

30. SICKLE CELL ANEMIA

31. INDICATIONS OF TRANSFUSION IN SICKLE CELL ANEMIA Recurrent acute chest syndrome ( ACS) Aplastic crisis Splenic sequestration Acute stroke Priapism Hb <7 g/dl with severe painful crisis P ulmonary hypertension R enal dysfunction S ickle hepatopathy

32. MANAGEMENT OF SICKLE CELL ANEMIA Hydroxyurea H ydroxyurea therapy should be given to all children with sickle cell anemia starting at 9 months of age regardless of clinical symptoms. Starting doses should be approximately 20 mg/kg/day. Dose escalation should be based on clinical and laboratory parameters . If necessary, dose increases should be in 5 mg/kg/day increments to a maximum of 35 mg/kg/day. CBC with differential and reticulocyte count should be checked within 4 wk after initiation of therapy or any dose change to monitor for hematologic toxicity , then every 8-12 wk.

33. MANAGEMENT OF SICKLE CELL ANEMIA Prophylactic Penicillin Children with sickle cell anemia should receive prophylactic oral penicillin V until at least 5 yr of age (125 mg twice daily up to age 3 yr , then 250 mg twice daily thereafter ) Immunizations Routine childhood i mmunizations , as well as influenza vaccine, immunizations to protect against encapsulated organisms , including pneumococcal and meningococcal vaccinations are recommended

34. INDICATIONS OF BONE MARROW EXAMINATION To evaluate severe anemia, megaloblastic anemia, refractory anemia Suspected leukemia Pancytopenia Severe thrombocytopenia Suspected storage disorder

35. BLOOD TRANSFUSION

36. INDICATIONS OF PRBC TRANSFUSION Acute loss of >25% circulating blood volume Hb <7 g/dl in case of symptomatic chronic anemia or marrow failure Hb <10 g/dl for any case of major surgery (pre-operatively) Hb <12 g/dl in case of severe cardiopulmonary disease (shock, mechanical ventilation, ECMO) Hb <12 g/dl in case of cyanotic heart disease

37. INDICATIONS OF PRBC TRANSFUSION IN NEWBORNS CONDITION Hb Severe pulmonary disease <12 Moderate pulmonary disease <10 Severe cardiac disease <12 Major surgery <10 Symptomatic anemia <7

38. INDICATIONS OF FFP TRANSFUSION Severe clotting factor deficiency AND bleeding Severe clotting factor deficiency AND invasive procedure Disorders with overt bleeding Disorders with risk of bleeding because of clotting factor abnormalities ( eg . Liver failure) PT/ aPTT greater than 1.5 times the reference range Emergency reversal of warfarin effects Dilutional coagulopathy and bleeding ( eg . Massive transfusion) Anticoagulant protein(anti-thrombin III, proteins C and S) replacement Plasma exchange replacement fluid for TTP or HUS

39. INDICATIONS OF PLATELET TRANSFUSION CHILDREN AND ADOLESCENTS Maintain PLT count > 50,000 with bleeding. Maintain PLT count > 50,000 with major invasive procedure; > 25,000 with minor. Maintain PLT count >20,000 and marrow failure WITH hemorrhagic risk factors. Maintain PLT count > 10,000 and marrow failure WITHOUT hemorrhagic risk factors . INFANTS ≤4 MO OLD Maintain PLT count > 1,00,000 with bleeding or during extracorporeal membrane oxygenation. Maintain PLT count > 50,000 and an invasive procedure. Maintain PLT count > 20,000 and clinically stable. Maintain PLT count > 50,000 and clinically unstable and/or bleeding or not when on indomethacin, nitric oxide, antibiotics, etc ., affecting PLT function .

40. Adverse effects & risks of transfusion MILD REACTIONS FEATURES- pruritus, rash, urticarial MANAGEMENT- Stop the transfusion Administer anti-histaminic If no improvement within 30 mins or worsening, manage as moderate category reaction

41. Adverse effects & risks of transfusion MODERATE REACTIONS SYMPTOMS- anxiety, pruritus, palpitations, headache SIGNS- flushing, urticarial, rigors, fever, tachycardia MANAGEMENT- STOP THE TRANSFUSION Send the infusion set, freshly collected urine and new blood samples (1 clotted and 1 anti-coagulated) from vein opposite infusion site with request form to blood bank for investigations Administer anti-histaminic Give IV corticosteroid and bronchodilators if anaphylactoid features present Collect urine for next 24 hours for evidence of hemolysis

42. Adverse effects & risks of transfusion SEVERE (LIFE-THREATENING) REACTIONS SYMPTOMS- anxiety, pruritus, pain at infusion site, chest pain, loin/back pain, palpitations, headache, dyspnea SIGNS- rigors, fever, restlessness, tachycardia, hypotension, hemoglobinuria , unexplained bleeding (DIC) MANAGEMENT- STOP THE TRANSFUSION Infuse NS bolus over 15 mins (20-30 ml/kg) if hypotensive and elevate patient’s legs Maintain airway and give high flow oxygen by mask Give adrenaline (1:1000) 0.01 mg/kg by slow IM injection Administer anti-histaminic, give IV corticosteroid and bronchodilators Send the infusion set, freshly collected urine and new blood samples (1 clotted and 1 anti-coagulated) from vein opposite infusion site with request form to blood bank for investigations Collect urine for next 24 hours for evidence of hemolysis Assess for bleeding from puncture sites or wounds. If evidence of DIC present, give platelets and FFP

43. ANEMIA MUKT BHARAT

44. TARGETS OF ANEMIA MUKT BHARAT

45. 6x6x6 STRATEGY UNDER ANEMIA MUKT BHARAT

46. DOSAGE OF IRON-FOLIC ACID PROPHYLAXIS Age group Dose and regime Children 6-59 months of age Bi-weekly 1ml Iron and Folic Acid syrup. Each ml Iron and Folic Acid syrup containing 20 mg elemental Iron + 100 mcg of Folic Acid . Bottle (50ml) to have an ‘auto-dispenser’ and information leaflet as per MoHFW guidelines in the mono-carton Children 5-9 years of age Weekly, 1 Iron and Folic Acid tablet. Each tablet containing 45 mg elemental Iron + 400 mcg Folic Acid, sugar-coated, pink-colour. School-going Adolescent Girls and Boys, 10-19 years of age Out-of-school Adolescent Girls, 10-19 years of age Weekly, 1 Iron and Folic Acid tablet. Each tablet containing 60 mg elemental Iron + 500 mcg Folic Acid, sugar-coated, blue- colour .

47. DEWORMING IN ANEMIA MUKT BHARAT Age group Deworming Children 6-59 months of age Biannual dose of 400 mg Albendazole (½ tablet to children 12-24 months and 1 tablet to children 24-59 months). Children 5-9 years of age Biannual dose of 400 mg Albendazole (1 tablet). School-going Adolescent Girls and Boys, 10-19 years of age Out-of-school Adolescent Girls, 10-19 years of age Biannual dose of 400 mg Albendazole (1 tablet).

48. SOURCES Nelson’s textbook of pediatrics 21 st edition Cloherty’s manual of neonatology Approach to the child with anemia : Author Lisa Bomgaars , MD