BLOOD TRANSFUSION and indication for it.pptx

Blood transfusion in pediatrics

1. BLOOD TRANSFUSION MODERATOR: DR PRIYANKA DR.HARINI PRESENTER: DR NIKITHA

2. Blood transfusion is an essential part of modern health care. Used correctly, it can save life and improve health. However, the transmission of infectious agents by blood and blood products has focused particular attention on the potential risks of transfusion . Transfusion practice for the neonatal and pediatric population requires an understanding of the physiologic changes that accompany the transition from fetus through the various intermediate stages to late childhood .

3. The most dynamic changes occur during the perinatal period and early infancy. Consequently, pediatric transfusion concerns are usually divided into two time periods: • From birth through 4 months • Older infants (>4 months) and children.

4. WHY COMPONENT THERAPY IS SUPERIOR IN PEDIATRICS COMPARED TO WHOLE BLOOD? Not all components are deranged Problem of volume overload Allosensitization Concentrated forms better given in specific conditions

5. WHAT ALL COMPONENTS CAN BE OBTAINED? RBC 1.PRBC 2.Leukoreduced 3.Gamma irradiated leukoreduced Granulocyte Platelets Plasma 1.FFP 2.Cryoprecipitate,Gamma Globulin,Albumin

6. WHOLE BLOOD Contains all the components,but they are present for 1 st 6 to 8 hours 1 st to disappear :Platelets :Between 4 to 48 hours Followed by Labile coagulation factors: Factor 7,Factor 5 In stored whole blood: K+ levels increases and 2,3 DPG ,ATP levels decreases Storage: 1 to 4 ‘C

7. Shelf life: 21 to 42 days CPD= Citrate Phosphate Dextrose :21days CPD-A1,CPD-A2 : 35 days + Nutrisol : 42 days

8. INDICATIONS OF WHOLE BLOOD Massive blood loss(>20 to 25%) Double volume exchange transfusion ECMO

9. 10ml/kg of whole blood raises Hct by 5% and Hb by1 to 1.5g%

10. RED BLOOD CELLS RBC concentrates are prepared from WB donations. These concentrates can be further modified for use of specific clinical settings . The aim of RBC transfusion is to replenish the RBCs in order to increase the oxygen capacity of the child blood Trauma - induced acute loss Chronic anaemia Unstable with low oxygen carrying capacity and low hematocrit who are Undergoing surgery and major procedures

11. Most commonly used in children : Packed RBC’s Ideal Hct PRBC is 70-75% and they contain only 22 to 50% of original plasma 10ml/kg of PRBC raises Hct by 10% and Hb by 3 to 4% The RBC Product of choice in neonatal and paediatrics age group is Pre storage leukocyte reduced RBC’s suspended in an anticoagulant /preservative storage solution The Hct is approximately 60-70% and storage time is upto 35 to 42 days

12. DIFFERENCE BETWEEN PRBC AND LEUKO REDUCED RBC’s When plasma with leukocytes is removed from the PRBCs : Leuko reduced RBCs Benefits of Leuko reduced RBCs include: * There will be fewer chances of Febrile disease related non haemolytic transfusion reactions,which are very common to obtain * Decrease in alloimmunisation or allosensitisation of the patient,which can occur due to the presence of antibodies * There are decreased chances of transfusion associated graft v/s host disease * Leuko reduced RBC has a relatively low volume,are found to be more hemodynamically stable when transfused than PRBC

13. PRBC contains 10 9 WBCs/unit NHFTRs occur when >5*10 6 lymphocytes are present per unit TA GVHD occurs when >10 7 lymphocytes are present5 per unit

14. METHODS OF LEKODEPLETION WBC FILTERS WASHED RBCs USING SALINE GAMMA IRRADIATION FROZEN RBCS

15. WBC FILTERS 99.5% efficacy in 3 rd generation filters in removing the leukocytes that are WBC’s The problem is that the WB filter doesnot present TA-GVHD They are costly

16. WASHED RBCs USING SALINE This is one of the most commonly used methods in many centres and medical colleges in our country It has less efficacy than filters but is easier to perform and relatively cheaper 90% removal of lymphocytes can occur and 99% removal of plasma occurs The problem is that they donot prevent TA-GVHD

17. GAMMA IRRADIATION It not only removes lymphocytes but also prevents TA-GVHD It is the only way to prevent TA GVHD The dose of gamma irradiation that is used varies from 2500 to 3500 Cgy The problem with gamma irradiation is that it can cause lysis of some cells,including RBCs, and produce hyperkalemia ,so gamma irradiation should be used only before being transfused to the patient

18. FROZEN RBC It has limited availability in India ,but the efficacy of frozen RBCs is similar to that of washed RBCs 90% removal of lymphocytes and 99% removal of plasma are seen in frozen RBCs Frozen RBCs can usually be stored at -70 degree C for many months

19. DOSE OF RBC CONCENTRATES Dose is 10-15 ml/kg It is given over about 2 to 4 hours

20. GUIDELINES FOR PEDIATRIC RBC TRANSFUSIONS INFANTS LESS THAN OR EQUAL TO 4 MONTHS AGE 1. Maintain Hb > 12 g/dl if child has Severe pulmonary disease Severe cardiac disease During ECMO 2. Maintain Hb >10 g/dl if child has Moderate pulmonary disease Major surgery pre op and intra operatively 3. Maintain Hb >7g/dl if child has Symptomatic anemia Postoperatively

21. FOR OLDER CHILDREN AND ADOLESCENTS 1. Maintain stable clinical status if child has acute blood loss >25% 2. Maintain Hb >12 g/dl if child has Severe cardio-pulmonary disease During ECMO 3. Maintain Hb >7g/dl if child has Symptomatic Chronic Anemia Perioperatively Bone marrow failure

22. ADDITIONAL INDICATIONS In case of pediatric oncological condition , then,the child will receive PRBC.If the child is having 1. Hb <8g/dl and the child is on chemo or radiotherapy 2. Hb <10g/dl if the child A.Planned Intensive chemotherapy,it has been planned * If the patient has a severe LRTI * If the patient is having febrile neutropenia B. If there is major thrombocytopenic bleeding,Hb <10g/dl should not be tolerated and then a transfusion should be given to bring Hb above 10g/dl

23. In massive acute blood loss >25%,if patient is unstable despite use of IV Crystalloids,PRBC transfusion should be given along with plasma transfusion at 1:1 ratio of RBC/Plasma volume

24. FRESH RBC v/s STORED RBC ? The earlier concept was that fresh RBCs were superior to older RBCs So the term fresh RBCs is used when the PRBC transfusion is used within 7 days of taking out blood So RBCs that are up to 7 days old are called fresh RBCs RBCs that have been stored from 7 th to 42 nd day are referred to as older stored RBCs According to Nelson ,there is no significant differences between the two

25. PREOPERATIVE AUTOLOGOUS BT IN CHILDREN? Childs weight is more than 30kg There are no serious co morbid conditions in the child There is a planned surgery within the next 6 weeks It is technically difficult to do Inadequate response to hematinics i.e , iron containing substances and erythropoietin therapy prior to surgery Now,preoperative autologous BT in children has a very limited role in pediatric practice It is used in adults

26. PLASMA A unit of plasma has a volume of 160-250 ml if obtained from WB donation or 400 -600 ml when obtained from plasmapheresis Immediately following collection from donor,plasma contains approximately 1U/ml of each coagulation factors as well as normal concentrates of other plasma proteins Labile coagulation factors ,are not stable in plasma stored at 1-6 degree C Plasma frozen within 8 hours of donation contains atleast 0.70U/ml of Factor 8 and is referred to as fresh frozen plasma FFP may be stored for 12 months at -18 degree C or colder Storage at -30 degree C or colder is recommended for optimal maintenance of Factor 8

27. DOSAGE AND ADMINISTRATION Plasma should be ABO compatible with the recipients RBCs Usually Rh group need not be considered However,when large volume of FFP are given to RhD negative pediatric patients or womenof child bearing age,prevention of RhD immunisation by use of Rh immune globulin should be considered Dose – 10 to 20 ml/kg

28. INDICATION A diminution of coagulation factors due to treatment with Vitamin K antagonist Severe liver disease DIC Massive transfusion Isolated congenital coagulation factoe deficiencies for which a safer and /or more appropriate product doesn’t exist

29. NOT INDICATED Intravascular volume expansion or repletion Correction or prevention of protein maknutrition Correction of hypogammaglobunemia Treatmet of any other isolated congenital procoagulant or anticoagulant factor deficiency for which a virus inactivated plasma derived or recombinant factor concentrates exists As a replacement fluid in therapeutic apheresis procedures for disorders other than TTP/Adult HUS unless proven to be beneficial

30. PLATELETS A platelet concentrate (pc) may be prepared from a random WB donation or by apheresis procedures in which a single donor donates the equivalent of 4-8 PCs Apheresis PCs contain a minimum of 3*10 11 platelets ,approximately 250-300ml plasma ,trace of 5 ml of RBCs and depending on the apheresis technique Overall platelet amount more than RDP products Costly but reduced chances of allosensitization PCs and apheresis Pcs are stored for upto 5 days at 20-24 degree C

31. 1 unit PC = 50 ml ,contains 5.5-10 * 10 10 platelets Easier to use in infants and small children

32. STORAGE AND ADMINISTRATION Storage time is usually 5 days,at room temperature and 22 degree C In case of aphersis products in strict condition ,they can be stored for 7 days The transfusion time should be within 2 hours but no longer than 4 hours To increase the platelet count above 50000/ cumm *In children weighing upto 30 kg 5 to 10 ml/kg of standard platelet concentrates can be given *For large children,the appropriate dose is 4 to 8 pooled platelet concentrates or 1 apheresis unit

33. INDICATIONS INFANT <4 MONTHS * Maintain platelet count >1 lakh/cc if the patient is bleeding or he/she is on ECMO,transfusion is done if count is <1 lakh *Maintain platelet count >50000/cc in invasive procedures *Maintain platelet count >50000/cc ,if the patient is clinically unstable or on a drug affecting platelet function like indomethacin,NO,antibiotics,etc *Maintain platelet count >20000/cc if clinically stable *Platelet transfusions are also needed at any level,if a patient is having platelet functional defects with either bleeding or invasive surgical procedures

34. OLDER CHILDREN Maintain platelet count >50000/cc in invasive procedures Maintain platelet count >50000/cc if bleeding present Maintain platelet count >25000/cc in minor procedure Maintain platelet count >20000/cc if BM failure is present withhemorrhage risk factors Maintain platelet count >10000/cc if bone marrow failure without hemorrhagic risk factors Platelet transfusions are also needed at any level,if the patient is having platelet functional defects with either bleeding/invasive surgical procedures

35. GUIDELINES FOR PLATELET TRANSFUSION IN NEONATE Prophylactic platelet transfusion Stable preterm neonates with platelet counts <30 × 10 9 /L Stable term neonates with platelet counts 20 × 10 9 /L Sick preterm neonates with platelet counts <50 × 10 9 /L Sick term infants with platelet counts <30 × 10 9 /L Preparation for an invasive procedure, e.g. lumbar puncture or minor surgery in neonates with platelet counts <50 × 10 9 /L and for major surgery in neonates with platelet counts <100 × 10 9 /L

36. Platelet transfusions in neonates with clinically significant bleeding Neonates with platelet counts 50 × 10 9 /L Neonates with conditions that increase bleeding (e.g. DIC) and platelet counts <100 × 10 9 /L Neonates with documented significant platelet functional disorders (e.g. Glanzmann thrombasthenia ) irrespective of the circulating platelet count

37. CONTRAINDICATIONS OF PLATELET TRANSFUSION THROMBOCYTIC THROMBOCYTOPENIC PURPURA HUS Platelet transfusion is ineffective in immune destruction ( acut ITP) AND HYPERSPLEENISM

38. CONCEPT OF CORRECTED COUNT INCREMENT Performed to judge platelet transfusion efficacy and also predicts type of platelet disorder Done at 1 hour and 24 hours after transfusion FORMULA CCI =Post transfusion platelet count- Pretransfusions platelet count – Pretransfusion *BSA platelet count Platelets infused

39. *NORMAL CCI >7.5 *10 9/L at 1 hour and more than 4.5*10 9 /L at 20 -24 hours *If the CCI is normal at 1 hour but low at 24 hours,there is consumption of coagulopathy in the patients *If the CCI value is low even at 1 hour ,immune destruction is seen in the patients

40. NEUTROPHIL OR GRANULOCYTE TRANSFUSION INDICATIONS A. Infants less than or equal to 4 months 1 st week of life :ANC <3.0 * 10 9 /L in the presence of fulminant bacterial infection Beyond 1 st week: ANC < 1.0*10 9 /L in the presence of fulminant bacterial infection

41. B. Older children and adolescents Severe neutropenia (ANC < 0.5*10 9 /L ) in the presence of infections,unresponsive to antimicrobial therapy Qualitative neutrophil defects in the presence of infections,unresponsible to antimicrobial therapy

42. GTX PREPARATION Obtain by leukapheresis,Buffy coat preparations not useful Each pack contains approximately 10 9 granulocytes in 200 cc of plasma Test for HIV,Viral hepatitis markers and CMV ABO/Rh cross matching needed since a significant number of RBCs are also present in the transfused product Transfuse as shortly as possible after collection ,within 24 hours Stored at room temperature,max upto 24 hours

43. DOSING OF GTX In neonates and infants with a weight of <10 kg ,the dose will be1-2 *10 9 of neutrophil per GTX In infants more than or equal to 10kg and small children,the dose will be 1*10 10 neutrophil per GTX For adolescents ,the dose is 5-8* 10 9 neutrophils per GTX This GTX transfusion should be given daily until either the infection resolves or the blood neutrophil count is sustained above 1.5*10 9 for a few days

44. It may be necessary to skip 1 to 2 days GTX to accurately access whether the bone marrow has recovered ,is producing neutrophils,or is simply passively transfusing the neutrophils,which is maintaining the count So there is a need to give it immediately for 4 or 5 days ,with a gap of 1 to 2 days ,and ascess whether it tends to fall or whether it tends to remain stable

45. CRYOPRECIPITATE It is prepared from FFP by thawng it to 1-6 degree C ,then centrifuged and precipitate is collected.The precioitate is resuspended in a small amount of residual plasma(Generally 10 to 15ml) is then re frozen for storage It can be stored at or below -18 degree C for 12 months It contains fibrinogen,Vwf , factor 8 and 13 It doesn’t contain Factor 9 or other factors Contains higher fibrinogen content than FFP Cryoprecipitate is ineffective in haemophilia B patients but superior to FFP in afibrinogenemia

46. INDICATIONS OF CRYOPRECIPITATE 1. Hemophilia A 2 . von Willebrand disease 3 . Congenital deficiencies of fibrinogen 4 . Factor XIII.

47. ALBUMIN Albumin is derived from pools of donor plasma obtained either from whole blood or from plasmapheresis It is prepared by cold alcohol fractionation (COHN FRACTIONATION ) process followed by heat treatment at 60 degree C for 10 hours Its composition is 96% albumin and 4% other plasma proteins Albumin is available as a 25 % solution in distilled water or as 5 % solution in saline These are stored upto 5 years at 2 to 10 degree C

48. INDICATIONS The indications for the use of albumin (or PPF) are controversial In particular, controversy remains concerning these of albumin versus crystalloids or nonblood colloids for intravascular volume expansion. The 25% solution should not be used in dehydrated patients unless it is supplemented by the infusion of crystalloid solutions.

49. DOSAGE AND ADMINISTRATION Dosage and rate of infusion depends upon the patients clinical condition In shock the usual dosage of 5% albumin is 500 ml in adults and 10-20 ml/kg in children

50. IMMUNOGLOBULINS Plasma-derived immunoglobulins are available in 2 forms: intramuscular and intravenous preparations. Intramuscular immunoglobulin, commonly known as human immune serum globulin (ISG), is prepared from large pools of donor plasma by cold alcohol fractionation (Cohn fractionation ). ISG is 95% IgG with the remaining 5% consisting of other plasma proteins . It is prepared as a sterile solution with a protein concentration of 16.5 g/1 .

51. ISG is for intramuscular use; it must not be administered intravenously as it contains aggregated IgG complexes which can activate complement causing adverse reactions if administered intravenously . The commonest use of ISG is for hepatitis A or measles prophylaxis. Several special human immune globulins are available. They are identical to ISG except that they have high titers to an infectious agent or the RhD antigen . The most commonly used preparations are hepatitis B immune globulin and varicella zoster immune globulin for the prevention of hepatitis B and varicella zoster infections, respectively, and immunization. An RhD human immune globulin for intravenous injection is also available

52. Human ISG may be further treated to prepare intravenous immunoglobulin ( IVIg ), a product virtually free of immunoglobulin complexes and therefore safe for intravenous infusion . Several IVIG preparations are commercially available . They differ in their mode of preparation, pH, use of additives, etc. but for practical purposes are generally therapeutically equivalent . Some contain less IgA than others and are therefore preferentially chosen if treating an IgA-deficient patient. IVIG is used as replacement therapy in primary immunodeficiency states and a wide variety of secondary immunodeficiency states. It can also be used as an immunomodulation agent to treat selected patients with autoimmune thrombocytopenia purpura or other autoimmune disorders.

53. COMPLICATION OF BLOOD TRANSFUSION Transfusion reactions are generally classified into 2 types Immune and non-immune. A . Immunologic transfusion reactions may be against red blood cells (haemolytic reactions), leucocytes, platelets or immunoglobulins . B. Non-immune transfusion reactions include circulatory overload, massive transfusion, or transmission of an infectious agent.

54. A . IMMUNOLOGIC TRANSFUSION REACTION 1 . HAEMOLYTIC TRANSFUSION REACTIONS It may be immediate or delayed,intravascular or extravascular *Intravascular: Very rapid cell destruction is usually due to ABO incompatibiltycsince both naturally occurring antibodies anti A and anti B are capable of fixing complement. S ymptoms mainly include restlessness,anxiety,flushing,tachyp nea,chest pain,followed by shock and renal failure

55. *Extravascular haemolysis: mainly due o immune bodies to Rh system. Clinical manifestation are relatively less severe(fever, malaise) Shock and renal failure are rare 2.TRANSFUSION RELATED ACUTE LUNG INJURY It is an uncommon reaction resulting from transfusion of donor plasma containing high levels of anti-HLA antibodies which bind to leucocytes of recipient. These leucocytes then aggregate in pulmonary micromutation and release mediators of increased vascular permeability resulting in acute pulmonary oedema and signs and symptoms of respiratory failure.

56. 3 . Other allergic reactions Besides haemo­lytic transfusion reaction, other reactions are as follows: i ) Febrile reaction which is usually attributed to immunologic reaction against white blood cells, platelets, or IgA class immuno­globulins . ii) Patients with antibodies against IgA molecule sometimes develop anaphylactic shock on transfusion of blood from other human subjects. iii ) Allergic reactions such as urticaria may occur . iv) Transfusion-related graft-versus-host disease mediated by donor T lymphocytes may occur.

57. B.NON IMMUNE TRANSFUSION REACTIONS 1.CIRCULATORY OVERLOAD Circulatory overload resultingin pulmonary congestion and acute heart failure is the most important and most common complication that may result in death following transfusion. The risk of circu­latory overload is particularly high in patients with chronic anaemia , and in infants and the elderly. The onset may be immediate, or may be delayed up to 24 hours.

58. 2.Transmission of infection Many diseases can be transmitted by transfusion of an infected blood . These include: hepatitis (HBV, HCV), CMV infection, syphilis, malaria, toxoplasmosis, infectious mononucleosis, brucellosis and AIDS (HIV infection). The incidence increases in patients who receive multiple transfusions such as cases of haemophilia , thalassaemia major, acute leukaemias , acute severe haemorrhage etc . It has, therefore, been mandatory that prior to any human transfusion, every unit of blood must be screened for the serologic testing of HIV, HBV, HCV and syphilis and for the presence of malarial parasite.

59. 3. Massive transfusion When the volume of stored blood transfused to bleeding patients exceeds their normal blood volume, it results in dilutional thrombo­cytopenia and dilution of coagulation factors . Air embolism Air embolism is unlikely to occur if the blood transfusion is carried out with plastic bags with negative pressure as is the usual practice nowadays. A debilitated person may develop symptomatic air embolism even if a small volume (10-40 ml) makes its way into the circulation, whereas a healthy indivi­dual is at lesser risk

60. 5 . Thrombophlebitis Thecomplication of thrombophlebitis is more commonly associated with venesection for blood transfusion, especially if it is done in the saphenous vein of the ankle rather than the veins of the arm. The risk of developing thrombophlebitis is further enhanced if the transfusion is continued longer than 12 hours at a single site . 6. Transfusion haemosiderosis Post-transfusion iron overload with deposition of iron in the tissues of the body occurs after repeated transfusions in the absence of any blood loss e.g. in thalassaemia major and in severe chronic refractory anaemias . The body has no other means of getting rid of extra iron except iron excre­tion at the rate of 1 mg per day. A unit of whole blood (400 ml) contains about 250 mg of iron. After approxi­mately 100 units, the liver, myocardium and endo­crine glands are all damaged.

61. TRALI TRALI is clinically defined as new ALI that develops during or within 6 hours of transfusion of any blood product. In the absence of other ALI risk factor such as sepsis, pneumonia or aspiration, and when onset clearly develops after the transfusion, the diagnosis is clear . However in the presence of another ALI risk factor, the new ALI may be caused by the transfusion and/or the ALI risk factor . The mechanism of TRALI is unclear and may be multifactorial, including donor and recipient factors .

62. It is characterized by bilateral pulmonary opacities on chest radiography and hypoxemia by arterial blood gas or pulse oximetry testing (Pao2/FiO2 < 300, SpO2 < 90% on room air, or other evidence of hypoxia The incidence was 1:5,000 units transfused in older studies, and new studies need to be performed to determine current incidence among transfusion recipients, especially those in intensive care units. The condition is under diagnosed and doctors should be aware of the possibility in their patients who develop new ALI after transfusion. Treatment is supportive.

63. PATHOPHYSIOLOGY ANTIBODY MEDIATED : Donor leukocyte antibodies present in the plasma of a transfused blood component are postulated to bind to cognate ( ie , corresponding) antigen in the recipient, resulting in capillary leak and lung injury . NON ANTIBODY MEDIATED : In ~20% of TRALI cases, HLA and HNA antibodies are not identified in the transfused product, despite the use ofsensitive assays.71,72 These cases of “ nonantibody -mediated” TRALI may be due to unidentified antibodies or exposure to other biological reactive molecules (BRMs) within the transfused blood component administered . POSSIBLE TRALI: The pathogenesis and clinical course of possible TRALI are very different from those of antibody-mediated TRALI. Pretransfusion elevations in inflammatory cytokine, such as IL-8, are prominent, but antileukocyte antibodies are infrequent in possible TRALI

64. TACO TACO is pulmonary edema primarily related to circulatory overload Acute respiratory distress, radiographic pulmonary edema , elevated central venous pressure, evidence of left heart failure, elevated B-type natriuretic peptide (BNP), and a positive fluid balance .

65. PATHOPHYSIOLOGY The pathophysiology of TACO resembles that of other forms of acute cardiogenic pulmonary edema. Normally, pulmonary capillary pressures are counterbalanced by colloid osmotic pressure, and small volumes of transudate are removed from alveoli by the pulmonary lymphatic system . The latter is able to adapt to a range of left atrial and pulmonary capillary pressures, thus maintaining homeostasis. Blood transfusion can rapidly increase left atrial and pulmonary capillary pressures, resulting in transudation of fluid into the pulmonary interstitium and alveolar space ( ie , TACO ).

66. Blood transfusion is thought to increase oncotic and pulmonary capillary pressures more significantly than an equivalent volume of intravenous crystalloid fluid, potentially accounting for its designation from other mechanisms ofcirculatory overload. However, similar to other mechanisms, TACO frequently occurs in patients with preexisting cardiac (left ventricular systolic or diastolic) dysfunction or renal impairment who are unable to compensate for an increase in circulating blood volumes . In these chronic conditions, pulmonary capillary wedge pressures may be persistently elevated with expansion of lymphatic capacity and result in pulmonary edema when further increased with transfusion.

67. SIGNS AND SYMPTOMS Signs and symptoms of TACO and TRALI begin within 6 hours of completion of blood transfusion and include tachycardia, tachypnea, and hypoxia . These clinical findings can be blunted, particularly in postoperative or intensive care patients who may not exhibit signs of respiratory distress due to sedation or preexisting ventilatory support . Cardiovascular risk factors predominate in TACO; patients tend to be older and frequently have a history of congestive heart failure and/or coronary artery disease ( Renal impairment as reflected by a history of chronic kidney disease is also common in TACO, whereas acute kidney disease and liver failure are prevalent in both TRALI and possible TRALI.

68. REFERENCES NELSON 21 ST EDITION IAP HEMATOLOGY BOOK ASH GUIDELINES PRACTICAL PEDIATRIC HEMATOLOGY BY ANUPAM SACHIDEVA

69. THANK YOU