Blood Transfusion in Clinical Practice · 24 頁
[[p.1]] 124 Essentials of Blood Banking and Transfusion Medicine Indications for Red Cell Transfusion • While defining indications for red cell transfusion, one cannot base it only on the values of haemoglobin (Hb) and haematocrit (Ht). Firstly, one has to evaluate patient’s age, nature of disease and co-morbidities, expected surgical procedures, coagulation abnormalities, the amount of blood expected to be lost because of bleeding, clinical and physio- logical parameters, showing an overall condition of a patient and tolerance to an expected tissue hypoxemia due to anaemia. • What is more, one must take into consideration is body temperature, heart function, heart rate, arterial blood pressure, renal function, venous blood oxygen saturation, and blood oxygen partial pressure. • The main indication for red cell transfusion is to keep adequate oxygen-carrying capacity of blood and to avoid or reduce tissue hypoxia. The red cell transfusion should not be done only to increase the Hb level (except the cases of severe symptoms of anaemia and the need to ameliorate the oxygen-carrying capacity). • In case of anaemia, the delivery of oxygen is ameliorated by physiological adaptability mechanisms: The haemoglobin affinity for oxygen decreases, oxygen-haemoglobin dissocia- tion curve shifts to right, oxygen release from red cells increases, peripheral vascular resistance and blood viscosity decrease; furthermore, the cardiac output increases due to increased heart rate, stroke volume and contractility. 14 Blood Transfusion in Clinical Practice 124 [[p.2]] 125 Blood Transfusion in Clinical Practice • The consumption of oxygen depends on these factors like physical activity, body temperature, sympathetic and metabolic activity, heart rate, and the effect of certain drugs (e.g. anaesthetics). • Young and healthy women without hypovolemia can tolerate acute anaemia quite well. The delivery of oxygen remains adequate, and there may not be severe symptoms of anaemia even though Hb concentration decreases to 6 g/dL. • When treating major haemorrhage, firstly, the volume of lost blood should be estimated. The goal of maintaining adequate tissue perfusion is normovolemia; therefore, one of the main principles in treating acute bleeding is to restore circulat- ing blood volume by fluids, but not by red cell transfusion. PCV/Hb should not be considered as the only laboratory markers when estimating bleeding level, because these markers can be influenced by the initial infusion therapy.10 • The average adult blood volume represents 7% of body weight (or 70 mL/kg of body weight). Estimated blood volume (EBV) for a 70 kg person is approximately 5 litres. Blood volume varies with age and physiologic state. Older individuals have a smaller blood volume. Children have EBVs of 8–9% of body weight, with infants having an EBV as high as 9–10% of their total body weight.11 Blood Transfusion in Anaemia In chronic anaemias, red cell transfusion is given according to the Hb level which is given below: • Hb >10 g/dL, if patient’s condition is stable—no indication for red cell transfusion. • Hb <6 g/dL, transfusion almost always indicated. • Hb 6–10 g/dL, indication for transfusion is based on any ongoing indication of organ ischemia, the rate and magni- tude of any potential or actual bleeding, the patient’s intra- vascular volume status and risk of complications due to inadequate oxygenation. • When Hb level is less than 7 g/dL and anaemia is asympto- matic, transfusion is needed if massive bleeding is expected during surgery or the patient belongs to a high anaesthetic risk group. [[p.3]] 126 Essentials of Blood Banking and Transfusion Medicine The AABB guidelines include the following recommenda- tions.12 • Hb <6 g/dL: Transfusion recommended except in exceptional cases. • Hb 6 to 7 g/dL: Transfusion generally likely to be indicated. • Hb 7 to 8 g/dL: Transfusion in postoperative cases. • Hb 8 to 10 g/dL: Transfusion generally not indicated except in exceptional cases (e.g. ongoing bleeding, acute coronary syndrome with ischemia, etc.). • Hb >10 g/dL: Transfusion generally not indicated except in exceptional cases. According to Kenyan Government, 2004 Guidelines for the Appropriate Use of Blood and Blood Products13 is given below. • Red cell transfusion is rarely indicated when haemoglobin levels are greater than 10 gm/dL, and is usually indicated when haemoglobin concentrations are less than 5 gm/dL. However, even severely anaemic patients (less than 5 gm/ dL Hb) who are clinically stable may not require transfusion. • Transfuse only to decrease symptoms and to minimize risk (generally at Hb of less than 5 gm/dL). Do not transfuse above 5 gm/dL Hb unless patient is symptomatic. • Treat nutritional and mild blood loss anaemia with specific therapeutic agents as indicated (iron, folic acid, B12). Use specific strategies for sickle cell disease and thalassemia. One unit of donor erythrocytes (around 250 mL), the usage of blood components in a 70 kg patient increases Hb by about 1 g/dL and PCV by 3%. A unit of whole blood has a volume of approximately 400 to 500 mL, with a haematocrit of 45 to 55%. A unit of PRBCs consists of the red blood cells concentrated from a unit of whole blood. Each unit of PRBCs contains approximately 180 to 200 mL of RBCs and 50 to 70 mL of plasma. The haematocrit of PRBCs is 65 to 75%. Red cell transfusion in blood loss • Loss of <15% of circulating blood volume (CBV) (up to 750 mL): No need to transfuse red cells, unless anaemia or severe heart or pulmonary diseases were diagnosed before haemorrhage. [[p.4]] 127 Blood Transfusion in Clinical Practice • Loss of 15–30% of CBV (around 750–1500 mL): Crystalloids and synthetic colloids should be given; usually there is no need for red cell transfusion, unless anaemia or severe heart or pulmonary disease is diagnosed and the bleeding continues. • Loss of 30–40% of CBV (around 1500–2000 mL): Hypovolemia is corrected by crystalloids and synthetic colloids and red cell transfusion is usually indicated. • Loss of >40% of CBV (>2000 mL): Urgent correction of hypo- volemia, including red cell transfusion, must be performed. Haemorrhage is broken down into four classes by the American College of Surgeons.14 • Class I Haemorrhage involves up to 15% of blood volume. There is typically no change in vital signs and fluid resuscita- tion is not usually necessary. • Class II Haemorrhage involves 15–30% of total blood volume. A patient is often tachycardic (rapid heart beat) with a narrowing of the difference between the systolic and diastolic blood pressures. The body attempts to compensate with peripheral vasoconstriction. Skin may look pale and be cool to the touch. The patient may exhibit slight changes in behavior. Volume resuscitation with crystalloids (saline or Ringer’s lactate) is all that is required. Blood transfusion is not typically required. • Class III Haemorrhage involves loss of 30–40% of circulating blood volume. The patient’s blood pressure drops, the heart rate increases, peripheral hypoperfusion (shock) and the mental status worsen. Volume correction with crystalloid and blood transfusion are usually necessary. • Class IV Haemorrhage involves loss of >40% of circulating blood volume. The limit of the body’s compensation is reached and aggressive volume correction is required to prevent death. • As a general rule, less than 15% loss of blood volume results in minimal symptoms; 15 to 30% results in tachycardia; 30 to 40% in signs of shock; and greater than 40% in signs of severe shock. Some patients with underlying diseases may [[p.5]] 128 Essentials of Blood Banking and Transfusion Medicine require transfusion at 30 to 40% blood loss. Almost all patients require transfusion with losses greater than this. Massive Haemorrhage Blood loss is considered massive if: • All blood volume is lost within a 24-hour period. (Normal blood volume in the adult is approximately 7% of ideal body weight); or • 50% blood volume loss within 3 hours; or • A rate of loss of 150 mL/minute. Management of massive blood loss • Aggressive volume correction with colloids/crystalloids (normal saline, Ringer’s lactate, dextrose). • A combination of packed red cells, FFP and platelets are indicated in 1:1:1 proportion. One proportion of platelets is one therapeutic dose (4–6 units of RDPs) or one pack of SDP. • FFP and cryoprecipitate ideally be of the same blood group as that of the recipient. Ways to minimize blood loss in massive haemorrhage • Use of antifibrinolytic drugs – Tranexamic acid (orthopedic and cardiac surgeries) – Alprotinin • Thrombo-elastography: Assesses dynamics of clot function, clot aggregation, clot strength and stability of clot. • Protamine in place of low molecular weight heparin. • Recombinant VIIa can be given. • Desmopressin can be used to release factor VIII and vWF. Other Guidelines for Red Cell Transfusion Transfusion guidelines from College of American Pathologists (CAP)15 Target population: General. RBC transfusion with following: 1. Hb <6 g/dL: Usually indicated. 2. Hb >10 g/dL: Rarely indicated. [[p.6]] 129 Blood Transfusion in Clinical Practice 3. Hb 6–10 g/dL: Decision depends upon extent of blood loss. 4. Previously healthy patients do not usually need transfusion even with losing 30–40% of their total blood volume and volume loss should be replaced by crystalloids and colloids RBC transfusion. 5. Transfusion decision should be made on peripheral tissue oxygenation, clinical signs and symptoms, Hb and extent and rate of bleeding. Transfusion guidelines from American Society of Anaesthesio- logists (ASA)16 In perioperative setting RBC transfusion is usually indicated as shown below. 1. In otherwise healthy individuals if Hb <6 g/dL. 2. Rarely indicated with Hb >10 g/dL. 3. In patients with Hb 6–10 g/dL with evidence of organ ischemia, rate and amount of bleeding, intravascular volume status and risk factors for inadequate oxygenation (e.g. low cardiopulmonary reserve) should be considered. Transfusion guidelines from Society of Thoracic Surgeons and Society of Cardiovascular Anaesthesiologists (STS/SCA)17 In general cardiology surgery patients, RBC transfusions are considered: 1. To be reasonable if Hb <6 g/dL. 2. To be reasonable in most postoperative patients if Hb <7 g/dL. 3. May not be unreasonable in certain patients with Hb <10 g/dL in the presence of critical ischemia in other organs (e.g. central nervous system). 4. Rarely indicated if Hb >10 g/dL. In patients undergoing cardiopulmonary bypass: 1. RBC transfusion is considered reasonable if Hb <6 g/dL. 2. May not be unreasonable to maintain Hb >7 g/dL in patients with risk of critical end organ ischemia. 3. Patient related factors like age, severity of illness, cardiac function, end organ ischemia, extent of blood loss, oxygen saturation, evidence of myocardial ischemia and other relevant parameters should be considered while decision making on RBC transfusion. [[p.7]] 130 Essentials of Blood Banking and Transfusion Medicine Transfusion guidelines from Society of Critical Care Medicine18 1. These guidelines are specifically for critically ill patients. RBC transfusions usually indicated with Hb <7 g/dL for patients requiring ventilation, critically ill trauma patients and patients with stable cardiac disease. 2. With Hb <8 g/dL in acute coronary syndrome, RBC trans- fusion may be beneficial. 3. Rarely indicated if Hb >10 g/dL. 4. Volume status, evidence of shock, duration/extent of anaemia cardiopulmonary parameters are considered while decision making on RBC transfusion. Transfusion guidelines from the American Association of Blood Banks19 These guidelines are for hospitalized haemodynamically stable adult and children. 1. RBCs transfusions usually considered if Hb <7 g/dL for critically ill patients and Hb of 8 g/dL or <8 g/dL for patients undergoing surgery. 2. Hb levels and presence of symptoms are considered for decision making on RBC transfusion. Transfusion of Platelets Indications of platelet transfusion are given below: • In prophylaxis of haemorrhage: Platelet count of <10 × 109/L coagulation disorders, petechiae, ecchymosis. • Prior to surgical or invasive procedures, with platelet count of <50 × 109 L. • In case of microvascular bleeding without thrombocyto- penia, when impairment of platelet function is confirmed by laboratory tests. Platelets are transfused if this impairment cannot be treated by other ways (e.g. in case of congenital platelet disorders). • Performing epidural anaesthesia or analgesia, with platelet count of <100 × 109/L. • In case of normal vaginal delivery, thrombocytopenia of <50 × 109/L is safe without need for prophylactic platelet transfusion. [[p.8]] 131 Blood Transfusion in Clinical Practice • Platelets should not be transfused (except the cases of life- threatening haemorrhage) under these circumstances: Auto- immune thrombocytopenia, thrombotic thrombocytopenic purpura, heparin-induced thrombocytopenia, post-trans- fusion purpura. Following are the AABB guidelines for platelet transfusion20 Recommendation 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends trans- fusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: Strong recommendation; moderate-quality evidence) Recommendation 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: Weak recommendation; low-quality evidence). Recommendation 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: Weak recommendation; very low-quality evidence). Recommendation 4: The AABB suggests prophylactic platelet transfusion for patients having major elective non-neuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: Weak recommendation; very low-quality evidence). Recommendation 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are non- thrombocytopenic and have cardiac surgery with cardiopulmo- nary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: Weak recommendation; very low-quality evidence). [[p.9]] 132 Essentials of Blood Banking and Transfusion Medicine Recommendation 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial haemorrhage (traumatic or spontaneous). (Grade: Uncertain recommendation; very-low- quality evidence). An usual dose of platelets is 1 unit/10 kg or 1 therapeutic dose (consisting of 4–6 units of RDP), or 1 pack of apheresed platelets (SDP). One unit of platelet concentrate (RDP) has on average 5.5–7.5 × 1010 of platelets. Conventionally 5–10 × 109 of platelet increment per RDP is accepted after one hour of transfusion. One unit of apheresed platelets has approximately 3.5–4 × 1011 platelets and increases recipient’s platelet count for 30–40 × 109/L. Transfused platelets should raise the platelet count of recipients who have not been immunized or factors that reduce platelet survival. The formula for calculating the corrected count increment is: 2 11 Observed increment per µl Body surface area (m ) Number of platelets given (10 ) × Calculation of body surface area: Mosteller’s formula × Ht in cm Weight in kg 3600 After platelet transfusion, the therapeutic effect is evaluated after 60 minutes (1 hr), and again at 20–24 hours. Clinical studies have showed that the best time to evaluate the effectiveness of platelet transfusion is after 1 hour. Failure to see the expected increment of platelets is mainly because of anti-platelet antibodies or splenomegaly (1 hour CCI reduced) or else due to decreased survival of the platelets as in sepsis, infections, DIC (24 hours CCI reduced). From CCI, effective dose (ED) of platelets can be calculated. ED = Desired platelet increment Body surface area Expected CCI × [[p.10]] 133 Blood Transfusion in Clinical Practice Post-platelet recovery (PPR): This is the percentage of platelets (platelet increment) circulating in the blood after platelet trans- fusion. Usually 2/3rd of the platelets remain in circulation, if no splenomegaly or any other pathology of platelets exist. PPR of less than 20% suggests platelet refractoriness. This is calculated by the following formula: 11 Platelet increment per µl Estimated blood volume 100 Number of platelet transfused (10 ) × × Transfusion of Fresh Frozen Plasma (FFP) • Fresh frozen plasma is transfused, if in case of haemorrhage, the prothrombin time or activated partial thromboplastin time is prolonged for 1.5 times. If there is no haemorrhage, FFP should not be used for correction of hypovolemia or normalizing coagulation parameters. A recommended initial dose of FFP is 10–15 mL/kg (average 3–4 units for a 70 kg adult patient); however, some repeated doses might be needed later on, after evaluation of therapeutic effect on bleeding. • FFP can be stored for a year at –20°C. FFP must be ABO compatible with the recipient’s red blood cells. • FFP has been used as an exogenous source of proteins, especially albumin, immunoglobulins, coagulation factors and certain protease inhibitors. Indications • Coagulopathy and bleeding of different origin. • Bleeding in case of disseminated intravascular coagulation (DIC). • Thrombotic thrombocytopenic purpura. • Congenital or acquired deficiency of different coagulation factors, when there is no possibility to get a certain factor concentrates (e.g. V or XI). • Deficiency of specific plasma proteins (e.g. antithrombin III). • Bleeding due to warfarin therapy. • FFP should not be used when a coagulopathy can be corrected with vitamin K. [[p.11]] 134 Essentials of Blood Banking and Transfusion Medicine Transfusion of Cryoprecipitate Indications • Factor VIII deficiency. • Haemorrhage due to hypofibrinogenemia or dysfibrinoge- nemia. • DIC syndrome. • von Willebrand’s disease. • Haemorrhage due to factor XIII deficiency. Treating hypofibrinogenemia and transfusing cryoprecipitate of 1–2 units/10 kg increases plasma fibrinogen concentration for approximately 500 mg/L. Fibrinogen in plasma of 1 g/L is sufficient to maintain hemostasis. Therapeutic Plasmapheresis or Plasma Exchange (TPE) TPE is defined as removal of pathological plasma component and replacement of lost plasma with normal plasma, crystalloids and colloids. Generally exchange is limited to 40 mL/kg body weight (for 40 kg person 1600 mL) and lost plasma is replaced by crystalloids and colloids. Indications of TPE is given below. Indications for Plasmapheresis Goodpasture’s syndrome Myasthenia gravis crisis (anti-GBM disease) Thrombotic thrombocytopenic Chronic inflammatory demyelinating purpura polyneuropathy Hemolytic uremic syndrome Eaton-Lambert myasthenic syndrome Cryoglobulinemia Post-transfusion purpura Hyperviscosity syndrome Refsum’s disease Myeloma cast nephropathy Cutaneous lymphoma (photopheresis) Acute demyelinating polyneuro- HIV-related syndromes (polyneuro- pathy (Guillain-Barré) pathy, hyperviscosity, TTP) Homozygous familial hyper- Bullous pemphigoid cholesterolemia Rapidly progressive glomerulo- Pemphigus vulgaris nephritis (without anti-GBM) Paraproteinemic peripheral Immune thrombocytopenia neuropathy Systemic vasculitis associated Hemolytic disease of the newborn with ANCA ABO-incompatible marrow Bullous pemphigoid transplant SLE (particularly in SLE cerebritis) [[p.12]] 135 Blood Transfusion in Clinical Practice Blood and Blood Component Transfusion in Obstetrics • The blood volume is markedly raised in pregnancy due to the increased vascularity of the enlarging uterus with interposition of the utero-placental circulation. The rise is progressive and consistent. All the constituents are affected with increased blood volume. The blood volume starts increasing from the 6th week, expands rapidly thereafter to maximum 40–50% above the non-pregnant level at 30–32 weeks. The level remains almost static till term. • Plasma volume: During pregnancy the plasma volume is increased to the extent of 30–40%. Total plasma volume increases to the extent of 1.25 litres. This increase is greater in multigravida, multiple pregnancies and with large baby. • The red cell volume is increased to the extent of 20–30%. The total increase in red cell volume is 350 mL. The reticulocyte count increases by 2%. Erythropoietin level is raised. • There is disproportionate increase in plasma volume as compared to RBC volume which produces a state of hemo- dilution during pregnancy. TABLE 14.1: To show principle blood changes during pregnancy Non-pregnant Pregnancy Total % increase near term increase Blood volume (mL) 4000 mL 5500 mL 1500 mL 30–40 Plasma volume (mL) 2500 mL 3750 mL 1250 mL 40–50 Red cell volume 1400 mL 1750 mL 350 mL 20–30 Haemoglobin (gm %) Haematocrit 38% 32% 18–20 • One woman dies from obstetric haemorrhage every minute. The blood transfusions in pregnancy should be considered in the following instances: • Acute blood loss of any amount with clinical evidence of inadequate oxygen carrying capacity or unstable vital signs. • Symptomatic anaemia regardless of haemoglobin level even if no bleeding. [[p.13]] 136 Essentials of Blood Banking and Transfusion Medicine • Haemoglobin less than 7 gm, not amenable to other timely therapies, antenatally, intrapartum or immediately post- partum. • Those receiving general anaesthesia, if the pre-operative haemoglobin is below 7 gm/dL. • Caesarean section with haemoglobin less than 10 gm%. Antepartum haemorrhage: Placenta previa and abruptio placenta are the two important causes of antepartum haemorr- hage. • Whenever the diagnosis of concealed variety of abruption has been made clinically, at least one litre of blood trans- fusion should be minimum to replenish the concealed blood loss irrespective of patient’s general condition. Peripartum/postpartum haemorrhage: Major obstetric haemorr- hage can be peripartum and postpartum period. At term the blood flow to placenta is approximately 700 mL/minute. The patient’s entire blood volume can be lost in 5–10 minutes. Unless the myometrium contracts on the placental site, blood loss will continue, even after the third stage of labour is complete. • It is essential to monitor and investigate a patient with an obstetric haemorrhage, even in the absence of shock. • Blood transfusion helps by preventing ischemic renal damage by maintaining blood pressure, prevents blood coagulation disorders and ensures patient to be in better form to withstand postpartum haemorrhage (PPH). • Best indication to adequate blood replenishment rests on use of CVP which should be maintained at about 10 mm of H2O. • To maintain adequate organ perfusion, it is important to keep a haematocrit of 30%, urinary output of at least 30 mL/hr with IV fluids and blood. Estimation of blood loss: Visual inspection is notoriously inaccurate. In obstetrics, part or all the haemorrhage may be concealed. It is important to realize that in a situation of acute blood loss the immediate haematocrit may not reflect actual blood loss. After the loss of 1000 mL, the haematocrit typically [[p.14]] 137 Blood Transfusion in Clinical Practice falls only 3 volume percent in the first hour. During the episode of acute significant haemorrhage, the initial haemato- crit is always the highest. ABO and Rh group with red cell antibody screening has to be carried out for a pregnant woman during her first visit to a doctor and at the 28th week of gestation. Another type of blood testing is cross-matching. It is performed to determine the compatibility of the donated blood with its intended recipient. Crossmatching of blood should be requested under the following circumstances: • Major antepartum, intrapartum and postpartum haemorr- hage • Placenta previa • Severe pre-eclampsia or eclampsia • Significant coagulation disorders • Anaemia (when Hb <10 g/dL) prior to cesarean section • Before an operation, when there are some significant obstetric abnormalities (uterine fibroids, previous classical caesarean section, previous placenta accreta) Some of principles to be observed are as follows: • For emergency cases, obstetric units should always reserve group ‘O’ Rh D negative, Kell-negative blood. • In the absence of acute blood loss, ante-natal and post-natal patients should only be transfused when reduction of haemo- globin is associated with significant symptoms of anaemia. Blood components used for transfusion in women of reproductive age must be Kell-negative in order to avoid alloimmunisation and subsequent haemolytic disease of the newborn (unless it is known that a woman is Kell-positive). • If anti-K antibodies are found during pregnancy, they most likely have appeared due to previous transfusion, so this should be kept in mind concerning future red cell trans- fusions. • It is recommended to use CMV-seronegative or leuco-depleted blood components (since it is thought that using leucocyte filters significantly reduces the risk of transmitting CMV). [[p.15]] 138 Essentials of Blood Banking and Transfusion Medicine However, in emergency circumstances, the transfusion should not be delayed if there are no CMV-seronegative blood components available. Some precautionary measures by the treating obstetrician during pregnancy and delivery: 1. Clinician to care to maximize Hb at delivery 2. To minimize blood loss 3. Appropriate use of blood 4. Women with high risk pregnancy, to deliver at hospital with all facilities and intensive care 5. Use of tranexamic acid 6. Use of recombinant VIIa factor 7. Check-up at 28 weeks of pregnancy 8. If placenta previa keep 2 units of blood ready 9. Every week crossmatch and keep the units reserved. RCOG Guidelines in Obstetrics21 1. If Hb level is less than 10.5 gm/dL in antenatal period, consider hematenic deficiency, once haemoglobinopathies have been excluded. Oral iron should be preferred first line of treatment for iron deficiency. Parenteral iron is indicated when oral iron is not tolerated, absorbed or patient com- pliance is in doubt. For parenteral therapy iron sucrose is given in multiple doses, whereas iron dextran may be given as single total dose infusion. Anaemia not due to iron deficiency should be managed by the blood transfusionist in close conjunction with haematologist. Transfusion almost always indicated when Hb is less than 6 gm/dL. 2. In pregnancy, pre-autologous deposit is not recommended. 3. Blood counts and coagulation screen are performed before giving FFP, cryoprecipitate and platelets. 4. Platelets should not fall below 50 × 109 in acute bleeding. Neonatal Transfusion • The total blood volume of neonates is small, although the volume is higher per kg of body weight than that of older [[p.16]] 139 Blood Transfusion in Clinical Practice children or adults (85 mL/kg for full-term and 100 to 105 mL/kg for pre-term). • In neonates, a dose of 15 mL/kg of packed red blood cells will increase the haemoglobin by approximately 3 g/dL and 5 mL/kg of packed red blood cells will increase Hb by 1 gm%. • Avoid using blood donated by blood relatives to transfuse neonates. • Blood transfusion in pre-term infants is often given for the anaemia of prematurity (associated with delayed renal production of erythropoietin due to decreased sensitivity to lower haematocrit levels). This commonly develops in neonates after 2 weeks of life. Neonates, especially pre-term, may require multiple transfusions. • Blood component therapy is a very common intervention practiced in newborns; nearly 85% of extremely low birth weight (ELBW) babies get transfusions during their hospital stay. • Indications of packed red blood cells (PRBCs) for trans- fusion in neonatal practice: PRBCs are the most commonly used blood product in neonatal transfusions. Indications for transfusion of PRBCs are mainly resolution of symptomatic anaemia and for improvement of tissue oxygenation. Tissue oxygenation depends on cardiac output, oxygen saturation and haemoglobin concentration. Once cardiac output and oxygen saturation are optimal, tissue oxygenation can only be improved by increasing the haemoglobin level. Canadian Paediatric Society recommends22 following guidelines for red blood cell transfusion in newborns: 1. Group O Rh-negative blood may be used in the emergency transfusion of newborns. Otherwise, either group O Rh- compatible or group-specific Rh-compatible blood must be used. Starting at four months postnatal age, crossmatching of donor blood is required (strong recommendation). 2. In cases of massive haemorrhage, for which a large volume of blood may be required, care should be taken to avoid hyperkalemia and dilution of coagulation factors, using combined replacement with fresh blood or frozen plasma, as necessary (strong recommendation). [[p.17]] 140 Essentials of Blood Banking and Transfusion Medicine 3. ‘Top-up’ transfusions should be used to maintain haemo- globin levels >7.5 gm/dL in convalescent preterm infants (moderate recommendation). 4. For infants in the first and second week of life, minimum haemoglobin levels of 10 gm/dL and 8.5 gm/dL, respectively, are recommended (weak recommendation). 5. Infants needing respiratory support may require transfusion at higher haemoglobin thresholds (weak recommendation). 6. Infants with cyanotic heart disease or similar haemodynamic disorders may require transfusion at higher haemoglobin thresholds (weak recommendation). 7. Transfusions should not be used to improve weight gain or to address apnea of prematurity when haemoglobin levels are already in excess of recommended levels for maintenance (weak recommendation). The guidelines for transfusion of PRBC vary according to age, level of sickness and haematocrit. TABLE 14.2: Guidelines for packed red blood cells (PRBCs) transfusion thresholds for preterm neonates23 Less than 28 1. Assisted ventilation with FiO2 more than 0.3: Hb days of age 12.0 gm/dL or PCV less than 40% 2. Assisted ventilation with FiO2 less than 0.3: Hb 11.0 g/dL or PCV less than 35% 3. CPAP: Hb less than 10 gm/dL or PCV less than 30% More than 28 1. Assisted ventilation: Hb less than 10 gm/dL or days of age PCV less than 30% 2. CPAP: Hb less than 8 gm/dL or PCV less than 25% Any age, breathing 1. On FiO2 more than 0.21: Hb less than 8 gm/dL spontaneously or PCV less than 25% 2. On room air: Hb less than 7 gm/dL or PCV less than 20% Red cells collected in CPDA-1 are kept as packed RBCs. CPDA-1 packed RBCs have a haematocrit of approximately 75% and a shelf life of 35 days. An infusion of 10 mL/kg of CPDA-1 packed RBCs would be expected to raise the patient’s haematocrit by 9% to 10%. [[p.18]] 141 Blood Transfusion in Clinical Practice CMV reduced RBCs are used to reduce the risk of trans- mitting CMV, which may be a cause of considerable concern in newborns. CMV reduction can be achieved by either leuko- reduction of blood components, or by pre-selecting donors who are CMV negative. Providing CMV reduced blood is important in preterm infants, as preterm neonates can have severe form of CMV infection than term newborns. Practical issues 1. Amount of transfusion to be given: It has been seen that transfusion with PRBCs at a dose of 20 mL/kg is well tolerated and results in an overall decrease in number of transfusions compared to transfusions done at 10 mL/ kg. There is also a higher rise in haemoglobin with a higher dose of PRBCs. 2. Properties of RBC products used in neonatal transfusion: RBCs should be freshly prepared and should not be more than 7 days old. This translates into a high 2, 3-DPG concentration and higher tissue extraction of oxygen. Other concerns with old RBCs are: Hyperkalemia, and a reduced RBC life span. In small and sick neonates, where it is anticipated that blood component therapy may be needed more than once, it may help to have aliquots from a single donor given as sequential transfusions. This is done practi- cally by reserving a bag of fresh PRBCs for up to 7 days for a newborn and withdrawing small aliquots required repeatedly from that bag under laminar flow using a sterile connecting device, into a fresh blood bag. The PRBC bag is immediately resealed under the laminar flow, and can be re-used for withdrawing similar small quantities of blood for up to 7 days. 3. The infant’s Hb concentration at birth tends to be approxi- mately 16.5 gm/dL and increases to 18.4 gm/dL within 24 hours at birth. During first 3 months of life all infants will have a normal or physiological decrease in their Hb down to approximately to 11.5 gm/dL. This decrease is greater in pre-term infants. By 12 years of age, the Hb levels will be as those of adults.24 [[p.19]] 142 Essentials of Blood Banking and Transfusion Medicine 4. At birth until six months of age, the concentration of vitamin K dependent coagulation factors (factors II, VII, IX and X) and vitamin K dependent inhibitors of coagulation (protein C and S) are lower than adult levels. By age of 6 months they will reach the levels approximately as that of adults.24 Choosing the blood group for neonatal transfusion: 1. It is preferable to take samples from both, mother and the newborn, for initial testing prior to transfusion. Mother’s sample should be tested for blood group and for any atypical red cell antibodies. 2. ABO compatibility is essential while transfusing PRBCs. Though ABO antigens may be expressed only weakly on neonatal erythrocytes, neonate’s serum may contain trans- placentally acquired maternal IgG anti-A and/or anti-B. 3. Blood should be of newborn’s ABO and Rh group. It should be compatible with ABO or red cell antibodies present in the maternal serum. 4. In exchange transfusions for haemolytic disease of newborn, blood transfused should be compatible with mother’s serum. If the mother’s and the baby’s blood groups are the same, use Rh negative blood of baby’s ABO group. In case mother’s and baby’s blood group is not compatible, use group O and Rh negative blood for exchange transfusion. For exchange transfusion, red cells should be less than 5 days old, sickle screen negative, collected in CPD anticoagulant and gamma irradiated. Volume and rate of transfusion: a. Volume of packed RBCs = Blood volume (mL/kg) × (desired minus actual haematocrit)/haematocrit of transfused RBC. b. Rate of infusion should be less than 10 mL/kg/hour in the absence of cardiac failure. c. Rate should not be more than 2 mL/kg/hour in the presence of cardiac failure. d. If more volume is to be transfused, it should be done in smaller aliquots. [[p.20]] 143 Blood Transfusion in Clinical Practice Expected response: Each transfusion of 9 mL/kg of body weight should increase haemoglobin level by 3 g/dL. Meticulous monitoring of input, output and vital signs are mandatory during blood transfusion. Neonatal Platelet Transfusion25–29 1. For a stable neonate <20,000 platelets/cmm 2. If unstable neonate <30,000 platelets/cmm 3. With active bleeding <50,000 platelets/cmm Practical issues for platelet transfusion in neonates 1. Platelets should never be filtered through a micropore blood filter before transfusion, as it will considerably decrease the number of platelets. 2. Rh-negative infants should receive platelets from Rh- negative donors to prevent Rh sensitization from the contaminating red blood cells. 1. The usual recommended dose of platelets for neonates is 1 unit of platelet per 10 kg body weight, which amounts to 5 mL/kg. The predicted rise in platelet count from a 5 mL/kg dose would be 20 to 60,000/cubic mm. Doses of up to 10–20 mL/kg may be used in case of severe thrombo- cytopenia. 2. Platelet count should not fall below 50,000/cmm in pre- term neonates who exhibit active bleeding or at a great risk of bleeding by an invasive procedure.25–29 3. In the selection of platelets units for transfusion, it is desir- able that the infant and the platelet donor to be of the same ABO blood group. 4. Repeated transfusions of O group platelets to A or B recipients should be minimized in view of the anti-A and anti-B antibodies causing lysis of the red cells.25–29 Following are to be kept in mind while transfusing the neonate: • Infectious complications: In India, it is mandatory to test every unit of blood collected for hepatitis B, hepatitis C, HIV/AIDS, syphilis and malaria. However, transfusion transmitted infections are still a considerable risk, because [[p.21]] 144 Essentials of Blood Banking and Transfusion Medicine of the relative insensitivity of screening tests, and several other organisms besides those tested for, which may be transmitted through blood. • Non-infectious complications: These can be immune mediated and non-immune mediated reactions, or can classified as acute and delayed complications. • Immune mediated haemolysis: Acute haemolytic trans- fusion reactions are common causes of transfusion related fatality in adult patients, but these are rare in neonates. Newborns do not have red blood cell (RBC) antibodies; all antibodies present are maternal in origin. • Newborns must be screened for maternal RBC antibodies, including ABO antibodies if non-O blood group transfusion to be given as the first transfusion. • If the initial results are negative, no further testing is needed for the initial few post-natal months. Infants are at a higher risk of passive immune haemolysis from infusion of ABO incompatible plasma present in PRBCs or platelet concen- trates. Smaller quantities of ABO-incompatible plasma (less than 5 mL/kg) are generally well tolerated. Newborns do not manifest the usual symptoms of haemolysis that are observed in older patients, such as fever, hypotension, and flank pain. An acute haemolytic event may be present as increased pallor, presence of plasma free haemoglobin, haemoglobinuria, increased serum potassium levels, and acidosis. Results of the direct antiglobulin (Coombs’) test may confirm the presence of an antibody on the RBC surface. Treatment is mainly supportive and involves maintenance of blood pressure and kidney perfusion with intravenous saline bolus of 10 to 20 mL/kg along with forced diuresis with furosemide. Enforcing strict guidelines for patient identification and issue of blood; and minimizing human error is essential in preventing immune mediated haemolysis. • Fluid overload: Neonates are at increased risk of fluid overload from transfusion because the volume of the blood component issued may exceed the volume that may be transfused safely into neonates. Care should be taken to ensure that, in the absence of blood loss, volumes infused [[p.22]] 145 Blood Transfusion in Clinical Practice do not exceed 10 to 20 mL/kg. There is no role for routine use of furosemide while transfusing newborns. • Metabolic complications: These complications occur with large volume of transfusions like exchange transfusions. a. Hyperkalemia: In stored blood, potassium levels tend to be high. It has been seen that after storage for around 42 days, potassium levels may reach 50 mEq/L in a RBC unit. Though small volume transfusions do not have much risk of metabolic disturbances, large volume transfusions may lead to hyperkalemia. Washing PRBCs before reconstituting with FFP before exchange transfusion helps in preventing this complication. b. Hypoglycemia: Blood stored in CPD blood has a high content of glucose leading to a rebound rise in insulin release, 1–2 hours after transfusion. This may lead to hypoglycaemia and routine monitoring is necessary, particularly after exchange transfusion, after 2 and 6 hours, to ensure that this complication does not occur. c. Acid–base derangements: Metabolism of citrate in CPD leads to late metabolic alkalosis. Metabolic acidosis is an immediate complication occurring in sick babies who cannot metabolize citrate. d. Hypocalcemia and hypomagnesemia: These are caused by binding of these ions by citrate present in CPD blood. • Transfusion associated graft-versus-host disease (TA- GvHD): Newborns are at risk for TA-GvHD, if they have received intrauterine transfusions or exchange transfusions. Unchecked donor T cell proliferation is the cause of TA-GvHD, and it can be effectively prevented by leuco-reduction and irradiation of the transfused blood. Blood and Blood Component Transfusion in Paediatric Patients • Blood transfusions are life saving in modern intensive care of premature neonates, children with cancer, children with haemolytic anaemias, coagulation disorders and children requiring transplants. The principles of transfusion in children and adolescents are similar to those of adults, but infant has special needs. [[p.23]] 146 Essentials of Blood Banking and Transfusion Medicine • Transfusions are not without any risks and are to given only when true benefits are likely. • A clear indication of transfusion must exist; otherwise, the child may be unnecessarily subjected to the risk of trans- fusion associated problems. • Components should not be unpacked until just before trans- fusion. An informed consent from parents after explaining the procedure and expected outcome must be taken. The blood can be warmed in a water bath which is thermostati- cally controlled, to ensure that the temperature of the water bath does not exceed 42°C. Adjust flow rate as outlined and never transfuse beyond 4 hours. Never inject any medication into transfusion line. Guidelines for Transfusion of RBCs in Full-term Infant under 4 Months of Age25–29 Hb less than 7 gm/dL with low reticulocyte count and with symptoms of anaemia Hb less than 10 gm/dL in an infant: • On <35% hood O2 • On O2 by nasal canula • On ventilation with mean airway pressure of <6 cm of H2O • With significant tachycardia and tachypnea • With significant apnea and bradycardia Hb less than 12 gm/dL in an infant: • On >35% hood O2 • On continuous ventilation with mean airway pressure of 6–8 cm of H2O Hb of 15 gm/dL in an infant: • On ECMO • With congenital cyanotic heart disease For more than 4 months of age25–29 1. Acute blood loss more than 15% of total blood volume 2. Hb less than 7 gm/dL with symptomatic anaemia 3. Significant pre-operative anaemia when corrective therapy is not available 4. Hb less than 13 gm/dL on ECMO [[p.24]] 147 Blood Transfusion in Clinical Practice 5. Chronic transfusion programs for disorders of RBC produc- tion. Guidelines for Platelet Transfusion in Children 1. 5–10,000 platelets/cmm with failure of platelet produc- tion. 2. <30,000 platelets/cmm in a neonate with failure of platelet production. 3. <50,000 platelets/cmm in premature neonate with active bleeding and in cases of invasive procedures. 4. <1,00,000 platelets/cmm in a sick premature with active bleeding and invasive procedures.