Transfusion Practice in clinical Medicine

Blood components transfusion practice requires the constant use of critical clinical judgement. The medical indications for every transfusion should be carefully evaluated, and each transufion should be monitered for therapeutic effectiveness. Adverse outcomes may follow hemotherapy, even when that therapy is indicated, transfusion should be undertaken only if the anticipated benefit outweighs the potential risks.

Principles of the clinical use of blood/blood products

1. The patient with acute blood loss should receive effective resuscitation (intravenous replacement fluids, oxygen, etc..) while the need for transfusion is assessed.

2. The specific clinical or laboratory indications for transfusion should be considered.

3. The patient’s haemoglobin vlaue, although important, should not be the sole deciding factor in starting transfusion. The decision to transfuse should be supported by the need to relieve clinical signs and symptoms and prevent significant morbidity and mortality.

4. Transfusion should be prescribed only when the benefits to the patients are likely to outweigh the risks of transmitting HIV, hepatitis B & C, or other infectious agents through blood products.

5. Informed consent for transfusion of blood and its products should be taken. The physician should explain the risks and alternatives of transfusion to the recipient or responsible family member and document in the medical record that it has been done. One time consent for repeated transfusion will suffice.

MULTIPLE TRANSFUSION

Multiple transfusion is the repeated transfusion of whole blood or red blood cells over a long period of time (months or year).

Indications:

■ Hypoproliferative anemia:

• Hypoplastic or aplastic anemias

• Drugs or chemicals induced hypo or aplastic anemias

• Radiation-induced marrow depression

■ Hemolytic anemias

• Thalassemia major

• Sickle cell anaemia

• Autoimmune hemolytic anaemia (AIHA)

• Paroxysmal nocturnal anaemia (PNH)

■ Anaemia associated with chronic diseases:

• Renal insufficiency

• Chronic inflamation

• Hepatic failure

• Malingnancy

Guidelines for multiple transfusion:

• Packed red blood cells transfusion is preferred to whole blood transfusion.

• Leukocytes-poor red cells should be used in patients having febrile non-hemolytic transfusion reactions.

• Red cells should be of the same ABO and Rh (D) group as that of the patient and should be cross-matched by anti-human globulin test.

• Patients receiving regular multiple transfusions should be given iron-chelating agents to prevent hemosiderosis.

CONGENITIAL HEMOLYTIC ANAEMIAS

The congenital hemolytic anaemias are due to hereditary abnormalities involving one of the three main components of erythrocytes - the membrane, hemoglobin and intracellular enzymes . Most common congenital hemolytic anemias relevant to the clinical practice of transfusion medicine are due to defects of hemogloublin.

Defects of hemoglobin are :

• Structural anomalies - HbSS , HbS (Sickle Cells)

• Synthetic anomalies -failure to synthesize Hb adequately
β - Thalassemia

α-Thalassemia

other thalassemia syndrome

SICKLE CELL ANAEMIA

Oxygen affinity of RBCs of sickle disease is decreased and 2, 3 - DPG levels are elevated. Symptoms of anaemia are usually less.

Indications for transfusion therapy in sickle disease are:

• Severe Vaso-occlussive or painful crises refractory to medical management.

• Severe infection

• Acute splenic sequestration

• Stroke

• Liver infarction

• Chronic leg ulcer

• Priapism

Severe vaso-occlussive crises (painful crises)

Transfusion is given for painful crises unresponsive or refractory to conservative medical treatment. It is not given to treat the anaemia but to reduce the proportion and number of sickle cells in circulation which ameliorate pain; the flow resistance of blood with sickle cells is reduced when a cells mixture of HbA, and HbS contains less than 40% sickle cells. Clinically when vaso- occulusion occurs the level for HbS usually exceeds 50%.

When atleast 60% of RBCs are replaced by normal HbA containing cells , the progress of symptoms usually ceases. Two therapeutic methods are available for achieving this objective:

Transfusion of fresher RBCs

• Fresher RBCs from non-sickle cells donors, 10-15 ml/kg body weight is given every 12 hours until the hemoglobin levels increase to 12-13 g/dl.

• Sickle cells, because of shorten survival, will disappear rapidly from circulation Thereafter, small RBCs transfusion given every 2-3weeks will maintain the level of HbS below 40%, suppress HbS synthesis and ensure that the majority of circulating RBCs will be normal

Exchange transfusion:

■ Simple transfusion is time consuming and increases the risk of fluid overload and congestive heart failure.

■ So partial - exchange transfusion is advised as an alternative which is more rapid, and efficient method to decrease the level of HbS

■ Partial-exchange transfusion in sickle cells anaemia is indicated in

• Painful crises

• Heart disease

• Cerebrovascular accidents (stroke)

Procedures

• Partial-exchange transfusion is done by transfusing RBCs, 15 ml/kg body weight, through one anticubital vein and simultaneously withdrawing. 20 ml blood /kg body weight, by gravity from the opposite anticubital vein

• Exchange transfusion can be repeated after 24 hours.
Indications

• Transfusion is indicated in Sickle cell anaemia with fatal pneumococol infections, such as sepsis, pneumonia and meningitis in addition to antibodies.

• Exchange transfusion may reduce immoglobulins, bacteria and endotoxins.

Splenic Sequestration Crises

• In children with homozygous sickle cell anaemia and with sickle cell - B thalassemia associated with splenomegaly are at risk of sudden acute splenic sequestration crises.

• During the crises the spleen enlarges massively, Hb drops from a stable level of 7-8 g/dl to 2 g/dl or less and hypovolemic shock and death may occur.

Treatment

• Prompt whole blood transfusion will correct the hypovolemia and reverse the shock. It regresses the enlarged spleen.

• Splenectomy should be consider to prevent further crises.

Stroke

• Transfusion is given to decrease the level of HbS to 20% or less by simple RBC or exchange transfusions.

• Clinical improvement occurs in cases whose transfusions program maintains the Hb above 10g/dl and HbS level below 20-30% for 2 years.

Pregnancy

• Pregnancy with Sickle cell anaemia is also life threatening

• Chronic transfusion program during the second or third trimister may reduce placental insufficiency, lower rate of still birth or prematurity

• Results of manual partial exchange transfusion or using continuous- flow automated erythrocytapheresis are also encouraging. Level of HbA is maintained at or greater than 40%. The procedure is repeated if the level of HbA is below 20% and the hematorcrit below 25 %.

Leg Ulcers and Priapism

The painful symptoms of leg ulcers and devasting sequely of priapism may be lessened by transfusion.

THALASSEMIA

Considerable progress has been made in transfusion therapy for patients with homozygous β- thalassemia ( major thalassemia)

• Treatment has been mainly supportive and consisted of intermittent RBC transfusion to control severe anaemia. Three programs of transfusion have been advocated.

1. Transfusion program correcting severe anaemia to a safe Hb level of 7 to 9 g/dl to avoid symptoms of anaemia.

2. Hyper transfusion program to maintain Hb level between 10-12 g/dl is probably dequate. It decreases the effect of chronic anaemia and prevents abnormal growth and development.

3. Super-transfusion program wherein Hb level is maintained at 12 g/dl is designed to completely suppress hematopoiesis. If this program is started from infancy, its advantages are:

• Normal growth and development

• Normal daily function and psychological well being

• Transfusion requirement is less

• Iron over load is also less

• Pathological bone changes are less

• Less cardiomegaly and hypersplenism

Blood Products used in thalassemics

■ RBC should be 6 days old.

■ Leukocyte -reduced red cells are preferred.

• Washed red cells-Washing of red cells is a cumbersome process, and has risk of contamination.

• Frozen - thawed and washed red cells - is costly process.

• Transfusion with leukocytes reduction filters - cost effective but very efficient

Dose

• 10-20 ml /kg body weight every 3-4 weeks

• As body size increase, 1 -2 units every 3 weeks

• Pre-transfusion Hb level should be maintained 10g/dl

Iron over load

As a result of multiple transfusions , transfusion hemosiderosis develops. About 200 mgm of iron accumulates with each unit of transfused blood.

Continuous iron accumulation leads to:

• Hyperpigmentation

• Deposition of iron in heart, liver, pancreas and other endocrine glands, results in fibrosis and organ disfunction

• Serum ferintin is high.

Iron chelation in Thalassemia

• Desferrioxamine is currently the most effective iron chelating agent

• It is started as early as possible

• Daily 8 hours subcutaneous infusion of desferrioxamine 20-40 mg/kg body weight during sleep with portable battery operated infusion pump, 5 days in a week is sufficient therapy to achieve a negative iron balance.

Vitamin C

It converts ferric form of iron to the ferrous form and also facilitates mobilization of iron stores to free iron. Ferrous form of iron and the free iron get bound with desferrioxamine easily. Vitamin C upto 200 mgm/day is given along with desferrioxamine.

Splenectomy

Splenectomy should be performed when yearly transfusion requirement exceeds 200-250 ml/kg/ year. Following splencetomy all patients should be given a proplylactic antibiotic regime of penicillin (250 mgm twice daily) as well vaccinate aganist penumococcus 2-4 weeks prior splenectomy.

Neocytes

Young patients with certain hematologic disorders especially the thalassemia, often require continuous red cells therapy. Each millilitre of RBCs contains approximately 1 mg of iron, which accumulates in the tissues and causes hemosidrosis, its traditional therapy is an iron-chelating .

Another approach is to transfuse younger red cells (neocytes). The preparation of neocytes involves the selective removal of the donor’s neocytes or younger red cells found in the upper portion the layer of red cells after centrifugation or neocytapheresis.

Half-life of young red cells i.e. neocytes is 90 - 100 days while that red cells is 60 days. Therefore some workers have attempted to use neocytes to (1) reduce blood requirement (2) to increase transfusion intervals and (3) to reduce iron overload. But neocytes therapy did not get wider acceptance because the preparation of neocytes by removing the upper layer of cells after centrifugation or neocytapheresis is time consuming and expensive.

NEONATAL AND PEDIATRIC TRANSFUSION PRACTICE

Transfusion practice in neonates and infants need special understanding due to their unique physiology. Pediatric anaemia is due to the reduction of hemoglobin concentration or red cell mass below the normal values for normal infants /children.

Hemoglobin:

• Average Hb concentration of full term infants at birth is about 18.0 g/dl. All infants have a normal physiological decrease in Hb during the first 3 months.

• Average Hb concentration in normal child from 3 months to 6 years is 11.0 to 12.0 g/dl. From 7 to 13 years of age Hb is 13.0 g/dl.

• Most of the Hb in neo-born is fetal hemoglobin (Hb F) which delivers less oxygen than HbA.

• Hb level of healthy children above 14 years is the same as those of an adult.

Blood Volume :

• Blood volume of full term neonates is 85 ml/Kg/body weight, while that of premature neonates is 100 - 105 ml/kg/body weight.

Transfusion

Transfusions are given in small volumes (10-20 ml RBCs/kg body weight), increasing the risk of multiple donors exposure. Therefore, a single donor unit assigned to an individual new born and the use of sterile tube sealing device for acquisition of small volumes for transfusions over the shelf-life of the donor unit or the single unit multipack division technique can decrease the number of multiple donors exposure.

Blood should be as fresh as possible and not more than 6 days old to lesson the risk of hyperkalemia and to maximize the 2,3-diphophoglcerate (2,3-DPG) levels. Transfusions of red cells are preferred. However for limited donor exposure RBCs stored up to 42 days is acceptable unless hyperkalemia is a known problem.

Guidelines for Neonatal Red Blood Cell Transfusion

Transfuse red cells ≤ 20ml/kg body weight, not to exceed Hct. of 0.45 or Hb of 15 g/1.

1. Hct. ≤ 0.20 or Hb ≤ 7 g/dl and reticulocyte count < 4%

2. Hct. ≤ 0.25 or Hb ≤ 8 g/dl with any of the following conditions:

i) Episodes of apnea/bradycardia ≥ 10 episodes/24 hours or ≥ 2 episodes requiringbag-mask ventilation,

ii) Sustained tachycardia > 180 heart beats/min.sustained tachpynea > 80 breaths per min.

iii) Cessation of adequate weight gain x 4 days (≤ 10 g/day)

iv) Mild respiratory distress syndrome

3. Hct. ≤ 3.0 (Hb ≤ 10 g/dl with moderate respiratory distress syndrome.

4. Hct. ≤ 0.35 (Hb ≤ 12 g/dl) with severe respiratory distress syndrome or congenital heart disease associated with cyanosis or heart failure.

5. Acute blood loss with shock: blood replacement to establish adequate blood volume and Hct. 0.40.

Modified Blood/red cells is prefered

• Cytomegalovirus seronegative or leukocytes-reduced blood should be given to decrease the risk of cytomegalovirus transmission in preterm and immunodeficient infants.

• Units of blood can be irradiated to decrease the risk of graft-versus-host disease, particularly in premature neonates with suspected immunodeficiency or for neonates who are potential transplant candidates. Transfusions in a full term new born infants do not require irradiation.

• Irradiation is recommended for RBCs used in intrauterine transfusion.

RED BLOOD CELLS TRANSFUSION IN ANAEMIA
Red Blood Cells Transfusion in Acute Anaemia/Blood Loss.

The Hb concentration prior to the hemorrhage, the extent of hemorrhage, and the existence of other conditions which alter the physiologic response to acute blood loss may affect the decision to transfuse RBCs.

Patients almost always require perioperative RBCs transfusion when their Hb is less than 6 g/dl. and rarely when their Hb is greater than 10 g/dl. Between 6 and 10 g/dl Hb, transfusion requirements depend on the extent of blood loss, underlying cardiac disease, and overall clinical condition.

In general, loss of less than 15% blood voloume results in minimal symptoms; 15% to 30% tachycardia; 30% to 40% increased signs of shock, and greater than 40% in severe shock .Previously healthy patients can be treated with crystalloid alone for less than 30% blood volume loss. Patients with underlying disease may need transfusion at 30% blood loss, depending on the degree of anaemia and the nature of disease.

Red Cell Transfusion Guidelines (Excluding Neonates) - Summary
Acute blood loss:

1. Evaluate the effects of blood loss and underlying diseases.

2. Estimate and/or anticipate degree of blood loss:

Loss of blood Replacement Fluid

< 20% of blood volume None

20 - 30% of blood volume Crysralloids / Colloids

30 - 40% of blood volume Red cells & crystalloids

> 40% of blood volume Whole blood or Red cells & crystalloids

Hb Level

. >10g/dl,RBCs rarely needed

. < 6 g/dl, RBCs usually needed

. 6-10 g/dl, RBCs need depends on other factors Measure vital signs and tissue oxygenation (useful when Hb is in the range of 6-10 g/dl and extent of blood loss is unknown)

Tachycardia, hypotension can not be corrected by volume replacement alone, RBCs needed when

Pvo2 < torr, extraction ratio > 50%

Vo2 < 50% of base line

Mote - Pvo2 - oxygen tension of pulmunary arterial blood at the completion of oxygen unloading.
Vo2 - oxygen consumption

Chronic Anaemia

1. Treat with specific pharmacologic agents like vitmain B 12, folic acid, iron, recombinant human erythropoietin. if diagnosis indicates

2. Use specific strategies for sickle cell disease and thalassemia

3. Transfuse to minimize symptoms and risk of anaemia at the Hb level of 5.8 g/dl

MASSIVE BLOOD TRANSFUSION

Several definitions of massive transfusion have been proposed:

• Massive blood transfusion is usually defined as the replacement of one or more blood volume(s) within 24 hours.

• Transfusion of about ten units of whole blood each of 450 ml of blood or 20units of red cells, within 24 hours.

• Replacement of more than 50% of the blood volume in 3 hours in an adult..

Normal blood volume usually being approximately :

• In adult about 70 ml per kg body weight or 7% of the body weight

• In children about 80 ml per kg. body weight or 8% of body weight

• In neonates 85-90 ml per kg body weight or 8.5 - 9.0% of body weight.
Massive transfusion may be required due to acute hemorrhage in :

• Surgical or medical emergencies (e.g. gastro-intestinal bleeding especially from varices.)

• Cardiac and vascular surgery

• Exchange transfusion in infants

• Obstetric cases.

• In multiple trauma

• Liver transplant

The blood transfusion strategy should be to maintain blood volume and its composition with in limits that are safe with regard to haemostasis, blood oxygen-capacity, and oncotic pressure and plasma biochemistry (Table 16.1). Blood sample should be sent to the laboratory at the earliest possible opportunity for blood grouping, antibody screening, compatibility testing, as well as baseline hematology, coagulation screening, including fibrinogen estimation and biochemistryinvestigation.

Table 16.1 Safe limits of Hb and Coagulation Factors

Investigation


Target value

Hemoglobin; (Hematocrit)


l0g/dl (0.33)

Platelet count


> 50 x 109 /L

Prothrombin time


< 1.5 x control

Partial thromboplastine time


< 1.5 x control

Fibrinogen


> 0.8 g/1

Management strategy for massive transfusion

1. Restore blood volume to maintain tissue perfusion and blood pressure

2. Maintain Oxygen carrying capacity

3. Treat any surgical source of bleeding

4. Correct coagulopathy by the judicious use of

• Fresh frozen plasma

• Platelet transfusion

• Cryoprecipitate (if fibrinogen is low)

5. Prevent hypothermia

Restoration of blood volume to maintain tissue perfusion and blood pressure

Restoration of blood volume is utmost important to maintain tissue perfusion, blood pressure and hypovolemic shock, preventing tissue damage, and worsening of thrombocytopenia and coagulopathy.

Restoration of circulating volume is initially achieved by rapid infusion of crystalloid like Ringer's lactate solution and normal saline or colloids through large-bore (14 gauge or larger) peripheral cannulae. The use of albumin and non-albumin colloids versus crystalloids for volume replacement have recently been the subject of debate. The use of colloids is not recommended inthe American college of surgeons Advanced Trauma life support guidelines.

Ringer's Lactate solution is rcommended as initial therapy and normal saline is an acceptable alternative to Ringer's lactate solution. Ringer's Lactate solution contain calcium, and if it isinadvertently mixed with a unit of blood, the blood may clot in the line or the bag.

Crystalloid is infused at 3:1 ratio for every unit of blood lost. Therapy is monitored by hemodynamic response and return of tissue perfusion (measured by mental status, urine output,capillary refill and absence of acidosis).

Resucitation then proceeds by the use of blood components, depending upon the patient's response. Patients who respond to about 2000 ml of crystalloid with return of stable vital signs and tissue perfusion do not generally require blood transfusion. Patients who do not respond to this, generally have major blood loss and require emergent red cells or whole blood transfusion and further fluid replacement.

Red cell transfusion is likely to be required along with fluid replacement when 30-40% of blood volume is lost. The loss of over 40% of blood volume is life threatening and whole bloodmay also be required.

Blood loss is usually underestimated and it must be remembered that hemoglobin and haemocrit values do not fall for several hours after acute hemorrhage. Determination of whether intermediate hemoglobin concentrations justify red blood cell transfusion should be based on patient's risk factors for complications of inadequate oxygenation such as:

• Rate of blood loss

• Cardiorespiratory reserve

• Oxygen consumption

• Measured cardiological variables, such as

heart rate

arterial pressure

pulse rate

cardiac output

These signs may assist in the decision making process, but it should be emphasized that silent ischaemia may occur even in the presence of stable vital signs.

Prevention of hypothermia

Hypothermia increases the risk of disseminated intravascular coagulation and other complications and may be prevented by prewarming the resuscitation fluids, patient-warming devices such as warm air blankets and use of temperature controlled blood warmers.

Massive transfusion of 100 ml/min or 1 unit of blood every 3 minutes requires blood warming otherwise recipient may develop hypothermia and arrhythmias.

Blood bank arrangements:

The degree of urgency for transfusion should be accurately conveyed to the blood bank.

1. Routine ABO and Rh(D) grouping, antibody screening and cross-matching by saline and Coombs' technique take about 3 hours.

2. If the blood is required urgently, the time of requirement should be mentioned on the requisition form. ABO and Rh typing is done by spin tube technique and cross-matching is done by saline spin technique or LISS method.

3. In very urgent cases uncorss-matched red cells of the same group as that of the patient, after doing ABO and Rh(D) typing of the patient are supplied with the concurrence of clinicians. Subsequently the cross-matching is done by saline spin tube method or byLISS technique.

4. In extreme urgent situation it may be necessary to supply uncross -matched group O red cells if the group of the patient is not known or there is no time to do ABO and Rh(D) grouping of the recipient.

In an emergency, pre-menopausal females, whose ABO and Rh(D) blood group is not known, O Rh(D) engative red cells should be given to avoid Rh(D) sensitization and the risk of hemolytic diseases of new born in subsequent pregnancy.

O Rh(D) positive red cells can be given to Rh(D) negative males and post-menopausal females patients if they do not have Rh antibodies in their blood and Rh (D) negative

blood is not available.

In case of (3) or (4) blood is supplied with the consent of the clinicians, and "Uncross-matched Blood" is written on the compatible report and on the label on the blood bag.

Hematological Monitoring:

The investigation shown in table 16.1 should be performed when the blood loss is substantially reduced to the order of (<0.5 L/h) and after the bleeding is under control. On the basis of laboratory findings correct haemostatic abnormalities.

1. Platelet Concentrates:

Platelet concentrates are given to maintain platelet counts 50 x 109 /L or above, the minimum level required to achieve effective haemostasis when platelet function is normal.
Expert consensus argues that platelets should not be allowed to fall below the critical level of 50x 109 / litre in acutely bleeding patients. A higher target level of l00x 109/litre has been recommended for those with multiple high-energy trauma or central nervous system injury.

During cardiac bypass surgery bleeding may occur at counts of platelet higher than this, probably because of an acquired functional defect in platelets. Empirical platelet transfusion may be required when platelet function is abnormal, as is found during orafter cardiopulmonary bypass.

2. Coagulation factor deficiency is the primary cause of coagulopathy.

• Massive or large volume transfusion can result in disorders of co-agulation due to dilution of clotting factors and platelets.

• Prolongation of activated partial thromboplastin time (aPTT) and prothrombin time (PT) to 1.5 to 1.8 times of the control values is correlated with an increased risk of clinical coagulopathy and requires correction.

Fresh frozen plasma (15 ml/kg body weight) is given to correct coagulation abnormalities.

• Continued bleeding together with severely disturbed coagulation, needs more energetic therapy. Platelet concentrates, FFP or cryoprecipitate are given particularly when there is evidence of disseminated intravascular coagulopathy (DIC).
Cryoprecipitate will replace fibrinogen and factor VIII.

Infusion of FFP should be considered after one blood volume has been lost. FFP alone, if given in sufficient quality will correct fibrinogen and most coagulation factor deficiencies, but large volume may be required if fibrinogen volume remains critically low (<10 g/litre), and cryoprecipitate therapy should be considered.

Problems of Massive or large volume transfusion:

• Acidosis

During blood storage, red cells metabolism generates acids which result in reduction of its pH. Acidosis in a patient is more likely due to inadequate treatment of hypovolemiathan due to the effects of transfusion.

Usually body can neutralize this acid load from transfusion and the use of bicarbonate or other alkalizing agent is not required.

• Hyperkalemia

In stored blood there is small increase in extra cellular potassium. This rise is rarely clinical significant. As preventive measure use fresher blood preferably which is less than 7 days old.

• Citrate toxicity and hypocalcemia

Citrate toxicity is a rare problem in transfusion of large volume of whole blood. Citrate in anticoagulants binds serum calcium which reduces ionized calcium level in body.
Hypocalcemia with acidosis and hypothermia can cause reduction in cardiac output, bradycardia and arrythymias.

Most patients who undergo massive transfusion do not require calcium supplementation.
In some cases, if calcium levels become critically low, calcium gluconate or calcium chloride can be given.

• Depletion of coagulation factors and platelets : Their management has already been explained earlier.

DISSEMINATED INTRAVASCULAR COAGUALTION

Disseminated intravascular coagulation (DIC) is an acquired coagulopathy. DIC is caused by the abnormal and uncontrolled activation and consumption of coagulation proteins, fibrinogen and platelets, causing small thrombi with in the vascular systems through out the body. Free thrombi in the vascular systems are the cause of DIC . There is over production of fibrinolytic enzymes which break down the clots formed, leading to an increase in fibrin degradation products. All the coagulation factors platelets, and fibrinogen are consumed faster than they are replaced, resulting in widespread bleeding.

Causes of DIC:

■ Septicemia

■ Disseminated malignancy

■ Obstetric complications

• Premature separation of placenta


• Retained products of conception

• Retained dead fetus

• Amniotic fluid embolism



■ Trauma

■ Hemolytic transfusion reaction

■ Neonatal DIC secondary to sepsis and necrotizing entrocollitis

■ Prolonged hypoxia or hypovolemia including shock.

Symptoms:

■ Severe bleeding from many sites in the body.

■ Sudden onset of blood from bruising

■ Oozing from venipunture site.

■ Microvascular thrombi may cause organs dysfunction:

• Respiratory distress.

• Renal failure

• Jaundice

• Coma

Laboratory investigation:

DIC is characterized by;

Reduced platelet count (thromboycytopenia)

Prolonged propthrombin time (PT) - 1.5 to 1.8 times of control (normal 10-14 sec.)

Prolonged activated partial thromboplastin time aPTT -1.5 to 1.8 times of control

(normal 25-35 sec.)

Prolonged thrombin time - 1.5 times of control (normal 10±lsec)

Decreased fibrinogen concentration - < 1.0 g/L suggestive of DIC (normal 2-4 g/L)

Elevated fibrinogen degradation products (normal < l0mg/L)

Management:

Immediate and appropriate treatment or removal of the underlying condition is essential to prevent tissue ischemia and shock.

■ Identify and treat or remove the cause of DIC

■ Maintain blood volume

■ If the patient is anemic give fresher whole blood available as it contains fibrinogen and other coagulation factors.

■ Maintain hemostatic functions



• If PT and aPTT are prolonged and the patient is bleeding, give FFP (15 to 20ml /kg body wt.)

• If fibrinogen is low (< 80mg/dl), cryoprecipitate (6 to 12 units /kg body wt.) can be given.

• If the platelet is count is less than 50 x 109 /L, and the patient is bleeding, give platelet concentrates 4-6 units or one unit of platelet apheresis.

■ Exchange transfusion may be effective therapy for infants who suffer severe symptomatic DIC following birth asphyxia.

■ Intravenous Heparin: Heparin inhibits fibrin formation and may result in increase plasma fibrinogen concentration but it does not inhibit the effect of fibrin split products. Heparin is not effective in gram - negative septicemia and in some other cases, Heparin is indicated in the cases of persistent thrombosis. The role of heparin is doubtful.

In some cases heparin may be useful preceding the transfusion of FFP. The recommended does of heparin for an adult is a loading dose of 5000 units I. V. followed by 1500 units / per hour for 6-12 hours. If bleeding occurs due to heparin give protamine sulphate(heparin reversal).

Heparin is contraindicated in surgery or already actively bleeding cases.

Monitoring of the case is done by estimating:

• Prothrombin time (PT)

• Activated partial thromboplastin time (aPTT)

• Fibrinogen level

• Hb and Hct.

IRRADIATION

Since past several years the use of irradiated blood products (primalary red blood cells and platelets) has increased dramatically. It has long been known that gamma irradiation inactivates lymphocytes in blood.

Viable lymphocytes in blood can be responsible for graft-versus-host disease (GVHD) in the recipient-host. The resulting disease has serious consequences like fever, skin rashes, hepatitis, diarrhea, bone marrow suppression and infection, all of them can progress to mortality.

Recipients at high-risk of GVHD are those who are severely immunsuppressed or immunocompromised, such as bone marrow transplant patients, neonates who have received intrauterine transfusion and exchange transfusion, and persons who are recipient of blood fromfirst-degree relatives.

Indications for Transfusion of Irradiated Blood

Generally accepted indications :

• Bone marrow transplant or Peripheral blood stem cells recipients

• Neonates intrauterine transfusion recipients

• Neonatal exchange transfusion recipients

• Premature new born s (less than 1200g)

• Immunocompromised or immunosuppressed recipients

• Recipients of first-degree relative donors blood

• Recipients of HLA-selected platelets or platelets known to be HLA homozygous

• Patients with Hodgkin's disease or non-Hodgkins's lymphoma

• Granulocytes transfusion recipients

Indications under review

• Patients with hematological malignancies such as acute leukemia

• Term newborns on extracorporeal membrane oxy-generators

• Organ transplant recipients

• Patients receiving crossmatched compatible platelets

No established indications in:

• Patients with AIDS or HIV infection

• Most patients receiving chemotherapy

• Patients with aplastic anaemia not receiving immunosuppressive therapy

• Full term neonates without other risks

Mostly either cesium-137 (137 Cs) or Cobalt-60 ( 60 Co ) is used as the source of gamma rays. The usual dose is 25 Gray (Gy) to 35 Gy (1 Gray=100 rads), This dosage inactivates 85 to 95% of lymphocytes in the blood components without any adverse effect on other cellular components (red cells, platelets and granulocytes) of the blood,

The shelf-life of irradiated blood (RBCs) is 28 days from the date of irradiation or original expiration date of unit, whichever comes first. Studies have shown that irradiation causes a modest leakage of potassium, reducing their survival after transfusion. Therefore irradiated red blood cells are given in a reduced storage time. Some physicians believe that irradiated red blood cells for exchange transfusion should be washed to remove potassium, this step is not regarded as routinely necessary and should be done only in selected problem patients - for example, neonates receiving exchange transfusion with pre-existing hyperkalemia or renal failure. Other concerns
about the effect of irradiation remain theoretical.

Products such as FFP and cryoprecipitate do not require irradiation because they do not carry viable lymphocytes.

Irradiation should not be performed on bone marrow or peripheral blood progenitor cells prior to their infusion.

TRANSFUSION IN OPEN HEART SURGERY

Transfusion of blood and its components is an important supportive therapy for patients undergoing open heart surgery requiring cardio-pulmonary bypass. The demand of blood and its components varies with each patient and depends upon:

■ The patients peri-operative hematological status, such as anaemia, thrombocytopenia, or coagulation disorder.

■ Priming of pump-oxygenators with electrolytes or blood depends upon the condition of the patient and personal preference of surgeons and anesthetist. Generally priming of pump-oxygenators is now done with electrolyte solutions (e.g. Ringer's lactate or Hartman's solution). However, it may be necessary to prime pump-oxygenator with blood in exceptional circumctances e. g. in patients with sever renal failure or in neonates and small children

Cardiac- vascular

Aortic aneurism resection


6

Aortic bypass with graft


4

Coronary artery bypass, adult


4(2)

Coronary artery bypass, children


2

Carotid endarterectomy


2

Femoral-popliteal bypass with graft


4

Urology

Bladder, transurethral resection


T&S

Nephrectomy radical


3

Prostectomy, perineal


2

Prostectomy, transurethral


T&S

Renal transplant


2(2)

Obstretic & Gynecology

Abortion, therapeutic


T&S

Cesarean section


T&S

D&C


T&S

Hystrectomy, abdominal/vaginal


T&S

Hystrectomy, radical


3

Labour/delivery, uncomplicated


T&S

Laproscopy


T&S

Tubal ligation


T&S

Tuboplasty


T&S

Vaginal repair


1

Vesico-vaginal or recto-vaginal-
fistula repair


T&S

Note: Numbers may vary with institutional practice T&S =Type and antibody screening

GENERAL TRANSFUSION PRACTICES

Filters for blood components

Generally two types of filters are used for blood transfusion: a 170-mm filter or a leukocyte- deletion filter. The 170-mm filter removes clots or cellular debris develop during storage from any blood products and is used in routine administration sets. A standard blood administration filter must be used for transfusion of all blood components.

Leukocyte-depletion filters are designed to remove white blood cells (WBCs). This filter is designed to prevent febrile nonhemolytic transfusion reactions, to prevent or delay the development of HLA antibodies, and to reduce the risk of CMV. Filtration in the blood bank seperatory. rather than at the bedside, is more reliable and better for reduction of leukocytes.

Administration of blood Products

A physician or a qualified nurse should administer blood and blood products.

2. Before starting transfusion, patient identity check should be done at the patient's bed side:

■ From the records of the patients

■ Ask the patient himself/herself the name, if he patient is unconscious identify the patient with wristband.

3. Check the following details on the compatibility report, and the compatibility label attached to the blood product:

■ Patient's name

■ Admission no.

■ Blood group

■ Donation no.

■ Collection and expiry dates

There should be no discrepancy

4. Check the blood pack:

■ Any sign of damage or leakage of the blood/its product.

■ Collection and expiry date on blood pack

■ Hemolysis in the plasma

■ Sign of contamination, such as change of colour in the red cells, which often lookpurple/black when contaminated.

■ Any clot

If the pack appear abnormal in any way, the unit must not be transfused and the blood bank must be informed immediately.

Time limits for infusion
Whole blood or red cells

1. The administration of whole blood or red cells should be started with in 30 minutes of issuing from the blood bank. If it is not required for transfusion it should be returnedimmediately to the blood bank with reasons.

After 30 minutes of issuing it from the blood bank, it is not taken back in the blood bank.

2. Transfusion should be completed within 4 hours of starting the transfusion. These time limits have been determined for temperate climates where temperature in hospital building are generally between 22°Cand 25°C. If the ambient (room) temperature is very high, shorter'out-of-refrigerator times' should be used.

3. Change the blood administration set after 12 hours, if the patient requires ongoing transfusionsupport.

Platelet Concentrates

1. Platelet concentrate should be administered as soon as they have been received.

2. Infusion should be completed with in about 15-20 minutes.

3. Should be kept at room temperature 22°C to 24°C. Do not put in refrigerator.

4. Should be administered with transfusion set with filter

5. Platelets once issued are not taken back in the blood bank.

Fresh Frozen Plasma

1. FFP should be infused as soon as possible after thawing to avoid loss of labile clottingfactors or thawed plasma stored at 2-4oC should be used within 12 hours.

2. In adult, I unit of plasma should generally be infused with in about 15-20 minutes.

3. Thawed or partially thawed plasma is not taken back in the blood bank.

Disposable equipment for transfusion

1. Must be sterile and must never be reused.

2. Whole blood, red cells, platelet concentrate, plasma and cryoprecipitate are infused though sterile blood administration set containing 170-200 micron filter.

3. Use flexible plastic cannulae, if possible, as they are safer and preserve veins.

4. Leukocyte-depleting filters are expensive but they are effective in reducing the fibrile non- hemolytic transfuion reactions and the development of anti-leukocyte antibodies in multiple-iransfused patients.

Monitoring the transfused patients

A physician or a qualified and trained nurse should administer blood and blood products

1. For each unit of blood transfused, monitor the patient at the following stages:

■ Before starting the transfusion

■ As soon as the transfusion is started

■ For 15 minutes after starting transfusion

■ At least every hour during transfusion

■ On completion of the transfusion

■ 4 hours after completing the transfusion

2. At each of these stages, record the following information :

■ Patient's general appearance

■ Temperature

■ Blood pressure

■ Respiratory rate

■ Sign of any adverse reaction - these signs are fever with back pain (acute hemolytic transfusion reaction), anaphylaxis, hives or pruritis (urticaria! reaction). Congestive heartfailure (volume over load) and fever alone (febrile non-hemolytic transfusion reaction).

3. Monitor the patient carefully during the first 15 minutes of the transfusion to detect any early signs and symptoms of adverse effects. The adverse effects of transfusion are usually dose- related. therefore, every slow transfuion rates are used at the start, 15 to 50 ml are given during the first 15 minutes. Once the transfusion is progressing satisfactorily, the infusion rate can be increased so that the product is transfused within a reasonable time depending on the clinical condition of the patient.

4. Only isotonic (0.9 percent) saline or 5% albumin should be used to dilute blood components or can be infused with the transfusion set used for blood products transfusion, because other I.V. solutions like dextrose solutions such as 5% destrose in distilled water may damage the red cells and cause hemolysis or calcium containing solutions such as lactated Ringer's solution initiate coagulation in the infusion set. In addition, many drugs will cause hemolysis if injected through the blood infusion set.

Blood Warming

Routine warming of blood is not needed; infusing 2-4 units of refrigrated blood over several hours causes no harm. Patients who may need benefit from warmed blood include:
Adults receiving multiple transfuin at rates greater than 50 ml/kg/h

2. Children receiving transfusion at rates greater than 15 ml/kg/hr.

3. Infants receiving exchange transfusion

4. Patients receiving rapid transfusion through central venous catheter

5. Patients with cold agglutinins

The rapid and massive transfusion of cold blood (2-6oC) is associated with an increased risk of ventricular fibrillation and cardiac arrest.

Blood warming procedure

■ It is carried our using approved blood warmer devices, such as the Level 1 Hot line.

■ Blood is not warmed above 37°C. Excessive warming can cause hemolysis and endanger the patient. If blood warmers are being used they should be tested before use to ensure that the temperature regulators are operating properly. The temperature of the blood should also be monitored.

■ Do not immerse whole unit of blood or red cells in a water bath, or run blood through an extended tubing or coil in water bath.

Pressure Devices for rapid infusion

Pressure devices or pumps are some times used to achieve very fast flow rates in rapid transfusion:

1. Transfusion with 18 gauge needle or cannula is recommended

2. A device of a pressure bag with a sphygmomanometer is required in emergency situation when blood has to be transfused rapidly (about 5 minutes per unit). The bag should be inflated to about 200 mm Hg till blood flow through the drip chamber is continuous. Pressure of300 mm Hg may cause the red cells to hemolyse and the blood bag seams to split.

Transfusion Reactions

Any adverse effect caused by transfusion may be considered a transfusion reaction. Some are mild, others are life-threatening. All reactions should be documented and reported.

Guidelines for the recognition of transfusion reactions are :
Category 1 - Mild reaction



Sign


Symptoms


Possible cause

* Localized



* Itching



* Hypersensitivity

- Urticaria





(mild)

- Rashes







Category 2 - Moderately Severe



Sign


Symptoms


Possible cause

* Rushing



* Anxiety
* Hypersensitivity (Moderately severe)
* Urticaria
* Pruritus (itching)
* Febrile non-haemolytic
* Rigor
* Palpitations
transfusion reations:
* Fever
* Mild dyspnoea
- Antibodies to while blood cells,

* Restlessness

* Headache
platelets.

* Tachycardia
- Antibodies to proteins, including IgA
* Possible contamination with
pyrogens and/or bacteria.

Category 3 - Life-Threatening

Sign
Symptoms
Possible Cause

* Rigors
* Anxiety
* Acute intravascular haemolysis
* Fever
* Chest pain
* Bacterial contamination and
* Restlessness
* Pain near infusion site
septic shock.
* - Hypotension (fall of

* Respiratory
* Fluid overload

> 20% in systolic BP)


distress/shortness
* Anaphylaxis.
* Tachycardia (rise of breath.
* Transfusion - associated ,20% in heart rate)
* Loin/back pain lung injury.
* Haemoglobinuria
* Headache
( red urine)
* Dyspnoea
> Unexplained bleeding
* (DIC)

Note: If an acute transfusion reaction occurs, first check the blood pack labels and the patient'sidentity. If there is any discrepancy, stop the transfusion immediately and consult the blood bank.In an unconscious or anaesthetized patient, hypotension and uncontrolled bleeding may be the only signs of an incompatible transfusion.

In a conscious patient undergoing a severe haemolytic transfusion reaction, signs and symptoms may appear quickly - within minutes of infusing only 5-10 ml of blood. Close observation at the start of the infusion of each unit is essential.

Management in Adverse Transfusion Reactions

Category I: Mild

1. Slow the transfusion.

2. Administer antihistamine IM (e.g. Chlorpheniramine 0.01 mg/kg or equivalent)

3. If no clinical improvement within 30 minutes or if signs and symptoms worsen, treat as

Category 2.

Category 2: Moderately Severe.

1. Stop the transfusion, replace the giving set and keep I.V. line open with normal saline.

2. Notify the doctor responsible for the patient and blood bank immediately.

3. Send blood unit with giving set, fresh blood samples (1 clotted and 1 in EDTA) from vein opposite infusion site with appropriate reaction form to blood bank for investigations.

4. Administer antihistamine IM (e.g. chlorpheniramine 0.01 mg/kg or equivalent) and oral or rectal antipyretic (eg. paracetamole 10 gm/kg; 500 mg - lg in adults). Avoid aspirin in thrombocytopenic patients.

5. Give I.V. corticosteroids and bronchodilators if there are anaphylactoid features (eg.broneospasm. stridor).

6. Collect urine for next 24 hrs for evidence of haemolysis and sent to laboratory.

7. In clinical imporvement, restart transfusion slowly with new blood unit if required and observe carefully.

8. If no clinical improvement with in 15 mintes or if signs and symptoms worsen, treat as Category 3.

Category : 3 Life-threatening

1. Stop the transfusion, replace the giving -set and keep I.V. line open with normal saline.

2. Infuse normal saline (initially 20-30 ml/kg) to maintain systolic BP.

3. Maintain airway and give high flow oxygen by mask.

4. Give adrenaline (as 1:1000 solution) 0.01 mg/kg body weight by intramuscular injection in severe allergic reaction.

5. Give I.V. corticosteroids and bronchodilators if there are anaphylactoid features (e.g. broncospasm, stridor)

6. Give diuretic: e.g. frusemide 1 mg/kg I.V. or equivalent (initially 40 mgm i.v., upto 250 mgm over 4 hours)

7. Notify the doctor responsible for the patient and the blood bank immediately.

8. Send blood unit with giving-set, fresh blood samples (1 clotted and 1 in EDTA) form vein opposite to the infusion site, with appropriate reaction form to blood bank for investigation.

9. Check a fresh urine specimen visually for signs of hemoglobinuria (red ro pink urine).

10. Start at 24 hour urine collection and fluid balance chart and record all intake and output. Maintain fluid balance.

11. Assess for bleeding form puncture sites or wounds. If there is clinical or laboratory evidence of DIC, give platelets (adult 5-6 units) and either cryoprecipitate (adult 12 units) or fresh frozen plasma (adult: 3 units)

12. Reassess. If hypotension persists:

■ Give further saline 20-30 ml/kg.

■ Give Inotrope (Dopamine, IV infusion, 1 gm/kg/min.)

13. If urine output falling or laboratory evidence of acute renal fialure (rising K+, urea, creatinine):

■ Maintain fluid balance accurately

■ Give further frusemide.

■ Consider dopamine infusion.

■ Seek expert help: the patient may need renal dialysis.

13. If bacteraemia is suspected (rigors, fever, collapse, no evidence of a haemolytic reaction), start broad spectrum antibiotics I.V. to cover pseudomonas and gram positives organisms.

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