Safe & effective blood transfusion
Blood is a precious resource and should not be wasted. It is a two-edged tool that needs to be used judiciously. Blood can be life saving in many circumstances but a grave threat to life when used carelessly. The rational use of blood involves using the right product at the right dose at the right time for the right reasons. It makes for greater economy, greater effectiveness and last, but not the least, greater safety. Let us consider these one by one.
RATIONAL USE OF BLOOD REDUCES WASTE
There is a great shortage of blood in India. About 2 to 3 million units are donated annually. This works out to 2 to 3 donations per thousand people per year. Compare this to an average of 52 per 1000 in developed countries and 10 per 1000 in middle-income countries. If India, with a billion people wanted to achieve the levels of at least the middle income nations, we would need 10 million donations a year. There is currently a shortage of about 7 to 8 million units annually.
We have profligacy on the one hand and penny-pinching on the other. The result of this paradox is the denial of the correct transfusion treatment to those that need it and the administration of transfusion (often in homeopathic doses) to those that don’t. Rational blood usage advocates that effective use be made of available resources by transfusing only when necessary, giving only what is needed and not otherwise. Two examples will illustrate what I mean.
RhD negative blood is often in short supply. RhD-negative females below the age of 40years must be given RhD negative red blood cells to avoid the risk of haemolytic disease of the newborn in the future. RhD negative blood is often not available when required by such patients because it has been used up for cases when it may have been possible (though not ideal) to use RhD positive blood. If, for instance, a 60 years old, RhD negative man is given RhD positive blood following an accident it would make little or no difference to him. What it would do is to conserve scarce RhD negative blood that might be needed the next day for a ten-year-old RhD negative girl.
Platelet concentrate is another component which is often hard to come by. Consider another situation. If platelets are given to a patient merely because his platelet count is low, say, 50 x 109 / litre, are we doing him a favour? Not necessarily. What we are doing is exhausting our stock of platelets which might well be needed urgently for a bleeding patient with a count of 5 x 109 / litre.
Rational blood usage also requires that blood components and products be used in preference to whole blood. Separation of components from donated blood and storing them under conditions appropriate for the component concerned makes utilisation of scarce resources more efficient.
RATIONAL USE OF BLOOD COMPONENTS INCREASES EFFECTIVENESS
Transfusion must be undertaken with a purpose. If anything worthwhile is to be achieved, the purpose must be clear and the ‘purpose’ must have a direct relation to the patient’s well being. For instance, an old lady may not thank you for raising her Haemoglobin from 10g / dl to 14g / dl but thanks could well be forthcoming if you made her less breathless by raising her Haemoglobin from 7g / dl to 9g / dl.
Rational blood usage entails using the right product at the right dose at right time. Often timely administration obviates the need for further doses by nipping the problem in the bud. The best example of this is in Haemophilia. These patients often have spontaneous haemarthroses. In the early stages there is usually nothing abnormal to find, though the patient may be aware of a ‘sensation’ in the joint. If a sufficient dose of Factor VIII is given at this stage, the haemarthrosis may quickly resolve – often just the one dose is sufficient. If treatment is delayed or if a sub-optimal dose is given, the haemarthrosis may worsen and then treatment may need to be continued for many days at great cost and inconvenience to the patient.
Thalassaemia is another condition where rational transfusion therapy contributes to patient well being. Hyper-transfusion regimens reduce ineffective erythropoiesis and haemolysis thereby reducing iron absorption from the gut. Iron overload is a serious and common problem in thalassaemics. In addition, regular transfusions permit optimal growth and development. Under-transfused children not only have retarded growth but also suffer from iron overload.
Knowledge of what the various blood components contain and how much of these they contain is obviously essential. Sometimes one hears (in this day and age!), of doctors requesting whole blood for the white cells or the platelets that they purportedly have. The fact is that whole blood which has been stored for even a short while has no white cells or platelets to speak of. Similarly, if one knew that cryo-supernatant plasma contained all factors other than VIII, XIII, Von Willebrand factor and fibrinogen, one would have no hesitation in using it in a case of vitamin K deficiency.
RATIONAL USE OF BLOOD ENHANCES SAFETY
Despite constantly improving transfusion safety every transfusion carries risks. These could be microbiological or non-microbiological. Even when the intended transfusion is perfectly compatible and microbiologically pure, the process of transfusion exposes the patient to unexpected risks such as the wrong unit of blood being transfused. Some risks, such as HIV transmission are potentially serious but fortunately rare. Others, such as febrile non-haemolytic transfusion reactions (FNHTR) are more common but less serious. All are unnecessary. A definite need does not mean that the risks are eliminated. What does happen is that when transfusions need to be used, the benefits outweigh the risks. So, transfuse only when the benefits are greater than the risks.
We have considered the benefits of rational blood usage. In the next part we will discuss the practicalities of rational blood transfusion. These are outlined below in the form of step-wise questions that one should attempt to answer whenever transfusion therapy is contemplated.
Q1 WHAT IS THE PROBLEM?
Q2 IS TRANSFUSION NECESSARY?
Q3 ARE ALTERNATIVES TO TRANSFUSION AVAILABLE?
Q4 WHAT EXACTLY DOES THE PATIENT NEED?
Q5 ARE THERE ANY SPECIAL NEEDS?
The answers to these questions come from clearly understanding the problem. Failure to do so may mean either unnecessary transfusion or giving the wrong component or product. Deciding what is wrong may be simple or may require special tests and the opinion of other specialists. For example, post-operative bleeding is quite common. This may be due to DIC in which case FFP would certainly be indicated. If however, bleeding were due to a leaking vessel then, no amount of FFP would be able to stop the bleeding. The leak would need to be identified and stopped. Similarly, breathlessness is not always due to anaemia. It may be because of heart or lung disease in which case red cell transfusions may be unnecessary or even contraindicated.
An exact diagnosis (or at least a good approximation) is essential. The two most common inherited coagulation factor deficiencies, Haemophilia A (FVIII deficiency) and Haemophilia B (FIX deficiency) present in identical ways. Without a definite diagnosis, it is hard to decide what is the best component or product to use. This is because FVIII and FIX are fractionated separately. FVIII is concentrated in the cryoprecipitate from fresh frozen plasma while FIX remains in the cryosupernatant.
Alternatives to transfusion must be considered in the early stages. These could be non-interventional or interventional. Non-interventional alternatives are usually simple but effective remedies such as advising bed rest to a person with anaemia or the avoidance of trauma to a person with thrombocytopenia! Interventional alternatives to transfusion range from the mundane, such as supplemental oxygen for anaemia or splenectomy for auto-immune haemolytic anaemia, to relative exotics such as Desmopressin for mild Haemophilia A or recombinant G-CSF for neutropenia. What is common to all of these is that they avoid all the risks of transfusion though they have their problems and may not be applicable in every case.
Autologous transfusions, an alternative to the standard allogeneic transfusion, may be possible in some categories of patients – example, for planned surgery in relatively fit patients when at least 2 but no more than 4 or 5 units of red cells are required. Autologous transfusions avoid the immunological and infectious risks of allogeneic transfusion.
When considering what the patient needs, it is also well to remember that some patients may require special products such as irradiated packed red blood cells or leukodepleted platelets. These are not commonly available in India at present but it does no harm to keep them in mind and to check their availability from time to time.
Q6 WHAT BLOOD COMPONENTS AND PRODUCTS ARE AVAILABLE FOR USE?
Q7 WHAT DO THESE COMPONENTS AND PRODUCTS CONTAIN?
Q8 WHAT ARE THEIR SPECIAL CHARACTERISTICS?
Rational prescribing is obviously impossible without knowing the answers to these three questions. The answer to the first question will vary from place to place and from patient to patient. For instance, If both FVIII concentrate and cryoprecipitate were available, the substance chosen to treat a haemophiliac would depend, at least partly, on what he could afford. On the other hand if FVIII concentrate were not available, the choice would be limited to cryoprecipitate.
Knowing what the different sorts of blood products contain, and equally importantly, what they do not contain will determine what needs to be used in a given situation. Table (1) below deals with this important aspect. Note that granulocyte transfusions are not often used. Neutropenic patients are treated with either prophylactic antibiotics or with colony stimulating factors such as G-CSF.
|Whole blood||RBC, non-viable platelets.& Neutrophils, viable lymphocytes & plasma||Viable platelets. & neutrophils, some coagulation factors.||Massive blood loss when both volume & O2carrying capacity have to be replaced||All complications of transfusion- infectious and non-infectious.||Rare indications; Equivalent to crystalloids plus packed RBCs.|
|Packed RBC||As above but less plasma.||As above.||To restore O2carrying capacity when volume loss is not great and when volume overload has to be avoided.||As above.||Reduces waste, Plasma less, so minor incompatibility less of a problem.|
|Washed RBC||As above but even less plasma||As above||RBC transfusion in IgA deficiency? In PNH & for repeated allergic reactions||As above.||Expensive and time consuming. 1st choice for IgA deficiency Pack is breached during preparation – so, needs to be used ASAP.|
|Platelet concentrate (single donor)||Platelets, non-viable neutrophils, viable lymphocytes, some plasma||RBC,viable neutrophils, coagulation factors.||Symptomatic thrombocytopenia or platelet function defect. Prophylactic when platelets are<10 x10 a/l or to cover surgery||As above but not those due to RBC unless RBC present in significant amounts||Shelf life 5 days|
|Leuko-depleted cellular products||RBC or platelets, viable lymphocytes.||Neutrophils and monocytes||Prevention of HLA alloimmunization, CMV transmission and febrile non-haemolytic tx. reactions||As for RBC or platelets other than those at left.||Leuko-depletion can be done in several ways. If 3rd generation filter used, residual neutrophils less than 5×106 / unit. Pre-storage filtration prevents formation of cytokines – febrile non- haemolytic reactions are avoided.|
|Irradiated cellular products||RBC or platelets, non-viable WBC||Viable lymphocytes||For immuno-compromised patients to prevent tranfusion associated GvHD. Also for tx. from close relatives||As for RBC or platelets but not A-GvHD||Irradiation facilities required|
|Single donor /HLA-matched cellular products||As RBC or platelets||Allo-reactive lymphocytes||Prevention of alloimmunization when multiple tx. envisaged. Treatment of refractoriness to platelet transfusion.||As for RBC or platelets but risk of alloimmunization less.||Difficult to obtain.|
|Fresh frozen plasma||All coagulation and natural anticoagulant factors in the same concentration as in the original donor plasma.||Cells||Coagulation factor replacement in inherited/acquired deficiency;replacement of natural anticoagulants in inherited / acquired thrombophilias.||As above but not those related to cells||Concentration of factors low relative to need. May be suitable for acquired deficiency and someinherited deficiencies. Use for other than coagulation factor deficiency a misuse.|
|Cryo-precipitate||F VIII, v WF, Fibrinogen (F1), F XIII and Fibronectin||Cells and factors XII, XI, IX,VII, X, V, II||Inherited and acquired deficiency of FVIII, XIII, fibrinogen and VW factor.||As above||Low concentration of FVIII means large volumes need to be given. FVIII concentrate preferred. Suitable for F XIII deficiency.|
|Cryo-supernatant plasma||Factors II, V, VII, IX, X, XI and XII||Cells and F VIII, vWF, FXIII and fibrinogen||Inherited and acquired deficiency of factors II, V,VII, IX, X, XI, XII||As above||Low concentration relative to need. Factor concentrates preferable esp. for inherited deficiency.|
|Plasma||Factors I, II, VII, IX, X and XII||Cells and factors V and VIII.||Inherited and acquired deficiency of factors I, II, VII, IX, X, XI, XII||As above||Low conc. relative to need. Factor concentrates preferable esp. for inherited deficiency.|
|F VIII concentrate||F VIII||Cells and all the other factors.||Inherited and acquired deficiency of F VIII||As above. No disease transmission risks with recombinant F VIII. Immuno-suppression with very pure FVIII||Product of choice for the uses mentioned.Expensive.|
|F IX concentrate||Factors IX, VII, X and II||As above.||Inherited and acquired deficiency of factors IX, VII, X and II||Disease transmission & thrombosis.||Product of choice for F IX deficiency. Useful in vit. K deficiency. Expensive.|
|Other factor concentrates(E.g., F VII or X conc. or ATIII conc.)||The relevant clotting or natural anticoagulant factors||Cells and other factors||Inherited and acquired deficiencies of the relevant factors.||Disease transmission – but not with recombinant products||Expensive|
|Albumin||Albumin||Cells and other proteins||Hypo-albuminaemia, diuretic-esistant oedema if protein is low||Raises plasma oncotic pressure.||Expensive|
|IV immunoglobulin||Immunoglobulins||As above||Inherited or acquired hypogammaglobulinaemia. ITP and autoimmune haemolytic anaemia, others||Disease transmission, anaphylactic reactions, positive direct Coomb’s test||Expensive|
Q.9 HOW MUCH OF THE COMPONENT OR PRODUCT NEEDS TO BE GIVEN?
Q.10 WHEN TO GIVE, HOW OFTEN TO GIVE AND WHEN TO STOP?
Q.11 WHAT BLOOD GROUPS TO CHOOSE?
The answer to the first of these questions comes from an understanding of:
- the volume of dilution or distribution.
- the minimum level required to achieve the desired end and thus the rise required in the patient.
- the recovery of the particular cell or substance in the body.
- the amount of the cell or substance contained in each unit of the product or component.
The volume of dilution is the total blood volume (70 ml per kg body weight) for cells and the plasma volume (40 ml per kg body weight) for other substances such as coagulation factors. The minimum therapeutic levels required vary between cells, from substance to substance and on the particular circumstances of the patient. For example, a platelet count of as little as 10 x 109 per litre is adequate to prevent spontaneous haemorrhage, but at least 100 x 109per litre is required if surgery is being performed. Similarly, with coagulation factors, what is sufficient under normal circumstances may be quite inadequate after trauma or surgery.
The actual level achieved in the patient depends not only on the dose administered and the volume of dilution but also on the percentage in vivo recovery. Obviously, the higher the recovery, the higher the levels achieved. Finally, to calculate the number of ‘units’ required, one needs to know the amount of cells or factor per ‘unit’ of the transfusion. In general terms then, the number of ‘units’ to be transfused is calculated as follows:
‘units’ required = volume of dilution (litres) x rise reqd. / litre x reciprocal of % recovery
amount of the substance per ‘unit’
Example: How many packed RBC units are needed to raise the haemoglobin level of a 60kg patient from 60g / litre to 100 g / litre?
- Volume of dilution is = blood vol. = 60kg x 70ml = 4200ml = 4.2litres
- Rise required per litre = 100g / litre – 60 g / litre = 40 g
- Recovery = c.80%
- Amount of Hb per unit of packed RBC (assuming av. donor Hb is 140g / litre and the av. donation volume is 0.4 litre) = 140 x 0.4 = 56g
- So, units reqd. = 4.2 x 40 x 100 = 3.7 units, or say, 4 units of packed RBC
- Volume of dilution = plasma vol. = 30kg x 40 ml = 1200ml = 1.2 litre
- Rise reqd. per litre = 1u / ml = 1000u / litre
- Recovery = 70%
- Units of FVIII per bag of cryoprecipitate = c.100 units
- So, no. of bags of cryo. reqd. = 1.2 x 1000 x 100 = c.17 bags of cryoprecipitate.
100 x 70
Of course, these calculations don’t have to be performed every time a transfusion is necessary, but it still helps to know. For general use, there are some rules of thumb, which work well with ‘average’ people. For example, one unit of packed RBC is needed for a 1g / dl (10g / litre) rise in haemoglobin; platelets are usually required in a dose of one unit of random donor platelets per kg body weight, etc. A pragmatic approach, taking into account the patient’s condition is essential. Post-transfusion levels are commonly checked, but ‘levels’ are notoriously unreliable and should only be used as a rough guide.
The question of when to give, how often to give and when to stop depend largely on the clinical condition. Particularly in the case of coagulation factors, how often to give is determined by the half-life of the factor. Factor XIII which has a long half-life (7-10 days) may need to be given only once a week or so. F IX (half-life 18-24 hrs) needs to be given once a day, F VIII (half-life 8-12 hrs), twice a day and FVII, with a very short half-life (3-4hrs), several times a day.
The blood group of the component is the final consideration. This is a contentious issue. Some doctors insist on having nothing but the patient’s own blood group. While this is certainly the counsel of perfection, it is really not always essential. Living as we do in a less than perfect world, group-specific blood is sometimes not available. When this happens, group-compatible rather than group-specific components may be used.
What groups are compatible with the patient’s blood group depends on whether RBC (which contains little plasma) or mainly plasma containing components (such as platelets or FFP) is going to be used. The main factors in deciding likely compatibility are the following. In the case of RBC transfusions, are there likely to be any antibodies in the recipient’s plasma capable of destroying transfused RBC, or, in the case of plasma transfusions, are there likely to be any antibodies in the donor plasma capable of destroying recipient RBC? Table (2) below should help to decide what groups to choose.
1. Some O group individuals may have high titre anti-A or anti-B but this is not a great problem with plasma- reduced RBC
2. RhD positive RBC must not be given to RhD negative females less than 45 years except in a dire emergency. If this is done, an adequate dose of anti-D should be given. 3. A small minority of A2 and A2B individuals may have clinically significant anti-A1
One other issue needs to be discussed – that of the directed donor. Directed donors are friends or relatives of the patient. Directed donations are unsafe because they are not voluntary in the strict sense of the term. There is usually an obligation to donate and the pressure may be sufficient to cause some directed donors to conceal information that a truly voluntary donor would not hesitate to reveal. The importance of pre-donation information in preventing the transmission of infections in the early stages or in the window period cannot be overstated. There is another problem, with transfusions from close relatives – transfusion- associated graft versus host disease, especially if donor and recipient happen to be HLA haplo-identical. This is a serious but preventable condition. Transfusions from close relatives must be allowed only in strictly limited circumstances.
The mantra of rational blood usage needs to be preached as well as practised by all those deal with blood. Only then, can the transfusion demand of the next century be met.
Dr.K.G.Badami MD, MRC (Path)
Email :[email protected]