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Indian Journal of Transfusion Medicine
  Indian Journal of Transfusion Medicine Indian Journal of Transfusion Medicine

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Rationale Use of Blood Components

                                                                                            Rajendra Chaudhary

                                                                                                                                                 MD, DNB

 Introduction

Blood transfusion remains the most commonly performed tissue transplant and is life saving in situations such as trauma, surgical blood loss, and severe anemia. The provision of transfusion services by hospitals, however, remains under pressure by concerns over safety, costs, and blood availability. There is little doubt that despite the best efforts of the transfusion services, a definite risk of complications remains with blood transfusion. The incidence of some of these, including transmission of infective agents and immunological reactions because of human error or undetected incompatibility, has been documented with a certain degree of precision. However, the clinical impact of immunosuppression, potentially leading to infection, cancer recurrence, and poor postoperative outcome, is difficult to quantify.

In the last decade, new procedures have been implemented in advanced countries to guarantee the safety of stored blood. These include routine nucleic acid testing for transfusion transmitted infections and universal leukodepletion. However, as a consequence, the cost of stored blood has risen dramatically and its inappropriate use will result in a progressively greater wastage of resources. Strict donor selection and a progressively ageing population already limit the number of potential blood donors. There is growing concern on the potential impact of transmissible disease screening on the number of volunteers willing to donate blood and the handling of those testing positive because shortages in supply may influence red cell use independently of clinical indications for transfusion. Therefore, hospitals have been forced to elaborate strategies to ensure appropriate use of blood and components.

Component therapy:

The goal of transfusion therapy is to correct an abnormality that will not respond to other modes of treatment of to provide a patient with life support when safer alternatives are not possible. Transfusion can be used in two ways: 1] the entire donor unit is administered (whole blood) or 2] a specific part of the donor unit is selected (component). In both cases, the needs of the patient will be met. However, if whole unit of blood is used then many of the patients will receive extraneous material, much of which is needed by other patients and some of which unnecessarily increase the risk of transfusion. If only the component or specific part of the donor unit is used then the patient will get maximum benefit from the transfusion at a minimum risk.

Blood can be separated into a variety of blood components for different clinical conditions. Introduction and subsequent widespread use of plastic blood collection bags with attached satellite containers made it feasible to separate one or more components from each donor blood. With these system, it is possible to maintain sterility while one or more manipulations, such as centrifugation, freezing, thawing etc, are done to obtain the desired cellular elements or fraction of the plasma. However, many countries have no facilities for component separation and whole blood remains the most widely used product in most developing countries.

Definitions

Definitions of the different blood products are given as under.

 Whole blood It is un-separated blood collected into an approved container containing an anticoagulant preservative solution.

 Blood product Any therapeutic substance prepared from human blood

 Blood component A constituent of blood, separated from whole blood, such as red cells, plasma, platelets, cryoprecipitate.

 Plasma derivative Human plasma proteins prepared under pharmaceutical manufacturing conditions, such as Albumin, Immunoglobulins, coagulation factor concentrates. Following table shows various components and plasma derivatives that are available for clinical use

 

Blood components Plasma derivatives

Oxygen carrying

Coagulation factor

components

concentrates

red cell components
leuko-poor red cells
frozen thawed red cell

f VIII concentrate
f IX complex

Platelet products

Oncotic agents

platelet rich plasma
platelet concentrate

Albumin
Plasma protein fractions

Plasma products

Immuneserum globulins

fresh frozen plasma

cryoprecipitate

stored plasma

Rh immunoglobulin

hepatitis B immunoglobulin

varicella zoster immunoglobulin

Overview of blood components:

Packed red blood cells:

Packed red cells are prepared from whole blood unit after centrifugation. The packed cells can be suspended in additive solutions to maintain the quality during storage and to increase the shelf life. The Hct of additive suspended red cells should be 55 to 60%. One unit of packed red cell transfusion should raise the Hb by 1gm/dl in the recipient. Packed red cells are indicated to restore O2 carrying capacity in an anemic patient.

Platelet concentrates:

Platelet concentrates can be prepared from single unit of whole blood after centrifugation [random donor platelets] or using apheresis machine [single donor platelet or apheresis platelets]. One unit of random platelet concentrate should contain minimum of 3.5 X 1010 platelets while one unit of apheresis platelet contains 3 X 1011 platelets per unit. Typically, one standard dose of platelet is 5 to 6 random platelets for an adult patient or one apheretic unit.

Indications:

Platelets are indicated in patients with thrombocytopenic bleeding such as in Aplastic anemia, leukemia. They can be used prophylactically to prevent the bleeding or therapeutically to stop the bleeding. The typical indications are -

  •   Aplastic anemia
  •  Emotherapy induced thrombocytopenia
  •  Leukemia
  •  Bone marrow failure
  •   Post cardio pulmonary bypass

Platelets are not effective in conditions in which there is increased destruction or consumption of platelets such as in ITP or heparin induced thrombocytopenia. Platelets are contraindicated in TTP.

Fresh frozen plasma

Fresh frozen plasma (FFP) is prepared by separating the plasma from whole blood within 6 hrs of collection and then rapidly freezing to –250 C or below. It contains the normal plasma levels of stable clotting factors, albumin and immunoglobin. The usual volume of a pack is 200-300 ml.

If untreated it carries the same risk of disease transmission as whole blood. If kept at -250 C it can be storedfor a year. Before use, it should be thawed in the blood bank to 30-370 C. Once thawed it should be stored in a refrigerator at 2-60 C. The dose for administration is 15 mlkg. ABO compatibility is required to avoid risk of haemolysis in the recipient. However compatibility testing (crossmatching) is notmandatory. Since it contains  labile coagulation factors that rapidly degrade, it should be used within 6 hrs of thawing.

Indications:

  • Replacement of single factor deficiencies where aspecific or combined factor concentrates is no available
  • Immediate reversal of warfarin effect in the presence of potentially life-threatening bleeding
  • Treatment of the multiple coagulation deficiencies associated
  • Acute disseminated intravascular coagulation;
  • Treatment of thrombotic thrombocytopenic purpura;
  • Treatment of inherited deficiencies of coagulation
  • inhibitors in patients undergoing high-risk procedures where a specific factor concentrates is unavailable
  •  In the presence of bleeding and abnormal coagulation parameters following massive transfusion or cardiac bypass surgery or in patients with liver disease.

Cryoprecipitate

Cryoprecipitate or cryoprecipitated antihaemophilic factor (cryo), is the cold precipitable protein fraction derived from FFP thawed at 1-60 C. It contains factor VIII, fibrinogen, fibrinonectin, Von willebrand’s factor and factor XIII. One unit of cryoprecipitate per 10 kg body weight raises plasma fibrinogen concentration by approximately 50 mgdl in the absence of continued consumption or massive bleeding. Its use in the operative setting is based on the assumption that: 

1. Patients with these coagulation factor deficiencies are at increased risk of haemorrhagic complications.

2. Replacement of coagulation factors is effective in decreasing these risks. Indications

  •  Hemophilia A
  •  Congenital fibrinogen deficiencies or
  •  Von Willebrand’s disease unresponsive to DDAVP.
  •  DIC
  •  Correction of microvascular bleeding in massively transfused patients

Apheresis components

Apheresis is an alternative method of prosducing blood components. It is a sterile process in which a donor is connected to a specialized device by which blood is withdrawn and a specific component, usually plasma or platelets, is mechanically separated and collected. The red cells and other components of the blood that are not required are then reinfused back into the donor. Depending on the component collected, procedure is called as plasmapheresis if plasma is collected or plateletapheresis if platelets are collected. The advantage of apheresis is that relatively large amount of plasma or platelets can be collected from a single donor. Since  the red cells are returned to the donor, the process can be repeated at frequent intervals.

Clinical use of blood components:

Following figure illustrates the rationale use of one unit of donated blood.

 


 

WHO principles for the Clinical use of blood components 

1.  Transfusion is only one element of the patient’s management.

2Prescribing decisions should be based on the national guidelines on the clinical use of blood components, taking individual patient needs into account.

3Blood loss should be minimized to reduce the patient’s need for transfusion.

4The patient with acute blood loss should receive effective resuscitation (intravenous replacement fluids,

Oxygen etc) while the need for transfusion is being assessed.

5The patient’s hemoglobin level, although important 

Storage and shelf life of components: Following table summarizes storage requirements and shelf life of various blood components. 

Component Storage Temp. Shelf life Compatibility

Packed Red cells

Plasma

Cryo deficient Plasma

Platelet Concentrate

 

Buffy Coat

Cryoprecipitate

2 to 6oC

- 30oC

- 30oC

22oC to 24oC

22oC

- 30oC

 

35 days

1 year

5 years

3 to 5 days

1 day

1 day

ABO/Rh Fresh frozen

ABO

ABO

Preferably ABO, in Rh Neg.
female in childbearing age
Rh negative PC

ABO

Any group

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. 

6. The clinician should be aware of the risks of transfusion-transmissible infection in the blood components that are available for the individual patient. 

7. Transfusion should be prescribed only when the benefits to the patient are likely to outweigh the risks. 

8. The clinician should record the reason for transfusion clearly.

9. A trained person should monitor the transfused patient and respond immediately if any adverse effects occur. 

Source: WHO 

Decision to transfuse:

Clinical judgment should be central to any decision to transfuse. The decision should be supported by the need to relieve clinical signs and symptoms and prevent significant morbidity and mortality. Blood component therapy should only be given when the expected benefits to the patient are likely to outweigh the potential hazards. The decision to transfuse red blood cells should be based on clinical assessment of the patient and his or her response to any previous transfusion as well as the hemoglobin level. 

Following figure illustrates this risk/benefit analysis for the use of red blood cells in relation to anemia. 

 

                               Risk/benefit analysis for the use of red blood cells 

Red blood cell transfusion

In deciding whether to transfuse red blood cells, the patient’s hemoglobin level, although important, should not be the sole deciding factor. The various factors that should be used in

deciding whether use of red blood cells is appropriate include patient factors, signs and symptoms of hypoxia, ongoing blood  loss, the risk to the patient of anemia in the setting of coexisting conditions and the risk of the transfusion. Some specific factors to consider are as follows. 

• Patient’s cardiopulmonary reserve— if pulmonary function is not normal it may be necessary to consider transfusing at a higher threshold. 

• Volume of blood loss—clinical assessment should attempt to quantify the volume of blood loss before, during and after surgery, to ensure the maintenance of normal blood volume. 

• Oxygen consumption—this may be affected by a number of factors including fever, anaesthesia and shivering; if increased then the patient’s need for red blood cell transfusion could be higher. 

Recommendations for red cell transfusion

Use of red blood cells is likely to be inappropriate when Hb>10 g/dL unless there are specific indications If red blood cells are given at this haemoglobin level, reasons should be well

documented. Use of red blood cells may be appropriate when Hb is in the range 7–10 g/dL In such cases, the decision to transfuse should be supported by the need to relieve clinical signs and symptoms and prevent significant morbidity and mortality. Use of red blood cells is likely to be appropriate when Hb<7 g/ dL. In some patients who are asymptomatic and/or where specific therapy is available, lower threshold levels may be  acceptable. 

Transfusion volume of red cells:

A unit of red blood cells is usually 300mL in volume and has a hemoglobin concentration of 180–230g/L. One unit of red blood cells will raise the hemoglobin level of an average sized adult by approximately 10g/L. The dose of the red blood cells is therefore based on the patient’s hemoglobin level and their 

volume requirements. It is desirable to repeatedly measure the patient’s hemoglobin level to assess the effect of the use of red blood cells. 

Platelet transfusion

The use of platelets is indicated for the prevention and treatment of haemorrhage in patients with thrombocytopenia or platelet function defects. The platelet count is the primary trigger for 

the use of platelets, with clinical risk factors for bleeding and the extent of bleeding also influencing the decision to transfuse.Following figure illustrates factors important in deciding whether or not to use platelets

                                                       Figure: Platelet therapy 

Recommendations for platelet transfusion 

Use of platelets is likely to be appropriate as prophylactic therapy:

  • In bone marrow failure when the platelet count is <10,000/ul without risk factors or <20,000/uL in the presence of additional risk factors (eg fever, antibiotics, evidence of systemic haemostatic failure) 
  •   To maintain the platelet count at >50«109/L in patients undergoing surgery or invasive procedures 
  • In inherited  or acquired qualitative platelet function disorders, depending on clinical features and setting In these situations the platelet count is not a reliable indicator for transfusion

Use of platelets is likely to be appropriate as therapeutic option 

  •   in any patient who is bleeding in whom thrombocytopenia is considered a major contributory    factor 
  • when the platelet count is <50,000/ul in the context of massive haemorrhage/transfusion 
  • when the platelet count <100, in the presence of diffuse microvascular bleeding.

Use of platelets is not generally considered appropriate 

  • in the treatment of immune-mediated platelet destruction, thrombotic thrombocytopenic purpura,   haemolytic uraemic syndrome or drug-induced or  cardiac bypass thrombocytopenia without haemorrhage (level IV evidence). 

Platelet transfusion triggers

 

Platelet count  threshold

Settings

< 100 X 109/L.

50 – 80 X 109/L.

< 50 X 109/L.

 

 

< 20 X 109/L.

coagulopathy

< 10 X 109/L.

Neurosurgery CNS trauma

Epidural catheter insertion or removal

Significant micro vascular bleeding

Lumbar puncture

Surgery

Vaginal delivery

Thrombocytopenia with fever or

Thrombocytopenia due to marrow
failure

Platelet transfusion in cardioplumonary bypass patients: 

Cardiopulmonary bypass results in the destruction of a significant fraction of the patient’s platelets. In addition, there is evidence that the remaining platelets may have their function impaired by the bypass procedure. However, the relationship between the thrombocytopenia and abnormal platelet function to postoperative hemorrhage in these patients is unclear and controversial.

Recommendations: 

  • Do not transfuse patients prophylactically 
  • If the patient has microvascular bleeding, as indicated by continued oozing from surgical incisions and venous cannulation sites, which is the hallmark of platelet-related bleeding consider administering platelet transfusions. Desmopressin also may be helpful in patients with severe platelet dysfunction. 
  • Attempt to utilize platelet counts and bleeding times to assist in guiding platelet transfusions. 

Platelet transfusion in bone marrow failure patients:

Patients with thrombocytopenia due to chemotherapy or aplastic anemia have traditionally been managed with prophylactic platelet transfusions until recovery of platelet production. This should theoretically require one therapeutic dose twice weekly in order to prevent dangerous bleeding. As a general rule in atients with hypoproductive thrombocytopenia, surgical bleeding due solely to thrombocytopenia does not occur until the platelet count is less than 50,000/μL and spontaneous bleeding in the absence of other risk factors does not usually occur until the plateletcount is less than 10,000/μL. The platelet count cutoff for

prophylactic platelet transfusion is determined in part by the concept that, while thrombocytopenic patients may develop petechiae and ecchymoses (“dry” bleeding), they will not suffer fatal hemorrhagic  omplications without first developing extensive mucous membrane bleeding (“wet” bleeding). The risk of mucosal injury due to bone marrow transplantation induced thrombocytopenia is higher than with chemotherapy for acute leukaemia. The threshold for platelet transfusion in these settings can again be safely lowered to 10 X 109/L.

Recommendation:

  • Transfuse platelets at count < 10,000/μL inpatients with no or only “dry” bleeding. 
  • Prophylactic threshold should be 20,000/μL in patients with infection or other risk factors such as    emperature >38°C or prior to minor surgery. 
  • herapeutic threshold be 50,000/μL in those with active bleeding or prior to an invasive procedure. 

Platelet transfusion in platelet function disorders: 

Disorders of platelet function can occur on a congenital or acquired basis. Patients with platelet function disorders rarely need platelet transfusions. Even patients with severe inherited platelet function disorders such as Glanzmann’s thrombasthenia only have sporadic bleeding and may have no bleeding for many years. Negligible or no excessive  bleeding can be expected in patients with acquired platelet function disorders as the impairment in platelet function is much less than in  lanzmann’s thrombasthenia. However, acquired causes of platelet dysfunction can exacerbate bleeding in patients who already have impaired haemostasis.  

Recommendations: 

  • Withdraw drugs known to have antiplatelet activity. 
  • Correct any underlying condition known to be associated with platelet dysfunction, if possible.
  • Correct the haematocrit to > 30% in patients withrenal failure.
  • Consider the use of DDAVP in patients with inherited dysfunction defects.
  • Consider the use of DDAVP or cryoprecipitate in patients with uraemia.
  • Use platelet transfusions where the above methods are not appropriate or are ineffective.

Measures to reduce inappropriate use of blood and components

  • Establishment of transfusion practice guidelines 
  • Functional Hospital Transfusion Committee
  • Retrospective monitoring of medical / transfusion records of the patients 
  • Prospective monitoring of requests for blood components before they are issued 
  • Introduction of new transfusion policies or algorithms;
  • Education of health professionals; and 
  • Peer review and self-audit.

 

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Dr. Rajendra Chaudhary
MD, DNB
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