The risk of blood transfusion

The risk of blood transfusionINTRODUCTION:Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another.

It can be life-saving in some situations, such as massive blood loss due to trauma , or can be used to replace blood lost during surgery.Blood transfusions may also be used to treat a severe anemia or thrombocytopenia caused by a blood disease.

People suffering from hemophilia or sickle-cell disease may require frequent B.T

Early transfusions used whole blood, but modern medical practice is to use only components of the blood.History:The first historical attempt at blood transfusion was described in 15th-century.

The first fully-documented human blood transfusion was administered by Dr. Jean- Denis, eminent physician to King Louis XIV of France, on June 15, 1667. He transfused the blood of a sheep into a 15-year old boy, who recovered In 1818, Dr. James Blundell, a British obstetrician, performed the first successful blood transfusion of human blood, for the treatment of postpartum hemorrhage.

Many patients had died and it was not until 1901, when the Austrian( Karl) discovered human blood groups, that blood transfusions became safer &awarded the Nobel Prize in Physiology or Medicine

World War II syringe for direct interhuman blood transfusionWhile the first transfusions had to be made directly from donor to receiver before coagulation, in the 1910s it was discovered that by adding anticoagulant and refrigerating the blood it was possible to store it for some days, thus opening the way for blood bank.

The first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, who used sodium citrate as an anticoagulant .Transfusion of blood products is one of the most common interventions in the hospital setting.

The number of blood components trans-fused in the United States was approximately 29 million in 2004 & This equates to nearly 80,000 units of blood components transfused every day.

Processing of blood prior to transfusion:The Donated blood is usually subjected to processing after it is collectedComponent separation.Leukoreduction, also known as Leukodepletion is the removal of white blood cell from the blood product by filtration.Irradiation.Viral screeningAlthough blood transfusion saves lives and reduces morbidities in many clinical diseases and conditions, it is associated with certain risks.

The most serious risks of blood transfusion are transfusion reaction which is include (immune-related reactions ,non immune reactions and infections). The transfusion reaction:There are several types of reactions and some are more severe than others. Some reactions may happen as soon as the transfusion is started, while some take several days or even longer to develop.

Immune-related reactions:occur when the immune system attacks components of the blood being transfused or when the blood causes an allergic reaction.

These reactions may be mild or severe. Most mild reactions are not life-threatening when treated quickly.1-Nonhemolytic fever reactions or febrile reaction:It is sudden fever during or within 24 hours of the transfusion may be associated with Headache, nausea, chills, or a general feeling of discomfort.

These reactions are a response by the body to white blood cells in the donated blood.

They are more common in people who have had transfusions before, and in women who have had several pregnancies.

The Acetaminophen (Tylenol) may help these symptoms.

Patients who have had febrile reactions or who are at risk for them are usually given blood products that are leukoreduced (This means that the white blood cells have been removed by filters or other means).2-The allergic reaction:This is the most common type of reaction&It occurs during the transfusion because of the body's reaction to plasma proteins in the donated blood.

Usually the only symptoms are hives and itching, which can be treated with antihistamines such as diphenhydramine. In rare cases these reactions can be more serious cause:

Anxiety Chest and/or back pain Trouble breathing Fever, chills, flushing, and clammy skin A high pulse or low blood pressure &nausea

Which can be life-threatening(anaphylactic shock) In this case we have to stop the transfusion immediately at the first signs of an allergic reaction. determines how mild or severe the reaction is, what treatments are needed, and if the transfusion can safely be restarted.3-Transfusion-related acute lung injury (TRALI): This is a very serious transfusion reaction, which happens in about 1 out of every 5,000 transfusions.

It can happen with any type of transfusion, but those that contain more plasma, such as FFP or plateletsIt often starts within 1 to 2 hours of the transfusion, but can happen anytime up to 6 hours after the transfusion.

The main symptom a patient will feel is trouble breathing

Doctors now believe that there are several factors involved in this illness such as(recent surgery, trauma, cancer treatment, transfusion, or have an active infection).Most of the time TRALI goes away within 2 or 3 days if the breathing and blood pressure are supported, but even with support it can cause death in 5% to 10% of cases.

It is more likely to be fatal if the patient was already very ill before the transfusion.Most often a patient will need oxygen, fluids, and sometimes support with a breathing machine.

If a patient who has had TRALI needs blood, we need to prevent future problems by "washing" the red cells in a dilute salt water solution to remove most of the plasma while saving the red blood cells.

4- Acute immune hemolytic reaction:is the most serious type of transfusion reaction, but it is very rare & It happens when donor and patient blood types do not match.

The patient's antibodies attack the transfused red blood cells, causing them to break open (hemolyze) and release harmful substances into the bloodstream.

Patients may have chills, fever, chest and lower back pain, and nausea.

The kidneys may be severely damaged, and dialysis may be needed.

It can be cause death if the transfusion is not stopped as soon as the reaction starts:5-Delayed hemolytic reactionThis type of reaction happens when the body slowly attacks antigens (other than ABO antigens) on the transfused blood cells.

The blood cells break down days or weeks after transfusion& usually no symptoms, but the transfused red blood cells are destroyed and the patient's red blood cell count falls.In rare cases the kidneys may be affected, requiring treatment.

People don't usually have these types of reactions unless they have had several transfusions in the past.

People who have this type of reaction need special blood testing before any more blood can be transfused.

6-Graft-versus-host disease (GVHD): occurs when white blood cells in transfused blood attack the tissues of a transfusion recipient who has a severely weakened immune system.

It is more likely to happen if the person getting the blood is a relative or has a similar tissue type to the donor

The recipient's immune system doesn't recognize the white blood cells in the transfused blood as foreign& This allows them to survive and attack the recipient's body tissues.

Within a month of the transfusion, the patient may have fever, liver problems, rash, and diarrhea

To prevent white blood cells from causing GVHD,the donated blood can be treated with radiation before transfusion.

Radiation stops white blood cells from working but does not affect red blood cells.

:Nonimmune reactions1-Fluid overload:

it is a common type of nonimmune reaction & it occur when Pt receive too much fluid through transfusions, especially if he has not experienced blood loss before the transfusion.

It may require treatment with (diuretics) medications to rid the body of the excess fluid.

2- Acquired hemochromatosis: Very rarely, a person can develop iron overload after having many repeated blood transfusions.

People with a blood disorder like thlassemia which requires multiple transfusions, are at risk of iron overload and because of this they are usually on chelating agent to remove the extra iron from there body.

Infections:Blood transfusions can transmit infections caused by bacteria, viruses, and parasites.

The chance of an infection being transmitted is very rare, but the exact risk for each type of infection varies.Bacterial contamination:Rarely, blood gets contaminated with tiny amounts of skin bacteria during donation.

Platelets are the most likely blood component to have this problem. Because platelets must be stored at room temperature, these bacteria can grow rapidlyIt is affects about 1 in 1000 to 3000 units of platelets.

Patients receiving these platelets may develop serious illness within minutes or hours after the transfusion is started

In 2004, blood banks started testing platelets before they are given and throwing out affected units. Hepatitis B and C:Hepatitis is the most common disease transmitted by blood transfusions.

According to the American Red Cross, about 1 blood transfusion in 205,000 transmits a hepatitis B infection, and 1 blood transfusion in about 2 million transmits hepatitis C.Several steps are routinely taken to reduce the risk of hepatitis from blood transfusion

People who are getting ready to donate blood are asked questions about hepatitis risk factors and symptoms of hepatitis & the Donated blood is also tested to find HBV,HCV and liver problems that might point to other types of hepatitis. Human immunodeficiency virus (HIV):Testing each unit of donated blood for HIV began in 1985, and tests for HIV are now used on all donated blood.

With improved testing for HIV, the number of transfusion-related AIDS cases continues to drop.The risk of HIV transmission from a transfusion now is about one in 2,135,000 & In addition to testing, the risk is reduced by asking donors questions about HIV risk factors and symptoms.Other infections tested: In addition to the tests noted above, all blood for transfusion is tested for syphilis, as well as T-cell lymph tropic virus types I and II (HTLV-I/II) linked to human T-cell leukemia/lymphoma, (CMV), (EBV), TT virus (TTV), human herpes virus type 6 (HHV-6), SEN virus (SEN-V), and human parvovirus (HPV-B19).

Since 2003, donated blood has been tested for the West Nile virus tooOther possible infections:Diseases caused by certain bacteria, viruses, and parasites, such as Chagas disease, malaria, Lyme disease, and others can also be spread by blood product transfusions But because potential donors are screened with questions about their health status and travel, such cases are very rare. Classification of transfusion-related adverse eventsNoninfectious Reaction

Infectious Reaction

Mechanism

Time of Occurrence

Acute hemolytic transfusion reactionTransfusion-related acute lung injuryFebrile nonhemolytic transfusion reactionUrticarial reactionAnaphylactic

Immune mediated

AcuteNonimmune hemolysis (e.g. hemoglobinuria)Circulatory overloadMetabolic (e.g. hyperkalemia)Embolic

Bacterial contamination

Nonimmune mediated

Delayed hemolytic transfusion reactionTransfusion associated graft-versus-host diseasePost transfusion purpura

Immune mediated

Delayed

Hemochromatosis (iron overload)

Transfusion Transmitted infections (viral, bacterial and parasitic)

Nonimmune mediated

Neonatal transfusion:hospitals are taking additional precaution to avoid infection and prefer to use specially tested pediatric blood units that are guaranteed negative forCMV.

There are pecific requirements place additional restrictions on blood donors who can donate for neonatal use.

Neonatal transfusions are usually top-up transfusions, exchange transfusions, partial exchange transfusions.

Top-up transfusions are for investigational losses and correction of mild degrees of anemia5-15 ml/kg ,removal of bilirubin, removal of antibodies and replacement of red cells

Ideally plasma-reduced red cells that are not older than 5 days are use.

Transfusion and Patient Outcomes

A large number of recent (within the last 7-10 years) studies have shown a profound association between transfusion and adverse outcomes.

Today there is mounting evidence that patients who are transfused do worse than patients who are notIn orthopedic surgery, patients who have received allogeneic (banked) blood have a 1.5- to 3.5-fold increased risk for preoperative major infection which includes wound infection, pneumonia, sepsis, and urinary tract infection which lead to prolonged hospital stay.In open heart surgery, those who receive units of blood have a longer stay in the hospital, have more chance for pneumonia, more infections , more respiratory complications, more kidney and heart problem , more strokes and ultimately at least twice the death rate than those not transfused.Patients who are transfused have more heart arrhythmias (atrial fibrillation), heart failure, inability to wean from the bypass machine, and other additional adverse outcomes.

Also, several studies have demonstrated higher cancer recurrence rates in transfused versus no transfused patients with cancer due to Transfusion-related immunomodulation (TRIM) but still there is controversy.

Blood Management StrategiesIn response to these issues, health care providers and hospitals are developing multiprofessional strategies to improve blood utilization, improve patient outcomes, and reduce costs.key principles for developing effective blood management

Early identification and intervention for patients at high risk for transfusions

Utilization of current scientific evidence and the promotion of clinical best practices

Coordination of all members of the health care team

Patient advocacy and patient safety

Stewardship of scarce and expensive hospital resources

Preoperative Preparation and Planning:Preoperative preparation and planning are essential elements for the safe and optimal management of surgical patients.

Formal protocols for preoperative testing of hemoglobin level for major blood loss surgeries and coagulation status testing in certain patient populations are important for this early identification and intervention.discontinuation of drugs such as aspirin, warfarin, and clopidogrel, as well as certain herbal supplements that increase bleeding including garlic, ginkgo, and ginseng.

Anemia management protocols are essential to blood management programs because they selectively use iron and erythropoiesis-stimulating agents to eliminate the need for allogeneic blood during moderate-to-high blood loss surgeries. :Nonpharmacologic Strategies

One such strategy is to minimize the impact of diagnostic phlebotomy on the development of iatrogenic anemia, especially in critically ill patients.

discontinuation of invasive lines (e.g., arterial catheters, central venous catheters) .

Use of small-volume sampling tubes (e.g., pediatric sampling tubes)

Point-of-care bedside analytic techniques (e.g., blood glucose analyzers, arterial blood gas analyzers) that require only small volumes of blood can be used to accomplish the same goal.

Intraoperative blood recovery (i.e., cell salvage methods) with subsequent reinfusion of shed blood into a patient that has experienced significant surgical bleeding.All these of measurement is apart the principles of bloodless surgery Minimally invasive surgical techniques which include laparoscopic, endoscopic, robotic, and transcatheter techniques, low central venous pressure anesthesia as well as use of advanced surgical instrumentation (e.g., ultrasonic scalpel, argon bean coagulator).

Iron Therapy:Inadequate iron stores will eventually result in iron-deficient anemia.

iron replacement therapy is warranted to reverse the anemia and minimize the use of red blood cell transfusions & it involves enteral administration of ferrous sulfate, gluconate, fumarate, or iron polysaccharide in ambulatory patients with iron-deficient anemia.

parenteral iron replacement therapy with iron sucrose, ferric gluconate, or iron dextran is often required because of gastrointestinal adverse effects associated with the enteral products or compromised enteral bioavailability in critically ill patients.

Erythropoiesis-Stimulating Agents:Among the pharmacologic strategies to minimize allogeneic blood transfusions.

Two such agents are available in the United States, namely, epoetin alfa and darbepoetin alfa. the FDA has recently recommended to use the lowest dose possible of (ESA)to gradually increase the hemoglobin concentration and to target hemoglobin concentrations that do not exceed 12 g/dl in the patients with chronic renal failure, patients with cancer who are receiving chemotherapy, and surgical candidatesOne of the biggest factors that could limit the use of epoetin alfa and darbepoetin alfa in all patient subsets relates to their pharmacoeconomicsHemostatic Blood Products and Drugs:a number of pharmacologic agents have been used as adjunctive therapies to control bleeding. One of the more controversial agents over the last few years is the off-label use of rFVIIa.

Adverse events (i.e., death, thromboembolic events, multiple organ failure, and acute respiratory distress syndrome +it COST in trauma 25,000

Other pharmacologic agents that have been investigated for their adjunctive role in reducing blood loss include desmopressin and the antifibrinolytics, aprotinin, tranexamic acid, and epsilon-aminocaproic acid.

Blood substitutes: also called artificial blood or blood-surrogates) are used to fill fluid volume and/or carry oxygen and other blood gases in the CVS.

The preferred and more accurate are volume expanders for inert products, and oxygen therapeutics for oxygen-carrying products

Examples of these two "blood substitute" categories:Volume expanders:These may be crystalloid-based (RL,NS, D5W)or colloid-based (Hespan, haemaccel).

Oxygen therapeutics:it is divided two categories based on transport mechanism perflorocarbon based, and hemoglobin based.Artificial Oxygen Carriers:The quest for artificial oxygen carrier solutions as alternatives to allogeneic B.T has spanned decades.

these products have focused primarily on the perioperative setting, sustaining regional perfusion (e.g., stroke, myocardial infarction), and acute hemorrhagic shock.

Artificial Oxygen CarriersHemoglobin basedPerfluorocarbon basedHemopure.

Oxyglobin.

PolyHeme.

Hemospan

Dextran-Hemoglobin

Oxygent

Oxycyte.

Although most of these products have been approved for use in the United States or Europe, clinical trials are investigating the safety and efficacy of these agents.

Oxyglobin solution is the first and only oxygen therapeutic to be both US FDA and European Commission approved for veterinary use

Promising techniques:Stem cell.dendrimers .Biodegradable Micelles.Placental umbilical cord blood.

At the moment, the complex three step method of producing the cells would make a unit of these red blood cells too expensive.

Autologous Predonation:Typically, patients will donate 13 units of packed red blood cells over a 34-week period before their elective surgery.

Risks associated with preoperative autologous donation include transfusion-associated circulatory overload and the potential for misidentification during the transfusion process.These two risks are due to lower hemoglobin levels in preoperative autologous donation cases & moving them closer to a transfusion trigger.

the use of autologous predonated blood can cause an iatrogenic anemia & There is also the potential for waste if the unit collected is not needed, which on average occurs in more than half of preoperative autologous donation cases.

Conclusion:In many cases, transfusions are the end result of the actions or interactions of health care providers and hospitals to manage a series of events in complex patients.

Alternatively stated, the goal of blood management is to ensure that each and every blood product that is transfused is appropriate, and that blood-related resources are used effectively. The corner stones of blood management programs are the implementation of evidence-based transfusion guidelines to reduce variability in transfusion practice, the employment of multidisciplinary teams to study, implement and monitor local blood management strategies.Our greatest glory is not in never falling , but in rising every time we fallTHANK YOU

Dr. Amani AL-HaddadPediatric surgery