Module 5. Cardiovascular System and Blood

Blood ordering processes • The attending Doctor must complete and sign the Request for Blood and Blood Components (FRM-ISS-006), requesting the required number of red cell concentrate units.

Blood ordering processes • Red Blood Cell Concentrate must be: – ABO and Rh compatible – Less than 5 days old – The units should as far as possible be leucodepleted

Blood ordering processes • IRRADIATED BLOOD PRODUCTS • Red cells stored at 1- 6°C and expire 14 days after irradiation • Paediatric packs that are irradiated expire within 24hours. • Irradiated products are used to prevent transfusion associated graft-vs-host disease in: • Immunosuppressed patients e.g. chemotherapy patients • Pre/post bone marrow transplant patients

Blood ordering processes • For the purpose of setting the parameters on the cell separator, an average haematocrit of 63% per unit can be used. • Each RCC unit must be checked, controlled and signed by a nursing staff member on the Therapeutic Worksheet before use. • All empty/unused blood containers transfused must be handed over to ward staff for storage in the ward’s blood fridge for 24 hours (in case of post-transfusion reactions).

Risks associated with Red Cell Transfusion • risk of serious haemolytic transfusion reactions. • can transmit infectious agents, including HIV, hepatitis B, hepatitis C, syphilis, malaria and Chagas disease to the recipient. • can become contaminated with bacteria and very dangerous if it is manufactured or stored incorrectly.

Risks associated with Red Cell Transfusion • can transmit most of the infections present in whole blood. • cause transfusion reactions.

Differences between bedside and lab leucofiltration Bedside Filtration Laboratory Filtration Medical staff who are sometimes not Trained laboratory personnel (SOP certified suitably trained on bed side filtration staff) perform the filtration procedure No quality checks are performed on the Quality checks are performed to monitor the blood to ensure max removal of WBC efficacy of the filtration process. Post storage temperature of blood is not The filtration process in performed in a monitored. controlled temperature environment. Blood filtered at bedside may not In the laboratory, blood is filtered within a few necessarily be fresh. hours after being bled. More likely to cause febrile transfusion Very unlikely to cause febrile reactions reactions as stored blood has an increased because fresh blood is used and the level of cytokines cytokines are removed together with the leucocytes.

Good transfusion practices • Checking of doctor’s orders • Checking of informed consent for blood products • Identification of recipient • Checking of blood and blood products • Blood administration sets and filters • Warming of products

Haemovigilance and Lookback programs

Blood Cold Chain

Storage and handling (Including post- transfusion retention of empty blood packs) • After processing, each component must be stored at the correct temperature to ensure survival of the elements during storage. • Red cells must be stored at 1-6°C • Packs need to be kept in the fridge 24hrs post transfusion

Transport • Transported from one area to another, temperature must be maintained • Transported in insulated containers validated for this purpose. • Must be packed in the shortest possible time to prevent warming. • Ensure that the blood does not come into direct contact with the ice bricks. • Temperatures are recorded on the documentation accompanying the units transported to its destination. • Red cells temperature should fall within 1-10°C

Transfusion • Final stage of the cold chain. • When the blood leaves the Service and arrives at its destination, it should be kept in the hospital refrigerator until is it ready for transfusion. • The refrigerator used for storage of blood must meet all the same specifications we use in the Service. • Blood issued in a hamper and was not used, may be returned to stock, provided that: – The lid is still sealed – The blood pack seals are intact – The temperature is acceptable

Patient Identification • Always compare the patient’s wristband identification to the delivery note. If the patient does not have a wristband and is coherent, it is permissible to ask the patient to give his full name. • If the patient does not have a wristband and is unable to identify himself as a result of being unconscious or disorientated, some form of positive identification must be attached to the patient before collection of sample. • Check that all details on the delivery note are the same as those relating to the patient

The requisition form must include • Full names, age or date of birth, sex, hospital ward and hospital patient identification number • Diagnosis • Previous transfusion history • Products required • Prescribing doctor’s name, signature and contact details. • Date and time of collection

Immune reactions • Haemolytic transfusion reactions • Anaphylactic reactions • TRALI • TA- GvHD • Post Transfusion Purpura • Allergic reactions • Platelet antibodies

Non immune reactions • Allergic reactions, being the most common of all • Bacterial contamination of donor blood • Pyrogens in products transfused • Other rare causes e.g. air embolism and haemolysis • Hypothermia • Circulatory overload • Toxicity of chemicals in donor blood • Citrate toxicity • Potassium toxicity

Long term complications • Transmission of disease • Allo-immunization • Jaundice • Iron Overload



Haemolytic reactions (intravascularly) • Usually ABO incompatibility • The antibodies present are usually IgM and are complement binding • Red cells are destroyed in the circulatory system (intravascularly) • Haemoglobin is spilled into the plasma • Free haemoglobin creates a problem in that the molecule causes damage to the renal tubules and can result in kidney failure. • These reactions are always severe and can result in death of the patient. • Severity of the reaction would depend on the avidity of the antibody and the volume of incompatible cells transfused.

Haemolytic reactions (extravascularly) • Antibodies causing extravascular reactions are usually not complement binding. Eg Anti-D and Anti-K. • IgG antibodies sensitize red cells carrying the corresponding antigen • These sensitized cells are not tolerated by the body and are removed extravascularly by the liver and spleen • The destruction of red cells results in the development of bilirubin and this can be seen in the blood instead of haemolysis. • The patient’s haemoglobin level drops due to red cell destruction and the patient may appear jaundiced. • Extravascular reactions can be immediate or delayed, depending on the strength of the antibody.

S&S Haemolytic reactions • Chills • Fever • Headache • Pain in the lower back and the joints • A burning sensation at the site of infusion • In some patients, the first sign of a haemolytic episode is haemoglobin or bilirubin in the patient's urine which alerts the doctor or nurse to the problem • Intravascular reactions may ultimately result in kidney failure due to damage to the urinary tubules caused by the haemoglobin excretion • Uncontrolled bleeding due to disseminated intravascular coagulation (DIC)

• Stop the transfusion immediately and to ensure that the blood was set up for the correct patient. • The doctor in charge of the patient must be informed immediately and should try and promote diuresis by giving the patient a diuretic. – to flush the kidneys as the presence of haemoglobin in the urine can result in renal failure. • In severe cases it may be necessary to dialyse the patient.

Causes • ABO mismatched transfusions – result of clerical errors and patient misidentification, (time of sample collection or cross match, labelling or issue of the blood) • A unit of blood may carry the corresponding antibody in the donor plasma to which the patient has the antigenA – rare each donation screened for irregular antibodies those which test positive not made available for transfusion) • Inter-donor incompatibility – when patient receives more than one unit of blood. There may be an antigen in one unit of blood and the corresponding antibody in the plasma of another unit of blood. In this case donor blood is incompatible with each other resulting in the reaction occurring in the patient. • ‘high titre’ blood – eg group O high titre blood to a group B patient.

Anaphylactic reactions • Can be fatal to the patient even if only a small amount of blood is transfused. • When patients are IgA deficient and their serum contains anti- IgA antibodies – most patients who are IgA deficient do not have these antibodies present in their serum. • IgA antibodies may develop as a result of exposure during a transfusion or even pregnancy. • S&S – Dyspnoea – difficulty in breathing – Oedema or swelling of the tissues of the throat – Abdominal pain – Respiratory collapse

Anaphylactic management • The transfusion must be stopped immediately. • It may be necessary to treat the patient with steroids and anti- histamines • All future transfusions must be free of all IgA i.e. by washing the cells to remove all traces of plasma, thus ensuring the blood is IgA free.

Allergic reactions • Most common type of reaction • Mild but the patient still experiences discomfort, rarely fatal • If the patient is allergic to something present in the unit of blood/ blood product and only a few millilitres of blood can bring about signs of a reaction • The patient will develops hives, known as urticaria

Allergic reactions • The allergen and antibody cause the mast cells to release histamine • Swelling of the face, especially the areas around the eyes and lips. • Swelling of the throat can occur • Bronchial asthma may occur

Allergic reactions • As soon as symptoms appear of an allergic reaction, stop the transfusion. • The administration set is left in place and the doctor administers antihistamines and sometimes cortisone depending on the severity of the reaction. • If the symptoms subside, the transfusion may be resumed with caution, but if the patient has respiratory problems, the transfusion must be discontinued.

TA- GvHD • Normally lymphocytes present in transfused blood are recognised and killed by a healthy patient’s immune system. If immune system is suppressed, the transfused lymphocytes try to take over the patient’s system by producing antibodies against the patient’s own cells. TA-GvHD can occur in the following cases: – Bone marrow transplants – Patients with impaired immune systems – Patients who are immuno-supressed such as cancer patients; patients suffering from aplastic anaemia or even those who have a hereditary immune deficiency. – Patients who receive blood from a close blood relative e.g. brothers. • These reactions can be severe and even fatal. • The patient’s system does not recognise the transfused lymphocytes as “invaders

TA- GvHD • The following signs and symptoms can develop 1 to 6 weeks after the transfusion: – Rash – Malaise – Fever – Diarrhoea – Malabsorption – Susceptibility to fungal and viral infections. – Hepatitis or liver dysfunction – Presence of donor white cells in patients circulation confirms suspicion of TAGvHD.

TA- GvHD • It is best to irradiate the blood – inactivates the lymphocytes without considerably affecting the function of the red cells and platelets • There is some evidence that irradiation causes a modest leakage of potassium, reducing the storage time of red blood cells and decreasing their survival after transfusion. Therefore, irradiated red blood cells are given a reduced storage time – 14 days after irradiation. • Should a patient contract TA GvHD, he/she will be treated with steroids and immuno- suppressive drugs

TRALI • Lipid products from donor blood cells have recently been implicated as the potential activators in the onset of TRALI. • The definitive cause of TRALI is not yet fully understood. • It is believed that TRALI may occur as a result of the presence of a high titre white cell antibodies present in the donor blood. • This type of reaction is also seen when the patients are transfused with plasma or platelet products.

TRALI • White cell antibodies can develop as a result of previous pregnancies or transfusion. • Effects of the reaction can be seen within 24 hours of the transfusion. • It is characterised by the development of nodules on the lungs • The donor white cell antibodies react with the corresponding antigen on the patient’s white cells and activate complement.

TRALI • Clumps are formed (leuko emboli) which often become trapped in the vessels of the lungs • The reaction can be severe and life threatening. • Fever, chills , non-productive cough – symptoms may be mistaken for respiratory distress syndrome

TRALI • As a form of treatment – the patient may require oxygen. • Avoid diuretics • If the reaction can be traced back to the presence of a white cell antibody in the donor, blood from that particular donor should not be used for the preparation of any plasma products. • Future transfusions for patients with a history of TRALI - Transfuse single donor plasma

TRALI • Donors who have been implicated in these types of reactions need to be either taken off the donor panel or we need to ensure that their plasma is not transfused. • Consider not using plasma from multiparous female donors or donors that have received multiple transfusions

Febrile non-haemolytic reactions (white cell antibodies) • Patients who have white cell antibodies present in their plasma • White cell antibodies or HLA (Human Leukocyte Antigen) antibodies can develop as a result of previous transfusions or pregnancy. • Increase in body temperature of 1° to 2° C. • Chills, fever, malaise, headache. • Can be severe. • To prevent this transfuse leucodepleted blood. • Filtration of blood to remove the leucocytes can either be done in the laboratory or may be done at the patient’s bedside

Potassium Toxicity • Patients who are hyperkalaemic (have high potassium levels) may experience problems if they are transfused with stored blood. • Plasma potassium levels increase on storage and can compromise the health of these patients (e.g. renal patients). • High plasma potassium levels in patients undergoing exchange transfusions may cause cardiac arrest. • It is best to use blood which is less than two weeks old to prevent an adverse event.

Reporting of reactions • Reported to the Blood Bank by the doctor in charge of the patient or a sister • Transfusion must be stopped immediately and the patients details checked – the patient’s information on the blood/blood product against the patient’s file/wristband – to ensure that the correct blood/blood product was being transfused to the correct patient. The doctor in charge must follow the appropriate protocol and submit the following items to the blood bank laboratory for investigation. – A full written report relating to the identity of the patient, location of the patient, diagnosis, indication/s for transfusion and course of the reaction (Transfusion Reaction Form) – All units transfused together with the administration sets (any administration set attached to the unit must not be removed). – 5 ml Post-transfusion blood specimen.

Thrombotic Microangiopathy (TMA) TMA

THROMBOTIC THROMBOCYTOPENIC PURPURA

History • 1924, Dr.Eli Moschcowitz described a 16- year old girl with abrupt onset of petechiae, pallor, followed by paralysis, coma, and death. – Autopsy showed ‘hyaline’ thrombi occluding terminal arterioles and capillaries. – He described the disease to a toxic cause • 1966 pentad • 1978 plasma infusions effective • 1982 vWF • 1991 plasma exchange • 2001 ADAMSTS 13 British J of Hematology 2000

Classic Pentad • Microangiopathic Haemolytic Anemia (MAHA) – Elevated LDH, elevated bilirubin – Schistocytes on the peripheral smear MUST BE PRESENT • Low platelets - MUST BE PRESENT • Fever • Neurologic Manifestations - headache, sleepiness, confusion, stupor, stroke, coma, seizures • Renal Manifestations - haematuria, proteinuria, elevated BUN/Creatinine



Diagnosis • At present there are no confirmatory test. • Other features in pentad support the diagnosis. • Tests for ADAMTS13 deficiency or inhibitors are not readily available and lack standardization.

Diagnosis • Primary diagnostic criteria – Thrombocytopenia ( often below <20,000) – Microangiopathic hemolytic anemia • Negative Coomb’s test. • Fragmented red cells (Schistocytes) on peripheral smear • LDH elevation is the hallmark of RBC destruction and tissue injury related to ischemia. • Presence of above criteria is sufficient to establish presumptive diagnosis & begin PE George,Blood Aug 2000

Neyrinck & Vrielink - Febr 2015 198

Differential Diagnosis • Haemolytic Uremic Syndrome • Thrombotic Microangiopathy • Disseminated Intravascular Coagulopathy • HELLP Syndrome • ITP

Type of TTP • Familial chronic relapsing • Acquired idiopathic • Drug related – Ticlopidine, Clopidogrel • Thrombotic Angiopathies that resemble TTP – Mitomycin, cyclosporine, tacrolimus, quinine – Chemotherapy, gemcitabine, TBI – BM and Solid organ transplant