BLOOD, COAGULATION AND TRANSFUSION DR RIZWAN ANSARI FCPS ANESTHESIOLOGY
Blood is composed of PLASMA(55%) and FORMED ELEMENT(45%) INTRODUCTION Blood is a specialized body fluid .
MAIN FUNCTIONS OF BLOOD Transporting oxygen and nutrients to the lungs and tissues. Forming blood clots to prevent excess blood loss. Carrying cells and antibodies that fight infection.
Red blood cells I n adults the majority of haemoglobin present is HbA (comprising two α- and two β- globin chains: α2β2 ). A small amount of HbA2 is also present (α2δ2 ), as is an even smaller amount of fetal haemoglobin , HbF (α2γ2 )
Efficiently correct tissue hypoperfusion Prevent coagulopathy Anaemic hypoxaemia M inimising the risk of transfusion-related adverse outcomes for patients. BLOOD COMPONENT THERAPY A im to give the right blood products to the right patients at the right time in the right amount . The goal of transfusion is to :
STEPS OF BLOOD AND ITS COMPONENT COLLECTION 1. Donation 2. Compatibility Testing 3. Screening for infectious diseases 4 . Blood processing
Donation and testing Whole blood donation Each donor provides 500mL of blood. A total of 470mL goes on to be processed while 30mL is utilised for routine testing. Donors can typically give blood four times annually Apheresis donation A cell separator is used to collect plasma, platelets, white cells or haematopoietic progenitor cells. Donor red cells are returned to the donor. Donors may give these fractions every 2weeks
PLATELET APHRESIS
Compatibility testing ABO compatibility prevents acute haemolytic transfusion reactions caused by recipient IgM antibodies binding A or B antigens on donor red cells. Red cells express ABO antigens and recipients must be transfused with ABO-compatible units to prevent serious harm or death. Platelets weakly express ABO antigens . Therefore, recipients should be transfused with ABO-compatible units . Non-ABO-compatible units of platelets can be used in the event of life-threatening haemorrhage , but these platelets will have a reduced lifespan Cryoprecipitate and FFP contain anti-B or anti-A IgM antibodies , depending on the donor blood group. For donated plasma to be compatible, it must not contain IgM antibodies against antigens expressed on recipient cells.
Red cells express RhD antigens. This is of particular importance for all ♀ of reproductive potential to prevent future haemolytic disease of the newborn (due to maternal anti-D harming RhD -positive fetuses). Platelets do not express RhD antigens . However, units should be RhDcompatible with the recipient as the RhD antigen is highly immunogenic and residual red cells in the units may sensitise RhD -negative patients Cryoprecipitate and FFP may contain red cell fragments ; however, these are far less immunogenic than whole red cells. Therefore, cryoprecipitate and FFP of any RhD type can be safely given. RhD compatibility
BLOOD COMPONENTS PACKED RED BLOOD CELL(PRBC) Derived from Centrifuged from singledonor whole blood Composed of Hct 50–70% suspended in SAGM Volume 300mL Storage 2–6°C Shelf-life 35d Dose 4mL/kg will increase Hb by 1g/ dL The glucose provides an energy source for the metabolic requirements of the cells, and adenine helps maintain cellular levels of ATP. Saline and mannitol provide an aqueous medium of appropriate osmolality and pH.
Platelets Derived from centrifugation from 4–6 whole blood donations or by apheresis from a single donor Composition >240 × 109 platelets Volume 300mL storage 20–24°C on an agitator Shelf-life 7days Dose 1 unit will increase platelet count by 20–40 × 109 /L
FRESH FROZEN PLASMA Derived from Apheresis donation from a male donor. Rapidly frozen within 8h of donation COMPOSITION: 0.5g fibrinogen, factor VII >0.7IU/ mL , labile factors Volume 300mL STORAGE –30°C SHELF LIFE 2y (frozen) 4h (thawed 2–6°C) DOSE 10–15mL/kg
Cryoprecipitate Controlled thawing of single-donor FFP. Pooled from 4–6 donors COMPOSITION :2g fibrinogen, vWF , factor VIII, factor XIII, fibronectin , factor VII >1.5IU/ mL VOLUME Pooled 100–200mL STORAGE –30°C SHELF LIFE 2y (frozen) 4h (thawed room temp) DOSE 1 unit per 30kg body weight to increase plasma fibrinogen by 1.0g/L
Other derived products Fibrinogen concentrate F reeze-dried powder containing 1g of purified human fibrinogen Stored at room temperature for up to 3 month R aises a patient’s fibrinogen by 0.25g/ dL No thawing or blood type matching is required. COST $2300
Recombinant factor VIIa A freeze-dried powder used in patients with congenital factor VII deficiency, in bleeding episodes in patients with haemophilia A or B, with inhibitors to factors VIII or IX, and occasionally in those with severe uncontrolled bleeding as part of a massive transfusion . Dose is 90 micrograms/kg IV
It is a sterile, freeze-dried powder for reconstitution containing 500IU of purified human factors II, XII and X. Prothrombin complex concentrate Prothrombinex ®) Used to replace congenital factor deficiencies when purified single-factor concentrates are unavailable, or for the reversal of vitamin K antagonist anticoagulants (e.g. warfarin ) Dosing is dependent on coagulation studies, desired clotting profile, patient weight and the factor deficiency being reversed .
Safe transfusion Informed consent. Confirm patient identity, verbally with the patient if possible and by identification band. Check unit to be transfused against prescription. Check unit is within expiry date and that unit numbers match between the laboratorygenerated label attached to the pack and the pack itself.
Inspect the bag, ensuring integrity of the plastic casing. Look for discoloration or evidence of clumping. Infuse through a blood administration set with a 170–200 micrometres integral screen filter. Typically each filter can be used for 4 units of packed red cells during normal transfusion or 8–10 units during a massive transfusion, provided flow rates are adequate without evidence of clogging of the filter.
Platelet concentrates should not be infused through giving sets that have been used for red cells due to risk of clumping. Infuse each unit within recommended time frames Monitor for adverse events. Documentation. A 100% traceability of transfused blood is a legal requirement around world.
Management of hemolytic reactions can be summarized as follows: If a hemolytic reaction is suspected, the transfusion should be stopped immediately and the blood bank should be notified. The unit should be rechecked against the blood slip and the patient’s identity bracelet. Blood should be drawn to identify hemoglobin in plasma, to repeat compatibility testing, and to obtain coagulation studies and a platelet count. A urinary bladder catheter should be inserted, and the urine should be checked for hemoglobin. Forced diuresis should be initiated with mannitol and intravenous fluids, and with a loop diuretic if necessary.
Transfusion indications and triggers Clinical judgement , lab results, POCT and best available evidence determine the blood components to be prescribed, as well as the timing, dose and rate of administration Globally, red cell transfusion policies have become increasingly restrictive in response to emerging evidence of harm associated with unnecessary transfusion. FFP should not be given for prolonged PT or INR in the absence of bleeding
TRANSFUSION RISK Common Febrile non- haemolytic transfusion reaction (1–3:100) occurs within 30min of transfusion and is mediated by either cytokines or alloimmune reactions to contaminant leucocytes. Simple cooling and paracetamol are sufficient for mild reactions Minor allergy (1–5:500) commonly presents with mucocutaneous manifestations, flushing, angio-oedema or urticaria due to recipient antibodies against leucocyte antigens or plasma proteins.
Transfusion-associated circulatory overload) (1–10:1000 Incidence is determined by both the volume transfused and patient comorbidity . Hypothermia Prevalent in rapid infusions of large volumes of blood products. Can worsen all physiological processes, including cardiovascular function and coagulation. Immunosuppression . Transfusion may influence the recurrence or spread of malignancies, as well as the incidence of postoperative bacterial infections through immunomodulation
Rare complication Acute haemolytic transfusion reaction (1–8:100 000). Severe, lifethreatening reaction occurring within 24h of red cell transfusion due to ABO incompatibility. Recipient antibodies bind to and haemolyse transfused erythrocytes, causing complement activation, inflammation, DIC and shock. Signs and symptoms may be indistinguishable from bacterial sepsis or anaphylaxis Delayed haemolytic transfusion reaction (1:5000). Usually occurs within 7d but may occur up to 28d after transfusion due to previous recipient allosensitisation to erythrocyte antigens during pregnancy or a previous transfusion . Results in jaundice, anaemia and rarely splenomegaly and renal injury due to haemoglobinaemia .
TRANSFUSION RELATED ACUTE LUNG INJURY (TRALI ) (<1:5000).). Non- cardiogenic pulmonary oedema which occurs within 6h of transfusion of plasma or plasma-containing components.. Severe microvascular injury results from recipient antibody reactions against transfused leucocyte or neutrophil antigen. Viral infection Screening of donors and donated blood for viral infections reduce most risk. Residual risk results from individuals donating blood during ‘window periods’ of active viral infection . TA- GvHD A usually fatal complication occurring 1–6w following transfusion. Transfused viable lymphocytes engraft within an immunocompromised host. These engrafted lymphocytes proliferate and precipitate multiorgan failure and death through autoimmunity
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Massive transfusion More than 5 units of PRBCs transfused in <4hrs or 10 units of PRBCs administered to a patient within 24h is considered as massive transfusion. DEFINITION
Physiology of massive haemorrhage and transfusion Rapid, large-volume haemorrhage results in systemic hypoperfusion and reduced O2 delivery to tissues, causing acidosis. Hypoperfusion also activates the protein C pathway, deactivating factors Va and VIIIa and initiating fibrinolysis and coagulopathy . Consumption of clotting factors may lead to DIC. Administration of cold IV fluids and exposure of the patient for vascular access and resuscitation may lead to hypothermia. Hypothermia and acidosis reduce myocardial contractility, precipitate bradycardia and dysrhythmias and cause vasodilation and hypotension. They also reduce activity of clotting factors and platelets, with clotting factor function d by 10% for every 0.1 reduction in pH. Transfused red cells are not as effective at O2 delivery as endogenous red cells
Resuscitation priorities during massive haemorrhage and transfusion 1. Adequate staffing and assistance 2. Maintain circulating volume Obtain rapid source control of haemorrhage (e.g. surgical, endoscopic, interventional radiology). Immediately request 3 units of PRBCs; use O-negative emergency blood if X-matched blood not immediately available. Obtain large-bore IV access; give crystalloid until blood arrives. Increase FiO2 to 100% to improve tissue O2 delivery. Consider reducing dose of anaesthetic agent administered.
3. Prevent hypothermia Forced air warming devices (e.g. Bair Hugger™) • Increasing the ambient room temperature Infusing fluids via fluid warmers. 4. Prevent and treat coagulopathy Balanced transfusion of blood products in 1:1:1 ratio. Identify factor deficiencies and detect DIC. ABG, formal FBC, coagulation studies and electrolytes sent to the lab and marked as urgent—should be performed every 30min. Consider dose of antifibrinolytic ( tranexamic acid, 1g IV over 10min) if within 3h of traumatic event. •
Treat sequelae of massive transfusion Treat Citrate toxicity which causes hypocalcemia and Treat Hyperkalemia by giving slow IV injection of 10mL of calcium chloride 10% Consider recombinant factor VIIa ( NovoSeven ®; 90 micrograms/kg IV) if surgical bleeding controlled and pH >7.2. Use with caution in patients at risk of thrombosis and discuss with haematologist . Discuss with haematologist in non-surgical uncontrolled bleeding (e.g. variceal bleeding) unresponsive to PRBCs/FFP/platelets, anticoagulated patients or patients with inherited bleeding disorders.
Treatment goals Mean arterial pressure : Do not aim to normalise until there is surgical control. >50mmHg (>70mmHg if head injury). Haemoglobin : >7g/ dL . Fibrinogen : >1.5g/L (>2g/L in obstetric patients). Platelets : >75 × 109 /L. Ionised calcium : >1mmol/L on blood gas sample. pH : 7.35–7.45. mmol /L on blood gas sample. PT/APTT : <1.5 times upper limits of normal