blood components therapy

Dr. P. Sivaraj MD DA

Govt Villupuram Medical College and Hospital

Blood component therapy

• Optimizes the resources

• Avoids constituents harmful effects

• Specific replacement

Indications

• Perioperative blood component therapy accounts for 23% of transfusions.

• General –

– Inadequate oxygen delivery

– Comorbidity, acuity of anaemia and ability to compensate

Definitions

• Blood product :

Any therapeutic substance prepared from human blood.

• Whole blood:

Unseparated blood collected into an approved container containing an anticoagulant-preservative solution.

Scheme for separation of whole blood for component therapy

Blood components

Comparison of whole bloodand packed red blood cells

Value Whole Blood PRBC• Volume (mL) 517 300• Erythrocyte mass (mL) 200 200• Hematocrit (%) 40 70• Albumin (g) 12.5 4• Globulin (g) 6.25 2• Total protein (g) 48.8 36• Plasma sodium (mEq) 45 15• Plasma potassium (mEq) 15 4• Plasma acid (citric-lactic) 80 25(mEq)• Donor-to-recipient ratio 1 unit per patient 4-6 patients

Properties of whole blood and packed red cell concentrates stored in cpda

Blood component

1. A constituent of blood, separated from whole blood, such as: Red cell components

2. Plasma or platelets

3. Cryoprecipitate, prepared from fresh frozen plasma, which is rich in Factor VIII and fibrinogen

Red cell components

• Red cell concentrate

• Red cell suspension (red cells + additive solution)

• Buffy coat depleted red cells

• Leucocyte-depleted (filtered) red cells

Plasma derivative

Human plasma proteins prepared are:

Albumin

Coagulation factor concentrates

Immunoglobulins

Whole blood

• Fresh whole blood 1. Warm 2. 450ml+63 ml CPDA(>60KG), 350+49 ml CPDA3. 1.5 -4 lakhs platelets4. 100% coagulation5. 1500mg fibrinogen• Restores – 1. Blood volume2. Hemoglobin 3. Platelets 4. Coagulation factors

Whole blood

Advantages• Simple and inexpensive• No special equipment • Red cells, volume and stable coagulation factors.

Disadvantages• Circulatory overload• Donor availability• Screening time • Infection risk

Whole blood

• Storage Between +2°C and +6°C

• May be stored up to 35 days if collected in a suitable anticoagulant such as citrate phosphate dextrose with added adenine [CPDA]

• During storage at +2°C to +6°C, changes in composition occur resulting from red cell metabolism

Whole blood

Indications• Red cell replacement in acute blood loss with

hypovolaemia• Exchange transfusion• Patients needing red cell transfusions where red cell

concentrates or suspensions are not available

Contraindications Risk of volume overload in patients with:• Chronic anaemia• Incipient cardiac failure

Packed red cells

• Concentrated to a hematocrit of about 75%

• volume is made to 200 ml.

• Giving packed red cells is the fastest way to increase the oxygen-delivering capacity of the blood.

• A unit of packed red cells will raise the hematocrit by 3% and the haemoglobin by 1 gm/dl.

RED CELL SUSPENSION

• 150–200 ml red cells with minimal residual plasma to which approximately 110 ml normal saline, adenine, glucose, mannitol solution (SAG-M) or an equivalent red cell nutrient solution has been added

• Haemoglobin approximately 15 g/100 ml• Haematocrit 50–70%Contraindications • Exchange transfusion of neonates.

RED CELL SUSPENSION

Advantages• Reduces viscosity and is therefore easier to

infuse• Longer shelf life than whole blood or red cell

concentrate• Permits the use of the separated components

(plasma/platelets) for other patients.Disadvantages• Cost• Expensive equipment.

Buffy coat’ depleted red cells

• Requires controlled centrifugation

• The white cells (and most of the platelets) remain in a layer called the ‘buffy coat’ which forms an interface between the red cells and the plasma.

Buffy coat’ depleted red cells

Advantages• 10% of the white cells in red cell concentrate• Less risk of transfusion reactions• Used to prepare platelet concentrates.Disadvantages• Costly• Special blood packs and equipment are

required• More skill and operator training is needed.

Washed red cells or micro- aggregate free blood

• RBCs are washed and suspended in sterile saline

• Hematocrits of 70–80%• Volume of approximately 180 ml. • Saline washing –1. Performed at any time during the shelf-life2. Plasma (98%), 3. Reduces the concentration of leukocytes and4. Removes platelets and cellular debris5. Stored for only 24 h at 1–6°C.

Irradiated red cells

• Gamma irradiation- 90% Cesium 137, 10% Cobalt 60

• Damage to WBC DNA

• Prevents GVHD.

• Immuno-compromised patients, lymphoma patients, stem-cell/marrow transplants and intrauterine transfusion.

Leukocyte depleted red cells

• 99.9% of the white cells are filtered out (pre- or post-storage) or removed by freezing/thawing/washing.

• Becoming very popular.

• These reduce (but do not eliminate) the risk of cytomegalovirus (CMV), Epstein-Barr, human T-lymphotropic virus (HTLV) infections and febrile reactions.

Red Cell Substitutes

• There are different types of red cell substitutes currently being studied.

• The goal is to enhance the oxygen-carrying capacity for patients.

• Useful in patients who refuse blood transfusion or in situations where blood is not readily available.

Haemoglobin-Based Oxygen Carriers

• These are purified cell-free hemoglobins• Globulin portion of the molecule has been

modified chemically by conjugation, cross-linking or polymerization.

• Modification increases the oxygen-releasing ability of the haemoglobin.

• The bovine Hemoglobin-Based Oxygen Carriers (HbOCs) has completed phase III clinical trials

Perfluorocarbon-Based Red Cell Substitutes

• These consist of carbon backbones highly substituted with fluorine.

• They can dissolve large amounts of oxygen. • The perfluorocarbons are biologically inert;

however, the phospholipids are required to emulsify them.

• The only perfluorcarbon that remains in clinical trials is Oxygent, an emulsion of perfluoro-ocytl bromide and egg yolk phospholipid.

• Oxygent is being studied for use in perioperative period to allow more extensive hemodilution.

Transfusion trigger

• Level at which a surgical patient needs blood transfusion

Recommendations- The ASA Task Force 2006

• A close watch on assessment of blood loss during surgery and assessment of tissue perfusion is to be maintained.

• Transfusion is rarely indicated when the haemoglobin concentration is greater than 10 gm/dl, and is almost always indicated when it is less than 6 gm/dl.

• For intermediate haemoglobin concentrations (6–10 gm/dl), transfusion based on the patient's risk for inadequate oxygenation.

Recommendations- The ASA Task Force 2006

• Use of a single haemoglobin “trigger” for all patients and other approaches that fail to consider all important physiologic and surgical factors affecting oxygenation are not recommended.

• When appropriate, preoperative autologous blood donation, intraoperative and postoperative blood recovery, acute normovolemic hemodilution and measures to decrease blood loss (deliberate hypotension and pharmacologic agents) may be beneficial.

Platelets

• Platelets are used in the perioperative setting, when a quantitative or qualitative platelet defect is the suspected cause of bleeding.

Normal values:

• Adult = 1.5- 4 lakhs/mm3

• Newborn = 250,000/mm3.

Collection and Storage Pooled Platelets

• Obtaining a “pooled platelet” preparation is a two-step procedure.

• First, one unit of platelets is harvested from a unit of whole blood.

• Then, four to six of these individual units (from different donors) are “pooled” together in a single pack.

Pooled Platelets

• Each bag containing 5000- 8500/mm3 platelets with 50–70 ml of residual plasma volume.

• Disadvantage

1.Exposure to multiple donors

2.Contains 108 – 109 WBCs

3.Platelets expires 4 hours after pooloing

Apheresis Platelets

• Collected from a single donor

• Blood cycles through the apheresis machine- 4000 to 5000 ml/ 1.5 to 2 hrs

• Units contain 3×1011 to 4×1011 platelets

• The amount of platelets collected with this procedure is equivalent of four to six units of random donor platelets.

Dosage

• One platelet concentrate will raise the platelet count in an adult by 7,000–10,000/mm3 at 1 hr in 70kg

• In children, 0.1–0.2 units/kg will increase the platelet count by 30–50,000/cumm.

• Increased consumption is seen in sepsis, splenomegaly, platelet antibodies or chemotherapy.

Platelets

• Leukocyte depleted platelets

1. Platelet pheresis2. Prevents FNHTR3. Reduction of HLA alloimmunisation, CMV,

immunomodulaion

• Irradiated platelets- ultra violet B

1. GVHD

ASA Task Force provided the following recommendations:

1. Prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (e.g., idiopathic thrombocytic purpura).

2. Prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia because of decreased platelet production

ASA Task Force provided the following recommendations:

3. Surgical and obstetric patients with microvascular bleeding usually require platelet transfusion if the platelet count is less than 50 lakhs /mm3

4. Vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss

5. Platelet transfusion may be indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding.

Platelet Products and Substitutes

Cryopreserved platelets• Platelets suspended in dimethylsulfoxide (DMSO)

at –80°C have been preserved up to 10 years.

• During the thawing and post-thaw processing, develop functional and morphologic defects.

• Because of the complexities of storing, processing and thawing frozen platelets, the current use is limited.

Lyophilized platelets

• Lyophilized platelets- paraformaldehyde solution and then freeze-dried.

• Specific advantages of this product include 1. storage measured in years instead of days,2. reduced storage space and true sterility.

• Once rehydrated, they appear to retain structural integrity and attach only to damaged subendothelial surfaces.

Infusible Platelet Membranes (IPMs)

• Infusible Platelet Membranes (IPMs) are manufactured from outdated platelet units.

• Platelet-derived microparticles (microvesicles)- collection and processing of components.

• They appear to have the ability to function as a platelet - primary hemostatic plug.

• One application for IPMs may be in patients who are refractory to platelet transfusions and for whom (HLA)-matched platelet apheresis donors is difficult.

• Disadvantage- relatively short life (less than 24 h) in vivo.

Plasma

FFP• Contain all plasma protein, sodium, phosphates and

some glucose

• FFP is used primarily to provide replacement coagulation factors.

• Concentration of coagulation factor- 0.6 to 1.4IU/ml

• Plasma cholinesterase

Collection, Storage and Transfusion

• Frozen plasma (FP) is prepared from whole blood by separating and freezing the plasma (200–250 ml) within 6 h of donation.

• It may be stored for up to 1 year at –18°C or lower.

• Maintain atleast 70% normal level of labile factors

FFP

• The FFP should be thawed between 30 and 37°C with constant agitation.

• After thawing, it may be stored at 2 – 6 0 C for upto 24 hrs.

• 4 to 6 platelet concentrates, one unit single-donor aphaeresis platelets or one unit fresh whole blood provide a quantity of coagulation factors similar to that contained in 1unit FFP.

FFP

• Therapeutic dose of FFP = 10–15 ml/kg [to achieve a minimum of 30% of plasma factor activity], except for urgent reversal of warfarin anticoagulation, for which 5–8 ml/kg FFP will usually suffice.

• Whenever depletion of coagulation factors is considered to be clinically important, 800–2,000 ml (four to eight packs of FFP) in a 70-kg adult for each blood volume lost should be given over 90–120 min.

• Slower rates of infusion or smaller volumes of FFP are probably ineffective.

Indications

• FFP is indicated for use in- – Bleeding patients with multiple coagulation

factor deficiencies secondary to liver disease,

– Disseminated intravascular coagulation (DIC) and

– Dilutional coagulopathy resulting from massive blood or volume replacement

Indications

It is also indicated for patients with • congenital factor deficiencies such as deficiencies of

Factor V or XI.

• FFP is also used along with plasmapheresis in the treatment of thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome.

• FFP should not be used as a source of protein for nutritionally deficient patients or as a volume expander.

Recommendations:

• Urgent reversal of warfarin therapy• Correction of known coagulation factor deficiencies • Correction of microvascular bleeding in the

presence of elevated (>1.5-times normal) prothrombin time (PT) or partial thromboplastin time (PTT)

• Correction of microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume and when PT and PTT cannot be obtained in a timely fashion

Recommendations:

• Heparin resistance in pts receiving unfractionated heparin

• FFP should be given in doses calculated to achieve a minimum of 30% of plasma factor concentration

• FFP is contraindicated for augmentation of plasma volume or albumin concentration

• FFP should not be used to reconstitute packed RBCs

• FFP should not be used as a source of proteins or routinely after cardiopulmonary bypass

Cryoprecipitate

• Contains 100 antihemophilic units (AHU) and 250 mg of fibrinogen.

• It is thawed at 37°C and administered through a standard blood filter and as rapidly as possible- 200 ml/hr within 6 hrs of thaw

• Contain fibrinogen, fibronectin, vWF,VIII,XIII.

• 1 unit of plasma – 10 to 20 ml of cryoprecipitate

• Dose- adult- 5 bags

• Frozen at -200 C

Indications

1. Microvascular bleeding with hypofibrinogenemia• DIC with fibrinogen < 80-100 mg/dl• Hemorrhage or massive transfusion with fibrinogen <

100-150 mg/dl

1. Prophylaxis in hemophilia A and vWD2. Prophylaxis in congenital dysfibrinogenemia

• One unit of cryoprecipitate per 10 kg body weight raises the plasma fibrinogen concentration by approximately 50 mg/dl in the absence of continued consumption or massive bleeding.

Cryoprecipitate Reduced Plasma

• Cryoprecipitate Reduced Plasma (CRP) is the plasma remaining once the cryoprecipitate has been prepared.

• Contain vWF enzyme- degrade the existing multimers.

• Therapeutic plasma exchange (TPE) is the only disease in which the component is used as therapeutic treatment

Virus ‘inactivated’ plasma

• Methylene blue/ultraviolet light- to reduce the risk of HIV, hepatitis B and hepatitis C.

• The ‘inactivation’ of other viruses, such as hepatitis A and human parvovirus B19 is less effective.

• The cost of these products is considerably higher than conventional fresh frozen plasma.

Fibrin Glue

• Two main components, i.e. fibrinogen and thrombin.

• The thrombin converts the fibrinogen to fibrin by enzymatic action.

• The concentrated thrombin solution produces a fibrin clot in about 10s.

• Both the extrinsic and the intrinsic mechanisms of blood coagulation are bypassed with the use of fibrin glue.

Plasma derivatives containing factor IX

Prothrombin Complex Concentrate (PCC)• Koyne, Proplex• Factor IX is recovered – ion exchange or inorganic

chemicals• Bebuin VH- vit k• Description Contains: PCC Factor IX• Factors II, IX and X • Some preparations also contain Factor VII • Usually about 350–600 i.u. of Factor IX• Infection risk As Factor VIII• Storage As Factor VIII

Prothrombin Complex Concentrate

• Indications

1. Treatment of haemophilia B (Christmas disease)2. Immediate correction of very prolonged

prothrombin time

• Contraindications

1. PCC not advised in patients with liver disease or thrombotictendency

Fibrinogen concentrate

• Derived from human plasma

• Potential to improve hemostasis more rapidly

• Low risk of immunologic reactions, infections and intra vascular volume overload

• Single dose of 4gm- 200mg/dl of fibrinogen

• Reduces platelets admin and number of donor exposure

Plasma Protein Fractions

• Albumin – 5% & 25%

• α & β Globulin

• Volume expanders

• No coagulation factors

• Given without ABO Rh typing

• Very expensive

• Short supply

• Bacterial sepsis- albumin- < 4hrs

Recommendations for Preadmission Patient Preparation

• Erythropoietin with or without iron may be administered when possible to reduce the need for allogeneic blood in selected patient populations (e.g., renal insufficiency, anemia of chronic disease, refusal of transfusion).

• Administer iron to patients with iron deficiency anemia if time permits.

• In consultation with an appropriate specialist, discontinue anticoagulation therapy (e.g., warfarin, anti-Xa drugs, antithrombin agents) for elective surgery.


• Transition to a shorter acting drug (e.g., heparin, low-molecular-weight heparin) may be appropriate in selected patients.

• If clinically possible, discontinue nonaspirin antiplatelet agents (e.g., thienopyridines such as clopidogrel, ticagrelor, or prasugrel) for a sufficient time in advance of surgery, except for patients with a history of percutaneous coronary interventions.

• Aspirin may be continued on a case-by-case basis.


• The risk of thrombosis versus the risk of increased bleeding should be considered when altering anticoagulation status.

• Assure that blood and blood components are available for patients when significant blood loss or transfusion is expected.

• When autologous blood is preferred, the patient may be offered the opportunity to donate blood before admission only if there is adequate time for erythropoietic reconstitution.

Recommendations for Preprocedure Preparation

• Blood Management Protocols.• Multimodal protocols or algorithms may be

employed as strategies to reduce the usage of blood products.

• A restrictive red blood cell transfusion strategy may be safely used to reduce transfusion administration.

– The determination of whether hemoglobin concentrations between 6 and 10 g/dl justify or require red blood cell transfusion should be based on potential or actual ongoing bleeding (rate and magnitude), intravascular volume status, signs of organ ischemia, and adequacy of cardiopulmonary reserve.


– Red blood cells should be administered unit-by-unit, when possible, with interval reevaluation.

• A protocol for avoidance of transfusion may be used as a strategy to reduce blood loss for patients in whom transfusion is refused or is not possible.


• A massive (i.e., hemorrhagic) transfusion protocol may be used when available as a strategy to optimize the delivery of blood products to massively bleeding patients.

• Use a maximal surgical blood order schedule, when available and in accordance with your institutional policy, as a strategy to improve the efficiency of blood ordering practices.


• Reversal of Anticoagulants

• For urgent reversal of warfarin, administer PCCs in consultation with the appropriate specialist, or administer FFP.

• Administer vitamin K for selected patients for nonurgent reversal of warfarin, except when rapid restoration of anticoagulation after surgery is required.

• Antifibrinolytics for Prophylaxis of Excessive Blood Loss.

• Use antifibrinolytic therapy for prophylaxis of the use of allogeneic blood transfusion in patients undergoing cardiopulmonary bypass.


• Antifibrinolytics for Prophylaxis of Excessive Blood Loss.

• Use antifibrinolytic therapy for prophylaxis of the use of allogeneic blood transfusion in patients undergoing cardiopulmonary bypass.– Consider using antifibrinolytic therapy for

prophylaxis in certain orthopedic procedures such as knee replacement surgery.

– Consider using antifibrinolytic therapy for prophylaxis in liver surgery and other clinical circumstances at high risk for excessive bleeding.


• Acute Normovolemic Hemodilution (ANH).

• Consider ANH to reduce allogeneic blood transfusion in patients at high risk for excessive bleeding (e.g., major cardiac, orthopedic, thoracic, or liver surgery), if possible.

Recommendations for Intraoperative and Postoperative Management of Blood Loss

• Allogeneic Red Blood Cell Transfusion.• Administer blood without consideration of duration of storage.

• Leukocyte-reduced blood may be used for transfusion for the purpose of reducing complications associated with allogeneic blood transfusion.

• Reinfusion of Recovered Red Blood Cells.

• Reinfuse recovered red blood cells as a blood-sparing intervention in the intraoperative period, when appropriate.


• Intraoperative and Postoperative Patient Monitoring.• Periodically conduct a visual assessment of the surgical field

jointly with the surgeon to assess the presence of excessive microvascular (i.e., coagulopathy) or surgical bleeding.

• Use standard methods for quantitative measurement of blood loss, including checking suction canisters, surgical sponges, and surgical drains.

• Monitor for perfusion of vital organs using standard ASA monitors (i.e., blood pressure, heart rate, oxygen saturation, electrocardiography) in addition to observing clinical symptoms and physical exam features.


– Additional monitoring may include echocardiography, renal monitoring (urine output), cerebral monitoring (i.e., cerebral oximetry and NIRS), analysis of arterial blood gasses, and mixed venous oxygen saturation.

• If anemia is suspected, monitor hemoglobin/hematocrit values based on estimated blood loss and clinical signs.

• If coagulopathy is suspected, obtain standard coagulation tests (e.g., INR, aPTT, fibrinogen concentration) or viscoelastic assays (e.g., TEG and ROTEM), if available, as well as platelet count.


– During and after transfusion, periodically check for signs of a transfusion reaction including hyperthermia, hemoglobinuria, microvascular bleeding, hypoxemia, respiratory distress, increased peak airway pressure, urticaria, hypotension, and signs of hypocalcemia.

– If signs of a transfusion reaction are apparent, immediately stop the transfusion, give supportive therapy, and initiate supportive care.

– Notify the blood bank of the transfusion reaction case.


• Treatment of Excessive Bleeding.

• In patients with excessive bleeding, the following recommendations are made based upon the evidence for each of these interventions when studied singly or when compared with placebo. The impact of combinations of these interventions is not addressed in these Guidelines.


– Obtain a platelet count before transfusion of platelets, if possible.In addition, obtain a test of platelet function, if available, in patients with suspected or drug-induced (e.g., clopidogrel) platelet dysfunction.


– Obtain coagulation tests (i.e., PT or INR and aPTT) before transfusion of FFP, if possible

– Assess fibrinogen levels before the administration of cryoprecipitate, if possible.


– Desmopressin may be used in patients with excessive bleeding and platelet dysfunction.

– Consider topical hemostatics such as fibrin glue or thrombin gel.

– Consider the use of antifibrinolytics (i.e., ε-aminocaproic acid, tranexamic acid) if fibrinolysis is documented or suspected and if these agents are not already being used.


– PCCs may be used in patients with excessive bleeding and increased INR.

– Consider recombinant activated factor VII when traditional options for treating excessive bleeding due to coagulopathy have been exhausted.

– Fibrinogen concentrate may be used.

ASA transfusion guidelines

Products Usually indicated Not usually indicated

RBCs < 6gdl-1 > 10gdl-1

FFPPT/aPTT > 1.5 times normal

PT/aPTT< 1.5 times normal

Platelets < 50000 > 100000

CryoprecipitateFibrinogen < 80-100 mg/dl

Fibrinogen > 80-100 mg/dl

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Date post:	23-Jan-2018
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blood components therapy

Health & Medicine