Blood Component Therapy

Presenter: Dr Manjunath GModerator: Dr Jaideep Ravi & Dr Jiju Joseph

• based on the concept that patients are best treated by administration of the specific fraction of blood that they lack.

• One donated unit can help multiple patients– Conserves resources– Optimal method for transfusing large

amounts of a specific component

PACKED RED CELLSGRANULOCYTESPLATELET CONCENTRATE

FRESH FROZEN PLASMACRYOPRECIPITATECOAGULATION FACTOR CONCENTRATES

PLASMA PROTEIN FRACTION• ALBUMIN• GAMMA GLOBULIN• IVIG

• Blood components are also collected by apheresis, in which the donor’s blood is processed by ex vivo centrifugation(apheresis machine), the desired component(s) are siphoned off into citrate anticoagulant(to recipient), and the rest returned to the donor.

• Reduces the number of donor exposures to a patient.

–Plasmapheresis- to harvest plasma

– Leukapheresis- to harvest leukocytes

–Granulocytapheresis- to harvest granulocytes

– Erythroaphersis- to harvest erythrocytes

–Plateletaphersis- to harvest platelets

Complications• Sudden fluid shifts – hypotension, volume

overload. • Paraesthesia and other manifestations of

hypocalcemia (large volume procedures).

• Donor’s discomfort- sit for three hrs

• Associated cost.

Whole bloodWhole blood has a shelf life of 35 days and

typically, 70ml of citrate preservative solution is added to 420 ml blood.

Whole Blood, Leucocyte DepletedA unit of blood collected into an

anticoagulant, containing less than 5*106 leucocytes.

Use of whole blood• Rarely used now a days• Infrequently used in massive trauma• Cardiac surgeries• Post operative bleeding unresponsive to

standard replacement therapy.• paediatric practice, mostly for neonatal

exchange transfusion or paediatric surgery (cardiac or craniofacial).

• no compelling evidence was found for its routine use.

Component vs. Whole Blood Trauma Trial(COW BITT)

4 year multicenter prospective randomized trial ‐ 300 patients,Ongoing trialConculsion awaited.

PACKED RED BLOOD CELLS

• produced by removing between 150-200ml of citrated plasma from a unit of whole blood.

• stored under refrigeration at controlled temperatures of 1 to 6°C to maintain the viability of the red cells and to prevent the growth of bacteria.

PACKED RED BLOOD CELLS

• Preservative solutionsCPD -21daysCPDA -35 daysSAGM – 42 daysAS-1 (Adsol), AS-3 (Nutricel), or AS-5 (Optisol) – 42 days

PACKED RED BLOOD CELLS

• Preservative solutionsCPD -21daysCitrate is an anticoagulant,phosphate serves as a buffer,dextrose is a red cell energy source

PACKED RED BLOOD CELLS

• Preservative solutionsCPDA -35 days

adenine allows RBCs to resynthesize adenosine triphosphate (ATP), which extends the storage time from 21 to 35 days.

PACKED RED BLOOD CELLS• Preservative solutionsAS-1 (Adsol)-adenine, glucose, mannitol, and

sodium chloride.

AS-3 (Nutricel)-glucose, adenine, citrate, phosphate, and NaCl

AS-5 (Optisol)-, adenine, NaCl, and mannitol

PACKED RED BLOOD CELLSLeukoreducedIrradiatedSaline washedCMV negative Antigen Negative Sickle negative Frozen thawed

Leukoreduced

A red cell component prepared by removing a proportion of the plasma from leucocyte depleted whole blood or by leuco-depleting plasma reduced red cells.

• Non-LR RBC contain 1-3 x 109 WBC • LR contain < 5 x 106 WBC and retains 85% of the

original cells.

Leukoreducedcertain complications of PRBCs are likely due to leukocytes, Eg- HLA alloimmunization against class I antigens, febrile reactions, and CMV infections.

By leuckoreduction, chances of a febrile reaction can be reduced, especially (alloimmunized from pregnancy, risk for HLA alloimmunization from blood transfusions can be reduced),

which would be especially helpful in minimizing refractoriness to platelet transfusions, and the risk for CMV can be reduced (CMV-ve PRBC more safe).

LeukoreducedIndications are-

chronically transfused patients,potential transplant recipients, patients with transplants, patients with previous febrile nonhemolytic

transfusion reactions, and CMV-seronegative at-risk patients for

whom seronegative components are not available.

Leukoreduced-leukoreduction has been seriously considered or implemented because of some anticipated benefits, including decreased transmission of variant Creutzfeldt-Jakob disease, leukocyte-induced immunomodulation, and even decreased postoperative mortality.

-universal leukoreduction is the direction in which transfusion medicine has gone.

Irradiated-PRBC units are exposed to gamma irradiation (2,500

cGy) to damage donor WBC DNA.

-prevent a cellular immune proliferative response to the recipient’s tissues.

-usually performed in cesium-137 blood irradiators,

Irradiated-PRBC units are exposed to gamma irradiation (2,500

cGy) to damage donor WBC DNA.

-prevent a cellular immune proliferative response to the recipient’s tissues.

-component must be irradiated within 14 days of donation and it then has a shelf life of 14 days from irradiation.

IrradiatedIndications: – Units from blood relatives – Allo/Auto HPC Transplant Recipients – Intrauterine transfusion – highly immunosuppressed patients at risk for this

complication(GVHD)– Neonates/Infants undergoing exchange transfusion or

ECMO – Hodgkin’s Disease – Cellular immune deficiency

-Solid Organ Transplants

Washed red cells (Microaggregate-free blood)designed machines are used to wash the red blood cells (RBCs), which are then suspended in sterile saline.

Saline washing removes residual plasma (98%), and reduces the concentration of leucocytes, platelets and cellular debris.

can carried out at any time during the shelf life of a unit of blood.

Washed red cells (Microaggregate-free blood)

Washed red cells usually have haematocrits of 70-80% and a volume of about 180ml.

Indications-• Patients with recurrent or severe allergic or febrile reactions to red

cells,

• Severely IgA-deficient patients with anti-IgA antibodies for whom red cells from an IgA deficient donor are not available

• Microaggregate-free blood is used to prevent reactions to leucocyte and platelet antigens.

CMV negative

Indications-• All neonates (up to 4 months old) • Intrauterine Transfusions • High risk lung transplant (-ve to -ve) • Allogeneic stem cell transplants (-ve to –ve) • DiGeorge Syndrome.

• Frozen RBC

Freezing to preserve rare RBC units

RBCs frozen in 40 percent glycerol are approved by the FDA and the AABB for storage at -80ºC for up to 10 years.

CHANGES DURING STORAGE OF BLOOD

• blood can be stored for 42 days is a mixed blessing, the obvious advantage is the increased availability of blood.

• Numerous changes occur during storage and affect the quality of transfusion.

During storage, RBCs metabolize glucose to lactate, hydrogen ions accumulate, and plasma pH decreases.

The storage temperatures of 1° to 6° C stimulate the sodium-potassium pump, and RBCs lose K+ and gain Na.

The osmotic fragility of RBCs increases during storage, and some cells undergo lysis, resulting in increased plasma Hb levels.

Progressive decreases in RBC concentrations of ATP and 2,3-diphosphoglycerate (2,3- DPG) occur during storage.

CLINICAL IMPLICATIONS: DURATION OF BLOOD STORAGE• Purdy and colleagues found that patients who received

17-day-old blood (range, 5 to 35 days) versus 25-day-old blood (range, 9 to 36 days) had a more frequent survival rate.

• Weiskopf and associates performed studies in healthy volunteers they concluded that erythrocytes stored for 3 weeks are as efficacious as those stored for 3.5 hours.

• Postulated that 2,3-DPG levels may not be the key factor in determining the delivery of O2

CLINICAL IMPLICATIONS: DURATION OF BLOOD STORAGE• Although conclusions cannot be definitive, logic dictates

that blood less than 14 days of storage should be better than older storage.

• The Age of Red Blood Cells in Premature Infants (ARIPI) trial

• The Age of Blood Evaluation (ABLE) trial• The Red Cell Storage Duration Study (RECESS).

• Underway, may provide in helping decisions in future.

Transfusion trigger-Clinical Practice Guidelines

• 1980: The National Institutes of Health• 1984: The American College of Obstetricians and Gynaecologists (ACOG)• 1990: The Transfusion Practices Committee of the American Association of Blood

Banks (coronary artery bypass surgery)• 1992: The American College of Physicians (ACP)• 1994: The College of American Pathologists (CAP) - fresh frozen plasma (FFP),

cryoprecipitate and platelet transfusion• 1994: The American Association of Blood Banks• 1996: American Society of Anaesthesiologists – Task Force on Blood Component

Therapy• 2006: An Updated Report by the American Society of Anesthesiologists Task Force on

Perioperative Blood Transfusion and Adjuvant Therapies.• Oct 2015- Awaiting.

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), justifying or requiring RBC transfusion should be based on the patient's risk for complications of inadequate oxygenation.

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.

• The indications for transfusion of autologous RBCs may be more liberal than for allogeneic RBCs because of the lower (but still significant) risks associated with the former.

Monitoring for blood loss.

A visual assessment of the surgical field should be periodically conducted to assess the presence of excessive microvascular bleeding (i.e , coagulopathy).

Standard methods for quantitative measurement of blood loss (e.g., suction and sponge) should be used.

Monitoring for inadequate perfusion and oxygenation of vital organs.

Conventional monitoring systems (e.g. , blood pressure, heart rate, oxygen saturation, urine output, electrocardiography) should be used to assess the adequacy of perfusion and oxygenation of vital organs.

Monitoring for inadequate perfusion and oxygenation of vital organs.

Clinical indications of tissue hypoxia Unstable vital signs• Tachycardia• Hypotension• Tachypnea or dyspnea

Laboratory and invasive monitor indices• Mixed venous O2 saturation (SVmO2) <50%• Central venous O2 saturation (SVcO2) <60%• Increased O2 extraction ratio (O2ER) >50%• Lactic acidosis (metabolic acidemia with lactate >2 mmol/L)

Clinical indications of tissue hypoxia

Signs of end-organ dysfunctionElectrocardiographic (ST changes, onset of arrhythmias) or

echocardiographic indications of myocardial ischemia

Electroencephalographic indications of cerebral hypoperfusion

New onset oliguria (less than 0.5 mL/kg/h for >6 h)

Monitoring for transfusion indications.• Measure hemoglobin or hematocrit when substantial

blood loss or any indication of organ ischemia occurs.

• Red blood cells should usually be administered when the hemoglobin concentration is low (e.g. , less than 6 g/dl in a young, healthy patient), especially when the anemia is acute.

• Red blood cells are usually unnecessary when the hemoglobin concentration is more than 10 g/dl.

Monitoring for transfusion indications-

• determination of whether intermediate hemoglobin concentrations (i.e. , 6–10 g/dl) justify or require red blood cell transfusion

• Based on– ongoing indication of organ ischemia, – potential or actual ongoing bleeding (rate and magnitude), – the patient's intravascular volume status, and – the patient's risk factors for complications of inadequate

oxygenation.

• The most recent update the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines

they state that “Transfusion is reasonable in most postoperative patients whose hemoglobin is less than 7 g/dL.” For patients with hemoglobin levels between 7 and 10 g/dL they recommend transfusion in patients with “critical noncardiac end-organ ischemia,” active blood loss, or clinical indication of tissue hypoxia (low mixed venous oxygen saturation or electrocardiographic or echocardiographic evidence of myocardial ischemia)

MASSIVE TRANSFUSION• Adults, as a transfusion of half of one blood

volume in 4 hours, or more than one blood volume in 24 hours (adult blood volume is approximately 70 mL/kg)

• Children, as a transfusion of more than 40 mL blood/kg (blood volume of children older than neonates is approximately 80 mL/kg).

put forward by different groups

• Transfusion which involve 10% blood volume replaced in 10 min or less(50ml/min in a average adult).

• Any transfusion in which 1 unit of blood is given in 5 min.

Indications• Trauma, crush injury• Orthopedic surgery• Liver surgery- transplantation

The decision to start, depends onthe physiological state of patientevidence of amount of blood losspotential for ongoing hemorrhage

Complications• Volume dependent– Dilutional coagulopathy– Volume overload– Micro-aggregates

• Rate dependent– Hypothermia– Citrate toxicity– Electrolyte imbalances– Acid- base abnormalities

•Massive blood transfusion is a life saving procedure, it

should not be taken too lightly

GRANULOCYTE TRANSFUSIONS• The buffy coat contains a high concentration of

white cells and platelets.

• Buffy coats that are not used to make platelet concentrates are used for granulocyte production.

• Apheresis technique can also be employed for collecting granulocytes.

GRANULOCYTE TRANSFUSIONS

• Granulocytes, Pooled, Buffy Coat Derived, in Platelet Additive Solution and Plasma, Irradiated.

• Leucocytes, Buffy Coat, Irradiated (If above not available).

GRANULOCYTE TRANSFUSIONS

• Granulocytes are stored at 22+2ºC without agitation.

• Each pack of Leucocytes, Buffy Coat, Irradiated – 50ml in volume, has a haematocrit of 45%, contains 1-2

x109 white cells, 90x109 platelets and 9.5g of haemoglobin.

GRANULOCYTE TRANSFUSIONS- Dosing

• A dose of ten packs for adults.

• 10 -20ml / kg for children less than 50kg (to a maximum of 10 packs).

• Children less than 30Kg should receive 10-20ml/Kg to a maximum of two packs.

Indications

• Therapeutic granulocyte transfusions indicated

-for patients with a known congenital disorder of

neutrophil function, regardless of neutrophil count with

proven or highly probable fungal or bacterial infection

unresponsive to appropriate antimicrobial therapy,

demonstrated by visible spreading lesions on skin, mucosa

or radiological examination.

Indications• Severe neutropenia, defined as ANC <0.5 x 109/L1 due to

congenital or acquired bone marrow failure syndromes.

• Receiving active treatment in an attempt to achieve disease remission.

• Proven or highly probable fungal or bacterial infection that is unresponsive to appropriate antimicrobial therapy as demonstrated by visible spreading lesions on skin, mucosa or radiological examination.

• In whom neutrophil recovery is expected (ANC>0.5x109/l) in the near future and / or in whom definitive therapy of curative potential is planned.

PLATELET CONCENTRATES

• Two methods to collect this component

– Random donor pooled platelets

– Single donor Apheresis platelets

PLATELET CONCENTRATES• A single unit of platelets can be isolated from

every unit of donated blood, by centrifuging the blood within the closed collection system to separate the platelets from the red blood cells (RBC).

• As the platelet number is inadequate, four to six units are pooled together. These are called whole blood-derived or random donor pooled platelets

PLATELET CONCENTRATES• Advantages– lower cost,– ease of collection and – processing (a separate donation procedure and

pheresis equipment are not required).

• Disadvantage-is recipient exposure to multiple donors in a single

transfusion and logistic issues related to bacterial testing.

Single donor Apheresis platelets• Platelets are collected in 2-3 hr apheresis procedure.

• Platelets and some white blood cells are removed, and red blood cells and plasma are returned to the donor.

• A typical apheresis platelet unit provides the equivalent of six or more units of platelets from whole blood (ie, 3 to 6 x 1011 platelets).

Single donor Apheresis plateletsAdvantages

-exposure of the recipient to a single donor rather than multiple donors,

-and the ability to match donor and recipient characteristics such as HLA type, cytomegalovirus (CMV) status, and blood type for certain recipients.

Forms of PC

• Platelets, Pooled, Buffy Coat Derived, Leucocyte Depleted pool of platelets, derived from buffy coats, which contains less than 5*106 leucocytes.

• Platelets,Apheresis, Leucocyte Depleted – a single donor platelet component containing less than 5*106 leucocytes.

• Platelets, Suspended in Additive Solution, Leucocyte

Depleted- platelet concentrate ,suspended in additive solution medium. This component is indicated for patients with reactions to plasma containing components.

Unit of PC

• Volume: 150–450 ml.

• pH: between 6.4 and 7.4 throughout the shelf-life.

• Leucocyte Count= <5* 106/pool

• Shelf Life - 5 days

• Practical Shelf Life (actually available to clinicians) - 2.5 to 3 days.

Platelets are stored at room temperature, because cold induces clustering of von Willebrand factor receptors on the platelet surface and morphological changes of the platelets, leading to enhanced clearance by hepatic macrophages and reduced platelet survival in the recipient.

Platelets are stored at a core temperature of 22°C +/- 2°C with continuous gentle agitation for up to five days in a closed system.

Platelet are stored at room temperature (20-24oC), which enhances bacterial growth, and is the third leading cause of transfusion-related deaths.

The incidence of platelet-related sepsis was approximately 1 case in 12,000 people.

The estimated incidence of bacterial contamination of platelets was approximately 1 case in 2000.

For any patient who develops a fever within 6 hours after receiving platelets, sepsis from platelets should be considered.

Platelet are stored at room temperature (20-24oC), which enhances bacterial growth, and is the third leading cause of transfusion-related deaths.

The incidence of platelet-related sepsis was approximately 1 case in 12,000 people.

The estimated incidence of bacterial contamination of platelets was approximately 1 case in 2000.

For any patient who develops a fever within 6 hours after receiving platelets, sepsis from platelets should be considered.

ASA Task Force recommendations:

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

• Prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia because of decreased platelet production when the platelet count is greater than 100 × 109/L and is usually indicated when the platelet count is less than 50 × 109/L.

• The determination of whether patients with intermediate platelet counts (50 to 100 × 109/L) require therapy should be based on the patient’s risk for bleeding.

ASA Task Force recommendations:

• Surgical and obstetric patients with microvascular bleeding usually require platelet transfusion if the platelet count is less than 50 × 109/L and rarely require therapy if it is greater than 100 × 109/L.

• Vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss may be undertaken in patients with platelet counts less than 50 × 109/L.

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

IndiCations

Stable patients without evidence of bleeding or coagulopathy <10,000/μL

Prophylaxis for invasive procedures such as lumbar puncture, neuraxial anesthesia, central venous catheterization, endoscopy with biopsy,liver biopsy, or major surgery <50,000/μL

Stable patients with clinical evidence of bleeding or coagulopathy <50,000/μL

IndiCations

Patients with DIC and signs of ongoing bleeding <50,000/μL Patients undergoing massive transfusion <75,000/μL Patients having surgery at critical sites(eye or central nervous System) <100,000/μL Microvascular bleeding attributedto platelet dysfunction such as uremia,liver disease, post-cardiopulmonary bypass Clinician judgment.

Calculation of dose• One platelet concentrate is usually given to most

adult patients.

• In small children (< 20 kg), 10–15 ml ⁄ kg up to the adult dose of one platelet concentrate is used;

• In older children, an adult dose of platelets should be used.

DoseUnder ideal circumstances, one platelet

concentrate usually produces an increase of approximately 7000 to 10,000 platelets/mm3 at 1 hour after transfusion to the 70-kg adult.

Ten units of platelet concentrates are required to increase the platelet count by 100,000 cells/mm3.

The dose of platelets (* 109) can be calculated in more detail, if required,desired platelet increment (PI),the patient’s blood volume in litres (BV, estimated by multiplying the patient’s body surface area by 2.5, or 70 ml ⁄ kg in an adult) and a correction factor (F) of 0.67 to allow for pooling of approximately 33% of transfused platelets in the spleen,

• Dose= PI * BV * F-1

• For example, if a platelet increment of 40*109 ⁄l is required for a patient with a blood volume of 5 l, a dose of 300* 109, is required.

The dose of platelets (* 109) can be calculated in more detail, if required,desired platelet increment (PI),the patient’s blood volume in litres (BV, estimated by multiplying the patient’s body surface area by 2.5, or 70 ml ⁄ kg in an adult) and a correction factor (F) of 0.67 to allow for pooling of approximately 33% of transfused platelets in the spleen,

• Dose= PI * BV * F-1

• For example, if a platelet increment of 40*109 ⁄l is required for a patient with a blood volume of 5 l, a dose of 300* 109, is required.

FRESH FROZEN PLASMA

• 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.

• Contains all of the coagulation factors and other proteins present in the original unit of blood.

• Usage– On order the FFP should be thawed between 30 and

37°C with constant agitation.

– After thawing, can be stored at 4oC(refrigerator) and can be used safely within 24 hours;

when kept at room temperature, must be used within 4 hours.

• Different types of frozen plasmas are available:

Fresh frozen plasma (FFP): Plasma frozen at - 18oC or colder within 6 hours of donation. F24 plasma: Plasma frozen at -18oC or colder within 24 hours

Cryosupernatant or cryo-reduced plasma (CRP):

Solvent-detergent treated plasma Liquid plasma:

Plasma F24 (PF 24):

Plasma frozen at -18oC or colder within 24 hours.

PF24 maintains all the clotting factors at the same levels as in FFP, except that factor VIII levels are in the range of 65 to 80 percent of normal and protein C is decreased.

Cryosupernatant or cryo-reduced plasma (CRP):

The plasma remaining after removing cryoprecipitate.

This product is also referred to as "Cryo-Poor Plasma.“

Used as plasma replacement in some patients with thrombotic thrombocytopenic purpura.

vitamin K deficiency or correction of major bleeding in the setting of warfarin anticoagulation because the removal of Cryoprecipitate from plasma does not deplete the vitamin K-dependent clotting factors.

Liquid plasma:

• Plasma not immediately frozen as FFP or F24 and stored at 1-6oC.

• Used for preparation of plasma derivatives like albumin, factor concentrate and immunoglobulins.

Solvent-detergent treated plasma (S/D Plasma)

• Treatment of pooled plasma prior to freezing with a solvent and a nonionic detergent inactivates a number of lipid envelopes virsues, including HIV, hep B and hep C.

• Non-enveloped viruses (eg, hep A, parvo B19) are not inactivated by this process, and even prions.

• Solvent/Detergent (S/D) method is similar to that used to inactivate viruses in immune globulin and coagulation factors.

• S/D Plasma has similar levels of most clotting factors and similar hemostatic properties as standard FFP.

Recommendations

Urgent reversal of warfarin therapy. Correction of known coagulation factor deficiencies

for which specific concentrates are unavailable.

Correction of microvascular bleeding in the presence of elevated (>1.5-times normal) prothrombin time (PT) or partial thromboplastin time (PTT).

Recommendations

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.

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

Recommendations

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

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

FFP should not be used to reconstitute packed RBCs.

Indications

• Correction of inherited factor deiciencies when there is no specific factor concentrate (e.g., factor V) and when the PT or aPTT is >1.5 times the mean control

• Correction of acquired multi-factor deiciencies with clinical evidence of bleeding or in anticipation of major surgery or an invasive procedure with PT or aPTT >1.5 times the control

• Liver dysfunction with clinical signs of bleeding

• DIC with clinical signs of bleeding

• Reversal of vitamin K antagonists (warfarin)

Indications

• Microvascular bleeding associated with massive transfusion and estimated blood loss > one blood volume (when PT and aPTT are >1.5 times the control or cannot be obtained)

• Heparin resistance secondary to anti-thrombin deficiency when AT concentrate is not available

• Treatment of thrombotic microangiopathies (thrombotic thrombocytopenic Purpura, HELLP syndrome, or hemolytic uremic syndrome)

• Treatment of hereditary angioedema when C1-esterase inhibitor is not available.

Dosing of FFP• The initial therapeutic dose of FFP averages 10 to

15 mL/kg in an attempt to obtain at least 30% factor activity.

• Repeat dosing should follow the results of serial diagnostic coagulation tests such as the PT and aPTT.

• The guidelines for FFP continue to recommend prophylactic transfusions in patients at risk for bleeding, – there is no evidence to support the efficacy of FFP

reducing red cell transfusion, morbidity, or mortality.

• The burden of adverse reactions in conjunction with limited prophylactic benefits and high frequency of inappropriate use makes FFP arguably the riskiest blood component transfused.

FFP in trauma• Traditional methods- fluids, RBC, FFP only abnormal

coagulation results.problem-dilutional coagulopathy resulting in prolonged microvascular bleeding.

• Recent studies show improved outcomes with higher ratios of red cell units to FFP (more than 3:2).

• The optimal management strategy for immediate resuscitation of trauma patients and those with acute massive hemorrhage is still under investigation.

CRYOPRECIPITATE (Con. AHF)

• Originally it was developed as a therapy for Haemophilia A (Used for 50 yrs).

• Enriched with fibrinogen, Fac VIII, vWF, Fac XIII.

• Prepared from processing FFP

- When FFP is thawed at 40C, a precipitate is formed, this is seperated from the supernatant plasma, and resuspended in a small volume of plasma and then refrozen at -180C.

- Can be stored for 1 year

- On ordering the cryoprecipitate is thawed in a 370C water bath & issued in individual bags or a pooled product

- After thawing- must be kept in room temperature

- Expiration time- 6hr for un-pooled & 4hr for pooled

• One unit of cryoprecipitate – derived from 1 unit of whole blood/ 250ml plasma- contains

– Volume- 10-20ml– 150-250 mg Fibrinogen– 80-100 units of Fac VIII– 50-100 units of Fac XIII– 50-60 mg of fibronectin– 40-70% of vWF Concentrate

Recommendations• Earlier,

– bleeding patients with hypofibrinogenemia, von Willebrand's disease and patients with haemophilia A (when factor VIII concentrate is not available).

• Current Recommendations are:– Prophylaxis in non bleeding perioperative or peripartum patients with

congenital fibrinogen deficiencies or von Willebrand's disease unresponsive to 1-desamino-8-D-arginine vasopressin (DDAVP).

– Bleeding patients with von Willebrand's disease

– Correction of microvascular bleeding in massively transfused patients with fibrinogen concentrations less than 80–100 mg/dl (or when fibrinogen concentrations cannot be measured in a timely fashion)

Other Indications-• As a source of fibrinogen– Congenital- Hypofibrinogenaemia/ Afibrinogenaemia– Acquired- severe coagulaopathy, DIC, massive transfusion

• Trauma– Significant bleeding after major trauma accompanied by a plasma

fibrinogen level < 100mg/dl– Significant bleeding accompanied with signs of functional fibrinogen

deficit on TEG

• Preparation of Fibrin sealant/fibrin glue used in sealing large raw surfaces.– Fibrin glue- Cryoprecipitate, bovine or human thrombin and calcium

chloride.

Dosing-

• 2-3 unit of cryoprecipitate per 10 kg body weight raises the plasma fibrinogen concentration by approximately 100 mg/dl in the absence of continued consumption or massive bleeding.

• Maintenance dose- I bag per 15 kg –can be given daily till the bleeding is controlled.

• Fibrinogen required(mg)= (Desired Fb – Current Fb) * plasma volume/ 100.

Bags required= Fibrinogen required mg/250mg.

Plasma volume= blood volume * (1- Hemotocrit)

Eg-Plasma volume=3500mlFb required= (150-50)* 3500/100=35003500/250=1414 bags required.

Complications-

• Same risk of transmitting blood borne pathogen

• Cryoprecipitate has been withdrawn from european countries(Safety concerns), instead, they advice for commerical fibrinogen preparations.

• Large volume of ABO-incompatible cryoprecipitate- can lead to intravascular hemolysis

COMPLICATIONS OF BLOOD PRODUCT ADMINISTRATION

• Infectious Risks

• Noninfectious Risks– Immune-mediated Transfusion Reactions– Nonimmune-mediated Transfusion Reactions

Infectious Risks• depends mostly on – the relative length of the window period determined

by the reproductive rate of each virus and the prevalence of the disease.

– additional risk of false negatives or mistaken release of quarantined blood products;

these events account for less than 0.5% of the residual risk of transfusion-transmitted viral infection.

Noninfectious Risks

• The extensive use of more sensitive methods for screening and controlling the infectious risks of blood product transfusion,

noninfectious complications have emerged as the major source of transfusion-related morbidity and mortality.

• Hemolytic transfusion reactions (HTRs) – Acute HTR– Delayed HTR

they occur with the transfusion of incompatible blood products when antibodies in recipient plasma complex with donor cellular antigens causing compliment activation and subsequent hemolysis.

Classically AHTRs result from ABO incompatibility secondary to native anti-A or anti-B antibodies, growing evidence exists for the implication of other RBC antigens such as Kidd, Kell, and Duffy.

• Manifests as fever, hypotension, and hemodynamic instability(bradykinin), bronchospasm and urticaria as well as symptoms of dyspnea, flushing, and severe anxiety(histamine).

• Severe hemolysis may lead to renal failure, disseminated intravascular coagulopathy, and death in 50% of cases.

• Under anesthesia several signs and symptoms will be masked; therefore vigilance during transfusion of an anesthetized patient must remain high.

• confirmed with laboratory analysis of free hemoglobin levels, low haptoglobin, bilirubin increases, direct antiglobulin (Coombs) test, and evidence of hematuria.

• Suspicion of a transfusion reaction should prompt immediate discontinuation of the transfusion and investigation into the donor and recipient blood type and antigen–antibody components.

• Treatment of AHTR involves supportive care for hemodynamic instability and microvascular bleeding as well as the maintenance of adequate urine output to avoid the renal failure.

• Delayed hemolytic transfusion reactions (DHTRs) result from alloantibodies to minor RBC antigens in the Rh, Kell, Kidd, Duffy, MNSs, and other blood groups.

• They generally present 3 to 10 days after transfusion of an apparent “compatible” blood component.

• Typically the recipient has IgG alloantibodies to a particular RBC antigen and will mount an an amnestic immune response, but the pre-transfusion antibody levels are too low for serologic detection.

• Symptoms are much milder than AHTRs and rarely result in major morbidity or mortality because the hemolysis occurs extravascularly in the liver and spleen.

• Patients experience mild fever & rash with laboratory and clinical signs of hemolysis such as jaundice, hematuria, low haptoglobin, positive direct Coombs test, and decreasing hemoglobin levels.

• Symptoms are generally self limited and treated supportively with hydration to protect the renal tubules.

Transfusion-related Immunomodulation(TRIM)

• multifactorial pathophysiology – implicates the role of transfused WBCs, donor plasma

HLA class 1 peptides, cytokines, and immune mediators released during blood product storage as well as the immune function of transfused RBCs within the microvasculature of the recipient.

• Several experts propose a “two-insult” model for TRIM similar to the patho-physiologic mechanism for TRALI and acute respiratory distress syndrome.

• Presumably most patients requiring blood products are suffering from a precondition that “primes” the immune system and vascular endothelium such as trauma, surgery, or acute illness.

• This constitutes the first insult and causes active neutrophils to adhere to vascular endothelial cells and become hypersensitive to blood-bound immune mediators.

• The second insult occurs with the infusion of transfused blood products which contain WBCs with HLA class I antigens as well as soluble immune response modifiers in the form of cytokines, complement factors, and the breakdown products of lipid membranes.

Transfusion-related Acute Lung Injury(TRALI)• as a new acute lung injury (ALI) within 6 hours of

blood component therapy.

• 1994 by the North American-European Consensus Conference as non-cardiogenic pulmonary edema with acute bilateral infiltrates and hypoxemia (PaO2/FiO2 <300 mm Hg or oxygen saturation <90% on room air and no evidence of left atrial hypertension)

Transfusion-related Acute Lung Injury(TRALI)

• Management– supportive measures to limit lung injury and optimize oxygenation, -

maximizing positive end expiratory pressures, avoiding volume overload, and low tidal volume strategies for mechanical ventilation.

• Furthermore, subsequent transfusions should be restricted as much as possible for patients with ALI and although there is little supportive evidence for the use of washed RBCs,

• all preventative measures should be encouraged for this high-risk population.

Reference: Miller’s Anaesthesia 8 th Ed Clinical Anaesthesia – Barash 7 th

Ed Redbook- 2005 Postgraudate topics- Dr Mahadevan,

Dr Anil kumar Ashokan Handbook of Transfusion Medicine

Dr Derek Norfolk 5 th Ed Blood Science-Principles and

Pathology Andrew Blann & Nessar Ahmed

ASA guidelines 2005 BJA- August issue 2014