Rational Use of Blood Components

Blood Components

• Stored Whole Blood

• Fresh Whole Blood

• Packed Red Cells

• Platelet Rich Plasma

• Platelet Concentrate – Random & Single

• Fresh Frozen Plasma

Advantages of Component Therapy

• Increases efficiency of patient needs

• Minimizes volume

• Maximal & Optimal use of donated blood

Techniques of Separation

• Centrifugation

- RBCs, platelets, plasma, cryoprecipitate 5000 rcf for 5 min

- PRP – 2000 rcf for 3 min• Apheresis – blood drawn from donor in

anticoagulant solution, separated into components, necessary component retained, others returned to donor circulation

Limitations of Components

• Stringent tecniques & regulation required

• Different methods of storage required

• WBCs are separated from RBCs with difficulty

• Does not reduce transmission of Hepatitis & HIV

• Higher costs

Stored Whole Blood

• Storage – 2-4oC

• Shelf Life – 35days

• Indications – Acute Blood Loss

• Quantity – 350ml

• 1 Unit increases Hb by 1gm%

• Rate of Transfusion - < 4 hours

Indications – Acute Blood Loss

• Healthy young person

- 500-1000ml – no need for transfusion

- 1000-2000ml – only fluids

- > 2000ml – blood transfusion

• During Anaesthesia - > 500ml needs blood transfusion

Indications - Perioperative

• Transfusion is rarely indicated for patients undergoing noncardiac surgery who have Hb > 7-8gm%

• Elderly patients & others at risk for myocardial ischaemia a Hb < 10gm% probably warrants transfusion

-ST depression >0.1mV -new ST elevation >0.2mV, -new wall motion abnormality on Echo

Unacceptable Indications

• To enhance patients general sense of well being

• To promote wound healing

• To expand vascular volume when O2-carrying capacity is adequate

Fresh Whole Blood(<24hrs)

• Storage – 2-4oC• Shelf Life – 24 hours• Indications – Acute Blood Loss requiring

massive transfusions• Quantity – 350ml• Rate of Transfusion – as per need• Within 6 hours in massive bleeding• 80-90% platelets lost in 24 hours• 40% of labile clotting factors lost in 24 hrs

Packed Red Cells

• Storage – 2-4oC

• Shelf Life – 35 days

• Indications – Anaemia

• Quantity – 200-300ml

• 1 unit increases Hb by 1gm%

• Rate of transfusion - < 4 hours

• Sedimented RBCs, Centrifuged RBCs, Leucodepleted RBCs

• Red cell use should be based primarily on the patient's risk for complications owing to inadequate oxygenation of tissue

Red Blood Cell Transfusion Requirements

• Chronic Anaemia – amount necessary to reverse symptoms & signs

• Patients with self limited anaemia (transient blood loss, haemolysis, bone marrow suppression) or nutritional deficiencies, anaemia of CRF – during myocardial ischaemia, heart failure, impaired CNS oxygenation, hypotension, or other evidence of tissue hypoxia

Consideration for Transfusion

• Age• General condition of the patient• Co-existing Cardiac, Pulmonary, Vascular• Ability to tolerate acute blood loss or

chronic anaemia• Degree & chronicity of anaemia• Cause of anaemia - (alternative therapy

like iron, B12, folate, erythropoietin may eliminate need for transfusions)

Anaemia in Critically Ill

• Rate of Hb decline is 0.5g/dl/day in 1st few days

• Loss through sampling – 40-60ml/day

• Functional Iron deficiency (↑ S Ferritin, ↓Transferrin saturation, ↓ S iron concentr.)

• Reduced RBC life span

• Decreased deformabilty

• Blunted Erythropoitic response

Age of RBC

• Open Heart Surgery - < 10 days

• Chronic Liver & Renal Failure Patients - < 14 days

• Chronic Anaemias - < 30 days

Indications – Chronic Anaemias

• Increased 2,3-DPG ->rightward shift –> increased tissue extraction of O2

• Increased Erythropoietin• Early release of young RBC• Transfusion rarely needed if Hb > 7gm%• High risk patients like older patients, CAD,

Vascular disease & other symptomatic patients may need transfusion at higher Hb

Administration

• Use standard blood filter to trap clots (170µm)

• Should not be administered by syringe/ syringe pump

• Nothing to be added to blood component• Administer slowly for first 5-10 min.• Periodically reassess for transfusion

reactions• Transfuse within 4 hours (20 gauge)

Adverse Effects

• Febrile Non-hemolytic Reactions• Acute Hemolytic Transfusion Reactions• Transmission of Infectious Diseases

(HBV, HCV, HIV, bacterial contamination)• Transfusion associated Graft VHD• Transfusion related Acute Lung Injury• Transfusion associate Immunomodulation• Coagulopathy

Adverse Effects

• Leucocytes present in RBCs are responsible for Transfusion-associated immunomodulation (TRIM), Febrile reactions, CMV, HTLV, EBV, Herpes, Parasites

• Contamination of platelets is more common than RBC

Metabolic Effects

• Significant acid load due to citrate

• Sodium load due to citrate

• Hypocalcaemia due to citrate

• Hypothermia leads to Hyperkalaemia & Coagulopathy

Massive Transfusions

• Replacement of total blood volume in 24hr

• Replacement of 50% blood volume in 3hr

• Total transfusion of 20 units

• Ongoing transfusion requirement of > 4 units/hr

• No need of prophylactic Ca, except in hepatic & cardiac failure

• Potassium only after S. K+ level

Lab in Bleeding Disorders

Abnormality Plat BT PTT PT TT FDP D-di

Thrombocytop A A N N N N N

TTP A A N N N N N

Pl.dysfunction N A N N N N N

DIC(schistocy) A A A A A A A

Hepati Failure N-A N A A A N-A N

Thrombolysis N N A A A A A

Heparin N N A N-A A N N

Coumadin N N N-A A N N N

Prothrombin Time

• Tests extrinsic pathway

• INR > 1.5

• Prolonged in - Vit K deficiency - Liver Disease - Oral anticoagulants - DIC

- Heparin – Factor II, V, VII, X

deficiency, Fibronogen

Prolongation of PT only

• Factor VII deficiency

Echis Time

• To distinguish between Vit K deficiency & Liver disease related PT prolongation

• Normal in Vit K deficiency (inhibitors - PIVKA)

• Prolonged in Liver disease

aPTT

• Tests intrinsic pathway – 28-34 secs• Prolonged in – Heparin therapy

- DIC - Factor deficiency

XII,XI,IX,VIII,(X,V,Pro,Fib) - Lupus anticoagulant

• Danaparoid prolongs aPTT minimally• Shortened in – poor specimen processing,

prothrombotic state, disseminated malignancy, oral contraceptive pill

Prolongation of aPTT only

• Deficiency of factor VIII, IX, XI

Mixing Test

• Done in case of prolonged aPTT

• Patients plasma & Normal plasma in a 1:1 ratio

• Prolongation occurs only if factor is < 70%

• If does not correct aPTT – Inhibitors

• Corrected - Factor deficiency

aPTT & PT prolongedNormal TT

• Heparin

• Warfarin (Vit K def)

• Liver disease

• Post Thrombolysis

• DIC

• Deficiency of X, V, prothrombin or fibrinogen

Thrombin Clotting Time (TT)

• Heparins

• FDP

• Fibrinogen

aPTT & PT prolonged

Prolonged aPTT, PT, TT

• Fibrinogen deficiency

• Heparin

• DIC

aPTT, PT, TT prolonged

• Deficiency of Fibrinogen

• Heparin

• DIC (FDP)

• Thrombolysis

Fibrinogen

• Liver disease

• DIC

Euglobin Lysis Time

• Decreased in Liver disease & high tPA

• Coagulation Abnormalities need 50% drop for showing abnormality on testing

• Does not detect abnormality due to LMWH & Anti-platelets

aPTT & PT prolonged

FDP

Bleeding Time

Prolonged• Platelet Count < 100,000• Aspirin• NSAIDS• Severe Hypofibrinogenemia• Uraemia• Platelet function defect• Post cardio-pulmonary bypass

Platelet Dysfunction

• Bleeding with platelet > 100,000• Cardiopulmonary Bypass• Uraemia• Antibiotics, drugsTreatment – Aprotinin,

- Dialysis in Uraemia - Desmopressin(0.3mcg/kg 12hr) - Conjugated oestrogen

(0.6mg/kg IV daily x 5 days)

DIC

• Elevation of D-dimer is the most useful & specific test for fibrinolysis

• FFP to replace coagulation factors• Cryoprecipitate if fibrinogen < 100mg%• Repeated transfusion of platelets may be

needed• E-aminocaproic & Tranexamic acid only

used topically for mucous membrane bleeding

Vit K Deficiency

• ICU patients with inadequate dietary intake treated with antibiotics

• Coumadins

• Vit K 5 to 10mg sc/IV

• Additional doses every 2-3 days

• Effects on PT seen in 8-12hrs with correction to normal by 24-48hrs

• Severe bleeding requires FFP

Vitamin K antagonists

• Inhibits vit K epoxide reductase

• Produces deficiency of vit K, preventing hepatic carboxylation of factors II, VII, IX & X, protein C & S to the active form

• Warfarin half life – 36 hrs

Liver Coagulopathy

• Altered vitamin K metabolism

• Impaired synthesis of coagulation factors (fibrinogen, V, VII, IX, protein C & S)

• Low grade DIC

• Enhanced fibrinolytic activity

• Quantitative & qualitative platelet dysfunction

Antifibrinolytics in Liver Failure

• PT < 30%

• Fibrinogen < 100 mg%

• Platelet < 30,000/mm3

• MCF ETEM < 35 mm

• CT AP shorter than CT EX (> 25%)

• Maximum Lysis that exceeds 15% in 60 mi

• Administer 1-2 mil APROTONIN or 1-2 g Tranexamic acid

Heparin• Accelerates the effects of Antithrombin III

• The heparin-AT III complex inactivates several factors in the coagulation cascade, most importantly thrombin(II) & X

• Half life – 90 min

• Stopping infusion for 2-4 hours will reverse effect

• Continuous infusion monitor aPTT 6 hrly (60-85 seconds)

Heparin induced Bleeding

• Increase antithrombin activity (thrombin & Xa)• Discontinue Heparin• Protamine reverse heparin effects• 1mg Protamine reverses 100units Heparin• 1mg Protamine reverses

1mg Enoxaparin within <8 hours

0.5mg Enoxaparin >8 & <12hrs• Protamine is less effective in LMWH (incomplete

reversal)

Heparin Induced Thrombocytopenia(HIT)

• Arises usually after 5-10 days after exposure to heparin

• Does not persist after 6 months of initial insult• Can cause venous & arterial thrombosis• 50% drop in platelets, • presence of thrombosis, • absence of other causes of thrombocytopenia, • skin lesion at site of injection

HIT• Thrombosis risk persists for more than a month• Anticoagulation with fondaparinux is indicated• Continue till platelets > 100,000/mm3• Overlap with oral anticoagulant by 5 days• Start oral anticoagulant in low dose, continue

direct thrombin inhibitor until platelet level is stable & INR in therapeutic range for 2 days

• If not followed Warfarin-induced skin necrosis & venous gangrene is likely to occur due to intense protein C depletion by anti PF4 -heparin

LMWH

• 2000 – 10,000 daltons

• Unable to cross link with AT III & thrombin

• Primarily inhibit factor X

• Does not prolong aPTT

• Long half life – 4 hrs

• Renal clearance

• Expensive

Fondaparinux

• Selectively inhibits factor Xa by binding to antithrombin & inducing a conformational change that increases AT III binding affinity for Xa

• Irreversibility & decreased clearance in renal dysfunction & elderly

Thrombolytics

• tPA (tissue plasminogen activator)

• Streptokinase

• Urokinase

• Dissolve thrombin by converting plasminogen to plasmin which lyses the fibrin clot

Thrombolytic Agents• Significant bleeding is treated with volume &

RBC transfusions• Local measures to stop bleeding• Fibrinogen drops with Streptokinase

administration• Hypofibrinogenemia leads to bleeding• Reversed by Tranexamic acid & FFP/cryo • Consider cryoprecipitate for serious

bleeding due to STK

Platelet Rich Plasma

• Storage – 20-22oC

• Shelf Life – 6 hours

• Indications – Thrombocytopenia & Coagulopathy

• Quantity – 200ml

• 1 unit increases platelet by 5000/cumm

• Rate of transfusion - < 4 hours

Single Donor Platelet

• Storage – 20-22oC

• Shelf Life – 5 days (closed) - 24 hours (open)

(with continuous agitation)

• Indications – Thrombocytopenia

• Quantity – 300ml

• 1unit increases Platelets by 30,000-60,000

Random Donor Platelet

• Storage – 20-22oC

• Shelf Life – 5 days in special bags - 2-3days in PVC bags

(with continuous agitation)

• Indications – Thrombocytopenia

• Quantity – 50-65ml

• 1 unit increases Platelets by 5000-10000

• Platelet use should be based on the risk for bleeding complications owing to qualitative and/or quantitative platelet disorders

Indications of Platelet Transfusion

• Bleeding due to thrombocytopenia or platelet dysfunction

• Massive bleeding if severe thrombocytopenia develops

• Cardiopulmonary bypass if excessive bleeding occurs

• Surgical procedures – prophylactic if platelet < 50,000

Indications of Platelet Transfusion

• Severe Thrombocytopenia(< 5000-10,000)

undergoing chemotherapy• Threshold may be higher if there is fever,

infection, or drugs that cause thrombocytopenia• Severe anaemia may contribute to bleeding in

severe thrombocytopenia• Response diminished in hypersplenism,

spleenomegaly, uraemia, coagulation disorders

Platelet Transfusion Requirements

• Platelet count < 5000

• Counts 5000-30,000 – if risk of bleeding or bleeding is present

• Surgery/Invasive procedures & DIC - > 50,000

• Life span – 3days

• ABO incompatibilty is of minor importance

Fresh Frozen Plasma

• Prepared within 6 hours of collection• Storage - <-18oC• Shelf Life – 1 year• Indications – Coagulation deficiency• Quantity – 150-250ml• 1 iu/ml each factor+Fibrinogen 200-400mg• Dose – 10-15ml/Kg 8 hourly• Rate of transfusion – immediately after thawing

(<12 hrs if stored at 2-6oC)

• Fresh frozen plasma use should be based on the risk for bleeding complications owing to qualitative and/or quantitative clotting factor disorders

Indications for FFP

• Severe Liver disease with bleeding

• DIC

• Oral Anticoagulant induced bleeding in1st 24 hrs (Vit K starts acting in 24 hrs)

• Massive Transfusions (> 5 lit) usually need platelet transfusions

• Not to be used for volume depletion

• Control of bleeding, PT & PTT monitored

FFP

• Caution

• Compatibility testing not necessary

• Group specific preffered

• Donors plasma should not contain ABO antibodies

• Rh(D)+ve plasma should not be transfused to Rh(D)-ve women in reproductive age group

Fibrinogen

• Fibrinogen 250 mg/10 kg

MCF EXTEM MCF FIBTEM

Bleeding Fibrinogen

<45 mm <8 mm Diffuse 250 mg/10 kg

<4 mm 500 mg/10 kg

0 mm 750 mg/10 kg

Cryoprecipitate

• When FFP is thawed at 4o C the precipitate is cryoprecipitate

• High concentration of VIII, fibrinogen, fibronectin, XIII, & vWF

Cryoprecipitate-poor Plasma

• Plasma within 5 days from whole blood

• By product of cryoprecipitate preparation

• Lack factor V, VIII, Fifrinogen

• Contain II, VII, IX, X

Prothrombin Complex concentrate

Thromboelastograph

• EXTEM – extrinsic pathway evaluation

• INTEM – intrinsic pathway evaluation

• FIBTEM – fibrinogen & platelet function evaluation

• APTEM – fibrinolysis evalution

Conservation of Blood Resources

• Ineffective Therapy- terminally ill- uncorrectable vascular defects- platelet & plasma transfusions for patients without demonstrated response to such transfusion- daily prophylactic platelet transfusions in patients with consumptive thrombocytopenia without bleeding

Risk vs Benefit Studies

• TRICC Trial : NEJM 1999

A restrictive strategy (Hb 7-9g%) of blood transfusion is at least effective as & possibly superior to the liberal strategy (Hb 10-12g%) with the possible exception of patients with IHD

Risk vs Benefit Studies

• Anaemia & Blood Transfusion in Critically Ill Trial : JAMA 2002- Higher transfusions increased ICU stay- ICU & overall mortality higher in transfused group- Receipt of blood in the ICU increased the risk of dying by a factor of 1.4 (due to Immunosuppression & disturbances in microcirculation)

Efficacy and Safety of Epoetin Alfa in Critically Ill Patients

• The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events.

NEJM 357:965-976, 2007

Transfusion in Trauma

• Class III (1500-2000ml) & IV (>2000ml) of Haemorrhagic Shock as per ATLS need blood transfusions

• After 48 hours Transfusion Threshold of 7g% is optimum for Trauma patients

Albumin

• Exogenous Albumin Half life - < 8 hours• Endogenous Albumin Half life – 20 daysIndications• Refractory ascites in Cirrhosis with loop

diuretics• Large volume paracentesis• Nephrotic patients with ascites• Use of Albumin in critically ill ↑mortality