Blood component therapy

Practice guidelines for blood component therapy A report by the American society of anesthesiologists task force on blood component therapy Anesthesiology, 1996; 84:732-47

Adverse effects Transfusion reaction Nonhemolytic transfusion reaction: 1-5% of all transfusions  fever, chills, urticaria Hemolytic transfusion reaction: the estimated risk of ABO-incompatible transfusion is 1:33000  hypotension, tachycardia, hemoglobinuria, microvascular bleeding

Infectious diseases Post-transfusion hepatitis: hepatitis C, 0 Infectious diseases Post-transfusion hepatitis: hepatitis C, 0.03% per unit transfused; hepatitis B, 1:200000 units HIV virus: uncertain; 1:450000-660000 per transfused units Cytomegalovirus: the most common viral agent; mostly subclinical, although immunocompromised patients may develop severe morbidity Parasitic and bacterial agents: 1:1000000 units

Immunosupression and blood transfusion Perioperative allogeneic blood transfusion may related to: - Earlier recurrence and lower survival rates with patients with colorectal, breast, prostate, and certain other cancer - Higher rates of postoperative infections ?

Costs In US, 18 hospitals: $155 per transfused unit of whole blood or RBCs; $397 per patient for all blood components. 12 million units transfused each year 5-7 billion dollars Almost 25% of the costs of RBC transfusions may attributable to inappropriate transfusions.

Red blood cells 12000000 units of RBC are transfused each year in the US Inappropriate rates of 18-57% have been reported. The scientific argument for perioperative RBC transfusion: (1) surgical patients experience adverse outcomes as a result of diminished oxygen-carrying capacity (2) RBC transfusions, be enhancing oxygen-carrying capacity, can prevent these adverse outcomes

Adverse effects of diminishing oxygen-carrying capacity Ischemic effects on the myocardium and brain DO2= CaO2* CO CaO2= (SaO2/100)*(1.39*Hb) + (0.003*PaO2) Hb, CO, autonomic nerve system effects on microcirculation

Anemia, hypovolemia Blood loss classification: class I : 15% of total blood volume, little hemodynamic effect class II: 15-30 %; tachycardia and decreased pulse pressure class III: 30-40%; marked tachycardia, tachypnea, systolic hypotension class IV: > 40%; life-threatening, marked tachycardia and hypotension, very narrow pulse pressure, low urine output

In young healthy patients, losses of up to 30-40% usually can be treated adequately with crystalloid therapy It is believed that oxygen delivery is adequate in most individual at Hb as low as 7g/dL In healthy, normovolemic individuals, tissue oxygenation is maintained and anemia tolerated at Hct as low as 18-25% Hct 15-20% the heart begins producing lactic acid Hct 10% heart failure occurs

In chronic anemia, oxygen delivery is facilitated through increases in 2,3-diphosphoglycerate level in RBCs CO does not change until the HB < 7g/dL In acute anemia, oxygen content is usually maintained by compensatory increased in cardiac output Left ventricular dysfunction, vasoactive pharmacologic agents higher Hb

Human tolerance of acute anemia is further affected by certain pharmacologic agents and by intraoperative conditions Anesthetics: myocardial depression, decreased arterial pressure, cardiac output, peripheral vascular resistance, total body oxygen consumption, and cerebral and myocardial oxygen demands Hepatic blood flow: how they influence the development of systemic lactic acidosis and base-deficit in patients with anemia or impaired oxygen transport

Human may tolerate lower Hb and O2 transport during anesthesia than awake due to an anesthetic and neuromuscular blockade induced reduction of oxygen consumption The impact of regional anesthesia on O2 transport is unclear No controlled prospective studies addressing this issue

Case series reports of Jehovah’s Witnesses indicate that some patients tolerate very low Hb ( < 6-8 g/dL) in the perioperative period without an increase in mortality. Hb alone was not a statistically significant predictor of outcome unless it was less than 3 g/dL

Decisions regarding perioperative transfusion are often difficult, necessitating clinical judgment Transfusion trigger: 10/30 rule; outdated, little scientific support Estimated of blood volume: unreliable, inaccuracies of intraoperative blood loss measurement, intercompartmental fluid shifts during surgery, dilutional effects of crystalloid therapy

Alterations of intravascular volume: concomitant administration of colloids and crystalloid can produce artificially lowered or elevated Hb Intraoperative measurements: location, invasive monitoring it is not possible to directly measure the adequacy of oxygen transport to specific organs or to regions within these organs

Myocardial ischemia is often silent and most frequent in the postoperative period, when monitoring is less intense Pain, fever, shivering, physical activity Wound healing oxygen carrying capacity Hb or oxygen tension and perfusion ?

Effectiveness of RBC transfusion One unit of whole blood or RBC increase the Hct about 3%, or the Hb about 1 g/dL, in a 70-kg non-bleeding adult Mild to moderated blood loss does not appear to be associated with increased perioperative morbidity or mortality Uncontrolled and lacked long term F/ U

Perioperative anemia and myocardial ischemia or infarction: - the incidence of postoperative myocardial ischemia and morbid cardiac events was higher with Hct < 28% (older, longer procedures) - Hb < 10 g/dL, RBC transfusions had little impact on O2 consumption

Recommendations of other groups 1992, ACP: patients with stable vital signs and no risk of myocardial or cerebral ischemia do not require RBC transfusion, independent of Hb level, and recommended transfusing patients with unstable vital signs only if risks of myocardial or cerebral ischemia were present RBC transfusion is indicated only to increase oxygen-carrying capacity

Expert opinion of task force Transfusion trigger, vital signs: inappropriate for anesthetized patients, the dynamic nature of surgical hemorrhage Patients with hypovolemia and anemia may be transfused more aggressively when rapid blood loss is anticipated Changes in vital signs  late sign of cardiovascular decompensation

Silent ischemia of the myocardium, cerebrum, liver, kidney, and other tissues can occur in the presence of stable vital signs Intraoperative myocardial ischemia is associated with tachycardia in only 26% of patients and with blood pressure changes in less than 10% of patients

The physician’s decision to transfuse: 1 The physician’s decision to transfuse: 1. the patient’s cardiopulmonary reserve (cardiopulmonary disease, hemodynamic indexes, and affected by drugs and anesthetics) 2. the rate and magnitude of blood loss (actual and anticipated) 3. O2 consumption ( affected by body temperature, drugs/anesthetics, sepsis, muscular activity) 4. atherosclerotic disease ( cerebrovascular, cardiovascular, peripheral, renal)

Recommendations Transfusion is rarely indicated when the Hb is greater than 10 g/dL and is almost always indicated when less than 6 g/dL, especially when the anemia is acute 6-10 g/dL should be based on the patient’s risk for complications of inadequate oxygenation The use of a single Hb 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 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

Platelets More than 7000000 units platelet are transfused each year in the US The scientific rationale rests on two principal arguments: (1) surgical patients experience adverse outcomes as a result of thrombocytopenia and/or platelet dysfunction (2) platelet transfusion can correct platelet defects and thereby reduce, minimize, or prevent bleeding

Adverse effect of thrombocytopenia and platelet dysfunction In nonsurgical patients, < 20K spontaneous bleeding Performance of paracentesis and thoracentesis was not associated with increased bleeding : 50-99K The platelet count at which surgical and obstetric patients are likely to experience increased bleeding is unknown

In massively transfused patients: >20 units of RBCs, 75% of patients’ PLT counts < 50K Consumption of platelets, as well as simple dilution, can lead to microvascular bleeding

Platelet dysfunction may be more important than platelet count in explaining a bleeding disorder The bleeding time is a poor predictor

Effectiveness of platelet transfusion 1 unit of platelet concentration will increase the platelet count by 5-10K in the average adult; 1 unit platelet concentration per 10 kg body weight Patients repeatedly transfused over a prolonged period may become alloimmunized and refractory to platelet transfusion human leukocyte antigen-matched or crossmatched platelets may be required

Controlled trials of prophylactic platelet transfusion have not demonstrated benefit for patients undergoing cardiopulmonary bypass or massive transfusion

Recommendations of other groups 1994, CAP: platelet transfusion in patients with decreased platelet production and platelet counts below 5K; consider prophylactic platelet transfusions in 5-30K; for major surgery with life threatening bleeding, maintain greater than 50K; the presence of microvascular bleeding, keep > 50K

Expert opinion of task force The type and extent of surgery, the ability to control bleeding, the consequences of uncontrolled bleeding, the actual and anticipate rate of bleeding, the presence of factors that adversely affect platelet function Massively transfused patients : intraoperative platelet counts

Recommendations Prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (ITP) Prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when the PLT > 100K, and is usually indicated when < 50K; 50-100K, based on the risk of bleeding

Surgical and obstetric patients with microvascular bleeding: PLT< 50K, transfusion; > 100K, rarely required; 50-100K, the risk for more significant bleeding Vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss may be undertaken in patients with PLT < 50K Platelet transfusion may be indicated despite and apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding

Fresh-frozen plasma 2000000 units of FFP are transfused each year in the US The scientific rationale for administering FFP: (1) patients are at risk of adverse effects from inadequate coagulation factors (2) FFP transfusions can decrease those risks

Adverse effects of inadequate plasma coagulation factors Blood usually coagulates appropriately when coagulation factor concentrations are at least 20-30% of normal and when fibrinogen levels area greater than 75 mg/dL Replacement of an entire blood volume leaves the patient with 1/3 of the original concentration of coagulation factors

Although PT and PTT may be abnormal, clinical coagulopathy from dilution does not usually occur until replacement exceeds one blood volume or when PT and PTT exceed 1.5-1.8 times control values

Shock, independent of blood loss, may be associated with a consumptive coagulopathy, leading to microvascular bleeding The prolongation of PTT corresponded with the duration of the preceding hypotension

Abnormal PT and PTT are poor predictors of surgical bleeding Paracentesis, thoracentesis, liver biopsy, CVP insertion: PT and PTT > 2 times control values no increased bleeding Surgical setting?

Effectiveness of fresh-frozen plasma transfusions Correction of PT and PTT with FFP administration in patients massively transfused with whole blood, no change in bleeding occurred until thrombocytopenia was corrected Albumin, FFP: no differences in blood loss or transfusion requirements Dilutional coagulopathy: hemostasis improved

Recommendations of other groups 1994, CAP recommended : massive blood transfusion( more than one blood volume) with active bleeding, urgent reversal of warfarin therapy, a history or clinical course suggestive of and inherited or acquired coagulopathy ( with active bleeding or before and operative procedure) Use of FFP as a volume expander or for wound healing was contraindicated

Expert opinion of task force In nonbleeding patients: urgent reversal of wafarin therapy and the treatment of known coagulation factor deficiencies for which specific factor concentrations are unavailable In patients with microvascular bleeding: PT/PTT test in OR are useful; a true dilutional coagulopathy does not ordinarily occur until more than 100% of the patient’s blood volume has been replaced

FFP is beneficial in patients with microvascular bleeding or hemorrhage who are massively transfused if PT/PTT values exceed 1.5 times the control values; empirical FFP therapy if PT/PTT can not be obtained

Recommendations For urgent reversal of warfarin therapy For correction of known coagulation factor deficiencies for which specific concentrates are unavailable For correction of microvascular bleeding in the presence of elevated PT or PTT( > 1.5 times normal) For 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( usually achieved with administration of 10-15 ml/kg of FFP), except for urgent reversal of warfarin anticoagulation, for which 5-8 ml/kg of FFP usually will suffice. 4-5 platelet concentrates, 1 unit of single-donor aphoresis platelets, or 1 unit of whole blood provide a quantity of coagulation factors similar to that contained in 1 unit of FFP ( except for decreased, but still hemostatic, concentrations of factors V and VIII in whole blood )

FFP is contraindicated for augmentation of plasma volume or albumin concentration

Cryoprecipitate 1000000 units of cryoprecipitate are transfused each year in the US Factor VIII, fibrinogen, fibronectin, von Willebrand’s factor, factor XIII Based on the assumptions: (1) patients with these coagulation factor deficiencies are at increased risk of hemorrhagic complications (2) replacement of coagulation factors is effective in decreasing these risks

Adverse effects of coagulation factor deficiencies There is limited evidence from observational studies that patients with certain inherited or acquired coagulopathies are at increased risk of perioperative or peripartum bleeding.

Effectiveness of cryoprecipitate transfusion 1 unit of cryoprecipitate per 10 kg body weight raises plasma fibrinogen concentration by approximately 50 mg/dL in the absence of continued consumption or massive bleeding Factor VIII deficiency factor VIII concentrates von Willebrand’s disease DDAVP uremia DDAVP, cryoprecipitate DIC cryoprecipitate can increase the plasma fibrinogen concentration

Recommendation of other groups 1994, CAP: cryoprecipitate transfusion in bleeding patients with hypofibrinogenemia, von Willebrand’s disease, and patients with hemophilia A ( when factor VIII concentrate is not available)

Expert opinion of task force There is little scientific evidence regarding the effectiveness of cryoprecipitate in improving clinical outcomes its perioperative and peripartum use should be limited to selected indications Cryoprecipitate is likely to be effective in patients with von Willebrand’s disease unresponsive to DDAVP, congenital fibrinogen deficiencies, and consumptive coagulopathies when fibrinogen levels are below 80-100 mg/dL

Recommendations Prophylaxis in nonbleeding perioperative or peripartum patients with congenital fibrinogen deficiencies or von Willebrand’s disease unresponsive to DDAVP ( whenever possible, these decisions should be made in consultation with the patient’s hematologist) 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 measure in a timely fashion)

Conclusions Adherence to proper indications for blood component therapy is essential because of the potential adverse effects and costs of transfusion The lack of data from prospective, randomized studies with adequate sample size, control groups, clinical outcome measurements and other features of well designed clinical effectiveness research impedes development of evidence-based clinical practice guidelines for blood component therapy

Strategies for transfusion therapy Best practice and research clinical anesthesiology, vol 18, No 4, pp. 661-673, 2004

RBC transfusions RBC transfusion : indicated when Hb < 6 g/ dL, very rare when Hb > 10 g/dL The first priority of perioperative fluid therapy in surgical patients is to achieve and optimal filling of the heart with crystalloids and colloids allogeneic RBC transfusion only to increase Hct or Hb and not to correct hypovolemia

Patients with coexisting cardiac disease Coronary artery disease: (1) trans stenotic coronary blood flow increases during progressive hemodilution (2) heart rate remains stable during hemodilution in anesthetized patients when normovolemia is maintained Hb < 6 g/dL were associated in patients with coexiting cardiovascular disease with and increased postoperative mortality and morbidity in patients declining allogeneic RBC transfusion

These patients should not be transfused simply due to “hemoglobin transfusion trigger”, but when signs of inadequate oxygenation start to develop Anemia- related myocardial ischemia is reliably reversible with RBC transfusions

Mitral valve insufficiency: moderate hemodilution to Hb 10 g/dL is well tolerated by patients with significant mitral valve insufficiency, even when they were in atrial fibrillation Patients with aortic and pulmonary stenoses may not well tolerate hemodilution because the hemodilution-associated increase in cardiac output may be limited due to the valvular stenoses

FFP transfusions

Platelet transfusions

These general guidelines are well accepted but not strictly respected