In The name of God ●

1. In The name of God●

2. Acute HTR • Acute HTRs typically occur early during the transfusion, after administration of as little as a few mL of incompatible blood due to ABO incompatibility. • In AHTRs, the temporal relationship to the transfusion is clear, but it may initially be challenging to determine what type of reaction is occurring.

3. EPIDEMIOLOGY •   The prevalence of acute HTRs (AHTRs) has been estimated at approximately 1 in 70,000 per blood product transfused • In a report of transfusion-associated deaths in the United States from 1976 to 1985, acute hemolysis was the most common cause of death • There were 158 fatalities from AHTRs, 26 fatalities from delayed HTRs (DHTRs), and 6 fatalities from non-immune hemolysis. • Of the AHTRs, 131 (83 percent) were due to ABO incompatibility errors, mostly involving a group O recipient who received non-group O blood

4. Of the deaths due to hemolysis, one-third (7 percent of the total) were due to ABO incompatibility and the remaining two-thirds (14 percent of the total) to non-ABO reactions.

5. ACUTE HEMOLYTIC REACTIONS •   Acute HTR (AHTR) refers to transfusion-associated hemolysis that occurs during the transfusion or within the first 24 hours after transfusion. • AHTR is a medical emergency that requires immediate cessation of the transfusion, if still in progress, as well as immediate evaluation and interventions to reduce the risks of serious organ damage to the patient and other potentially affected patients.

6. presentation • The most common presentation of AHTR is after red blood cell (RBC) transfusion, and the most commonly implicated RBC antigens are those of the ABO blood group, due to clerical error, as noted above

7. ABO-associated AHTRs • ABO-associated AHTRs often occur during the early minutes of the transfusion, although they may not be immediately appreciated (eg, if the patient is under anesthesia). • An ABO-associated AHTR may be suspected when a patient develops chills, fever, hypotension, hemoglobinuria, renal failure, back pain, or signs of disseminated intravascular coagulation (DIC). The serum or urine may be pink due to the presence of free hemoglobin. • In a patient under anesthesia or in a coma, oozing from venipuncture sites due to DIC or change in the urine color to red or brown due to hemoglobinuria may be the only finding.

8. ABO-associated AHTRs • The presence of hemoglobinemia (red or dark plasma), hemoglobinuria (red or dark urine), DIC, shock, and acute renal failure due to acute tubular necrosis are indicative of intravascular hemolysis.

9. The initial steps • The initial steps are similar to those for any suspected acute transfusion reaction, and include • immediately stopping the transfusion, • providing hemodynamic support, and • contacting the transfusion service (or following the institutional protocol) to help with the evaluation • Many of the initial interventions such as vigorous hydration and hemodynamic support are made immediately, without waiting for the results of laboratory testing.

10. Repeat testing • Repeat ABO compatibility testing. • ●Additional antibody studies if ABO incompatibility is excluded. • ●Repeat crossmatch with pre- and post-transfusion specimens using an indirect antiglobulin (IAT; also called indirect Coombs) method. IAT is likely to be positive in an AHTR that is not caused by ABO incompatibility.

11. ●Direct antiglobulin (Coombs) testing (DAT), which may be positive in AHTR but may be negative in ABO incompatibility or if hemolysis is so severe that all RBCs with antibody on the surface have been lysed. • ●Visual inspection of the serum and urine for pink or dark brown color. The serum should be analyzed for free hemoglobin, and a urine sample should be saved in case analysis of the urine for free hemoglobin is required. Pink or dark brown serum and/or urine and a positive test for free hemoglobin will be present in severe intravascular hemolysis but not in extravascular hemolysis. • ●

12. Testing for hemolysis • Testing for hemolysis with serum haptoglobin, lactate dehydrogenase (LDH), and unconjugated (indirect) bilirubin levels. In hemolysis, haptoglobin will be low; LDH and bilirubin will be increased • , although the increase in unconjugated bilirubin may be delayed and is more likely to be helpful in evaluating the patient for a DHTR than for an AHTR.

13. ●Testing for DIC • ●Testing for DIC if the patient has obvious signs of intravascular hemolysis (eg, pink serum or urine, hypotension) or signs of DIC such as oozing from intravenous sites or increased bleeding; • DIC is a sign of severe intravascular hemolysis. Tests include prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen level, D-dimer, and platelet count.

14. Electrolyte testing and cardiac monitoring • Electrolyte testing and cardiac monitoring if the patient has obvious signs of intravascular hemolysis, since lysis of RBCs releases potassium into the circulation and may cause severe hyperkalemia. • ●Serial hemoglobin levels, because hemoglobin levels may decline to the point that additional transfusions are needed.

15. normal saline should be infused • normal saline should be infused immediately to reduce the risks of hypotension and renal injury. An infusion rate of 100 to 200 mL/hour is typically used to support a urine output above 1 mL/kg/hour or 100 to 200 mL/hour to reduce the likelihood of acute oliguric renal failure • The beneficial effect of urinary alkalinizationin patients with marked hemoglobinuria is uncertain. Vasopressors may be required to treat hypotension. A nephrologist may be consulted for advice on prophylactic measures to prevent or reduce renal damage and in some cases to treat severe hyperkalemia; a hematologist may be consulted if the patient has evidence of DIC.

16. Ringer's lactate solution should be avoided • Ringer's lactate solution should be avoided in the tubing used for the transfusion because it contains calcium, which may initiate clotting of any blood remaining in the intravenous line. Dextrose-containing solutions should be avoided because the dextrose may promote hemolysis any of the remaining RBCs

17. Intraoperative transfusion of blood products in adults • Dr Fariba Behnamfar Esfahan University of Medical Sciences

18. Emergency surgery with massive blood transfusion  •  For patients with hemorrhage requiring massive transfusion and emergency surgery, we employ protocols for ordering appropriate amounts and types of blood components. Typically, RBCs, plasma products such as Fresh Frozen Plasma (FFP), and platelets are ordered and transfused in approximately equal (1:1:1) • ratios as soon as these blood products are available, either before and/or during the intraoperative period. Early communication with the institutional blood bank is necessary to activate a massive transfusion protocol.

19. Peripheral venous access • – Large-bore (eg, 14 or 16 gauge) peripheral intravenous catheters or a short 7 French rapid infusion catheter inserted with the modified Seldinger technique may be selected Peripheral catheters are typically placed in the upper extremities, and may be left in place for short periods. • Compared with a central venous catheter (CVC), peripheral catheters are generally associated with fewer complications. However, large-bore peripheral venous access may not be possible in some patients due to body habitus, vein fragility, or prior use of multiple peripheral veins. (

20. Warming before administration  •  Cold and previously thawed blood products (eg, allogeneic RBC units and plasma products) are administered via a blood warmer to avoid hypothermia with resultant coagulopathy and other adverse effects . • Cryoprecipitate units are thawed to room temperature and should be administered within four to six hours of thawing; use of a blood warmer is unnecessary. • Platelets are stored at room temperature and are typically infused via separate administration tubing that is not connected to a blood warmer. However, use of a blood warmer is not prohibited in hypothermic patients

21. Hemoglobin concentration for transfusion of red blood cells • Typical thresholds for RBC transfusion are a hemoglobin (Hgb) concentration ≤7 to 8 g/dL(≈ hematocrit ≤21 to 24 percent); • a slightly higher threshold (Hgb ≤9 g/dL; ≈ hematocrit ≤27 percent) may be used in a patient with moderate to severe ongoing bleeding or evidence of myocardial or other organ ischemia • In the absence of ongoing active bleeding, accurate assessment of a post-transfusion Hgb level can be performed as early as 15 minutes following RBC administration

22. American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management*. Anesthesiology 2015; 122:241. • Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Brown JR, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann ThoracSurg 2011; 91:944

23. platelet transfusion • ●We administer platelet transfusions as a component of massive transfusion protocols. In actively bleeding patients, we maintain platelet count >50,000/microL, or >100,000/microL for central nervous system bleeding. • Although exact platelet quantities vary, each platelet dose (ie, one apheresis unit or a pool of whole blood derived platelets) contains approximately 3 to 4 x 1011 platelets suspended in 200 to 300 mL of plasma and will increase the platelet count by approximately 30,000/microL to 50,000/microL • . Risk of bacterial infection is higher compared with other blood components since platelets are stored at room temperature.

24. Fresh Frozen Plasma (FFP) • ●We administer plasma products such as Fresh Frozen Plasma (FFP) as a component of massive transfusion protocols. • Other indications include emergency surgery in patients with severe bleeding or anticipated severe bleeding • if there are deficiencies of multiple coagulation factors, particularly if intracranial hemorrhage is present

25. Cryoprecipitate • We transfuse Cryoprecipitate to treat hypofibrinogenemia in massive transfusion protocols when fibrinogen cannot be measured in a timely fashion, and in bleeding surgical patients with known fibrinogen concentrations <50 to 100 mg/dL, or an inherited disorder of fibrinogen • Cryoprecipitate has also been used to treat life-threatening intraoperative bleeding in patients with disseminated intravascular coagulation (DIC), hepatic insufficiency, or uremia.