Patient Blood Management - Blood Safety and Component Utilization Lowell Tilzer M.D. Pathology and Lab Medicine Kansas University Med Center Risk of ID transmission Pre NAT Post NAT HIV 1:607,000 ~1:2.5 million Hep B 1:63,000 same Hep C 1:103,000 ~1:1.9 million HTLV 1:1.5 mill same WNV N/A 1:1.4 million Syphilis Unknown same BSE 5 patients in U.K to date Emerging infectious disease XMRV Dengue fever Other Transfusion Reactions Febrile Nonhemolytic (1-4:100) Delayed Hemolytic (1:2,500) TRALI (1:5000) TACO (frequent) TRIM (frequent) Acute Hemolytic (1:38,000) Blood delivery errors (1:12,000) Fatal Hemolytic reaction (1:1,000,000) Anaphylactic (1:150,000) Decreased Erythropoiesis Always 3 Transfusion Related Immunomodulation (TRIM) Dose-dependent reduction in cellular immunity - Decreases in NK cell and macrophage activity, activation of T-suppressor cells (anergy) - Effect has been known and well-documented for years 7 10 fold increase in postoperative infection rates leading to increased LOS, resource consumption, total hospital costs Increased cancer recurrence rates in transfused patients, increased 5 year mortality in CABG Transfusion and Cancer Nosocomial Infection Rates in Critically Ill Patients N = 1,717 n = 416 n = 1,301 Taylor RW, et al. Crit Care Med. 2002;30:1-6. 1
Overuse of Transfusion Increases Risk of Hospital Acquired Infection JAMA April 2014 Among hospitalized patients, a restrictive RBC transfusion strategy was associated with a reduced risk of health care associated infection compared with a liberal transfusion strategy. Implementing restrictive strategies may have the potential to lower the incidence of health care associated infection. 1 in 20 could avoid infection by using restrictive threshold Mortality Rates in Critically Ill Patients n=1,717 N=416 N=1,301 Taylor RW, et al. Crit Care Med. 2002;30:2249-5 Red Cell Storage Lesions Patient Safety is Number 1 Decreased 2,3 DPG shifts O2 dissociation curve to the left less O2 delivered to the tissues, lasts 12 to 24 hours Decreased Nitric Oxide > vasoconstriction > less O2 delivered to the capillaries lasts hours Decreased deformability harder RBCs to squeeze through the capillaries less O2 delivered to the tissues lasts until the trxn RBC s are cleared Blood has become safer But it is not as safe as we would like Use blood with caution, not a cavalier attitude There may very well be more risk than benefit Use one unit whenever possible and reassess the patient Keep the patient safe! Blood Component Therapy Blood Preservatives Apheresis RBC + Platelet + 2
Whole Blood No longer readily available Used in trauma and rapid bleeds WB spin RBC RBC express RBC Fluid overload common No viable platelets or granulocytes Reduced Factors V & VIII (labile factors) 200 ml 250 ml Can cause hemolytic, febrile, and allergic reactions Red Blood Cells Increase Oxygen carrying capacity Transfusion trigger ~ 7 g/dl Hgb No viable platelets or granulocytes Hemolytic reactions possible Reduced febrile and allergic reactions LeukoReduced RBCs Decrease febrile non-hemolytic reactions Reduce CMV transmission Reduce HLA Alloimmunization Possible Decreases immunomodulation Decrease GVHD Decrease TRALI Leuko Reduction Methods Removal of Buffy coat Cell Washing Filters Prestorage Bedside How many randomized Clinical Trials for Red Cell Transfusion efficacy have there been in the last 100 years? One! 3
A multicenter, randomized controlled clinical trial of transfusion requirements in critical care 1 Prospective, randomized multicenter Canadian study with 838 critically ill ICU patients Liberal transfusion strategy (Hgb 10.0 g/dl) vs restrictive strategy (Hgb 7.0 g/dl) - Restrictive transfusion group had a mean HgB of 7.5 and received 2.6 +/- 4.1 units - Liberal transfusion group mean Hgb 10.7 and received 5.6 +/- 5.3 units A multicenter, randomized controlled clinical trial of transfusion requirements in critical care 1 Overall, the adjusted multi-organ dysfunction score and in-hospital mortality were significantly higher in the liberal transfusion group than in the restrictive transfusion group No sub-group of these critically ill patients demonstrated an added benefit of higher Hgb levels, and most patients in the liberal transfusion group had worse outcomes. Restrictive (%) Liberal (%) p MI 0.7 2.9 0.02* Pulm edema 5.3 10.7 <0.01* ARDS 7.7 11.4 0.06 Angina 1.2 2.1 0.28 Infections 10.0 11.4 0.38 1 Hebert et al NEJM 1999, 340(6) 1 Hebert et al NEJM 1999, 340(6) A multicenter, randomized controlled clinical trial of transfusion requirements in critical care 1 Mortality Restrictive (%) Liberal (%) p All patients 18.7 23.3 0.10 Death (in hospital) 22.2 28.1 0.05* APACHE 20 8.7 16.1 0.03* <55yo 5.7 13.0 0.02* Cardiac Dx 20.5 22.9 0.69 Severe inf/ sepsis 22.8 29.7 0.36 Adult Blood Transfusion Order Set Packed Red Blood Cells, Leukoreduced: Most recent hgb g/dl or hct % (within 24 hours) Special product requirements: Irradiated Washed CMV negative Sickle Cell negative Type and Crossmatch units. One unit of packed red cells in an adult will increase hct by approximately 3% and hgb by 1 g/dl. Please order one unit and evaluate clinically before ordering additional units. Hold for surgery Date: Procedure: Hematocrit 21% or hemoglobin 7 g/dl Hematocrit 24% or hemoglobin 8g/dL in a patient with unstable angina/ myocardial infarction/ cardiogenic shock Rapid blood loss with > 30-40% of estimated blood volume (>1500-2000 ml) not responding to appropriate volume resuscitation, or with ongoing blood loss. 1 Hebert et al NEJM 1999, 340(6) Adult Blood Transfusion Order Set Continued The patient has been determined to be normovolemic and there is evidence to support the need for increased oxygen carrying capacity as witnessed by (indicate): Tachycardia, hypotension not corrected by adequate volume replacement alone Sepsis protocol Other - specify Research Protocol/Other - specify Frozen, Deglycerolyzed RBCs Rarely used Used for storing rare antigen-negative units for patients who have antibodies to the rare antigens Expensive Time consuming 4
Washed Red Blood Cells Platelets Single Donor Platelets (by Apheresis) Patients with IgA deficiency and antibodies to IgA. Patients with repeated severe transfusion reactions to plasma proteins unresponsive to medications. Random Donor Platelets (derived from Whole Blood) As of March 1, 2004 few available Hard to test for bacteria Single Donor Platelets Platelets collected by a special instrument (Apheresis) from one donor in 2 hours. Equivalent to 6-8 random donor platelets WBC s removed by instrument Only Platelets & 300 ml plasma Cytapheresis Platelets Yield: 3 x 10 11 platelets/ unit Volume: 200-300 ml Shelf Life: 5 days at 22 C with agitation As of March 2005, Apheresis platelets must be tested for bacteria and negative before release from Blood Center Platelets Indications Thrombocytopenia (e.g. Bone Marrow Failure or Massive Trauma) Thrombocytopathies (e.g. Drug induced or Congenital Defects) Caution: Transfusion Reactions Febrile (difficult to LR) Allergic Infectious (especially bacteria) Factors affecting Post transfusion platelet count increment Fever Sepsis Hypersplenism Consumptive Coagulapathy (DIC) Platelet Antibody Autoimmune Alloimmune (HLA & platelet Abys) 5
Random Donor Platelets Random Donor Platelets Each bag contains 5.5 x 10 10 platelets/bag Expected increment 5-10,000/ ul PRP spin Platelet 50 ml 250 ml Usual Adult Dose 5-10 bags Pediatric dose: 1 bag/ 10 kg b.w. Shelf Life 5 days at 22 C with constant rotation Adult Blood Transfusion Order Set Apheresis Platelets, Leukoreduced: Most recent platelet count / µl Special product requirements: Irradiated CMV negative Crossmatched units A single dose of platelets (adult: one apheresis product) will increase the platelet count by 30,000-60,000/ µl Hold for surgery Date: Procedure: Platelet count 10,000/ µl prophylactically in a patient with failure of platelet production Platelet count 20,000/ µl and signs of hemorrhagic diathesis (petechiae, mucosal bleeding) Platelet count 50,000/ µl in a patient with (indicate): Active hemorrhage Invasive procedure (recent, in-progress, planned) specify Platelet dysfunction as documented by- specify Research Protocol/Other - specify Platelets before a procedure Granulocytes Replaced by antimicrobials and G-CSF Indications Neutropenia (<500 PMNs/ul) Bacterial infection unresponsive to antibiotics Reversible Bone Marrow Hypoplasia Limitations Prophylactic Use of Doubtful Value Febrile & Pulmonary Reactions Clinical Trials using G-CSF primed donors Types of FFP - frozen within 8 hours of collection 24 hour plasma - frozen within 24 of collection Thawed 5 day plasma Stored at - 18 C for up to one year Volume: 200-300 ml Dose: Start with 2 units and check Coags 6
Adult Blood Transfusion Order Set : Most recent coagulation studies: INR PTT Fibrinogen units A dose of two units of plasma is usually adequate to correct a coagulopathy. Hold for surgery Date: Procedure: Abnormal coagulation studies and significant hemorrhage Prophylactic use for INR > 2.0 prior to a procedure specify Emergent reversal of coumadin Research Protocol/pheresis/Other -Specify Indications: Labile and Stable Coagulation Factor Replacement (one ml of FFP contains one unit of each coag factor) Caution: Not for volume or protein replacement Limitation: Not a concentrate (~300 ml per bag) Use Massive blood transfusion: bleeding with transfusion of more than one blood volume if PTT >45 seconds or INR >2.0, if test results available. exchange for TTP. Antithrombin III deficiency (if specific concentrate unavailable), or Protein C, Protein S, or Heparin Cofactor II deficiency. Coumadin reversal most importantly with CNS bleeds Recommendations for Not bleeding but going to OR, deep bx, or large cannula stick with INR >2, give 2 u of FFP & Vit K. If INR does not correct stop. Not bleeding and low risk procedure (LP or transesphogeal echo) don t give plasma. If increased INR and bleeding not controlled by plasma, consider other possibilities Platelet count, fibrinogen, mechanical rviia, but it would be off-label & expensive (get Heme consult 1 st ) Amicar Remember therapeutic INR is 2-3, UHC recommends not transfusing until INR > 2.0 Use of prior to procedure US hospitals have a higher FFP/RBC usage than the rest of the world Most of the time coagulation studies do not predict when someone will bleed during a procedure Only 25% of factor is required for hemostasis, yet coag tests (PT, INR, & PTT) become abnormal below 50% 7
Reduction in plasma transfusion after enforcement of guidelines Maria Taveres Transfusion 2011 Why worry about Usage? TRALI Transfusion Related Acute Lung Injury Donor antibody against recipient WBCs 1 in 7500 transfusions X-ray white out of lungs Clinical ARDS 5-10% mortality Cryoprecipitate Cryoprecipitate Hypofibrinogenemia: consumptive coagulopathy with recent or active bleeding or prior to invasive procedure or massive transfusion and fibrinogen level <100 mg/dl. Fibrinogen levels above 100 mg/dl are generally considered adequate for hemostasis. Patients with von Willebrand s disease who are bleeding, when bleeding is unresponsive to desmopressin (DDAVP), or prophylactically prior to surgery. Cryoprecipitate Fibrin surgical adhesive. To enhance platelet function in patients with uremic platelet dysfunction and hemodialysis with active bleeding or prophylactically prior to surgery, if unresponsive to DDAVP or dialysis Factor VIII deficiency (Hemophilia A) if Factor VIII concentrates are not available, and no inhibitor present. Factor XIII deficiency. 8
Adult Blood Transfusion Order Set Blood Administration Cryoprecipitate: Most recent coagulation Studies: INR PTT Fibrinogen units One unit per 10 kg for peds patients is usually adequate when cryoprecipitate is required. A standard adult dose is 10 bags. (product may be available in pre-pooled packs of 5) Fibrinogen 100 mg/ dl Fibrinogen 150 mg/dl with active hemorrhage Research Protocol/Other - Specify Always do careful Clerical Check, verify: Patient name & ID (on wristband) Check unit number on the bag Check the Transfusion form Use 170 micron filter Check vitals pre, 15, & 30. Then q 30-60 Transfuse in < 4 hours. Summary Patient Safety is Number 1 Blood has become safer But it is not as safe as we would like Use blood with caution, not a cavalier attitude There may very well be more risk than benefit Use one unit whenever possible and reassess the patient Keep the patient safe! 9