Joint Commission, AABB and CAP requires monitoring of blood utilization within institutions, to develop transfusion guidelines. The blood utilization committee evaluate patients who do not meet the established transfusion criteria and update previous guidelines every 3 years. It is very important to know that there is no definite criteria for use of blood components and the use is usually based in recommendations. Rules are flexible and not mandatory and transfusions that fall outside the guidelines may be clinically indicated but should be reviewed to see if it is possible to improve the clinical practice.
RED BLOOD CELLS.
Signs and symptoms of anemia and acute blood loss:
Transfusion is frequently given based in symptoms of anemia and acute blood loss. Sign and symptoms of anemia are: tachycardia, palpitations, hypotension, weakness, headache, dizziness, disorientation, dyspnea and angina. Signs and symptoms of acute blood loss are: tachycardia, palpitations, cooling of extremities, pallor, hypotension, reduced arterial pressure, reduced central venous (jugular pressure), acidosis, increased respirations, decline in urinary output, mental status changes, dizziness and disorientation.
RBCs RECOMMENDED GUIDELINES:
1. As a general rule (including perioperative patients before general anesthesia), Hb < 6 g/dl is in most patients a reasonable indication for RBCs transfusion and Hb > 10 is usually not indicated. Benefits of transfusion are not obvious in most patients with Hb between 8 and 10 g/dl and many of this patients receive unnecessary transfusions.
8 g/dl is a very common threshold applicable to most patients including acute bleeding and acute coronary events. Some doctors consider that the threshold for patients with acute coronary events should be less than 10 g/dl but this is controversial, many disagree and recommended 8 g/dl as the threshold.
The 8 g/dl threshold may be used before elective surgeries and for postoperative surgical patients (including orthopedic surgeries) and may perfectly includes patients with preexisting chronic cardiac or pulmonary disease and arteriosclerosis. Elderly hospitalized patients or patients with preexisting pulmonary, cardiovascular or atherosclerotic disease (not unstable myocardial situations) may have reduced morbidity and mortality with a threshold of 8 g/dl or symptomatic anemia, instead 10 g/dl
Anyway, there is no definitive criteria for RBCs administration, and although the recommended threshold is 8 g/dl for most cases, some doctors still consider that Hb between 8 and 10 g/dl may be an indication but this is definitely something up to the clinician judgment and assessment. You have to consider the Hb level but also signs and symptoms of anemia and blood loss (blood volume) and oxygen requirements. In young healthy individuals, hemoblobin over 6 may be well tolerated before oxygen deliver is deteriorated and venous oxygen drops. RBCs are transfused to improve oxygen carrying capacity, regardless of the Hb concentration. If possible please try to compare arterial vs. venous saturation (normal extraction ratio is 25% vs extraction ratio > 50% that is definitely critical and supports transfusion). Always considere in your desicion comorbidities like the presence of coexisting cardiovascular disease that predispose to ischemia or pulmonary disease.
2. Young healthy patients going to elective surgery may tolerate Hb reductions from 6 to 7 g/dl with adequate oxygen deliver with only minimal rise in perioperative mortality risk. In healthy preoperative patient in which blood loss or adverse effects associated with anesthesia are expected, a threshold of 7 g/dl may be used.
3. Acute blood loss or hemorrhage in surgery or trauma between 15 to 30% of the blood volume generally require blood transfusion. In young healthy patients the threshold may be increased to 30% but this may not be valid for elderly patients with comorbidities like cardiac or pulmonary disease. Bleeding patient may require more than 72 hours for compensation, and thus the hematocrit or hemoblobin cannot be followed as indicator of patient status. Best way to follow this patients is with symptoms of blood loss.
4. In preoperative elective surgeries in patients with atherosclerosis a threshold used is 8 g/dl or symptomatic anemia. Preoperative surgery in patients with atherosclerosis studies show that mortality may increase with threshold below 8 g/dl. This studies suggest to increase the threshold for this patients to 9 g/dl or 10/dl.
5. Postoperative patient after CABG do well with a transfusion goal in the range of 24% hematocrit (8g/dl Hb). There are even some studies showing that patients reaching the intensive care with Hct above 24% appears to have increase probability of MI.
6. Critically ill patients like trauma patients, burn patients or patients with central nervous ischemia, mesenteric ischemia or severe cardiopulmonary compromise may be transfused in some cases with hemoglobin of <10 g/dl and generally tolerate Hematocrit of 30% or more through increase oxygen extraction. Patients with trauma or burned, not critically ill and without cardiopulmonary compromise may be transfused with the threshold of < 8 g/dl without any problem. In these patients is important to always maintain Hb > 7 g/dl.
7.There are studies showing that for most adults in intensive care units transfusion should be considered at hemoglobin concentration of 7g/dl or less. Why ? Because in patients in intensive care you can easily control de oxygen extraction to guide the use of RBCs. If patients are severely ill and elderly with comorbidities the trigger may be increased to 8 g/dl or symptomatic anemia.
8. For patients with chronic anemia, only consider transfusion as a last resort in patient where etiology cannot be addressed or in patients transfusion dependent with a chronic transfusion regimen showing inability to maintain adequate red cell mass. These patients may have a threshold of 8 g/dl.
9. Acute coronary syndrome: Indications are controversial. No clear recommendations are given for these patients. Further research is necessary. Studies are confusing and conclusions not clarified to support clear recommendations. Some studies show improvement in outcome if transfusion given below hematocrit of 30%. Other studies associate transfusion below this threshold with increased mortality. Many studies consider reasonable to transfuse patients with acute MI with a higher threshold of 9-10 g/dl and express concern withholding RBC transfusion in patient with obvious ischemic disease. However, many studies accept the 8 g/dl trigger for acute coronary disease. This is definitely a controversial topic.
10. In patients with thalassemia the aim of transfusions may be to maintain hemoglobin between 9-11 g/dl.
11. If transfusions required in sickle cell disease (rarely happen) you should maintain Hct below 35% to avoid hyperviscosity.
SITUATIONS NOT RECOMMENDED FOR RBCs:
1. Definitely, less than 15% blood loss in elderly or 30% blood loss in young healthy patients may be treated with crystalloids and generally do not require RBCs.
2. As a universal rule for most patients ( including patients before general anesthesia) Hb >10 g/dl is not an indication. Transfusion is unlikely to improve oxygen transport when Hb is greater than 10g/dl. Only very rarely these patients require transfusion but they should be clearly symptomatic for anemia with comorbidities.
3. Chronic anemia generally compensate very well and is not an indication for transfusion. Most patients with chronic anemia may tolerate hemoglobin values more than 5 g/dl without symptoms.
Most cases are treated addressing the etiology, giving iron, vit B12, folate, reducing rate of autoimmune hemolysis, treating sickle cell disease or giving erythropoietin in patients with chemotherapy, bone marrow suppression or end stage renal disease.
DOSES FOR RBCs:
Standard order for adult red cell transfusion has been 2 units regardless of patient size and target hemoglobin. One unit of blood in 30 minutes increase 1g/dl of hemoglobin. Massive transfusion are common in patients with acute bleeding and it is defined as patient given more than one blood volume or 10 units of RBCs with accompanying liquids in 24 hours or 5 RBCs units/5 hours. If transfusion is required to treat a chronic anemia, a typical dose is 2 units of RBC every two weeks. In transfusion for cardiac surgery there are studies proving adverse effects if the stored blood supplied is part of the old inventory. For this reason, many doctors are lately requesting new blood and this is seriously affecting our blood bank inventories and creating outdating of blood products.
RECOMMENDED GUIDELINES FOR ADMINISTRATION OF PLATELETS IN ADULTS:
1. <10000 for prophylaxis of non bleeding patients, uncomplicated patient. Most patients in this group are patients chronically thrombocytopenic due to chronic hypoproliferative thrombocytopenia due to chemotherapy especially in leukemia or lymphoma or marrow transplant. Aplastic anemia and MDS only require prophylactic transfusion if minor bleeding is happening. For medical legal reasons, some doctors prefer to increase this prophylactic threshold to < 15000
2. <20000 for prophylaxis in complicated patients with fever, sepsis, thrombocytopathy or patients in risk of bleeding with other coagulative disorders, DIC or using heparin.
3. < 50000 in patients already bleeding due to trauma or surgery or going to a haemostatic challenge like a major surgery (some includes liver biopsy and endoscopy).
4. With plt counts between 50000 and 100000, the decision to transfuse platelets is based on the extent of surgery/trauma, ability to control bleeding with local measures, rates of bleeding, risk of bleeding, presence of microvascular bleeding, presence of platelet dysfunction and other coagulation abnormalities.
5 <100000 is the threshold accepted if the haemostatic challenge is intracerebral hemorrhage or neurosurgical procedures, ophthalmic bleeding or pulmonary hemorrhage.
6. Platelet may be indicated to correct functional problems like thrombocytopathy or qualitative platelet defect before an invasive procedure, in situations like: glanzmann, MDS, GPIIb/IIIa antagonists like abciximab, ADP receptor inhibitors like ticlopidine or clopidogrel, liver failure, ECMO, other congenital defects in platelets function.
7. After cardiac bypass or use of intraaortic balloon pump, even if platelet number is normal, patient has dysfunctional platelets and may present with diffuse microvascular bleeding or oozing. In these situations decision to transfuse is based in clinical status rather than platelet count. Patients with excessive microvascular bleeding postsurgery whose heparin has been reversed may benefit from a dose of platelets. Patients going to bypass should have discontinued P2Y12 receptor inhibitors or clopidogrel 3-7 days before the surgery. If patients go to surgery immediately after catheterization with clopidogrel may need one or more doses of platelets. DDAVP also help antagonizing the effect of these drugs.
Six risk factors that are associated with excessive bleeding after cardiac procedures commonly requiring transfusions of platelets and other blood components are: 1. advance age 2. preoperative anemia or low red blood cell volume due to low body mass (some use preoperative EPO in these patients) 3. preoperative anticoagulation or antiplatelet therapy. 4. emergency operation 5. prolonged CABG. 6. comorbidities like congestive heart failure, renal failure or pulmonary disease.
8. Hyperresponders to ASA bleeding in emergency or cardiac surgery. If patient is not bleeding it is not necessary to discontinue ASA.
9. Diffuse microvascular bleeding in patient who has lost more than one blood volume with platelet result not yet available.
NOT RECOMMENDED FOR PLATELETS TRANSFUSIONS:
1. Plats are contraindicated in TTP, HUS, HIT and postransfusion purpura. In this situations they are considered to add more fuel to the fire.
2. Platelets are not useful for the treatment of ITP.
3. In significant renal disease with creatinine > 3 mg/dl platelets may be dysfunctional. In uremic patients, platelets may be indicated only if improvement not obtained after other treatments like dialysis + DDAVP + cryo + estrogens.
4. There is no role for prophylactic platelets transfusion in routine primary open heart surgery. Platelets do not improve homeostasis after cardiac surgery.
DOSES FOR PLATELETS:
For platelets give 1 unit/10 Kg, typically pool of 6 to 10 bags for random platelets or platelets concentrates and 1 bag or single doses for apheresis unit. Today random plats are rarely used in USA, most units are apheresis platelets. Apheresis plats have same indications than random platelets but with only one donor exposure, decreasing the risk of viral transmission and bacterial contamination. HLA immunization is not decreased with apheresis plats. HLA depends more of the number of foreign antigens (leukoreduction is really the key to avoid HLA immunization). After a single doses of apheresis platelets, you expect an increase of at least 25000 plats.
RECOMMENDED GUIDELINES FOR ADMINISTRATION OF FFP IN ADULTS:
1.Significant coagulation factor deficiencies in:
- Dilutional of coagulation factors due to massive transfusion and serious bleeding. These are patients with microvascular bleeding due to excess of RBCs and crystalloids (more than 5 units or RBCs in 5 hours or 10 to 15 in 24 hours)
- Consumption of coagulation factors in DIC
- Lack of production of coagulation factors in liver failure. Severe bleeding is not common in liver disease because coag factors are decreased but also anti coagulants like prot S and C. Use of FFP in liver disease may be limited only to patients actively bleeding, not prophylactically.
2. Many use INR of 2 as threshold for serious factor deficiency. The American Society of Anesthesia recommend no correction of INR < 2.
3. The guideline for correction of excessive anticoagulation with warfarin by the American College of chest physicians only consider plasma supplementation when serious bleeding present at any elevation of INR in patients with Warfarin. Cases with INR > 9 with no significant bleeding can be treated only omitting warfarin and giving Vit K oral. For urgent Warfarin reversal, prothrombin complex concentrate (PCC) is preferred. FFP only should be used if PPC is not available. PCC contains high level of factors II, IX, X and in some preparations VII, it is administered in small volumes and is free of the risks of plasma.
4. Plasma is recommended in reversal of warfarin anticoagulation in all patients with intracranial hemorrhage.
5. Factor VIII and IX deficiencies if specific concentrates are not available until a 30% level of activity reached.
6. FFP in trauma: Some military studies recommend the strategy of damage control resuscitation giving 1:1 ratio of RBCs to plasma transfused for better survival in patients showing coagulopathy, acidosis and hypothermia. The idea of aggressive FFP is more to prevent than to treat coagulopathy. Some also use a ratio of 1:1:1 RBCs/FFP/Platelets for these trauma patients.
7. Other indications of plasma:
-Plasmapheresis for TTP
-Patients undergoing CPB with heparin resistance if antithrombin III concentrate unavailable.
-Deficiencies with the following concentrates not available: prot C or S, factor XIII deficiency (common after cardiac bypass) and other coagulopathies without available factors like V, X, XI.
-C1 estearase deficiency
ONTROVERSIAL USE FOR FFP:
Many doctors do not use FFP for mildly elevated coagulation factor tests and prophylactic transfusions. Previously 2 units of FFP were recommended prophilactically prior to bedside or interventional procedures when they PTs (or PTTs) exceed normal or 1.5 times the midpoint of the reference range. These cases usually fall at an INR about 1.5 to 2. Today, there are many doctors that consider FFP ineffective and unnecessary for mild elevation of PT/PTT or INR < 2. Some studies prove that with 2 units of FFP you only correct the laboratory values in less than 5% of patients with minimally elevated INR < 2
FFP NOT INDICATED:
Do not abuse of FFP. FFP may be related with risk of TACO, TRALI, allergic reactions, hemolysis and transmission of virus.
1. Do not give prophylactic plasma infusion in acute pancreatitis or critically ill nonsurgical noncardiac patients.
2. Intraoperative prophylactic use of 3 to 4 units of plasma in cardiac operations in absence of coagulopathy is not indicated. The use of FFP in coagulopathic patients not bleeding is not recommended. Prophylactic use of plasma in cardiac surgeries is not associated with reduced blood loss or less transfusion requirements.
3. Do not use FFP as volume expander to replace fluids. As volume expander in trauma use albumin, crystalloids or dextran.
4. Do not use FFP for heparin reversal.
5. Do not use FFP for warfarin reversal in non bleeding patients. Stop warfarin and try Vit K first.
6. Do not use FFP to treat mild elevation of INR in absence of bleeding.
7. Do not use to correct low protein level or hypoalbuminemia.
8. FFP is not effective to treat coagulation factor inhibitors
Plasma is frozen within 8 hours of collection (1 year to -18C). Once thawed or no longer frozen has to be transfused within 24 hours (within 24 hours of thawing). Usual dose of plasma is 10 ml/kg or 3 to 7 bags in average adult. One doses increase coagulation factors by 20%. If correction is required before a haemostatic challenge like surgery, give plasma shortly before the procedure to solve problems like short half live of factors like factor VII that is only present in the FFP for 5 hours. To emergency reverse of vit K dietary deficiency or overdose of Coumadin in a bleeding patient, as much as 6 units of FFP may be required. Frequently in USA, 2 units of plasma may be combined with Prothrombin complex concentrate. For situations like liver failure, DIC, trauma and dilution coagulopathy with multiple factors deficient (first factor commonly deficient is VII), you may need FFP for hemostasis until factor levels reach levels closer to 40% ( 6 to 8 units often). If correction of markedly abnormal PT/INR or PTT decided before surgery, FFP should be given immediately before the patient is called to the OR, not the night before. In particular, factor VII only has a half life of 5 hours and will not remain after 8 hours.
RECOMMENDED GUIDELINES FOR USE OF CRYOPRECIPITATE IN ADULTS:
1. For Von willebrand and hemophilia when DDAVP ineffective or contraindicated and specific concentrates not available.
2. For congenital afibrinogenemia.
3. Congenital or acquired dysfibrinogenemia (liver disease).
4. For acquired fibrinogen deficiency or hypofibrinogenemia < 100 mg/dl prior to an invasive procedure (common in DIC, liver disease, dilution after massive transfusion or after massive hemorrhage) with threshold of 100 mg/dl
5. For patients with fibrinogen < 150 mg with severe bleeding
6. For uremic thrombocytopathy unresponsive to DDAVP, estrogens, dialysis and erythropoietin.
7. Factor XIII deficiency in association with bleeding if specific virus inactivated concentrate not available.
CRYOPRECIPIPTATED NOT INDICATED:
1. Role in improving platelets function in the acquired platelet dysfunction in cardiopulmonary bypass surgery is unproven.
2. To treat bleeding from excessive anticoagulation, FFP plasma is better choice and contains most of the coagulation factors.
3. Cryo may be used in the treatment of massive hemorrhage but RBCs and volume expanders are preferred therapies.
DOSES FOR CRYOPRECIPITATE:
10 bags has 2500 mg fibrinogen and 150 cc and it is the common dose (frequently pooled) used for adults with deficiencies of fibrinogen. 2 units of cry/10Kg or 1 pool of 10 bags generally raise fibrinogen concentration by 100 mg/dl, except in DIC or continued bleeding with massive transfusion. The goal is to achieve 100 mg/dl of fibrinogen.
-AABB Technical manual, seventeenth edition
-New York State Council on Human Blood and Transfusion Services, third edition, 2012
-ASH Education Program blood. asheducationbook.hematologylibrary.org.
-Transfusion Medicine Bulletin from American's Blood Centers.
-John Bernard Henry, MD. Clinical Diagnosis and Management by Laboratory Methods
-Standards for Blood Banks and Transfusion Services, 26th edition, AABB, Bethesda
-Guidelines for Blood utilization review from the AABB
-2011 Update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Practice Guidelines. Ann thoracic surg 2011;91:944-982