TOC | Heme

TRANFUSION
RBC | Platelets | FFP | Cryoprecipitate |
See Transfusion Reactions

Practice guidelines for blood component therapy. - Anesthesiology 1996 Mar; 84(3):732-47
A report by the American Society of Anesthesiologists Task Force on Blood Component Therapy.

Red blood cell transfusions
The transfusion of one unit of whole blood or RBCs increases the hematocrit by approximately 3%, or the hemoglobin concentration by 1 g/dL, in a 70-kg nonbleeding adult.

The task force concludes that for RBS transfusion

RBC transfusion is rarely indicated when the hemoglobin concentration is greater than 10 g/dL and is almost always indicated when it is less than 6 g/dL, especially when the anemia is acute;
the determination of whether intermediate hemoglobin concentrations (6-10 g/dL) justify or require RBC transfusion should be based on the patient's risk for complications of inadequate oxygenation;
the use of a single hemoglobin "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 (deliberate hypotension and pharmacologic agents) may be beneficial; and
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.

Preparation and administration of RBCs

Type-and-screen the recipient's RBCs for the A, B, and D (Rh) antigen and also the recipient's serum for antibodies against other RBC antigens. Cross-matching tests the patient's serum for antibodies against antigens on the donor's RBCs and is performed prior to dispensing a specific unit of blood for a patient.
Leukocyte-depleting (leukopoor) filters remove 99.9% of WBCs from blood products and are recommended in the following circumstances:
(a) in patients who have had prior nonhemolytic febrile transfusion reactions not responsive to acetaminophen and diphenhydramine;
(b) in patients undergoing RBC exchange transfusions;
(c) in patients in whom cross-match incompatibilities are identified; and
(d) to prevent CMV infection in patients who require CMV-negative blood products that are unavailable.
Leukocyte-depleting filters may help also to decrease the risk of platelet alloimmunization ( Ann Intern Med 117:151, 1992).
Irradiation of blood products eliminates immunologically competent lymphocytes and is recommended for immunocompromised bone marrow or organ transplant recipients or in any patient receiving directed donations from HLA-matched donors or first-degree relatives.
Washed RBCs should be considered in patients in whom plasma proteins may cause a serious reaction (e.g., IgA-deficient recipients or in patients with paroxysmal nocturnal hemoglobinuria).
CMV-negative blood products are indicated in immunocompromised bone marrow or organ transplant recipients who are CMV-antibody-negative.
Premedication with acetaminophen and diphenhydramine, 25-50 mg PO or IV, should be used in patients who have developed previous nonhemolytic transfusion reactions. Occasionally, glucocorticoids (e.g., hydrocortisone, 50-100 mg IV) also will provide benefit.
Administration must include careful patient and blood-product identification procedures to avoid mishandling errors. The IV catheter should be at least 18 gauge to allow adequate flow. All blood products not leukocyte-depleted should be administered through a 170- to 260-mum "standard" filter to prevent infusion of macroaggregates, fibrin, and debris. Only 0.9% NaCl should be used with blood components to prevent cell lysis. Patients should be observed for the first 5-10 minutes of each transfusion for adverse side effects and at regular intervals thereafter. Each unit of blood should be administered within 4 hours.

Prophylactic platelet transfusion

The magnitude of increased platelt count is variable and is influenced by the release of stored platelets from the spleen and peripheral platelet destruction. Transfusion of one platelet concentrate will increase the platelet count by approximately 5-10 x 1,000/mc1 in the average adult. The usual therapeutic dose is one platelet concentrate per 10 kg body weight. Single-donor platelets obtained by apheresis are the equivalent of approximately six platelet concentrates. Patients repeatedly transfused over a prolonged period may become alloimmunized and refractory to platelet transfusion. In such patients, human leukocyte antigen-matched or crossmatched platelets may be required. The platelet count at which surgical and obstetric patients are likely to experience increased bleeding is unknown.

In nonsurgical patients, spontaneous bleeding is uncommon with platelet counts greater than 20 x 1,000/mcl and some studies suggest low complication rates in surgical patients with thrombocytopenia. Performance of paracentesis and thoracentesis was not associated with increased bleeding in patients with platelet counts of 50-99 x 1,000/mcl.

The task force concludes that for platelet transfusion

prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (e.g., idiopathic thrombocytopenic purpura);
prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when the platelet count is greater than 100 x 1,000/mcl and is usually indicated when the count is below 50 x 1,000/mcl . The determination of whether patients with intermediate platelet counts (50-100x 1,000/mcl ) require therapy should be based on the risk of bleeding;
surgical and obstetric patients with microvascular bleeding usually require platelet transfusion if the platelet count is less than 50 x 1,000/mcl and rarely require therapy if it is greater than 100 x 1,000/mcl . With intermediate platelet counts (50-100 x 1,000/mcl ), the determination should be based on the patient's risk for more significant bleeding;
vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss may be undertaken in patients with platelet counts less than 50 x 1,000/mcl ; and
platelet transfusion may be indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding.

Platelet transfusion guidelines

Transfusion of a fresh, single-donor apheresis unit should produce the same increment in platelet count (approximately 30,000/mul) in a patient with a pure production problem as that of six stored units derived from whole blood. Platelets are infused IV over 30 minutes. Premedication is unnecessary.
Transfusion threshold. Approximately 5 × 10¹⁰platelets (roughly the content of a single apheresis unit) are needed each day to satisfy basal requirements (to saturate the splenic reservoir and to repair sites of endothelial damage).
Each patient has a threshold at which the perceived risk of spontaneous hemorrhage warrants prophylactic platelet transfusion. Patients with chronic thrombocytopenia generally do not require platelet transfusion unless they develop overt bleeding or a superimposed coagulopathy. A rational guideline for asymptomatic acutely thrombocytopenic patients is to measure the platelet count once daily and to transfuse a single product for a platelet count of less than 10,000/mul.
Prophylactic transfusion is reasonable for patients to keep count above
10,000-20,000/mul if a minor invasive procedure is performed , if a coagulopathy or minor mucosal bleeding (minor epistaxis, occult GI bleeding, petechiae) is present,
50,000/mul if a major invasive procedure is performed .
100,000/mul for high-risk surgery (e.g., neurosurgery, ophthalmic surgery, cardiopulmonary bypass) .
Platelet transfusion thresholds change if there is evidence of bleeding.
Platelet refractoriness. This condition develops in approximately half of multiply transfused patients. It can be documented by measuring the platelet count before and 60 minutes after transfusion. An increment of less than 5000/mul after one apheresis unit or six random-donor units is an indication of refractoriness. The mechanism is development of alloantibodies, usually directed at donor lupus anticoagulant or ABO antigens expressed on platelets and leukocytes. The following interventions may improve platelet increments in alloimmunized patients: transfusion of ABO-identical platelets; use of fresh, rather than stored platelets; use of lupus anticoagulant-matched donors (preferably family members); and, in actively bleeding patients, administration of IVIG (400 mg/kg qd for 5 days) prior to transfusion ( Am J Hematol 38:15, 1991).

Fresh-frozen plasma
is indicated for urgent reversal of warfarin therapy, correction of known coagulation factor deficiencies for which specific concentrates are unavailable, and correction of microvascular bleeding when prothrombin and partial thromboplastin times are >1.5 times normal. It is contraindicated for augmentation of plasma volume or albumin concentration.

The task force recommends the administration of FFP with the following guidelines:

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 (>1.5 times normal) PT or PTT;
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. Four to five platelet concentrates, one unit of single-donor apheresis platelets, or one unit of whole blood provide a quantity of coagulation factors similar to that contained in one unit of FFP (except for decreased, but still hemostatic, concentrations of factors V and VIII in whole blood);and
FFP is contraindicated for augmentation of plasma volume or albumin concentration.

Cryoprecipitate
Cryoprecipitate, which contains factor VIII, fibrinogen, fibronectin, von Willebrand's factor, and factor XIII, is used for the correction of inherited and acquired coagulopathies.

One 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. However, most patients with factor VIII deficiency are treated with factor VIII concentrates, and patients with some subtypes of von Willebrand's disease respond to administration of desmopressin acetate (DDAVP). Similarly, coagulopathy associated with uremia can be treated with cryoprecipitate, but DDAVP is usually the first-line therapy.

It has been observed that patients with certain inherited or acquired coagulopathies (e.g., hemophilia A, von Willebrand's disease, hypofibrinogenemia, disseminated intravascular coagulation, hepatic insufficiency) are at increased risk of perioperative or peripartum bleeding. It should be considered for patients with von Willebrand's disease unresponsive to desmopressin, bleeding patients with von Willebrand's disease, and bleeding patients with fibrinogen levels below 80-100 mg/dL. The task force recommends careful adherence to proper indications for blood component therapy to reduce the risks of transfusion.

The task force recommends considering the administration of cryoprecipitate for

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, and
correction of microvascular bleeding in massively transfused patients with fibrinogen concentrations less than 80-100 mg/dL (or when fibrinogen concentrations cannot be measured in a timely fashion).

Factor VIII replacement. A good rule of thumb is that factor VIII levels will increase 2% for every 1 unit/kg infused. Thus, 50 units/kg IV bolus will raise factor VIII levels to 100%. This dosage can be followed by 25 units/kg IV bolus q12h. Dose adjustment based on trough factor VIII levels should be made every 1-2 days in patients with moderate to severe hemorrhage. The recombinant products are the most expensive and may be associated with a greater risk of inducing inhibitor formation. They should be reserved for use in HIV-seronegative and hepatitis C virus-seronegative or previously untreated patients.

Factor VIII Products:

Low purity: Cryoprecipitate
Intermidiate purity: Humate-P, Koate-HP, Factor VIII-SD, Proliferate-OSD
High purity: AHF-M, Alphanate, Hemophil-M, Monoclate-P, Recombinate, Bioclate, Kogenate, Helixate

What are the current risk estimates for Transfusion-Transmitted Infection with HIV, HTLV, HCV or HBV?

Actual transmission rates for Transfusion-Transmitted Infection may exceed reported estimates of risk. Based on the most recent estimates, the risk per unit of viral exposure of a transfusion recipient ranges from 0.52 (for HIV) to 7.21 (for HBV) per million donations, with an overall risk of 10 per million units for the four viruses combined.

HIV 1 in 1,930,0002
HTLV 1 in 641,0001
HCV 1 in 1,543,0002
HBV 1 in 138,7002

1. New England Journal of Medicine 6-27-96: Retrovirus Epidemiology Donor Study (REDS). Study focused on the likelihood that a donor would be in the infectious window period when he/she donated, and that the unit of blood would pass all screening tests. Actual incidence of viral exposure via transfusion may be higher.

2. Dodd, RY. Blood Safety in the New Millenium, 2001.