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BLOOD TRANSFUSION SERVICES

BWH -Amory 2; 617-732-7290

The BWH Blood Bank is registered with the FDA and is accredited by the American Association of Blood Banks. The department performs tests and procedures designed to ensure safe and beneficial transfusion therapy for BWH and Joint Venture Oncology patients. The Clinical Pathology Resident rotating in the Blood Bank is available for questions and problems: 24 hour on call, beeper 13734. Alternatively, call (617)732-7290 and ask for the Medical Director on call. More detailed information on blood products and transfusion is available online in the BICS Handbook.

Ordering Transfusions
Orders can be placed using the BICS system. Indications for transfusions that are entered when ordering are tracked for blood utilization review by the BWH Transfusion Committee and should be as accurate as possible. The following requests can be used for type, screen and crossmatch. If the request is for STAT products, it is advised that the Blood Bank be called directly in addition to computer ordering. The status of blood work requests can be checked on the BICS clinical computer system.

Release Times
* Routine: type, screen and crossmatch time is approximately 4-6 hours

* ASAP: type, screen and crossmatch time is 1 hour (if type, screen and crossmatch already performed, time is 15 minutes)

* STAT: un-crossmatched blood can be released in 10 minutes

• Emergency patient, already crossmatched, can be released in 10 minutes


• Emergency patient, type and screen already performed can be released 15 minutes


• Emergency patient, type and screen not done can be released in 45-60 minutes

* Pre-op: Orders should be received by 7 pm on the day prior to surgery. Crossmatched blood is reserved for the patient for 48 hours. The Blood Bank maintains a list of suggested guidelines for common procedures that should be followed except in unusual circumstances. All blood products should be transfused within 4 hours from time of acquisition. Any blood products unused for any reason should be returned to the Blood Bank within 30 minutes.

Emergency Release: In life-threatening emergencies blood can be released prior to the completion of compatibility testing. An Emergency Blood Release Form must be filled out and signed by a physician and returned to the Blood Bank. This form documents the urgency and the acceptance of additional risk of transfusion before compatibility test results are known.
ABO and Rh type specific blood will be given whenever possible. Blood type reports from other institutions or from prior admissions are not accepted. Compatibility testing will be performed promptly and incompatible results reported immediately to the physician. The risk of incompatibility with type specific blood is approximately 4-6%.
Autologous units: Every autologous unit must be transfused before allogeneic units are used. If only one autologous unit is available for the OR, you may request additional allogeneic units be sent in the same cooler.

Transfusion Guidelines
The MGH Transfusion Committee Guidelines are approved by the General Executive Committee. These guidelines are based on a combination of NIH Consensus Guidelines, literature recommendations and clinical experience. It is the intent of the Transfusion Committee that these guidelines serve as a basis for making informed decisions about transfusion therapy. However, such guidelines cannot cover every possible circumstance. Clearly, the thorough evaluation of the physiological and clinical condition of the patient must supersede any transfusion plan based on formula or a single laboratory result. It is hoped that the combination of these guidelines with careful patient assessment will result in appropriate transfusion therapy for every patient. A system of blood utilization review is performed which is based on these guidelines

Blood Component Guidelines:
Transfusion care should be individualized to the needs of each patient.
Packed RBCs should be considered for:

1. Hct < 21 in the absence of cardiovascular disease

2. Among stressed patients for the prevention of ischemia:

• Age < 40 years, Hct < 24.


• Age 40-60 years, Hct < 27


• Age 60-70 years, Hct < 30

Platelets:
1. Prophylaxis against spontaneous bleeding for adults with platelet count < 10,000/µL
    (< 50,000/µL in neonates).
2. Bedside invasive procedure and platelet count < 10,000/µL.
3. Bleeding intraoperatively or post-operatively and platelet count < 50,000/µL.
4. Bleeding after cardiopulmonary bypass and platelet count < 100,000/µL.

Do NOT transfuse platelets in the setting of HIT and TTP. Platelets may NOT be useful in ITP, PTP, DIC or uremia.

Fresh Frozen Plasma (FFP):
FFP is indicated:

1. Bleeding among patients with PT > 17 sec (for newborns, > 19 sec)
N.B. For bleeding patients on coumadin or with vitamin K deficiency, see below.

2. Preparation for bedside invasive procedure if PT > 17 sec (for newborns, > 19 sec)

3. As part of the emergency management of coumadin reversal:

The decision to actively intervene (using Vitamin K or clotting factors) or to simply reduce or discontinue warfarin sodium therapy is based in part on the INR but in large measure on the clinical circumstances. Reversal of the anticoagulant effects of warfarin sodium is not a benign procedure with the risk of thrombosis dependent on patient factors such as the presence of an artificial heart valve, neoplasm, the need for rapid reversal and others. Although clinical judgment should prevail, some general guidelines can be considered:

3a) Management of asymptomatic elevations in the INR
* If the INR is above the therapeutic range but below 5 and rapid reversal is not indicated, omit the next dose or two of warfarin sodium and resume therapy at a lower maintenance dose when the INR returns to the therapeutic range.

* If the INR is > 5 and < 9 or rapid reversal is required, Vitamin K 0.5-1 mg IV* or Vitamin K 1-2.5mg subcutaneously or orally may be administered. If there is a high thrombotic risk the option to withhold warfarin for 2 or more doses may be preferred.

* If the INR is > 9 and < 20, Vitamin K 2.5 mg IV or 5mg subcutaneously may be administered.

* If the INR is >20, administration of fresh frozen plasma** is indicated along with Vitamin K 2.5 mg IV or 5mg subcutaneously
3b) Management of patients on coumadin who are bleeding

* If the INR is elevated and the patient is bleeding, administration of fresh frozen plasma is indicated along with Vitamin K 2.5 mg-5 mg IV.

Notes on coumadin reversal:
Intravenous vitamin K is associated with a small risk of severe allergic reaction. When administered intravenously, the rate should not exceed 1mg/minute. Reversal of anticoagulation by any means (vitamin K or FFP) is associated with a risk of thrombosis depending upon the patient's underlying need for anticoagulation.

Fresh frozen plasma should be dosed based on patient weight (usual adult dose is 10 mL/kg) If FFP is administered without concomitant vitamin K, the effect of FFP will dissipate in 8-12 hours so the INR must be monitored closely.

3. Among non-bleeding patients with abnormal hemostasis not due to vitamin K deficiency, FFP may be given as prophylaxis to prevent spontaneous bleeding if PT > 30 sec or INR > 6

FFP is Not indicated:

1. For non-bleeding patients with a PT < 15 sec (for newborns, < 17 sec)
2. For volume
3. Among non-bleeding patients on coumadin or with vitamin K deficiency, treatment with vitamin K alone is preferred (see above).

Studies suggest that FFP is widely overused among hospitalized patients. In particular, clinicians should recognize that no study has demonstrated any value to the patient from the transfusion of FFP prior to invasive bedside procedures among patients with mild - moderate prolongation of the PT or aPTT.

Cryoprecipitate:
Indication: Bleeding in the setting of:

1. fibrinogen < 100 mg/dL
2. von Willebrand’s Disease

Leukoreduced Blood Components:
The leukocytes present in cellular blood components (red blood cells and platelets) are responsible for three transfusion complications: febrile non-hemolytic reactions, sensitization to HLA antigens, and transmission of CMV.

The MGH Transfusion Committee recommends that the following groups of patients receive leukoreduced cellular blood components:

• 1. Patients who have experienced febrile, non-hemolytic transfusion reactions;


• 2. Patients who will require long-term transfusion support, particularly long-term platelet support;


• 3. Transplant recipients or candidates;


• 4. Patients requiring CMV-reduced risk transfusions. (see section on CMV-reduced risk blood)

Irradiation of Blood Components:
Residual donor lymphocytes, present in red blood cells and platelet concentrates, can initiate Graft vs Host Disease when transfused into an immunocompromised host. Transfusion-associated Graft vs Host Disease (TA-GVHD) has a very high fatality rate because, unlike the GVHD occurring in bone marrow transplantation, host marrow is also a target for the transfused T cells. Gamma irradiation of cellular blood components eliminates the ability of lymphocytes to proliferate thereby preventing them from mounting an effective immunological response to host tissues. Irradiation of blood components has been shown to be effective in preventing TA-GVHD in susceptible hosts. Irradiation does not remove lymphocytes from the blood component, hence alloimmunization and febrile transfusion reactions antigens may still occur. It has no effect on the transmission of infectious diseases. Irradiation results in a small but significant increase in the plasma K+ concentration of RBCs.

Based on the reported experience and our understanding of the pathophysiology of TA-GVHD, the Transfusion Committee recommends that the following patients be transfused with irradiated cellular blood components:

1. Bone marrow and stem cell transplant recipients - from day 1 of pre-transplant chemotherapy
2. Congenital T cell immunodeficiency syndromes - e.g. SCIDS, Wiskott-Aldrich, DiGeorge
3. Intrauterine transfusion
4. Neonatal exchange transfusion
5. Premature neonates weighing < 1200 g
6. Transfusions from blood relatives
7. Patients with some hematologic malignancies (Hodgkin's, Non-Hodgkin’s Lymphoma, acute leukemias) and neuroblastoma while they are being treated with marrow ablative chemotherapy

It is the responsibility of the ordering physician to request irradiated blood components, when they are required. Requests for irradiated blood should be made by writing "irradiate" and the indication for irradiation on the blood requisition. When ordering through the Physician Order Entry software, you may request irradiated blood using the "Restrictions" button.

CMV Reduced-Risk Blood Components
Cytomegalovirus (CMV) is a ubiquitous member of the herpes virus family to which approximately 30-60% of adults in developed countries have been exposed as indicated by the presence of antibodies. Three patterns of CMV infection have been described: primary infection, reactivation and re- or co-infection. Only primary infection has been documented to occur following blood transfusion. Primary infection occurs in CMV-seronegative recipients and may be detected by seroconversion (IgM followed by IgG), viral shedding (viruria typically), fever or lymphocytosis. Although CMV infection rarely produces serious disease in immunologically intact hosts, it is associated with systemic infection in immunocompromised patients and may be manifest as pneumonitis, gastritis, retinitis or other infections. CMV infection in immunocompromised patients is also associated with allograft rejection and dysfunction, and superinfection with other organisms. Following recovery, CMV may remain in a latent form in infected cells for years. Neither reactivation infection nor second-strain infection has been documented to occur as a result of blood transfusion.

CMV can infect many tissues including blood mononuclear cells as well as kidney, lung, liver and brain. Therefore, in addition to the usual routes of infection, susceptible patients may also become infected by transplantation or transfusion from an infected donor. The following groups of patients have been shown to be susceptible to transfusion-transmitted CMV primary infection and disease and should receive CMV reduced-risk cellular blood components:

1. Low birth weight (<1200g) neonates
2. CMV-seronegative pregnant women (including intrauterine transfusions)
3. CMV-seronegative recipients of, or candidates for, bone marrow or peripheral blood progenitor cell transplants
4. CMV-seronegative recipients of, or candidates for, solid organ transplants
5. CMV-seronegative, HIV-infected patients

CMV reduced-risk blood components can be obtained in two ways. Donors can be screened for CMV antibody (IgG) which indicates past exposure. Although approximately 30% of MGH blood donors are CMV seropositive, only a small minority of CMV-seropositive donor units are capable of transmitting CMV. A substantial portion of CMV seronegative donors are CMV PCR positive. As an alternative to choosing CMV seronegative blood components, blood mononuclear cells, which may carry CMV in its latent form, can be effectively removed from the blood by filtration with leukocyte filters or by freezing/deglycerolizing the unit. CMV serologic screening and leukocyte removal have been shown to be equally effective in preventing transfusion-transmitted CMV infection. At MGH, orders for CMV reduced risk, CMV "safe", or CMV seronegative blood will be filled by providing either CMV seronegative or filtered units at the discretion of the Blood Transfusion Service, depending on the inventory. Only cellular components (red blood cells, platelets and single donor platelets) need to be CMV reduced-risk since intact mononuclear cells are required to transmit CMV.

Patients Refractory to Platelet Transfusion
Poor response to platelet transfusion is observed in 10-20% of patients who require long term transfusion support. The failure to achieve a satisfactory elevation in the platelet count is referred to as refractoriness. An inadequate response may be the result of a number of factors, among them alloimmunization to HLA and platelet-specific antigens. Although platelets themselves are poorly immunogenic, passenger mononuclear cells are capable of eliciting an alloimmune response from the recipient. The frequency of alloimmunization can be effectively reduced by leukoreduction. Patients who are likely to require long-term platelet transfusion support should routinely receive leukoreduced cellular components.

The MGH Transfusion Committee has established 10,000 platelets/mL as an appropriate level for prophylactic transfusion for adults; however, this guideline should not be applied blindly. Attempts to achieve this arbitrary level by repeated platelet transfusions to refractory patients who are stable and not bleeding are not warranted.

The following is a suggested strategy to assess and manage the refractory patient. It is important, first of all, to establish that the patient is indeed refractory. A low platelet count the morning after a platelet transfusion does not constitute sufficient evidence of refractoriness. Secondly, non-alloimmune causes should be ruled out or treated. Immunologic compatibility will not protect platelets from consumption or sequestration. Finally, while these strategies are useful in prophylactic platelet transfusion, they play no role in the treatment of major bleeding.

Strategy for Managing Platelet Refractoriness

• 1. Obtain a platelet count 10-60 minutes after the platelet transfusion is completed. Usually each unit of platelets increases the count more than 5,000/µL.


• 2. If the increase is less than 5,000/µL for the transfusion, request ABO-compatible platelets.


• 3. If the increase is less than 5,000/µL with ABO-compatible platelets on two occasions, consult Transfusion Medicine for possible HLA matched platelets.

PHYSICIAN RESPONSIBILITIES
Special blood components: The ordering physician must request special blood components when they are required by calling the Blood Transfusion Service (BTS) at (617)726-3623 or by writing the special request and the indication on the blood requisition.

Emergency transfusions: Blood may be issued prior to the completion of a crossmatch in emergency situations of potentially life-threatening hemorrhage. The Emergency Waiver must be signed by the responsible physician with a statement as to the nature of the emergency.

Transfusion reactions: If the patient has signs or symptoms suggestive of a transfusion reaction:

• (1) stop the transfusion immediately; keep the line open with normal saline


• (2) verify that the transfused unit was given to the intended recipient


• (3) evaluate the patient and treat as necessary; send a urine specimen for urinalysis


• (4) write an order in the chart for a ''transfusion reaction work-up'' and fill out the "Transfusion Reaction Report Form". Send it to the BTS (GRB 2) with the implicated unit and a 10cc purple top labeled appropriately