AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Allogeneic blood transfusion is a form of temporary transplantation. This procedure introduces a multitude of foreign antigens and living cells into the recipient that will persist for a variable time. A recipient who is immunocompetent often mounts an immune response to the donor antigens, resulting in a variety of clinical consequences depending on the blood cells and specific antigens involved. The antigens most commonly involved are classified in the following categories: (1) HLAs, class I shared by platelets and leukocytes and class II present on some leukocytes; (2) granulocyte-specific antigens; (3) platelet-specific antigens (human platelet antigen [HPA]); and (4) RBC-specific antigens.

The consequences of alloimmunization to blood include the following clinical manifestations:

• Alloimmunization against RBCs
  • Acute intravascular hemolytic transfusion reaction, which is rarely a consequence of alloimmunization

  • Delayed hemolytic transfusion reactions (DHTRs)

  • Hemolytic disease in newborns (mother's alloimmunization against fetal antigens, most often resulting from previous pregnancies)

• Alloimmunization against platelets (platelet-specific or HLA class I antigens)
  • Refractoriness to platelet transfusion

  • Posttransfusion purpura

  • Neonatal alloimmune thrombocytopenia (mother's alloimmunization against fetal antigens, most often resulting from previous pregnancies)

• Alloimmunization against granulocytes (granulocyte-specific or HLA antigens)
  • Refractoriness to granulocyte transfusion

  • Febrile nonhemolytic transfusion reactions

  • Transfusion-related acute lung injury, ie, a transfusion reaction in which donor HLA antibodies react against recipient antigens

• Transplant rejection
  • Alloimmunization against HLA antigens

  • Alloimmunization against blood cell antigens (in bone marrow transplantation)

Hemolytic transfusion reactions, posttransfusion purpura, febrile nonhemolytic transfusion reactions, and transfusion-related acute lung injury are discussed in Transfusion Reactions. Hemolytic disease in newborns and neonatal alloimmune thrombocytopenia are discussed in the Neonatology section of eMedicine. Transplant rejection is discussed in Renal Transplantation (Medical).

DHTR and refractoriness to platelet transfusions are discussed in this article. Refractoriness to granulocyte transfusions involves either anti-HLA or granulocyte-specific antibodies and is similar to platelet refractoriness, except that refractoriness to granulocyte transfusions results in the patient failing to respond to the granulocyte transfusions. Because granulocyte transfusions are rarely used, they are not discussed further in this article.

Pathophysiology

The main mechanism for alloimmunization to antigens present in transfused cells may involve presentation of the donor antigens by donor antigen–presenting cells (APCs), ie, monocytes, macrophages, dendritic cells, B cells, to recipient T cells. Recognition of the MHC class I alloantigens by CD4⁺ recipient T cells and their subsequent activation requires a co-stimulatory signal from either the donor or recipient APCs. Alloimmunization by non–leukoreduced platelets involves shared donor HLA antigens (HLA-restricted) and live functional donor APCs. The T_H2 subset of CD4⁺ T helper cells secretes interleukin (IL)–4, IL-5, IL-6, and IL-10; activates B cells; and initiates the antibody response.

Leukoreduction of transfused platelets virtually eliminates donor APCs, but 20% of patients still develop alloimmunization. Alloimmunization from leukoreduced platelets involves recognition of the alloantigen and activation of recipient CD4⁺ T cells by alloantigen-presenting recipient APCs. This process also involves initial recognition of alloantigens by natural killer cells, which secrete interferon-gamma. This cytokine, in turn, is involved in the activation of CD4⁺ T_H2 cells.

After initial activation and development of the primary immune response, T cells become memory cells. Memory T cells do not need co-stimulatory signals to become activated and can recognize signals in the absence of class II HLA molecules. Thus, donor RBCs, platelets, and inactivated APCs can induce restimulation of the immune response. Blood transfusion (mainly through the T_H2 subset) can actively suppress the host immune response and induce tolerance to donor antigens. Another mechanism of immunosuppression involves stimulation of CD8⁺ suppressor T cells, which can recognize MHC class I alloantigens in platelets as well as donor APCs. Primary immunization with blood transfusion reflects the balance between clonal expansion and tolerogenic mechanisms. The secondary response depends on the restimulation of memory cells. Repeated immunization eventually results in sustained clonal expansion and clinically significant antibody production.

Refractoriness to platelet transfusions

The presence of HLA antibodies on the platelet surface is the most common cause of platelet refractoriness. Other non-HLA antigens present on the platelet surface (eg, platelet-specific antigens, HPA) are also involved in a number of cases. Patients not previously sensitized develop antiplatelet antibodies approximately 3-4 weeks (10 d to 26 wk) after the transfusion. Patients previously immunized by transfusion, pregnancy, or organ transplantation develop antiplatelet antibodies as early as 4 days after transfusion. Macrophages in the liver, spleen, and other tissues of the mononuclear phagocyte system phagocytize and destroy antibody-coated platelets.

Risk factors for developing antiplatelet antibodies include the presence of more than 1 million donor leukocytes in transfused products, transfusing ABO-mismatched platelets, the presence of an intact immune system (ie, absence of cytotoxic or immunosuppressive therapy), female sex (approximately 75% of cases), and a history of multiple transfusions (>20).

Delayed hemolytic transfusion reactions

DHTRs occur between 24 hours and 3 months (frequently 2 wk) after transfusion and usually represent a secondary immune response. Anti-RBC antibody titers frequently drop below detectable levels. Patients are transfused with incompatible RBCs, resulting in restimulation of memory cells and an increase in antibody titer. Antibodies bind to the surface of RBCs and, depending on the number of antigen-antibody interactions, activate complement with deposition of C3b. Usually, more than 10⁵ antigenic sites per cell are required for potent complement activation.

Rarely, binding of immunoglobulin M antibodies to RBCs activates the classic complement pathway and leads to intravascular hemolysis. RBCs coated with immunoglobulin G antibodies and/or complement bind to C3b and immunoglobulin Fc receptors present on mononuclear phagocytes and are destroyed by phagocytosis (ie, extravascular hemolysis). Immunoglobulin G antibodies that efficiently activate complement (eg, those in Kidd and Duffy systems) tend to cause more intense extravascular hemolysis compared with antibodies that do not efficiently activate complement (eg, Rh and Kell).

Frequency

United States

Refractoriness to platelet transfusions

With regard to the frequency of alloimmunization, approximately 20-85% of patients who receive multiple transfusions become immunized against platelet antigens (eg, HLA, HPA), and approximately 30% of patients who are alloimmunized develop refractoriness to platelet transfusions.

Platelet refractoriness occurs in approximately 20-70% of patients who receive multiple transfusions. In approximately 66% of these patients, nonimmune factors (see Differentials) alone are the cause, whereas alloimmunization may be involved in 33% of refractory patients, often in combination with nonimmune causes.

With regard to the frequency of type of antibody involved in platelet refractoriness, HLA class I antibodies are involved in most alloimmunization cases, whereas platelet-specific antigens (ie, HPA) may be involved in approximately 10-20% of refractory cases. Both types of antibodies are involved in approximately 5% of cases. A single random RBC or platelet transfusion induces anti-HLA antibodies in less than 10% of recipients (most likely related to the tolerogenic effect of blood transfusions). If patients have more than 20 transfusions, they become sensitized in increasing proportions; after 50 transfusions, most (as many as 70%) patients have anti-HLA antibodies.

The presence of HLA antibodies shows better correlation with platelet refractoriness than antibodies directed against platelet-specific antigens. In the minority of cases of platelet refractoriness due to HPA antibodies, HPA-1b, HPA-5b, and HPA-1a antibodies are most commonly involved. Platelet-specific antigen systems are listed in Table 1.

Table 1. Human Platelet-Specific Antigen Systems

Delayed hemolytic transfusion reactions

Approximately 0.1-2% of patients who receive transfusions develop anti-RBC antibodies. In patients who are transfused regularly (eg, patients with sickle cell disease), the frequency of alloimmunization is much higher, affecting 10-38%. Despite the relatively high frequency of RBC alloimmunization, clinical manifestations of hemolytic transfusion reactions are rare (approximately 0.05% of patients transfused). The most frequent clinically significant RBC antibodies are shown in Table 2.

Table 2. Frequent Clinically Significant Anti-RBC Antibodies

Mortality/Morbidity

• The risk of death from a DHTR is approximately 1 fatality per 3.85 million units (1 per 1.15 million U in patients who have received transfusions).
• Data regarding the impact of platelet refractoriness on morbidity and mortality for thrombocytopenic patients are inconsistent. Failure to achieve platelet counts greater than 5 X 10⁹/L significantly increases the probability of life-threatening bleeding.

Race

Individuals from ethnic minority groups have an increased risk of alloimmunization from transfusion because notable differences exist in the frequency of blood cell antigens between races. Efforts to increase the blood supply from minority donors are essential to reduce the frequency of alloimmunization in these groups.

Sex

DHTRs and platelet refractoriness are more common in females than in males, possibly because of previous sensitization from pregnancy.

Age

Older patients (ie, >50 y) tend to have reduced immune responsiveness to blood transfusions.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Physical

• Delayed hemolytic transfusion reactions
• • Hemolysis is usually extravascular, but, in some cases, a component of intravascular hemolysis is present.

  • Most cases manifest during the second week after transfusion, but the reaction can occur from 24 hours to 3 months after the transfusion.

  • Many patients are asymptomatic, and the condition is detected only by laboratory methods.

  • In some patients, fever and/or chills (50%), jaundice (10%), pain (3%), and dyspnea (1%) can occur.

  • Rarely, cases may be complicated with renal failure (6%) or disseminated intravascular coagulation (1%).

  • In sickle cell patients, a DHTR can precipitate sickle crisis.

• Refractoriness to platelet transfusions
• • Frequently, patients with refractoriness to platelet transfusion are asymptomatic and diagnosed by laboratory methods; however, failure to achieve hemostatic levels of platelets may preclude these patients from important procedures, including bone marrow transplantation. Alloimmunization should be avoided at all costs in candidates for bone marrow transplantation.

  • Preexisting bleeding resulting from thrombocytopenia may persist after transfusion of an appropriate therapeutic dose of platelets. Rarely, spontaneous bleeding may occur after prophylactic transfusion of platelets.

Causes

• Alloimmunization to blood antigens occurs after the following:
• • Transfusion

  • Pregnancy

  • Transplantation

  • Sharing intravenous needles (rare)

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Delayed hemolytic transfusion reactions

• Immune hemolysis
  
  
  • Paroxysmal nocturnal hemoglobinuria
  
  
  
  • Autoimmune hemolytic anemia
  
  
  
  • Cold agglutinin disease
  
  
  
  • Cold agglutinin immune hemolysis
     
• Nonimmune hemolysis
  
  
  • Sepsis (particularly clostridial species), malaria, babesiosis
  
  
  
  • Mechanical hemolysis (eg, prosthetic valve, left ventricular assist device, small phlebotomy needles, infusion pumps, other devices)
  
  
  
  • Infusion of incompatible solutions together with RBC units
  
  
  
  • Accidental freezing or excessive heating of RBC units
  
  
  
  • Microangiopathic anemia
  
  
  
  • Drug-induced hemolysis
  
  
  
  • Congenital hemolytic anemia (eg, glucose-6-phosphate dehydrogenase deficiency, spherocytosis)
     
• Reabsorption of hematoma (eg, high lactic dehydrogenase or bilirubin, low haptoglobin)

• Active bleeding (even subclinical)



• Bone marrow transplantation



• Splenomegaly (eg, splenic sequestration)



• Autoimmune thrombocytopenia



• Disseminated intravascular coagulation



• Thrombotic thrombocytopenic purpura



• Drug-induced thrombocytopenia (ie, amphotericin B, vancomycin)



• Fever



• Sepsis



• Circulating immune complexes



• Platelet age (>3 d) and poorly stored platelet concentrates

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Delayed hemolytic transfusion reactions
• • The most reliable laboratory sign is a failure to observe the expected posttransfusion increase in blood hemoglobin levels (approximately 1 g/dL/U) in the absence of bleeding.

  • In some cases, the loss of circulating cells can be higher than expected if only antigen-positive cells were cleared. This phenomenon results from bystander hemolysis, which is caused by the deposition of activated complement on both donor and recipient RBCs.

  • Laboratory signs of hemolysis include elevated lactate dehydrogenase, indirect bilirubin, and reticulocyte levels and decreased hematocrit and haptoglobin levels.

  • Intravascular hemolysis is characterized by the presence of free plasma hemoglobin and possibly hemosiderinuria.

  • The results of direct and indirect antiglobulin tests (ie, Coombs test) are often positive.

  • Alloantibodies can be eluted from RBCs, and their specificity can be determined. Type the antigens and re-crossmatch them with the patient's serum if segments from the transfused units are available.

• Refractoriness to platelet transfusions
• • Refractoriness to platelet transfusions is defined as repeated failure to achieve the expected increment in platelet count after 2 or more platelet transfusions. The expected increment can be calculated based on the number of platelets transfused and the patient's blood volume using the formula as follows:
    % Maximum increment = ([pretransfusion count – posttransfusion count in platelets/µL] X blood volume in mL) ÷ (number of platelets transfused, ie, number of U X 6 X 10⁵)

  • The expected increment is 45-75% of the maximum increment, resulting from normal sequestration by the spleen.

  • Blood volume can be calculated roughly as body weight (kg) multiplied by 69 (males) or by 65 (females); the number of platelets transfused assumes an average content of 6 X 10¹⁰ platelets/U; an average apheresis unit contains the equivalent to 6 units of platelets (4 X 10¹¹ platelets).

  • Observed increments of less than 25% at 1 hour or less than 12% at 24 hours indicate platelet refractoriness.

  • Physicians must recognize that many cases of refractoriness result from causes other than alloimmunization (see Differentials).

  • In general, alloimmunization results in the rapid removal of platelets and in lower counts at 10 minutes to 1 hour posttransfusion, whereas nonimmune causes mostly affect the 4- to 24-hour posttransfusion count. Mild alloimmunization, however, can be present with 1-hour increments within the reference range.

  • Microcytotoxicity assays against a panel of 30-60 different lymphocyte cells can demonstrate lymphocytotoxic anti-HLA antibodies. The percentage of cells to which the patient's serum reacts is referred to as the panel-reactive antibody (PRA) level. PRA values greater than 20% indicate significant alloimmunization to HLA antigens and correlate with an increased risk for platelet refractoriness.

  • The presence of antiplatelet antibodies can be demonstrated by flow cytometry or by immunoassays such as the modified antigen capture enzyme-linked assay, the solid-phase RBC adherence assay, and the monoclonal antibody immobilization of platelet antigens assay. Most of these assays permit screening for HLA and HPA antibodies as well as specific identification of the most commonly involved HPA antigens.

  • A negative result from platelet antibody screening indicates nonimmune causes of refractoriness.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Delayed hemolytic transfusion reactions
• • Most patients tolerate DHTR well and only require observation and supportive care.

  • Good communication with a blood bank is essential to attempt to provide transfusion support with antigen-negative RBCs. If these RBCs are not available, weigh the risk of further hemolysis against the indications for transfusion.

  • If the load of antigen-positive packed RBCs is large (>5 U), consider exchange transfusion. Administer intravenous human immunoglobulin (IVIG) to block further hemolysis in cases in which antigen-positive blood is transfused. The IVIG dose is 400 mg/kg, infused slowly within 24 hours posttransfusion.

• Refractoriness to platelet transfusions
• • Avoiding the use of platelet transfusions as much as possible is important in alloimmunized patients. Preventive transfusions are not recommended. Measures to minimize the likelihood and extent of bleeding (eg, rapid treatment of infection; avoidance of invasive procedures; correction of coagulation deficiencies, anemia, and renal insufficiency; use of antifibrinolytic agents) should be used extensively.

  • After diagnosing alloimmune platelet refractoriness, use the sequence of measures that follows, initiating each subsequent intervention if the previous one fails.

  • Rule out nonimmune, autoimmune, and drug-related causes of platelet refractoriness, or treat accordingly.

  • Transfuse ABO-compatible fresh (aged <48 h) platelet concentrates. ABO-matched and fresher platelets result in more recoveries than mismatched and older (aged >3 d) platelets.

  • Transfuse with platelets from blood relatives. Obtaining platelets from blood relatives is worthwhile because the chance of matching 2 or more HLA and platelet antigens is high (resulting in good recovery) and relatives are often willing to donate frequently. Irradiation of blood products from relatives is mandatory to prevent graft versus host disease.

  • Select HLA-matched platelets. Perform HLA typing of patients who receive multiple transfusions before they become pancytopenic. Matching for both private (ie, HLA-A, HLA-B) and public (ie, cross-reacting groups) antigens is best achieved by computerized selection of donors, based on the results of the PRA assay.

  • Select crossmatched platelets. Crossmatch-compatible platelets can significantly improve platelet recovery in approximately 50% of patients who are refractory to random-donor platelets. Selecting crossmatched platelets is indicated especially for patients with high PRA levels or those who do not respond to HLA-matched platelets.

  • The use of HPA1a/5b-negative platelets has been successful in cases of posttransfusion purpura and neonatal platelet alloimmunization. These antigens are involved in most (95%) cases of neonatal or posttransfusion purpura, but they represent no more than 10-20% of immune refractoriness to platelet transfusions.

  • Pretreat with IVIG before transfusion. IVIG pretreatment can result in successful recovery after platelet transfusion in patients who are alloimmunized. Success rates vary (as much as 70%) and depend on the degree of alloimmunization. IVIG does not reduce the number of alloantibodies but does decrease platelet-associated immunoglobulins and possibly interferes with platelet destruction mechanisms.

  • Use high-dose platelet transfusion. Empirical use of high doses of random platelet units (eg, 1 U per 10 kg tid) may result in titration of the antibody, overwhelming of the mononuclear-phagocyte system, and increased survival of transfused platelets.

  • Attempt large-volume plasmapheresis. Plasmapheresis (eg, 2 plasma volumes for 1-3 d) before bone marrow transplantation results in beneficial responses in most patients alloimmunized to platelets. Perfusion of the plasma through a staphylococcal protein A column is an experimental treatment undergoing evaluation.

  • Consider administering immunosuppressive drugs. Isolated reports suggest that immunosuppressive therapy is effective for reverting platelet refractoriness. The use of vincristine and cyclosporin A has been successful but requires 2-3 weeks to take effect.

Consultations

Transfusion medicine specialist or hematologist

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Immunosuppressive agents such as IVIG can be as much as 70% effective in patients with platelet refractoriness resulting from alloimmunization. Consider using cytotoxic agents only in person clearly unresponsive to the other treatment modalities. Only physicians familiar with the use and toxicity of cytotoxic agents should prescribe these drugs because few data support their use for alloimmunization. This indication is considered investigational.

Drug Category: Immunosuppressive agents

Inhibit activity of immune system.

Drug Category: Cytotoxic agents

Inhibit immune cell growth and proliferation.

Drug Name	Cyclosporin A (Sandimmune, Neoral)
Description	Two reports describe use in patients with aplastic anemia and platelet refractoriness. Both patients dramatically improved in response to platelet transfusions after treatment. Use for platelet alloimmunization remains investigational.
Adult Dose	Not established
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because may increase risk of cancer
Interactions	Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Delayed hemolytic transfusion reactions
• • To assess the effectiveness of RBC transfusions, measure hemoglobin levels 1 and 24 hours posttransfusion.

  • More than 40% of RBC antibodies become undetectable after the first detection, but these antibodies may cause hemolysis upon restimulation.

  • Maintain accurate records of the antibodies present, and notify patients (eg, with a carry-on card) that they have clinically significant alloantibodies.

• Refractoriness to platelet transfusions
• • To assess the effectiveness of platelet transfusions, obtain platelet counts at 1 and 24 hours posttransfusion.

  • If the specificity of antibodies is identified, keep a permanent record and notify the patient (eg, with a carry-on card).

  • Consider planning future platelet transfusion needs in advance by selecting donors who lack the involved antigens.

Deterrence/Prevention

• Delayed hemolytic transfusion reactions
• • Properly identify the serology of alloantibodies prior to transfusion, and properly identify antigen-negative RBCs if alloantibodies are present.

  • Patients with alloantibodies require fully crossmatched (ie, anti-immunoglobulin phase) donor units.

  • In ethnic minorities who have received multiple transfusions, testing patients for commonly involved antigens (eg, Rh, Kell, Kidd, Duffy) and using antigen-negative units can significantly reduce the frequency of alloimmunization. However, the cost effectiveness of this approach must be considered because most patients who have received multiple transfusions do not form clinically significant alloantibodies. A more cost-effective approach is to match the ethnic origin of donors and recipients, reserving extensive antigen typing for recipients who have been previously alloimmunized. These patients may also benefit from leukodepleted RBCs because leukoreduction appears to decrease the frequency of alloimmunization to RBC antigens, possibly due to decreased stimulation of T_H2 lymphocytes associated with transfusions.

  • If attempting to transfuse Rh-positive units (RBCs, platelets, or granulocytes) into an Rh-negative recipient, prevent alloimmunization to the D antigen by administering intravenous Rh-immunoglobulin (eg, WinRho SD, 10-12 mcg/mL of transfused Rh-positive RBCs). If transfusing a large number of Rh-positive units, reduce the dose of Rh-immunoglobulin after removing the antigen load by RBC exchange.

• Refractoriness to platelet transfusions
• • Primary alloimmunization to class I HLA antigens present on platelets involves active donor APCs.

  • Removing leukocytes by filtration or buffy coat removal or deactivating APCs by ultraviolet-B irradiation reduces the frequency of alloimmunization.

  • Leukocyte reduction is indicated in all patients who are expected to be transfused repeatedly, especially candidates for bone marrow transplantation. These patients may also benefit from initial HLA typing and transfusions from crossmatched or HLA-matched platelets.

  • Pooled, random-donor, leukocyte-reduced platelets do not increase the frequency of alloimmunization compared with leukocyte-reduced, single-donor apheresis platelets.

Patient Education

• Inform patients that they have alloreactive antibodies and educate them about the names of these antibodies (eg, with a wallet carry-on card). Instruct patients to present the carry-on card if they are admitted to a care facility different from their usual one.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to provide leukocyte-depleted blood products to patients who will be transfused multiple times or patients who are candidates for bone marrow transplantation
• Failure to prevent or recognize alloimmunization and treat accordingly because alloimmunization to platelets, and occasionally to RBCs, can result in fatal or unintended consequences
• Failure to inform patients that they have alloreactive antibodies, to educate them about the names of these antibodies (eg, with a wallet carry-on card), and to instruct patients to present the carry-on card if they are admitted to a care facility different from their usual one

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Allen DL, Samol J, Benjamin S, et al. Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet concentrates in proven or suspected platelet alloimmunization. Transfus Med. Dec 2004;14(6):409-17. [Medline].
• Blumberg N, Heal JM, Gettings KF. WBC reduction of RBC transfusions is associated with a decreased incidence of RBC alloimmunization. Transfusion. Jul 2003;43(7):945-52. [Medline].
• Delaflor-Weiss E, Mintz PD. The evaluation and management of platelet refractoriness and alloimmunization. Transfus Med Rev. Apr 2000;14(2):180-96. [Medline].
• Friedberg RC. Clinical and laboratory factors underlying refractoriness to platelet transfusions. J Clin Apheresis. 1996;11(3):143-8. [Medline].
• Friedman DF, Lukas MB, Jawad A, et al. Alloimmunization to platelets in heavily transfused patients with sickle cell disease. Blood. Oct 15 1996;88(8):3216-22. [Medline].
• Heddle NM, Soutar RL, O'Hoski PL, et al. A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion. Br J Haematol. Dec 1995;91(4):1000-5. [Medline].
• Kekomaki R. Use of HLA- and HPA--matched platelets in alloimmunized patients. Vox Sang. 1998;74 Suppl 2:359-63. [Medline].
• Kickler T, Herman JH, eds. Current issues in platelet transfusion therapy and platelet alloimmunity. Bethesda, Md: AABB Press; 1999.
• Legler TJ, Fischer I, Dittmann J, et al. Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol. Apr 1997;74(4):185-9. [Medline].
• Novotny VM. Prevention and management of platelet transfusion refractoriness. Vox Sang. 1999;76(1):1-13. [Medline].
• Pineda AA, Vamvakas EC, Gorden LD, et al. Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions. Transfusion. Oct 1999;39(10):1097-103. [Medline].
• Sayeh E, Sterling K, Speck E, et al. IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-gamma response that is regulated by CD8+ T cells. Blood. Apr 1 2004;103(7):2705-9. [Medline].
• Schiffer CA. Diagnosis and management of refractoriness to platelet transfusion. Blood Rev. Dec 2001;15(4):175-80. [Medline].
• Schonewille H, Haak HL, van Zijl AM. Alloimmunization after blood transfusion in patients with hematologic and oncologic diseases. Transfusion. Jul 1999;39(7):763-71. [Medline].
• Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med. Dec 25 1997;337(26):1861-9. [Medline].
• Warkentin TE, Smith JW. The alloimmune thrombocytopenic syndromes. Transfus Med Rev. Oct 1997;11(4):296-307. [Medline].
• Werch J, Todd C. Resolution by erythrocytapheresis of the exposure of an Rh-negative person to Rh-positive cells: an alternative treatment. Transfusion. Jun 1993;33(6):530-2. [Medline].
• Werch J. Use of Rh immune globulin when transfusing large volumes of Rh-positive cells. Am J Clin Pathol. May 1999;111(5):712. [Medline].

Article Last Updated: Jan 13, 2005