Page 2388 - Williams Hematology ( PDFDrive )

2358 Part XIII: Transfusion Medicine Chapter 137: Human Leukocyte and Platelet Antigens 2359

reactions occur within a few hours of a transfusion and can be associ- Platelet GPIV (CD36) is expressed on various human cells includ-
ated with chills and rigors. These reactions are a result of neutrophil ing platelets, macrophages, capillary endothelium, erythroblasts, and
antibodies in the transfusion recipient binding to leukocytes in the adipocytes. 114,115 Some apparently normal individuals lack CD36 on
transfused blood component. Febrile transfusion reactions can be pre- their platelets (type II deficiency) or platelets and monocytes (type I
116
117
vented in recipients of platelet and red blood cell component transfu- deficiency). CD36 deficiency is common in Asians (3 to 11 percent)
118
sions by the use of leukocyte-reduced blood components. and Africans (3 to 6 percent), but is rare in white populations (0.1
A more serious type of neutrophil antibody-mediated transfusion percent). CD36 deficiency may confer protection from malaria and
118
reaction is TRALI. TRALI is often caused by the transfusion of neu- has been shown to be a receptor for red cells infected with Plasmodium
trophil antibodies in the plasma portion of a blood component. TRALI falciparum. However, one report suggests CD36 deficiency may actu-
119
occurs within 6 hours of a transfusion when hypoxia and noncardio- ally increase the risk for more severe forms of malarial infection. The
genic pulmonary edema occur, as measured by a fall in hemoglobin role of CD36 deficiency as either a protective or aggravating factor in
oxygen saturation to less than 90 percent or a partial pressure of arterial malarial infection remains controversial. 120,121 Type I CD36-deficient
oxygen (PaO )-to-fraction of inspired oxygen (FIO ) ratio (PaO :FIO ) individuals can become immunized via transfusion or pregnancy and
2
2
2
2
of less than 300 torr. 91 make isoantibodies against CD36 that have been implicated in cases of
Many case reports have associated TRALI with the inadvertent FNAIT, PTP, and platelet transfusion refractoriness. 117,122–125
transfusion of neutrophil antibodies. Investigations of transfusion
recipients of blood components from donors with neutrophil antibod-
ies who have been implicated in cases of TRALI suggest that a large PLATELET ANTIGENS: GENETICS
proportion of neutrophil antibodies can cause TRALI and less-severe AND STRUCTURE
pulmonary transfusion reactions. 78,92–94 A prospective case study with
controls and a prospective nested case-control study have confirmed Platelet-specific alloantigens result from genetic polymorphism in
126
that the transfusion of blood products containing antibodies directed to genes encoding platelet surface proteins. These alloantigens were first
neutrophil antigen are an important cause of TRALI. 95,96 defined by antiplatelet antibodies discovered in the sera of multiparous
Antibodies to HNA-2 and -3a have most frequently been impli- females who gave birth to thrombocytopenic infants (FNAIT) or in
cated in lung injury. Animal models also show that the transfusion of patients who developed PTP. Many of these alloantibodies were subse-
anti–HNA-2 and anti–HNA-3a can cause acute lung injury. 97–99 quently found to recognize allotypic determinants of platelet-associated
membrane GPs, such as GPIIb/IIIa (CD41/CD61). Almost all of these
determinants are generated by single-amino-acid substitutions encoded
127
by SNPs in the GP genes (Table 137–4). In some cases, differential
HUMAN PLATELET ANTIGENS glycosylation may contribute to or influence the expression of certain
human platelet antigen (HPA) epitopes, such as those associated with
Platelets express a variety of immunogenic markers on the cell surface. HPA-3. 128,129 In any case, these amino acid substitutions generally do not
Some of these antigens are shared with other cell types as in the case appear to affect platelet function in vitro. However, the genetic polymor-
of HLAs or blood group (ABO) antigens, whereas others are specific phism in platelet GPs may be associated with more subtle differences in
to platelets. Some of these platelet-specific markers can be recognized platelet physiology that can contribute to the relative risk for thrombo-
by autoantibodies 100–103 or by antibodies induced by certain drugs, 104–106 sis and/or atherosclerosis. 130–135
and still others by antibodies made by pregnant women or recipients of To date, 33 HPA expressed on six different platelet GPs: GPIIb
blood transfusions.
(CD41), GPIIIa (CD61), GPIbα (CD42b), GPIbβ (CD42c), GPIa
(CD49b), and CD109 have been described including localization to
PLATELET ALLOANTIGENS platelet surface GPs, quantification of their density on the platelet sur-
face, and determination of DNA polymorphisms in genes encoding for
Platelet alloantigens are associated with polymorphisms of platelet sur- them (see Table 137–4). 127,136 For a current list see http://www.ebi.ac.uk/
face GPs and can induce production of alloantibodies when individ- ipd/hpa/table1.html and http://www.ebi.ac.uk/ipd/hpa/table2.html.
127
uals lacking a particular polymorphism are exposed via pregnancy or Thirteen antigens are clustered into one triallelic (HPA-1) and five
137
transfusion. Immune responses to platelet alloantigens are involved in biallelic groups (HPA-2, HPA-3, HPA-4, HPA-5, HPA-15). HPA for
107
the pathogenesis of several clinical syndromes, including fetal or neona- which antibodies against only one of the alleles have been detected are
tal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura labeled with a “w” for workshop, for example, HPA-8bw. To date, 20
(PTP), and occasionally in unresponsiveness to platelet transfusion. such low-frequency single-allele HPAs have been discovered, essentially
108
Alloimmune thrombocytopenia can also be an unusual complication of all involved in FNAIT cases. 138
solid-organ transplantation in which donor lymphocytes make alloan- Although the frequencies of HPAs have been most extensively
tibodies specific for the platelets produced by the recipient of an organ studied in white populations, it should be noted that they have been
allograft. 109 determined for other racial and ethnic groups as well and in some
cases vary significantly from white frequencies. For example, HPA-lb
PLATELET ISOANTIGENS is expressed on the platelets of approximately 15 percent of persons of
European ancestry but of less than 1 percent of persons of Asian ances-
A condition similar to alloimmune platelet destruction occurs in try. For more information re HPA frequencies in different populations,
patients who lack part or all of a particular platelet GP because of defec- readers are directed to: http://www.ebi.ac.uk/ipd/hpa/freqs_1.html 127
tive alleles of the GP-encoding genes. Such patients can make isoanti-
bodies against platelets of virtually all donors that bear the platelet GP.
For example, patients with Bernard-Soulier syndrome, who lack plate- NOMENCLATURE
let GPIb-V-IX (CD 42a-c), or patients with Glanzmann thrombasthe- A nomenclature for human platelet alloantigens has been adopted to
nia, who lack expression of GPIIb (CD41) and GPIIIa (CD61), can be replace the old complex “classic” nomenclatures that previously were
induced to make broadly reactive antiplatelet isoantibodies. 110–113 developed independently in laboratories throughout the world (see

Kaushansky_chapter 137_p2353-2364.indd 2359 9/21/15 3:50 PM