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1994 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 1995

ex vivo platelet clumping is shown in Chap. 1, Fig. 1–6H, accompanied by of platelets from patients with type I Glanzmann thrombasthenia or in
platelet–neutrophil satellitism (see “Platelet Satellitism” below). the presence of neutrophils from patients with congenital absence of
32
FcγRIII. Typically, the platelets form a rosette around the periphery of
ANTIBODY-INDUCED PLATELET leukocytes. Neutrophils are most frequently involved, but the phenom-
37,38
AGGLUTINATION enon also is occasionally observed with monocytes. These antibodies
also are naturally occurring, and their presence does not clearly correlate
Platelet agglutination ex vivo can be induced by antiplatelet antibodies with any specific clinical situation, disease, or drug. As with the anti-
or by activation of the platelets during collection. The responsible anti- bodies that induce only platelet clumping, exposure of a cryptic antigen
bodies do not appear to be associated with a pathologic process, as they on EDTA-treated platelets and leukocytes may trigger this phenomenon.
are found in normal individuals. One hypothesis put forth to explain
their presence is that the antibodies are responsible for clearing aged ANTIPHOSPHOLIPID ANTIBODIES
and damaged platelets. Most antibodies implicated in pseudothrombo-
cytopenia recognize platelet membrane glycoproteins that are modified Some antiplatelet antibodies from patients with pseudothrombocytope-
to expose new epitopes when calcium is chelated. Typically, the artifact nia crossreact with negatively charged phospholipids and may exhibit
30
is most prominent in the presence of EDTA, but other anticoagulants anticardiolipin activity. The sera of these patients lose their ability to
can also cause platelet clumping, including sodium citrate, sodium clump platelets when adsorbed onto either cardiolipin or activated nor-
oxalate, acid citrate dextrose, and heparin. The antibodies usually are mal platelets, supporting the hypothesis that antibody subpopulations
of the immunoglobulin (Ig) G type; IgM and IgA antibodies also have directed against negatively charged phospholipids can bind to antigens
been described. 29–31 Most antibodies react at room temperature; thus, modified by EDTA on the platelet membrane. Another possibility is that
the reaction can be prevented by keeping the blood sample at 37°C. In the antigens in this case are negatively charged phospholipids on the
20 percent of cases, however, the antibodies, usually of the IgM type, are surface of platelets.
reactive at both 22°C and 37°C. Clumping usually is evident within 60
30
minutes after the blood is drawn, but may require incubations of 2 to INTEGRIN α β ANTAGONISTS
IIB 3
3 hours. Agglutination can be reproduced by incubating plasma from Thrombocytopenia has been described in patients suffering from acute
patients with pseudothrombocytopenia with blood from normal indi- coronary syndromes treated with the abciximab and other integrin
viduals in the presence of EDTA. α β antagonists. 39–41 Abciximab is associated with both pseudothrom-
IIb 3
In most cases, the antibodies are directed against the integrin bocytopenia and true thrombocytopenia. The mechanism for platelet
α β (also termed glycoprotein [GP] IIbIIIa), a conclusion supported clumping with abciximab is unknown; the drug itself likely is not cross-
IIb 3
by the observation that platelets from patients with Glanzmann throm- linking the platelets because it is monovalent. More likely, other agglu-
basthenia, who lack the integrin α β complex, fail to agglutinate in the tinins bind integrin α β at new epitopes induced by the combination
IIb 3
IIb 3
presence of patient sera. 32–35 Moreover, pretreatment of fresh blood with of abciximab binding and calcium chelation. True abciximab-induced
anti–integrin α β dramatically reduces EDTA-induced platelet agglu- thrombocytopenia occurs in approximately 0.3 to 1 percent of patients
IIb 3
36
tination. The responsible epitope normally is cryptic and located in the treated with the drug. The mechanism is incompletely understood,
42
integrin α subunit. Low temperature and calcium chelation combine but likely includes reaction of preformed antibodies with a neoepitope
IIb
to change the conformation of integrin α β and expose the epitope. 33 expressed after binding of abciximab to integrin α β (ligand-induced
IIb 3
IIb 3
PLATELET SATELLITISM binding sites) or abciximab-induced platelet activation with subsequent
platelet sequestration from the circulation. In some abciximab-treated
Antibodies directed against integrin α β may react simultaneously patients, high antibody titers are detected in the plasma.
IIb 3
with the leukocyte Fcγ receptor III (FcγRIII) and attach the plate- The incidence of pseudothrombocytopenia and thrombocy-
lets to neutrophils and monocytes, inducing a phenomenon known as topenia related to abciximab was determined in four large placebo-
platelet-leukocyte satellitism, another form of pseudothrombocytopenia controlled trials: c7E3 Fab Antiplatelet Therapy in Unstable Refractory
40
32
(Fig. 117–1). These antibodies fail to produce satellitism in the presence Angina (CAPTURE), Evaluation of 7E3 for the Prevention of Ischemic

A B
Figure 117–1. Platelet satellitism. A. Direct (non–anticoagulated) marrow film. No platelet satellitism. B. A concentrated marrow film anticoagu-
lated with disodium ethylenediaminetetraacetic acid (Na EDTA) from same specimen as in (A). Note platelets are adherent to the mature neutrophil
2
surface (satellitism) in the presence of Na EDTA. The neutrophil precursors do not have surface features that interact with platelets, apparently a
2
feature only present after the final steps in maturation. (Reproduced with permission from Lichtman’s Atlas of Hematology, www.accessmedicine.com.)

Kaushansky_chapter 117_p1993-2024.indd 1995 9/21/15 2:31 PM