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Ineffective Platelet Production in Thrombocytopenic Human
Immunodeficiency Virus-Infected Patients
James L. Cole,
Ulla M. Marzec,
Clifford J. Gunthel,
Simon Karpatkin,
Lydia Worford,
I. Birgitta Sundell,
Jeffrey L. Lennox,
Janet
L. Nichol, and
Laurence A. Harker
From the Department of Medicine, Emory University School of Medicine,
Ponce de Leon Center, Atlanta GA; New York University Medical Center,
New York, NY; and Amgen, Inc, Thousand Oaks CA.
Thrombocytopenia has been characterized in six patients infected
with human immunodeficiency virus (HIV) with respect to the delivery of
viable platelets into the peripheral circulation (peripheral platelet
mass turnover), marrow megakaryocyte mass (product of megakaryocyte
number and volume), megakaryocyte progenitor cells, circulating levels
of endogenous thrombopoietin (TPO) and platelet TPO receptor number,
and serum antiplatelet glycoprotein (GP) IIIa49-66 antibody
(GPIIIa49-66Ab), an antibody associated with thrombocytopenia in HIV-infected patients. Peripheral platelet counts
in these patients averaged 46 ± 43 × 103/µL
(P = .0001 compared to normal controls of 250 ± 40×
103/µL), and the mean platelet volume (MPV) was 10.5 ± 2.0 fL (P > 0.3 compared with normal control of
9.5 ± 1.7 fL). The mean life span of autologous
111In-platelets was 87 ± 39 hours (P = .0001
compared with 232 ± 38 hours in 20 normal controls), and immediate
mean recovery of 111In-platelets injected into the systemic
circulation was 33% ± 16% (P = .0001 compared with
65% ± 5% in 20 normal controls). The resultant mean peripheral
platelet mass turnover was 3.8 ± 1.5 × 105 fL/µL/d
versus 3.8 ± 0.4 × 105 fL/µL/d in 20 normal controls
(P > .5). The mean endogenous TPO level was 596 ± 471 pg/mL (P = .0001 compared with 95 ± 6 pg/mL in 98 normal control subjects), and mean platelet TPO receptor number was 461 ± 259 receptors/platelet (P = .05 compared with 207 ± 99 receptors/platelet in nine normal controls). Antiplatelet GPIIIa49-66Ab levels in sera were uniformly increased in
HIV thrombocytopenic patients (P < .001). In this cohort of
thrombocytopenic HIV patients, marrow megakaryocyte number was
increased to 30 ± 15 × 106/kg (P = .02
compared with 11 ± 2.1 × 106/kg in 20 normal
controls), and marrow megakaryocyte volume was 32 ± 0.9 × 103 fL (P = .05 compared with
28 ± 4.5 × 103 fL in normal controls). Marrow
megakaryocyte mass was expanded to 93 ± 47 × 1010 fL/kg
(P = .007 compared with normal control of
31 ± 5.3 × 1010 fL/kg). Marrow megakaryocyte
progenitor cells averaged 3.3 (range, 0.4 to 7.3) CFU-Meg/1,000
CD34+ cells compared with 27 (range, 0.1 to 84)
CFU-Meg/1,000 CD34+ cells in seven normal subjects
(P = .02). Thus, thrombocytopenia in these HIV patients was
caused by a combination of shortening of platelet life span by two
thirds and doubling of splenic platelet sequestration, coupled with
ineffective delivery of viable platelets to the peripheral blood,
despite a threefold TPO-driven expansion in marrow megakaryocyte mass.
We postulate that this disparity between circulating platelet product
and marrow platelet substrate results from direct impairment in
platelet formation by HIV-infected marrow megakaryocytes.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3239-3246
© 1998 by The American Society of Hematology.
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