INEFFECTIVE PLATELET PRODUCTION IN THROMBOCYTOPENIC HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS

Thrombocytopenia has been characterized in six patients infected with human immunodeficiency virus (HIV) with respect to the delivery of via ble platelets into the peripheral circulation (peripheral platelet mas s turnover), marrow megakaryocyte mass (product of megakaryocyte numbe r and volume), megakaryocyte progenitor cells, circulating levels of e ndogenous thrombopoietin (TPO) and platelet TPO receptor number, and s erum antiplatelet glycoprotein (GP) IIIa(49-66) antibody (GPIIIa(49-66 )Ab), an antibody associated with thrombocytopenia in HIV-infected pat ients. Peripheral platelet counts in these patients averaged 46 +/- 43 x 10(3)/mu L(P = .0001 compared to normal controls of 250 +/- 40 x 10 (3)/mu L), 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 sp an of autologous (111)n-platelets was 87 +/- 39 hours (P = .0001 compa red with 232 +/- 38 hours in 20 normal controls), and immediate mean r ecovery of In-111-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 x 10(5) fL/mu L/d versus 3.8 +/- 0.4 x 10(5) fL/mu L/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/pla telet (P = .05 compared with 207 +/- 99 receptors/platelet in nine nor mal controls). Antiplatelet GPIIIa(49-66)Ab levels in sera were unifor mly increased in HIV thrombocytopenic patients (P < .001). In this coh ort of thrombocytopenic HIV patients, marrow megakaryocyte number was increased to 30 +/- 15 x 10(6)/kg (P = .02 compared with 11 +/- 2.1 x 10(6)/kg in 20 normal controls), and marrow megakaryocyte volume was 3 2 +/- 0.9 x 10(3) fL (P = .05 compared with 28 +/- 4.5 x 10(3) fL in n ormal controls). Marrow megakaryocyte mass was expanded to 93 +/- 47 x 10(10) fL/kg (P = .007 compared with normal control of 31 +/- 5.3 x 1 0(10) fL/kg). Marrow megakaryocyte progenitor cells averaged 3.3 (rang e, 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 = .0 2). Thus, thrombocytopenia in these HIV patients was caused by a combi nation of shortening of platelet life span by two thirds and doubling of splenic platelet sequestration, coupled with ineffective delivery o f viable platelets to the peripheral blood, despite a threefold TPO-dr iven expansion in marrow megakaryocyte mass. We postulate that this di sparity between circulating platelet product and marrow platelet subst rate results from direct impairment in platelet formation by HIV-infec ted marrow megakaryocytes. (C) 1998 by The American Society of Hematol ogy.