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CLINICAL STUDY: CONGENITAL HEART DISEASE

Overproduction of platelet microparticles in cyanotic congenital heart disease with polycythemia

Hitoshi Horigome, MD^*,*, Yuji Hiramatsu, MD, Osamu Shigeta, MD, Toshiro Nagasawa, MD and Akira Matsui, MD^*

^* Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
Department of Cardiovascular Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

Manuscript received August 6, 2001; revised manuscript received December 18, 2001, accepted January 2, 2002.

^* Reprint requests and correspondence: Dr. Hitoshi Horigome, Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
hhorigom{at}md.tsukuba.ac.jp

OBJECTIVES: We sought to clarify the role of platelets in the pathogenesis of abnormal coagulation in patients with cyanotic congenital heart disease (CCHD) with polycythemia; we evaluated the production of platelet microparticles (MPs), platelet degranulation and aggregation response, as well as the correlations of these variables with polycythemia.

BACKGROUND: A shortened life span and suppressed aggregability of platelets are well known in patients with CCHD. Although platelet MPs are overproduced and play an important role in the coagulation process in various hematologic and cardiovascular disorders, the production of MPs remains to be elucidated in CCHD.

METHODS: We studied 19 patients who had CCHD with polycythemia and 21 age-matched subjects with acyanotic congenital heart disease (ACHD). Flow cytometry, using monoclonal antibodies, showed the presence of MPs as particles positive for the surface antigen (glycoprotein IIb/IIIa) specific to platelets, and platelet alpha-degranulation was recognized as platelets positive for the surface antigen of P-selectin. Platelet aggregation was assessed as the response to adenosine diphosphate (ADP). Relationships between these indexes and hematocrit (Hct) values were also evaluated.

RESULTS: Production of MPs correlated positively with Hct and markedly increased at Hct values above 60% in patients with CCHD. Surface P-selectin and the mean platelet volume in patients with CCHD were comparable with those in patients with ACHD. The platelet aggregation response to ADP significantly and negatively correlated with Hct. In two subjects who showed hemoptysis and underwent phlebotomy, MPs were reduced 6 h after the procedure.

CONCLUSIONS: Platelet MPs are overproduced in patients who have CCHD with polycythemia, probably due to a high shear stress derived from blood hyperviscosity. Circulating incompetent platelets, which have already been activated, as well as MPs, might play an important role in the coagulation abnormalities identified in such patients.

Abbreviations and Acronyms   CCHD   ACHD   acyanotic congenital heart disease   ADP   adenosine 5"-diphosphate   CCHD   cyanotic congenital heart disease   Hct   hematocrit   mAb   monoclonal antibody   MCV   mean corpuscular volume   MP   microparticle   MPV   mean platelet volume   PPP   platelet-poor plasma   PRP   platelet-rich plasma

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