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Blood, 1 December 2001, Vol. 98, No. 12, pp. 3228-3233
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Thrombophilia in sickle cell disease: the red cell
connection
B. N. Yamaja Setty,
A.
Koneti Rao, and
Marie J. Stuart
From the Department of Pediatrics, Division of Research
Hematology, Jefferson Medical College, Thomas Jefferson University; the
Department of Medicine and Thrombosis Research, Temple University
School of Medicine, and The Marian Anderson Comprehensive Sickle Cell
Center, Philadelphia, PA.
Complex pertubations of hemostasis occur in sickle cell disease
(SCD). Although the procoagulant property of sickle erythrocytes in
vitro is tied to exposure of phosphatidylserine (PS), no study has
directly linked this PS positivity to in vivo thrombin generation. This
study was designed to determine if thrombin generation in SCD
correlates with erythrocyte PS, or whether platelets play a significant
role. PS was quantified on erythrocytes and platelets from 40 patients
with SCD (SS genotype = 25; SC genotype = 15) and 11 controls.
Markers of thrombin generation (prothrombin fragment F1.2;
thrombin-antithrombin or TAT complexes) and fibrin dissolution (D-dimer; plasmin-antiplasmin or PAP complexes) were also evaluated. Thrombin generation and activation of fibrinolysis occurred with elevations in F1.2, TAT, and D-dimer. Although numbers of both PS-positive erythrocytes and platelets were elevated, there was no
correlation between PS-positive platelets and any hemostatic markers.
In contrast, correlations were noted between PS-positive erythrocytes
and F1.2 (P < .0002), D-dimer
(P < .000002), and PAP (P < .01).
Correlations between F1.2 and D-dimer (P < .0001) demonstrated that fibrinolysis was secondary to thrombin generation. In
patients with the SC genotype, abnormalities in coagulation, although
present, were of a lesser magnitude than in SS disease. This study
suggests that the sickle erythrocyte is the cell responsible for the
thrombophilic state in SCD because associations between erythrocyte PS
and thrombin generation were observed. No such relationship with
platelet PS was noted. The use of erythrocyte PS as a surrogate marker
in trials testing new therapeutic modalities may provide insights into
the vascular complications of SCD.
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