Elevated D Dimer in the Lungs and Blood of Patients With Sarcoidosis (6)

Results
Bronchoalveolar Lavage and Plasma D Dimer
The D dimer levels in the BAL fluids and plasma of healthy volunteers and sarcoidosis patients are displayed in Figure 1. None of the 18 healthy volunteers had detectable BAL D dimer, but three had plasma D dimer at the lowest level of detection. Eight of ten patients with sarcoidosis had detectable levels of BAL D dimer, and seven had detectable plasma levels. Plasma D dimer did not correlate with BAL D dimer in these patients (r= —0.554, p = 0.10). Table 1 lists the clinical features of all ten patients with sarcoidosis.

The individuals with BAL D dimer were characterized by types 2 and 3 chest radiographs and a mean percent of predicted forced vital capacity (FVC) of 71 ± 13. The two sarcoidosis patients without BAL D dimer had type 1 and type 2 chest radiographs and a percent predicted FVC of 117 and 104, respectively. In comparison, the mean percent predicted FVC for the healthy subjects was 101 ± 14 which was significantly higher than for the sarcoidosis patients with BAL D dimer (p<0.001).
Autoradiography revealed no fibrinogen or FDP in the concentrated BAL fluids from three healthy individuals, but showed a variety of bands in the BAL fluids of all six sarcoidosis samples tested (Fig 2). The heaviest label migrated closely with soluble fibrin (270,000 MW) and fibrinogen (MW340,000). Fainter bands migrating more slowly represent higher molecular weight fibrin degradation fragments (YY and larger). Lower molecular weight FDP are seen in the region of D dimer (MW 190,000). Fibrinogen fragments X, Y, and D also migrate in this region (especially fragment Y, MW 150,000) and cannot be distinguished from D dimer by the autoradiographic method used.

Figure-1

Figure 1. Distribution of BAL D dimer (panel A) and plasma D dimer (panel B) in healthy individuals and patients with sarcoidosis. The D dimer was measured by EIA in BAL fluids concentrated 100 times and in plasma. Data points below 78 ng/ml (shaded region) represent samples in which D dimer was not detectable by the assay used. Data points by the asterisk in panel A represent D dimer levels of610, 984, and 2,540 ng/ml. The x* analysis comparing detectable and undetectable levels of D dimer between healthy and sarcoidosis subjects showed highly significant differences (p<0.005) in both BAL and plasma.

Figure-2

Figure 2. Autoradiogram of BAL fluids and plasma labeled with goat anti-human fibrinogen. No label is seen in the BAL samples of normal individuals. All six BAL samples from sarcoidosis patients showed a variety of bands representing fibrinogen, fibrin, fibrin polymers, and FDP including D dimer. NP, normal plasma; Dd, D dimer; FM, fibrin monomer; SP, sarcoidosis plasma; N BAL, normal BAL; S BAL, sarcoid BAL.

Table 1—Bronchoalveolar Lavage Fluid Analysis: Сей, Total Protein, D Dimer, and Plasma D Dimer in Patients With Sarcoidosis

Age,yr Race Sex ChestRadiograph % FVC BAL Fluid D Dimer, ng/ml
Cells/ml х 1,000 %Macrophages %Lymphocytes %Neutrophils %Eosinophils Protein,mg/ml
BAL Plasma
43 В М Type 2 49 211.0 85 15 0 0 0.33 110 91
37 В F Туре 2 83 294.2 66 32 1 1 0.31 448 164
35 В F ТУреЗ 70 140.0 79 17 1 2 0.29 130 90
35 В F Туре 2 80 268.6 83 17 0 0 0.30 81 194
28 В F Туре 2 66 349.0 53 46 0 1 1.67 610 169
32 В F 1Уре2 85 158.0 59 41 0 0 0.37 144 283
29 В М Туре 2 56 407.7 60 40 0 0 0.74 984 106
34 I* М ТУре 2 78 1,050.0 9 90 0 1 15.40 2,540…
43 В F ТУре 2 117 91.0 93 7 0 0 0.13 … 132
36 W F ТУре 1 104 131.6 70 29 1 0 0.12 … 78