Summary
Renal transplant rejection is associated with platelet activation in vivo which may
lead to partially α- and γ-granule-depleted platelets that continue to circulate.
These “exhausted” platelets are hemostatically defective. Tb quantitate the extent
of platelet granule depletion following kidney transplantation, we determined intraplatelet
levels of β-thromboglobulin (βTG), platelet factor 4 (PF4), and serotonin (5-hydroxytryptamine,
5-HT) ex vivo in Tiiton X-1O0-treated platelet lysates. To explore biochemical alterations
of partially depleted platelets, we studied platelet thromboxane A2 (TXA2) synthesis in citrated plateletrich plasma (PRP) upon stimulation with thrombin or
collagen in 45 recipients of renal allografts and 10 healthy volunteers. The patients
were divided into subjects with acute and chronic allograft rejection (N = 15), those
with compensated renal failure after kidney transplantation but without evidence of
allograft rejection (N = 15), and those with functioning renal transplant (N = 15).
The mean intraplatelet content of βTG (38.6 ± 4.2 μE/109 platelets), PF4 (11.8 ± 1.8 μg/109 platelets), and 5-HT (274 ± 31 μg/109 platelets) in patients with acute or chronic renal allograft rejection was significantly
lower than in other recipients off < idney transplants or healthy volunteers (βTG:
59.9±4.7 μgl 109 platelets; PF4: 20.4±2.3 ¼g/n platelets; s-rrr: 46lraB ngl 10e platelets; p < 0.ffi5
in all casls). Platelet TxB2 formation upon stimulation with thrombin (10 U/ml) or
collagen (6.25 ¼g/ml) for 5 min was significantly reduced in patients with acute or
chronic renal allograft rejection (2.25±0.29 and 0.641 0.08 nmoUl0e platelets for
thrombin- and collagen-stimulated platelets, respectively) compared to that of healthy
volunteers (4.72± 0.60 and 1.35 ± 0.12 nmol/109 platelets, respectively; p <0.05 in all cases). In contrast, platelet TXB2 formation of patients with functioning kidney transplant or those with compensated
renal failure but without evidence of transplant rejection did not differ significantly
from that of normals. These results confirm that platelets with reduced levels of
α- and β-granular constituents are detectable in the circulation following kidney
transplantation when acute or chronic renal allograft rejections occur. These platelets
are incapable of forming normal amounts of thromboxane upon stimulation with thrombin
and collagen in vitro. This dysfunction of thromboxane synthesis, due to alterations
in the platelet arachidonate pathway, may reflect the previous activation of platelets
in vivo associated with acute or chronic renal allograft rejection.
