Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion.

The template bleeding time is still the screening test for defects of platelet function, although it is an invasive and poorly reproducible technique. The PFA-100 measures platelet function at high shear. Whole blood is aspirated through a capillary to an aperture of a membrane coated with platelet agonists. The system measures the time required to obtain occlusion of the aperture by a platelet plug (closure time). We measured the closure times in the PFA-100 system and the bleeding time in seven patients with delta-storage pool deficiency, 10 patients with "primary secretion defect" (not due to abnormalities of platelet granules or the arachidonate pathway), and 40 controls. Measurements were repeated I and 4 hours after intravenous infusion of desmopressin in six delta-storage pool deficiency and eight primary secretion defect patients. Baseline bleeding time and closure times with the collagen/epinephrine cartridge were longer in delta-storage pool deficiency and primary secretion defect patients than in controls. In contrast, closure times with the collagen/adenosine diphosphate cartridge were normal in both delta-storage pool deficiency and primary secretion defect patients. Treatment with desmopressin increased the plasma von Willebrand Factor levels, shortened the prolonged bleeding time, shortened the closure times with the collagen/adenosine diphosphate cartridge, and normalized the closure times with the collagen/ epinephrine cartridge. Therefore, the PFA-100 test may be a less invasive alternative to the bleeding time in the diagnosis and therapeutic monitoring of patients with platelet secretion defects. The collagen/epinephrine cartridge is more sensitive than the collagen/adenosine diphosphate cartridge to defects of platelet secretion.

Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease.

We have evaluated platelet function at high shear with the PFA-100 system in different subtypes of von Willebrand disease (vWD), before and after the intravenous infusions of desmopressin or a factor-VIII/von Willebrand factor (vWF) concentrate. Closure times with the PFA-100 system were determined for both the collagen/ADP and the collagen/epinephrine cartridges in 52 patients with vWD (9 type 1 "platelet normal", 5 type 1 "platelet-discordant", 8 type 1 "platelet-low", 6 type 2A, 9 type 2B, 6 type 2M Vicenza. 6 type 3 and 3 acquired vWD) and 40 controls. Measurements were repeated 1 and 4 h after the i.v. infusion of desmopressin (0.3 microg/Kg) in 26 patients with types 1, type 2M Vicenza or type 2A vWD, or of a factorVIII/vWF concentrate (Alphanate HT, 60 U/Kg) in 4 patients with type 3 vWD. At all time points, vWF plasma levels and the bleeding time (Symplate II) were also determined. Baseline closure times were longer in vWD patients than in controls with both the collagen/ADP and the collagen/ epinephrine cartridges. The sensitivity of the PFA-100 system (88% and 87% with the two cartridges) was higher than that of the bleeding time (65%). Treatment with desmopressin normalized the closure times in patients with type 1 "platelet-normal" or type 2M Vicenza vWD, had no significant effects in patients with type 1 "platelet-low", type 1 "platelet-discordant" or type 2A vWD. Infusion of a factorVIII/vWF concentrate in patients with type 3 vWD slightly shortened their prolonged closure times. In general, changes in PFA-100 were paralleled by shortenings of the bleeding times and increases in plasma vWF levels. The PFA-100 test reflects vWF-dependent platelet function under high shear stress and could be useful in the diagnosis and therapeutic monitoring of patients with vWD.