Use of a microchip flow-chamber system as a screening test for platelet storage pool disease

Abstract

Platelet storage pool disease (SPD) is a platelet function disorder characterized by a reduction in the number or content of α-granules, dense granules, or both, and is diagnosed by specialized tests. Patients with SPD often present with prolonged bleeding time (BT), but the sensitivity and reproducibility of this test have limitations, often resulting in false negatives. It has recently been reported that an automated microchip flow-chamber system (T-TAS(®)) is useful in the assessment of anti-platelet therapy, and could have potential as a screening test for SPD. We examined the utility of T-TAS in three individuals from one family diagnosed with δ-SPD. The propositus had a mildly prolonged BT, and the standard tests for platelet function were close to the normal range. Whole blood samples were anti-coagulated with hirudin and applied to T-TAS microchips coated with collagen (PL-chips) at shear rates of 1000 and 2000 s(-1). Platelet thrombus formation (PTF) was monitored with a pressure sensor. Markedly depressed PTF was observed in all cases at both shear rates. These findings indicate that T-TAS is highly sensitive to the defect in these patients with SPD, and may represent a good candidate screening test for a wide range of platelet function disorders.

Evaluation of the Total Thrombus-Formation System (T-TAS): application to human and mouse blood analysis

“…Interestingly, T-TAS also detected all patients with COX-like defects and secretion defects ( Figure 2D). This finding is consistent with earlier reports showing that T-TAS was able to detect all patients diagnosed with SPD [12]. T-TAS also showed high consistency in detecting abnormalities in patients with multiple defects.…”

“…T-TAS also showed high consistency in detecting abnormalities in patients with multiple defects. This finding supports the earlier report suggesting that T-TAS is reliable in detecting more severe forms of platelet defects such Bernard-Soulier syndrome [12]. However, T-TAS failed to detect thrombus formation in all patients with thrombocytopenia including three patients that gave normal responses by lumi-LTA (Figure 2A and 2B).…”

“…direct thrombin and factor Xa inhibitors [9]. T-TAS has also demonstrated high sensitivity in detecting coagulation disorders such as haemophilia [10] and von Willebrand disease [11], as well as platelet function defects for example, storage pool disease (SPD) [12]. In assessing acquired haemorrhagic conditions, the T-TAS was able to predict the risk of bleeding in atrial fibrillation patients undergoing catheter ablation [13].…”

Assessing the clinical severity of type 1 von Willebrand disease patients with a microchip flow‐chamber system

“…Also, haplotype(s) of platelet GP polymorphisms have been described that affect the bleeding phenotype in VWD , and coinherited platelet function disorders may complicate the diagnosis and assessment of bleeding severity in VWD . In this respect, we have reported that the T‐TAS is highly sensitive to the defect in patients with platelet storage pool disease , and might be a good candidate as a screening test for a broad range of platelet function disorders. It is unclear, however, how the platelet GP haplotype modulates the T‐TAS results independently of VWF.…”

Role of red blood cells in the anemia‐associated bleeding under high shear conditions

“…In addition, we have recently described a novel microchip, whole‐blood, flow chamber procedure that automatically and reproducibly analyzes thrombus formation under various shear conditions. This total thrombus analysis system (T‐TAS ® ; Fujimori Kogyo, Yokohama, Japan) is easy to use and appeared to be useful for the screening and diagnosis of bleeding disorders including VWD and platelet function abnormalities . Furthermore, the occlusion times in T‐TAS correlated with bleeding score in type 1 VWD , suggesting that T‐TAS data could provide a good index of primary hemostasis, especially in different hemodynamic environments .…”