PracticeUpdate: Haematology & Oncology

ASH 2016 11

Handheld device offers rapid, comprehensive assessment of blood clotting W ith less than a drop of blood, a prototype for ClotChip, a port- able, disposable sensor provides Willebrand factor defect; and one, mild congenital hypodysfibrinogenemia.

Taken together, these findings might indicate that some patients are being unnecessarily overtreated. The other important implication is that patients do not have to have extremely low levels of leukaemia on very sensitive tests to safely try reducing their dose of tyrosine kinase inhibitor. >19 Large percentage of patients who reached target second- maintenance-dose antithrombin-III level achieved complete response. Additional treatment strategies may be needed, however, for patients who do not reach the target second- maintenance-dose antithrombin-III level with their current antithrombin-III dosage. >20

Compared to the normal curve, all samples from patients with coagulopathy exhibited an abnormal curve with an extended rise to peak [range 7 to 15 minutes (P = 0.0004)]. A receiver operating characteristic curve was generated, and the true positive rate plotted against the false–positive rate. The area under the curve for ClotChip (1.00) was higher than those of both acti- vated partial thromboplastin time (0.7813) and partial thromboplastin time (0.5859), illustrating that the ClotChip rise-to-peak parameter exhibits superior sensitivity than conventional screening coagulation tests. Next, ClotChip measurements were per- formed with whole blood from four healthy donors after the samples were treated with 1 µM prostaglandin E2 to inhibit platelet aggregation. Dr Stavrou determined that prostaglandin E2-treated samples exhibited a statistically significant (P = 0.03) lower peak height than that of untreated samples while rise-to-peak values remained unchanged between treat- ed and untreated samples. This showed that the lower peak height parameter was sen- sitive in response to platelet function and that ClotChip was able to detect platelet function defects. Dr Stavrou said that ClotChip showed a higher degree of sensitivity than convention- al diagnostic tests for coagulation defects. Compared to conventional tests, ClotChip reduced the rate of false-negative results. ClotChip is sensitive to multiple coagu- lation factors and platelet activity, there- by allowing whole blood assessment of hemostasis in a single disposable sensor. The ClotChip will bring blood coagulation testing closer to the patient for time-sensi- tive applications such as diagnosis of the bleeding patient and in trauma-induced coagulopathy. “Our device gives you different informa- tion – and more information – than other devices out there,” Dr Stavrou said. “The sensitivity and discriminatory ability of the device compared to standard coagulation tests is what excites me.” Dr Stavrou and coinvestigators are recruit- ing volunteers to participate in an expanded round of testing. The team is also working to optimise the device’s construction to enhance its sensitivity.

a complete report on a patient’s coagula- tion status in less than 15 minutes, finds a comparative study of ClotChip versus conventional coagulation evaluations. Evi X. Stavrou, MD, of Case Western Re- serve School of Medicine, Cleveland, Ohio, explained that the miniaturised microfluidic dielectric sensor provides for point-of-care assessment of blood coagulation. Such results are now obtainable only with spe- cialised laboratory testing. Accurate information about coagulation status is associated with better survival. Early identification of coagulopathy carries crucial clinical implications in the man- agement of patients who are critically ill, severely injured, or taking anticoagulation therapy. Conventional laboratory-based coagulation tests are time-consuming, labour-intensive, and costly. Available point-of-care devices are intended for use in specific patient populations (those taking warfarin). Measurements are insensitive due to interference from the device surface. A low-cost, easy-to-use, portable platform is needed for point-of-care assessment of the complete haemostatic process outside of the laboratory setting. The device has the potential for use in health-care settings that lack easy access to specialised laboratory testing. Unlike standard blood coagulation and platelet testing procedures that use specially trained personnel, large machines, and collected blood samples, ClotChip uses dielectric spectroscopy to detect markers of coagu- lation activity in real time. Dr Stavrou and colleagues measured coagulation in whole blood from healthy volunteers (n=10) collected in 3.2% sodium citrate. Coagulation was induced with cal- cium chloride. ClotChip curves exhibited a reproducible rise to peak within 4.5 to 6 minutes. Conventional coagulation tests were also performed in each of the healthy samples in duplicate and confirmed normal activated partial thromboplastin time and partial thromboplastin values. ClotChip measurements were then per- formed in seven clinical samples obtained from patients with coagulopathy. These patients were referred to a specialised haematology clinic for workup of coagu- lopathy. Four patients suffered from intrin- sic pathway defects (two, haemophilia A; three, haemophilia B); one, acquired von

The findings will help inform the first guidelines on how to use and select central

venous lines in children and when anticoagulants might be recommended to prevent blood clots. >21

PracticeUpdate Editorial Team

VOL. 2 • NO. 1 • 2017