The Use of the PFA-100^® and Thromboelastograph in Assessing Haemostasis and Drug Efficacy in Essential Thrombocythemia.

Introduction. Essential thrombocythemia (ET) is associated with an increased risk of thrombosis. Many patients are treated with anti-platelet agents and/or cytoreductive therapy in order to minimise the risk but some still develop thrombotic events. The PFA-100^® is an effective near-patient platelet function analyser and the Thromboelastograph (TEG^®) Haemostasis Analyser assesses global haemostasis in whole blood. The usefulness of these technologies has not been fully evaluated in ET.

Patients and Methods. We compared results from the PFA-100^® and TEG^® in 25 ET patients and 19 controls. Overall the ET patients comprised 18 females and 7 males, their median age was 55 yrs, median platelet count 423x10⁹/l. Twenty-two were on anti-platelet therapy (21 on 75mg aspirin, 1 on aspirin and clopidogrel). Seventeen patients were receiving cytoreductive therapy (10 hydroxyurea, 2 a-interferon, 4 busulphan and 1 busulphan with anagrelide). Eight patients had previous thrombosis (4 transient ischaemic attacks, 1 stroke, 1 central retinal vein occlusion, 2 multiple events [1 stroke, erythromelalgia and digital ischaemia; 1 central retinal vein occlusion and digital ischaemia]) and 2 had haemorrhagic events.

Results. All had normal INR, APTT and fibrinogen levels. Using the PFA-100^®, Collagen/ADP closure times were prolonged in 15 (60%) patients compared to normal controls, suggesting platelet dysfunction, which included both patients with previous bleeding episodes. Twenty (91%) patients on aspirin had prolonged Collagen/Epinephrine closure times but for 2 (9%) patients these were within the normal range indicating aspirin-resistance. Both these patients had a history of thrombosis whilst on aspirin alone. Using TEG^®, ET patients when compared to controls, took longer to initiate and to reach maximal clot strength (significantly longer R and K times, p=0.001, p=0.012 respectively and smaller angle, p=0.01) but the developed clot had a higher tensile strength (larger MA, p=0.024). There was a positive correlation between fibrinogen levels and MA (r=0.54, p=0.006) as well as APTT with R time (r=0.437, p= 0.029). There was no correlation between platelet count or prior history of thrombosis with any PFA-100^® or TEG^® variables.

Conclusion. Low-dose aspirin had biochemical efficacy as assessed by PFA-100^® Collagen/Epinephrine closure times in most but not all ET patients. Further studies are necessary to assess whether Collagen/ADP times can identify those at risk of bleeding. In ET, the TEG^® demonstrates slower formation but a higher tensile clot strength than controls. Larger studies are needed to fully evaluate these findings and their clinical relevance.