Is Platelet Aggregation a Useful Investigation in Assessing the Risk of Thrombosis in Patients With JAK-Positive Chronic Myeloproliferative Disorders? Brief Report: A Study on 14 Patients

Patients with chronic myeloproliferative disorders have frequently thrombosis, especially for JAK2-positive patients. The aim of this study is to identify and correlate abnormalities of platelet aggregation for 14 JAK-positive patients, with thrombosis incidence. Thromboses were present more frequently in the JAK-positive group than the JAK-negative group. Patients with JAK2 genotype have more diminished platelet response for ADP, epinephrine, and collagen than the JAK-negative group and normal response for ristocetin, but these results do not have statistical significance to correlate with a higher risk of thrombosis

Full Abstract

Background

Patients with chronic myeloproliferative disorders (CMPD) have a variety of structural and functional abnormalities of platelets. JAK2, which is constitutively activated in most patients with CMPD, might be involved in signal transduction for thrombopoietin-induced aggregation of platelets in these disorders. The patients with JAK2-positive CMPD have a higher incidence of venous thrombosis compared with noncarriers; these are more frequent in patients with the wild-type JAK2 genotype.

Aim

We aim to identify abnormalities of platelet aggregation for CMPD patients with JAK present and to correlate these findings with increased risk of thrombosis.

Materials and Methods

We present a retrospective study on 14 cases with JAK2-positive CMPD compared with 6 cases with JAK2-negative CMPD admitted in University Emergency Hospital Bucharest. We analyzed the clinical and laboratory parameters for both groups. Platelet function was investigated by platelet aggregation on Chrono-log aggregometer. As stimuli, we used ADP, collagen, epinephrine, and ristocetin.

Results and Discussion

We studied 14 JAK2-positive patients (5 patients, ET; 6, PV; 1, IMF; and 2, unclassifiable CMPD), 9 men and 5 women, with a median age of 58.35 years; and 6 JAK2-negative patients (1 patient, ET; 2, PV; 3, IMF), 4 men and 2 women, with a median age of 67.16 years. Thrombosis was present in 69.12% of the JAK2-positive patients. Of these, 3 patients presented with portal vein thrombosis as the first clinical manifestation; all 3 patients were young (median age, 33 years). Ischemic stroke was presented in 5 patients (median age, 74.75 years), arterial or venal thrombosis in 2 patients. Patients who were JAK negative rarely presented with thrombosis (1 patient in our study). Platelet aggregation studies showed decreased response to ADP (49.75 vs. 50.92), epinephrine (23.05 vs. 11.53), and collagen (42.93 vs. 66.51). For ristocetin, we obtained normal value for JAK2-positive patients (60.67 vs. 44). We also obtained higher duration of collagen lag phase for JAK2-positive patients (153.97 vs. 61.57) and no differences for amplitude or duration of ADP lag phase (4.27 vs. 5.1; 8.14 vs. 9.46) or amplitude of collagen lag phase (6.21 vs. 7.61). Deaggregation is more frequent for JAK2-positive patients: 6 cases (42.85%) versus 5 cases (83.33%) for ADP; 4 cases (28.57%) versus 2 cases (33.33%) for collagen.

Conclusion

Patients with CMPD frequently present with venal thrombosis (portal/suprahepatic veins) or ischemic strokes. In patients with JAK2-positive CMPD, platelet aggregation is diminished for ADP, epinephrine, and collagen; also, the lag phase was longer for collagen in JAK2-positive patients. Platelet aggregation is not enough of a technique for the investigation of platelet function in order to correctly establish the risk of thrombosis. In our study, the low number of cases does not allow obtaining statistically significant results.