Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments.
BACKGROUND
Prior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence.


METHODS
We retrospectively estimated the rate of recurrence in a multicenter cohort of 494 patients (poly-cythemia vera/essential thrombocythemia 235/259) with previous arterial (67.6%) or venous thrombosis (31%) or both (1.4%). First thrombosis was cerebrovascular disease in 191 cases, acute coronary syndrome in 106, peripheral arterial thrombosis in 44, and venous thromboembolism in 160. Microcirculatory events were not computed.


RESULTS
Thrombosis recurred in 166 patients (33.6%), with an incidence of 7.6% patient-years. Sex, diagnosis (polycythemia vera or essential thrombocythemia), and presence of vascular risk factors did not predict recurrence, whereas age >60 years did (multivariable hazard ratio [HR], 1.67; 95% confidence interval [CI] 1.19-2.32). Increased leukocyte count at the time of the first thrombosis was a risk factor for recurrence in patients <60 years old (HR 3.55; 95% CI 1.02-12.25). Cytoreduction halved the risk in the overall cohort (HR 0.53; 95% CI 0.38-0.73) and the combination with antiplatelet agents or oral anticoagulants was more effective than administration of single drugs. Significant prevention of rethrombosis was independently achieved in patients with venous thromboembolism by both oral anticoagulants (HR 0.32; 95% CI 0.15-0.64) and antiplatelet agents (HR 0.42; 95% CI 0.22-0.77), in those with acute coronary syndrome by cytoreduction (HR 0.30; 95% CI 0.13-0.68), and in those with cerebrovascular disease by antiplatelet agents (HR 0.33; 95% CI 0.16-0.66). The overall incidence of major bleeding was 0.9% patient-years and rose to 2.8% in patients receiving both antiplatelet and anti-vitamin K agents.


CONCLUSIONS
In patients with polycythemia vera and essential thrombocythemia, cytoreduction protects against recurrent thrombosis, particularly after acute coronary syndrome. The contemporary use of oral anticoagulants (after venous thromboembolism) or antiplatelet agents (after cerebrovascular disease or venous thromboembolism) further improves the protective effect. Such findings call for prospective studies aimed at investigating whether strategies tailored according to the type of first thrombosis could improve prevention of recurrences.
De Stefano
Valerio
V
Institute of Hematology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy. valerio.destefano@rm.uni-catt.it
Za
Tommaso
T
Rossi
Elena
E
Vannucchi
Alessandro M
AM
Ruggeri
Marco
M
Elli
Elena
E
Micò
Caterina
C
Tieghi
Alessia
A
Cacciola
Rossella R
RR
Santoro
Cristina
C
Gerli
Giancarla
G
Vianelli
Nicola
N
Guglielmelli
Paola
P
Pieri
Lisa
L
Scognamiglio
Francesca
F
Rodeghiero
Francesco
F
Pogliani
Enrico M
EM
Finazzi
Guido
G
Gugliotta
Luigi
L
Marchioli
Roberto
R
Leone
Giuseppe
G
Barbui
Tiziano
T
D054058:Acute Coronary Syndrome / Q000453:epidemiology / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001157:Arterial Occlusive Diseases / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011087:Polycythemia Vera / Q000097:blood / Q000150:complications* / Q000628:therapy; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D013920:Thrombocythemia, Essential / Q000097:blood / Q000150:complications* / Q000628:therapy; D019851:Thrombophilia / Q000209:etiology / Q000235:genetics; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors