Thalidomide-dexamethasone as up-front therapy for patients with newly diagnosed multiple myeloma: thrombophilic alterations, thrombotic complications, and thromboprophylaxis with low-dose warfarin.
BACKGROUND
Venous thromboembolism (VTE) is a major complication of myeloma therapy recently observed with the increasing use of up-front thalidomide and dexamethasone (thal-dex). The pathogenesis of thal-induced VTE is not well recognized, and the role of prothrombotic factors, especially of thrombophilic abnormalities, is not yet determined.


METHODS
Two hundred and sixty-six patients with newly diagnosed multiple myeloma (MM) were primarily treated with thal-dex in preparation for subsequent high-dose therapy and autologous stem-cell transplantation. Out of these 266 patients, 190 were evaluated for thrombophilic alterations at baseline, and 125 of them were also re-assessed after thal-dex therapy.


RESULTS
The presence of genetic thrombophilic polymorphisms among patients with MM was superimposable to that of normal controls and was associated with a twofold increase in the relative risk of VTE. aAPCR and elevated factor VIII levels were frequent, albeit transient, alterations and were not associated with a significant increase in the risk of VTE. Two hundred and forty-six patients received a thromboprophylaxis with fixed low-dose warfarin (1.25 mg/day) during thal-dex therapy. Of these patients (or 10.6%), 26 had symptomatic VTE events. Their patients-years rate of VTE (35.5%) was significantly lower in comparison with the 86.2% rate recorded among the first 19 patients who initially entered the study and did not receive any kind of thromboprophylaxis (P = 0.043).


CONCLUSIONS
On the basis of these data, a baseline thrombophilic work up is not recommended in patients with receiving up-front thal-dex. For these patients, fixed low-dose warfarin may be a valuable prophylaxis against VTE.
Cini
Michela
M
Unità Operativa di Angiologia e della Coagulazione "Marino Golinelli", Azienda Ospedaliera-Universitaria S. Orsola-Malpighi, Bologna.
Zamagni
Elena
E
Valdré
Lelia
L
Palareti
Gualtiero
G
Patriarca
Francesca
F
Tacchetti
Paola
P
Legnani
Cristina
C
Catalano
Lucio
L
Masini
Luciano
L
Tosi
Patrizia
P
Gozzetti
Alessandro
A
Cavo
Michele
M
D020016:Activated Protein C Resistance / Q000235:genetics; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D016022:Case-Control Studies; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005165:Factor V / Q000235:genetics; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D013927:Thrombosis / Q000139:chemically induced* / Q000517:prevention & control*; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage
D000925:Anticoagulants; C095381:factor V Leiden; D013792:Thalidomide; D014859:Warfarin; D003907:Dexamethasone; D005165:Factor V; D011516:Prothrombin; D005169:Factor VIII