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Patients with plasma cell dyscrasia are at risk to develop DVT (prevalence in MGUS was 8%, in MM 10%) (Cancer101(3):558–566, 2004). The risk has been reported to be higher in newly diagnosed (ND) patients treated with Thalidomide and anthracyclines (Clinical Lymphoma. 4(1):32–5, 2003). DVd-T is effective in the treatment of MM patients but carries an increased risk of DVT. Our incidence of DVT with Thalidomide and Thalidomide/Dexamethasone with slow dose escalation and less frequent Dexamethasone was not different from non-Thalidomide containing regimens. We treated 105 patients with DVd-T from 8/2001to 4/2004. We included an algorithm to evaluate patients with symptoms of DVT aggressively and assayed different coagulation parameters (including Platelet Aggregation studies (PA) with Collagen, Epinephrine, ADP, Arachidonic Acid and different concentration of Ristocetin, factor V Leiden (FVL), Activated protein C resistance (APCR), and Von Willebrand factor (vWF)) at baseline and before each cycle of DVd-T. Because the first 35 patients had a high rate of DVT, the protocol was amended to add Aspirin (ASA) 81 mg daily based on preliminary laboratory data preformed on the first group of patients. Two patients on Warfarin for other indications were excluded from the analysis. Of the 103 patients remaining 54 were ND MM and 49 had (Relapsed/Refractory RR) MM. Mean age was 58.9 years, 56% were males and 26%, 42%, 19% and 13% had SWOG stage I, II, III and IV respectively. Four patients were heterozygous for FVL and did not develop DVT. Fifty-eight patients received ASA at the start of treatment while 26 received ASA after the start of treatment and 19 did not receive ASA. Twenty six post treatment (pRx) DVT occurred at a mean 109 days pRx with 15/84 (17.8%) occurring after the start of ASA and 11/19 (57.8%) occurring off ASA (p=0.0002). No significant bleeding complications were noted in patients on ASA. Two patients receiving ASA discontinued therapy; another patient during his travel was immobile for 5–6 hours at a time and inconsistent with ASA therapy, all three developed DVT. One patient on ASA developed below the knee DVT not requiring anticoagulation. Thus, pRx DVT on ASA that required anticoagulation was 11/82 (13%) versus 13/21 (61.9% p<0.001). When compared to pretreatment levels, PA 30 days after initiation of therapy to Arachidonic acid (P<0.001), ADP (P=0.025), Collagen (P<0.001), Epinephrine (P<0.001), Ristocetin 1500 mcg/ml (p=0.06) and 1200 mcg/ml (p=0.05) and vWF (p=0.01) were exaggerated. Following ASA therapy, 30 days pRx PA to ristocetin and vWF levels were not statistically different to pretreatment level suggesting that ASA has blunted the increase in PA. Baseline PA to Epinephrine was higher in patients who did not develop DVT and pRx PA to epinephrine was higher in patients who developed DVT (p<0.001 and p=0.08 respectively). ASA decreases the incidence of DVT following the DVd-T regimen without increasing the risk of bleeding. The mechanism of thrombosis prevention of ASA may involve attenuating the increase of vWF and PA that occurs after DVd-T.

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