• **VTE in Monoclonal gammopathy of undetermined significance**

In 2004, Sallah S et al and Srkalovic G et al published in Ann Oncol and cancer respectively (201-202) two small hospital based studies on the association of monoclonal gammopathy of undetermined significance (MGUS) and subsequent risk of DVT and reported an elevated risk of DVT in MGUS. Kristinsson Y et al (203) conducted a retrospective study on 4,196,197 veterans hospitalized at least once. MM was identified in 2374 (0.06%) cases of MGUS 6192 (0.15%). A total of 31 and 151 DVTs occurred among MGUS and multiple myeloma, respectively (crude incidence 31 and 8.7 per 1000 person-years, respectively). The RR of DVT Pathophysiology and Clinical Aspects of 92 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

to treatment and recurrence of VTE. Records of 299 ALL patients and 996 AML patients were included (Nov 1991-May 2005). The authors concluded that acute leukemia patients have a high prevalence of VTE but the occurrence of VTE prior to initiation of chemotherapy was not associated with poor prognosis similar finding to that reported by Ku GH et al.

Blast cells with their procoagulant properties, central venous catheters, chemotherapeutic agents (as discussed earlier in this chapter) concomitant infections, patient-and supportive treatment related factors are major determinants of haemostatic mechanism activation in acute leukemia. The clinical manifestations range from VTE to diffuse life-threatening hemorrhage. Anti-coagulant therapy in this clinical setting is fraud with major difficulties as the patients are at very high risk of haemorrhage because of thrombocytopenia. To date, no guidelines are available for prophylaxis or treatment of VTE in this group of

The use of the differentiating agent all-trans-retinoic acid (ATRA) in the treatment of APL allowed achievement of complete remission in more than 90% of the cases and improved dramatically the coagulopathy typical of this disease (198). The modifications induced by ATRA in the balance between procoagulant and fibrinolytic properties of the pathological promyelocytes before complete differentiation have been proposed to induce a

Multiple myeloma (MM) has been associated with increased risk of VTE events. Specific risk factors for VTE in MM are production of autoantibodies to haemostatic factors, high incidence of acquired protein C resistance, increased VIII:C levels and VWF and increase of production of inflammatory cytokines e.g. IL-6, TNF and C-reactive protein and paraprotein. These unique risk factors may operate along other common cancer VTE risk

Treatment regimens for MM include thalidomide, Lenalidomide combined with glucocorticoids and cytotoxic chemotherapy are associated with an increased risk of VTE particularly when the immunomodulatory agents are combined with anthracyclines. Combination chemotherapy including thalidomide plus dexamethasone and/or alkylating agents are associated with intermediate risk for VTE. The use of newer immunomodulator e.g. bortezomib seem to reduce the VTE risk **(200).** This topic has been well covered in

In 2004, Sallah S et al and Srkalovic G et al published in Ann Oncol and cancer respectively (201-202) two small hospital based studies on the association of monoclonal gammopathy of undetermined significance (MGUS) and subsequent risk of DVT and reported an elevated risk of DVT in MGUS. Kristinsson Y et al (203) conducted a retrospective study on 4,196,197 veterans hospitalized at least once. MM was identified in 2374 (0.06%) cases of MGUS 6192 (0.15%). A total of 31 and 151 DVTs occurred among MGUS and multiple myeloma, respectively (crude incidence 31 and 8.7 per 1000 person-years, respectively). The RR of DVT

factors e.g. age, immobility, cancer procoagulant factors and chemotherapy.

• **VTE in Monoclonal gammopathy of undetermined significance** 

patients (197)

prothrombotic effect (199).

chapter 5 of the book.

• **VTE in Multiple Myeloma** 

• **VTE in Acute Promyelocytic Leukemia** 

after a diagnosis of MGUS and MM was 3.3 and 9.2 respectively with excess risk of DVT in the first year of diagnosis. Compared to the background population, patients with multiple myeloma have a 9-fold increased risk of developing DVT especially during the first year of diagnosis while the risk for DVT in MGUS was stable at 3-fold increased risk over time with no statistical association between DVT in MGUS and risk for progression into MM.

### • **VTE in Myelodysplastic Syndrome**

Yang X et al (204), in 2009, reported a total of 7764 MDS patient who were prescribed Lenalidomide during the first two years of its commercial use in the USA. VTE was reported in 41 patients (rate of 0.53%) denoting a computed signal that did not exceed the statistical threshold for identification of a significant disproportional signal for VTE in MDS on Lenalidomide without erythropoietin. However, the authors found that a disproportional signal of VTE where erythropoietin was concurrently administered with Lenalidomide.
