Activation of Coagulation by Lenalidomide-Based Regimens for the Treatment of Multiple Myeloma

Isozumi, Yu; Arai, Reina; Fujimoto, Kazumi; Koyama, Takatoshi

doi:10.1371/journal.pone.0064369

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…It also causes apoptosis, leading to the phosphatyl-serine induced activation of procoagulant tissue factor on cell membranes thus making these cells more thrombogenic. [12] However, it was seen that incidence of VTE in MM doesn't increase solely with Thalidomide. [13] When Thalidomide is combined with chemotherapeutic agents such as Doxorubicin or melphalan with prednisone, there was a sharp increase in the incidence of VTE [14,15].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Embolism: A Rare Initial Manifestation of Multiple Myeloma

Sen¹,

Kumar²,

Mathews³

et al. 2015

AJMCR

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Multiple Myeloma usually presents with end organ damage like bone symptoms such as pain, pathologic fracture, renal dysfunction, chronic fatigue from anemia or symptoms of hypercalcemia. Although frequently associated with venous thromboembolisms, the presentation of multiple myeloma with pulmonary embolism as its initial manifestation is extremely rare. We report the case of a 60 y/o Hispanic male who presented with a Pulmonary Embolism, further diagnostic test revealed an underlying diagnosis of Multiple Myeloma.

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Section: Discussionmentioning

confidence: 99%

Pulmonary Embolism: A Rare Initial Manifestation of Multiple Myeloma

Sen¹,

Kumar²,

Mathews³

et al. 2015

AJMCR

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“…We avoided freeze-thaw cycles. After incubation at 37°C for 3 min, 50 μL of 25 mM calcium chloride was added, and the plasma recalcification time was measured using a semi-automatic coagulator (CA-50; Sysmex, Kobe, Japan) [ 12 , 13 ]. CA-50 detects a change in plasma optical density during blood coagulation, that is, fibrin formation.…”

Section: Methodsmentioning

confidence: 99%

Cell-based evaluation of changes in coagulation activity induced by antineoplastic drugs for the treatment of acute myeloid leukemia

2017

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Idarubicin (IDR), cytarabine (AraC), and tamibarotene (Am80) are effective for treatment of acute myeloid leukemia (AML). In acute leukemia, the incidence of venous thromboembolism or disseminated intravascular coagulation is associated with induction chemotherapy. Procoagulant effects of IDR, AraC, and Am80 were investigated in a vascular endothelial cell line EAhy926 and AML cell lines HL60 (AML M2), NB4 (AML M3, APL), and U937 (AML M5), focusing on tissue factor (TF), phosphatidylserine (PS), and thrombomodulin (TM). IDR induced procoagulant activity on the surface of vascular endothelial and AML cell lines. Expression of TF antigen, TM antigen, and PS were induced by IDR on the surface of each cell line, whereas expression of TF and TM mRNAs were unchanged. Conversely, Am80 decreased TF exposure and procoagulant activity, and increased TM exposure on NB4 cells. In NB4 cells, we observed downregulation of TF mRNA and upregulation of TM mRNA. These data suggest IDR may induce procoagulant activity in vessels by apoptosis through PS exposure and/or TF expression on vascular endothelial and AML cell lines. Am80 may suppress blood coagulation through downregulation of TF expression and induction of TM expression. Our methods could be useful to investigate changes in procoagulant activity induced by antineoplastic drugs.

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“…After incubation at 37°C for 3 min, 50 µL of 25 mM calcium chloride was added and the plasma recalcification time measured using a semi-automatic coagulator (CA-50; Sysmex, Kobe, Japan). 9 , 12 …”

Section: Methodsmentioning

confidence: 99%

“…The relative signal intensity of bands was determined and standardized using imaging software (Scion, Frederick, MD, USA), as described previously. 9 , 12 …”

Section: Methodsmentioning

confidence: 99%

Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

et al. 2016

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Objectives:Combining vorinostat, L-asparaginase, and doxorubicin (Dox) led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear.Methods:We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma), Molt4 (acute T-lymphoblastic leukemia), and Ramos (Burkitt lymphoma) were employed to investigate these procoagulant effects.Results:Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase.Conclusion:These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

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Activation of Coagulation by Lenalidomide-Based Regimens for the Treatment of Multiple Myeloma

Cited by 9 publications

References 24 publications

Pulmonary Embolism: A Rare Initial Manifestation of Multiple Myeloma

Pulmonary Embolism: A Rare Initial Manifestation of Multiple Myeloma

Cell-based evaluation of changes in coagulation activity induced by antineoplastic drugs for the treatment of acute myeloid leukemia

Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

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