Disturbances in Hemostasis in Patients with B-Cell Malignancies

Glaspy, John A.

doi:10.1055/s-2007-1002582

Cited by 9 publications

(3 citation statements)

References 79 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous diseases have been reported in association with AvWS (Table 1), most of which are clonal hematoproliferative diseases. Monoclonal gammopathies and/or lymphoproliferative disorders (10,11) have been found in about half of the reported cases of AvWS while myeloproliferative disorders (12,13) are less frequently found. Among monoclonal gammopathies, monoclonal gammopathies of undetermined significance (MGUS) (14-21) as well as malignant monoclonal gammopathies such as myelomas (22)(23)(24)(25)(26)(27)(28) and Waldenström macroglobulinemia (29,30) have been described.…”

Section: Associated Disordersmentioning

confidence: 99%

Acquired von Willebrand Syndrome: from Pathophysiology to Management

Veyradier¹,

Jenkins²,

Fressinaud³

et al. 2000

Thromb Haemost

103

View full text Add to dashboard Cite

SummaryAcquired von Willebrand syndrome (AvWS) is a rare and probably underestimated bleeding disorder which mimicks most of the clinical symptoms and laboratory features of hereditary von Willebrand disease (vWD) in patients devoid of both personal and familial history of bleeding diathesis (1). AvWS and congenital vWD both result from a defect in von Willebrand factor (vWF), a large multimeric glycoprotein present in megakaryocytes, platelets, endothelial cells, subendothelium and mainly in plasma (2). vWF is essential to platelet adhesion and aggregation at the site of vascular injury by acting as a bridge between platelet receptors and the collagen of the subendothelium as well as between platelets themselves. vWF binds to both platelet receptors glycoprotein (GP) Ib and GP IIb/IIIa and also to coagulation factor VIII (F.VIII) acting as a stabilizing carrier protein in plasma. The revised classification of hereditary vWD (3) includes three major types: type 1 and type 3 are respectively related to a partial or a total quantitative defect while type 2 (variants including several subtypes) results from a qualitative defect of vWF. Although vWD is well known to be the most common inherited bleeding disorder with a worldwide prevalence of 1 to 2% (1), more than 200 cases of AvWS have been reported since it was described in 1968 (4). It is likely, however, that this number is underestimated since isolated case-reports of AvWS tend to be less published and its diagnosis remains difficult. AvWS is most commonly found together with a variety of concurrent diseases which are mainly clonal hematoproliferative, neoplasia and autoimmune disorders (5-7). The pathophysiological basis of AvWS as well as its response to treatment depend clearly on the associated underlying disease. In this paper, we summarized all the situations where an AvWS may be observed as a function of the anamnestic and clinical data, the pathogenic mechanisms and the laboratory features. Moreover, we propose a therapeutic flow chart based on both data from the literature and personal experience.

show abstract

Section: Associated Disordersmentioning

confidence: 99%

Acquired von Willebrand Syndrome: from Pathophysiology to Management

Veyradier¹,

Jenkins²,

Fressinaud³

et al. 2000

Thromb Haemost

103

View full text Add to dashboard Cite

show abstract

“…Although several clinical characteristics of patients with myeloma are factors predisposing to thrombosis, including immobilization [10], hyperviscosity and hypercalcemia [11], amyloidosis [6], increased levels of plasma fibrinogen [12], activated protein C resistance in the absence of factor V Leiden mutation [13], hypercoagulability underlying MM has not been precisely defined. Thromboembolic events associated with lupus anticoagulants, protein C, and free protein S deficiency are rarely reported in MM [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Fibrinolytic activity in multiple myeloma

Yağcı¹,

Sucak

Haznedar

2003

American J Hematol

View full text Add to dashboard Cite

The incidence of thromboembolic events is high as a result of disease, disease-related complications, and therapy in multiple myeloma (MM). In patients with hematologic tumors, impaired fibrinolysis may be present and may contribute to the development of thrombotic complications. Therefore, we designed a study to investigate fibrinolytic activity in MM. We compared plasma levels of interleukin (IL)-6, C-reactive protein (CRP), IL-1b, IL-11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow-up period of 7 months in our myeloma group. Results are given as mean (median, range). Plasma levels of .32] pg/mL versus 2.64 ± 0.66 [1.80, 0.10-11.86] pg/mL, P < 0.001), CRP (45.57 ± 9.92 [21.00,.00] mg/L versus 1.96 ± 0.50 [1.05, 0.19-8.03] mg/L, P < 0.001), PAI-1 (7.40 ± 0.67 [5.57, 2.40-31.80] IU/mL versus 4.73 ± 0.65 [3.60, 2.32-11.00] IU/mL, P < 0.01), GFC score (1.90 ± 0.02 [2, 1-3] versus 2.50 ± 0.14 [3, 1-3], P < 0.001) were increased compared with controls. In patients with MM, the level of IL-6 was positively correlated with CRP (r = 0.66, P < 0.001), IL-1b (r = 0.29, P < 0.05), and PAI-1 (r = 0.35, P < 0.01) and negatively correlated with GFC (r = À0.37, P < 0.01). CRP level was positively correlated with plasma PAI-1 level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = À0.44, P < 0.001). A significant negative correlation between PAI-1 level and GFC (r = À0.75, P < 0.001) was also detected. IL-1b levels were negatively correlated with tPA level (r = À0.26, P < 0.05). These results suggest that patients with myeloma have a decreased fibrinolytic activity mainly because of increased PAI-1 activity. In MM, increased PAI-1 activity seems to be related with elevated IL-6 level. MM should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic activity. Achieving a plateau by means of conventional chemotherapies does not improve the decreased fibrinolytic activity. Am.

show abstract

“…AVWS has been associated mostly with clonal hematoproliferative diseases such as monoclonal gammopathy of uncertain significance (MGUS) (5,6), lymphoproliferative disorders (6,7), and myeloproliferative disorders (6,8). The second and third most common group of disorders associated with AVWS are neoplasia (9,10) and immunological diseases such as systemic lupus erythematosus (11).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Studies with FVIII/von Willebrand Factor Concentrate Can Be a Diagnostic Tool to Distinguish between Subgroups of Patients with Acquired von Willebrand Syndrome

Luboshitz¹,

Lubetsky²,

Schliamser³

et al. 2001

Thromb Haemost

View full text Add to dashboard Cite

SummaryAcquired von Willebrand syndrome (AVWS) has been associated mainly with monoclonal gammopathy of uncertain significance (MGUS), clonal lymphoproliferative or myeloproliferative disorders and autoimmunity. In the present work we studied 6 patients with AVWS: four with MGUS IgG (λ or κ), one with small lymphocytic lymphoma and one with agnogenic myeloid metaplasia (AMM). All the patients underwent a pharmacokinetic analysis at presentation in order to study potential differences in recovery, clearance (CL) or terminal half-life (THL) following administration of von Willebrand factor (VWF) concentrate. In all the patients with AVWS an increase in clearance and a decrease in THL was observed as compared to these parameters in patients with hereditary type 3 von Willebrand disease (VWD). No difference in recovery was observed among the groups. The increase in clearance and the decrease in THL were significantly more pronounced in the group of MGUS patients (57.93 ± 25.6 ml/h/kg, and 1.39 ± 0.5 h, respectively) as compared to these parameters in the AMM (8.06 ml/h/kg, and 6.96 h, respectively) or the lymphoma (4.76 ml/h/kg, and 6.76 h, respectively) patients (p = 0.03 for clearance and 0.001 for THL). These data indicate that the pharmacokinetic analysis can be a useful tool to distinguish between MGUS-related and other causes of AVWS, and to plan an appropriate treatment accordingly.

show abstract

Disturbances in Hemostasis in Patients with B-Cell Malignancies

Cited by 9 publications

References 79 publications

Acquired von Willebrand Syndrome: from Pathophysiology to Management

Acquired von Willebrand Syndrome: from Pathophysiology to Management

Fibrinolytic activity in multiple myeloma

Pharmacokinetic Studies with FVIII/von Willebrand Factor Concentrate Can Be a Diagnostic Tool to Distinguish between Subgroups of Patients with Acquired von Willebrand Syndrome

Contact Info

Product

Resources

About