Assessment of Thalidomide Therapy Effect on Platelet Activation and Selected Blood Coagulation Parameters in Multiple Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5181-5181
Author(s):  
Marta Robak ◽  
Jacek Trelinski ◽  
Krzysztof Chojnowski
Keyword(s):  
Multiple Myeloma ◽  
Platelet Count ◽  
Factor Viii ◽  
Platelet Activation ◽  
Factor Vii ◽  
Control Group ◽  
High Dose ◽  
Closure Time ◽  
Therapy Effect ◽  
D Dimer

Abstract Background: Patients with multiple myeloma are at relatively high risk of developing thromboembolic events (TEE). These life-threatening complications may arise from hypercoagulability associated with malignancy and/or may be connected with anticancer therapy. The risk of developing TEE appears to be particularly high during treatment with thalidomide alone or combined with chemotherapy and/or high-dose dexamethasone. The pathogenesis of thalidomide-related thrombosis in myeloma patients remains unexplained. Some authors suggest that platelet activation can contribute to development of this complication in multiple myeloma patients on thalidomide therapy but until now it has not been a subject of investigation. Patients and methods: The study was performed in 20 patients with multiple myeloma. The tests were done at diagnosis and after one month of thalidomide therapy at a dose of 100–200 mg/24h. All patients had normal renal function and did not take drugs affecting platelet function. The control group consisted of 15 healthy subjects of similar age. In each patient closure time with ADP/Collagen and Epinephrine/Collagen cartridges by PFA-100 method was assessed. Platelet expression of membrane activation marker P-selectin (CD62p) on resting platelets and after stimulation with ADP/Collagen and Epinephrine/Collagen was analyzed by flow cytometry. Additionally, activity of factor VII, factor VIII and von Willebrand factor (vWF), concentration of fibrinogen and D-dimer, and platelet count were evaluated. Results: The mean PFA-100 closure time was significantly shortened with ADP/Collagen (87.2 ±17.1 s vs 100.4 ± 19.3 s, p=0.008) and Epinephrine/Collagen cartridges (118.5 ± 20.3 s vs 132.2 ± 27.9 s, p=0.04) after one month of therapy in comparison to baseline. The median CD62p percentage increased markedly after treatment-on resting platelets 5.1 (0.76–22.2) vs 3.6 (0.1–21.5) p=0.03. and after stimulation with Epinephrine/Collagen 16.6 (2.3–57.3) vs 11.1 (1.4–19.5) p=0.03. The observed increased P-selectin expression after ADP/Collagen stimulation 26.3 (8.5–42.8) vs 19.7 (1.0–35.4) was not statistically significant. The median values of P-selectin expression at diagnosis and after thalidomide therapy were also higher than in the control group. The results of factor VIII, vWF activity, fibrinogen and D-dimer concentration did not differ markedly before and after therapy. Significantly lower mean activity of factor VII (p=0.004) and higher mean platelet count (p=0.03) after therapy were observed. Conclusions: These results demonstrate that platelet activation is one of the pathogenetic factor of thalidomide-related thrombotic complications and can explain some observations that acetylsalicylic acid may protect against TEE during myeloma treatment with thalidomide.

Changes in Platelet Aggregability after Ovariectomy

1979 ◽  
Vol 42 (04) ◽  
pp. 1332-1339 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Takeshi Motomiya ◽  
Minoru Sonoda ◽  
Noboru Miyagawa
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Ovarian Hormones ◽  
Control Group ◽  
Platelet Aggregability ◽  
Appearance Rate ◽  
Before And After ◽  
The Difference ◽  
Induced Aggregation ◽  
Observation Period

SummaryChanges in platelets in 48 patients with uterine myoma before and after hysterectomy with and without ovariectomy were examined. Bilateral ovariectomy in 25 cases (ovariec-tomized group) and unilateral or non-ovariectomy in 23 cases (control group) were performed at the hysterectomy. Platelet count and an appearance rate of secondary aggregation decreased at one day after and increased at one week after the operation, similarly in both the ovariectomized and the control group. The appearance rate of secondary aggregation was reflected in an intensity of aggregation at 5 min after the addition of reagent to PRP. At one month after the operation, the appearance rate of secondary aggregation induced by 3 μM ADP showed a statistically significant decrease in comparison with the preoperation value (P <0.05) and the enhancement of 5-min aggregation was still observed in the control group, while ceased in the ovariectomized group. The difference between the two groups was significant (P < 0.05). There was almost no change in the speed and intensity of primary and secondary aggregation during the observation period. No significant differences in collagen-induced aggregation were noted between the two groups. The results suggest that ovarian hormones, mainly estrogen, facilitate platelet activation which is mediated by the so-called secondary aggregation.

Calculation of Predictive Odds for Possible Carriers of Haemophilia

1975 ◽  
Author(s):  
G. D. Forbes ◽  
A. D. McLaren ◽  
C. R. M. Prentice
Keyword(s):  
Biological Activity ◽  
Discriminant Analysis ◽  
Factor Viii ◽  
Factor Vii ◽  
Control Group ◽  
Posterior Odds ◽  
Linear Discriminant ◽  
Bayesian Calculation ◽  
Using Data ◽  
Betting Odds

The predictive odds for possible carriers of haemophilia have been calculated using data derived from normal and known carrier populations. For each individual the concentration of factor VII-related antigen (A) and factor VIII biological activity (B) was measured. The data has been studied by linear discriminant analysis linked to a Bayesian calculation of posterior odds using the predictive distributions of both the normal and obligatory carrier populations. The proportion of possible carriers assigned to the definite carrier group or control group is dependent on which betting odds are regarded as most suitable for counselling patients. For instance, if betting odds of 5 : 1 were given it was possible to assign 22 of 32 possible carriers (69 per cent) to control or carrier groups. Of this group of 22 possible carriers, 11 were thought to be normal and 11 were thought to be haemophilia carriers.

scholarly journals Correlation of coagulation markers with axillary lymph node metastasis in breast malignancy: a tertiary care centre study in North India

2020 ◽  
Vol 7 (4) ◽  
pp. 1045
Author(s):  
Vaibhav Srivastava ◽  
Nandan Rai ◽  
Shabi Ahmad ◽  
Vikram Singh ◽  
Shirish Kumar
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Factor Viii ◽  
Sentinel Node ◽  
Factor Vii ◽  
Carcinoma Breast ◽  
Node Metastasis ◽  
Node Biopsy ◽  
D Dimer

Background: Breast cancer is the most common female cancer worldwide representing nearly a quarter (25%) of all cancers. Search for a marker which can predict lymph node metastasis in clinically negative axilla has been a matter of research for long. The present study is an attempt to evaluate role of coagulation makers with special reference to D-dimer and factor 7 and 8 in patients of carcinoma breast in predicting lymph node metastasis in carcinoma patients.Methods: The study was a prospective study conducted in 50 diagnosed patients of carcinoma breast in whom D dimer levels and factor 7 and 8 levels were measured at the time of commencement of the treatment and at six weeks after surgery.Results: Most of the patients in the study group were in the age group 41-70 (80%) years. 22% patients were of early Breast cancer. The reduction in D-dimer, factor VII and factor VIII value after 6 weeks of surgery were significant (p value 0.0001 for all three).Conclusions: D-dimer and factor VII were found to be an independent predictive factor for lymph node metastatsis, thus providing as a safe, easy, objective and convenient supplement to sentinel node biopsy in assessing metastatic disease in axilla. Combined- with other biomarkers, it may prove to be an alternative to sentinel node biopsy in assessing metastatic disease in axilla. Significant postoperative decrease in D-dimer, factor VII and factor VIII may provide objective criteria to assess completion of surgery.

N-Acetylcysteine Treatment in Two Patients with Relapsed Thrombotic Thrombocytopenic Purpura Increased ADAMTS13 Activity, Free Thiol Concentration in Plasma, and Inhibited Platelet Activation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 239-239
Author(s):  
Junmei Chen ◽  
Tahsin Özpolat ◽  
Colette Norby ◽  
Jennie Le ◽  
Minhua Ling ◽  
...  
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Platelet Activation ◽  
Research Funding ◽  
Specific Activity ◽  
High Dose ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Free Thiol

Abstract Introduction: Thrombotic thrombocytopenic purpura (TTP) is a catastrophic and potentially fatal disorder caused by systemic microvascular thrombosis due to von Willebrand factor (VWF)-platelet thrombi. TTP is caused by congenital or acquired deficiency of the plasma metalloprotease ADAMTS13. Based on an earlier study (Chen J et al., J Clin Invest 2011, 121:593-603), we proposed N-acetylcysteine (NAC) as an adjunct treatment for TTP. This study showed that NAC reduced the size and activity of VWF in vitro in human plasma and in vivo in a TTP mouse model. In 2013 and 2014, two case reports described treatment of refractory TTP patients with NAC, one receiving a low dose of NAC [300 mg/kg (total 15 g) for the 1st 24 hrs, followed by 2.5 g/day for two weeks concurrently with plasma exchange] (Shortt J et al., N Engl J Med 2013, 368: 90-92; Shortt J et al., Transfusion 2014, 54:2362-2363) and the other receiving high-dose NAC [300 mg/kg/day (11 g/day) for 10 days between plasma exchanges] (Li GW et al. Transfusion 2014, 54: 1221-1224). The patient treated with high-dose NAC improved rapidly (the patient woke up from coma 18 hr after NAC treatment was initiated), but the patient treated with lower dose NAC did not appear to respond. Thus, it is as yet unclear whether NAC is an effective treatment for TTP. Therefore, more clinical studies and detailed analyses are required to examine the effects of NAC in TTP patients. Here we report the results of clinical and biochemical studies on two patients with relapsed TTP treated with NAC. Before, during, and after NAC treatment, we determined the concentrations of NAC, cysteine, and glutathione in plasma; VWF concentration, multimer structure, and functions; ADAMTS13 concentration and activity; and platelet counts and activation status (P-selectin expression and phosphatidylserine exposure). Methods: Two females with a history of prior episodes of TTP presented with acute TTP [ADAMTS13 < 10%, positive for ADAMTS13 inhibitors, platelet count ≤ 10,000/uL, lactate dehydrogenase (LDH) > 600 IU/L] and both were treated with NAC per IRB-approved protocol [150 mg/kg bolus over 1 hr and 150 mg/kg as continuous infusion until the next therapeutic plasma exchange (TPE)]. They received daily TPE until their platelet counts normalized, and intravenous NAC during days 2-5. Blood was collected daily for 8 days for research assays. ADAMTS13 concentrations in patient plasma were measured by ELISA. ADAMTS13 activity was measured using HRP-conjugated A2 peptide substrate (Wu J-J et al. J Thromb Haemost 2006, 4:129-136). Concentrations of NAC, total cysteine, and total free thiols (free thiol cysteine and free thiol NAC) in plasma were determined by mass spectrometry. Plasma VWF multimer patterns were analyzed by 1.5% agarose gel electrophoresis followed by western blotting with an HRP-conjugated polyclonal VWF antibody. Platelets in whole blood were labeled for platelet markers (CD41a or CD42b) together with one of the activation markers, P-selectin or phosphatidylserine (lactadherin). The labeled platelets were analyzed by flow cytometry. Results: Platelet counts in both patients started to increase 1 day after NAC infusion and continued to increase after discontinuation of NAC and TPE. After NAC infusion, the free thiol concentration (NAC and cysteine) in plasma increased 4 and 59 fold in patients 1 and 2, respectively. This was accompanied by increasing ADAMTS13 specific activity (ADAMTS13 activity/ADAMTS13 antigen). In patient 1, the specific activity increased from 127% (prior to NAC infusion but after TPE) to 270% during NAC infusion; in patient 2, the specific activity increased from 56% to 86%. In patient 1, the VWF multimer size decreased during NAC treatment and the VWF multimers migrated slightly faster. NAC also appeared to inhibit platelet activation. Before NAC infusion, the platelets in both patients were positive for phosphatidylserine (PS, > 30%) and P-selectin (> 15%), compared to 2% and 5%, respectively, in a normal control. The percentages of PS- and P-selectin-positive platelets decreased to less than 18% and 10% respectively, during NAC treatment. Summary: NAC treatment of two patients with TTP in conjunction with TPE was well tolerated and associated with recovery of platelet count and LDH, increased ADAMTS13 specific activity and total free thiol concentration in plasma, reduced platelet activation, and decreased VWF multimer size in one patient. Disclosures Konkle: CSL Behring: Consultancy; Pfizer: Consultancy; Baxalta: Consultancy, Research Funding; Biogen: Consultancy, Research Funding; Octapharma: Research Funding; Novo Nordisk: Consultancy.

scholarly journals Prospective, Randomized, Multicenter, Controlled Trial (TRIATHRON 1) on a New Antithrombogenic Hydrophilic Dialysis Membrane

2017 ◽  
Vol 40 (5) ◽  
pp. 234-239 ◽  
Author(s):  
Claudio Ronco ◽  
Alessandra Brendolan ◽  
Federico Nalesso ◽  
Monica Zanella ◽  
Massimo De Cal ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Removal Rate ◽  
Controlled Trial ◽  
Control Group ◽  
Platelet Factor ◽  
Reduction Test ◽  
Randomized Clinical Study ◽  
Significant Difference ◽  
Heparin Reduction

Introduction Hemodialysis treatment requires anticoagulation to prevent thrombosis of the dialyzer. The Hydrolink® (NV series; Toray) has been designed to reduce thrombotic complications by increasing membrane hydrophilic properties. Previous studies have confirmed reduced platelet activation, improved removal of β2-microglobulin and excellent small-solute removal. Methods We designed a prospective, multi-centered, randomized clinical study to compare the antithrombogenic effects (platelet count) of NV dialyzers versus conventional treatment. To compare the possibility of performing heparin-free dialysis, we carried out progressive heparin reduction tests. Patients with an average platelet count lower than 170,000 cells/mm3 using standard high flux membranes in the 6 months prior to the study were enrolled and randomized. Patients were either dialyzed for 6 months without changing the previous membrane (control group) or treated with the Hydrolink® membrane (NV group). After the third week, the heparin reduction test was conducted for 5 weeks in order to assess the minimum amount of anticoagulant needed to safely perform a 4-hour dialysis treatment. Performance and safety were evaluated measuring platelet count and activation, middle-molecule removal rate and nutritional status. Results We found no significant difference in platelet count, platelet activation factors β-thromboglobulin and platelet factor 4 (PF-4), between the groups. More patients in the study group reached heparin-free dialysis without clotting events during the heparin reduction test. The NV dialyzers displayed anti-thrombogenic effects as compared to conventional dialyzers. Conclusions The NV dialyzer series is safe with no adverse events reported. Further studies are required to understand the mechanisms of anti-thrombogenic effects.

Platelet function in cats with hyperthyroidism

2020 ◽  
Vol 22 (12) ◽  
pp. 1214-1218
Author(s):  
Elizabeth C Hiebert ◽  
David L Panciera ◽  
Katie M Boes ◽  
Lara Bartl
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Control Group ◽  
Closure Time ◽  
Function Analyzer ◽  
The Mean ◽  
Platelet Function Analyzer ◽  
Von Willebrand ◽  
Willebrand Factor

Objectives Cats with hyperthyroidism have been reported to develop thromboembolism, with and without echocardiographic abnormalities consistent with hyperthyroidism. The objective of this study was to compare platelet function in cats with hyperthyroidism with euthyroid age-matched cats. We hypothesized that cats with hyperthyroidism have shortened collagen and adenosine diphosphate (C-ADP) closure times as measured with the platelet function analyzer (PFA-100) in comparison with healthy, age-matched controls. Methods Sixteen hyperthyroid and nine euthyroid healthy cats >7 years of age were recruited from the hospital population. Platelet function, measured using the C-ADP closure times by the PFA-100, and platelet count were measured in healthy euthyroid cats and cats with hyperthyroidism. Results Mean ± SD closure times were not significantly different between control (66.3 ± 9.6 s) and hyperthyroid cats (65.9 ± 11.5 s; P = 0.75). The mean ± SD closure times of hyperthyroid cats that either were untreated or received methimazole for ⩽3 weeks (n = 6; mean 68.5 ± 15.4 s) was not different than that of cats treated for >3 weeks (n = 10; mean 64.3 ± 8.9 s; P = 0.57). The mean automated platelet count was higher in the hyperthyroid group than in the control group ( P = 0.023). Conclusions and relevance Platelet function, as measured by closure time under high shear conditions using C-ADP as an agonist, was not affected by hyperthyroidism in this group of cats. Further research is needed to determine if a hypercoagulable state exists in hyperthyroid cats and the potential roles platelets and von Willebrand factor may have.

scholarly journals Intravascular Clotting After Endotoxin in Rabbits With Impaired Intrinsic Clotting Produced by a Factor VIII Antibody

Blood ◽  
1973 ◽  
Vol 42 (4) ◽  
pp. 523-534 ◽  
Author(s):  
S. M-C. Shen ◽  
S. I. Rapaport ◽  
D. I. Feinstein
Keyword(s):  
Factor Viii ◽  
Rabbit Model ◽  
Saline Group ◽  
Factor Vii ◽  
Test Material ◽  
Control Group ◽  
Inert Material ◽  
Factor V ◽  
Mean Values ◽  
Human Factor Viii

Abstract A rabbit model in which intrinsic clotting was selectively impaired by injection of a human factor VIII antibody was used to evaluate the mechanism of endotoxin-induced intravascular clotting in cortisone-treated rabbits. Three groups of animals were studied: a control group given factor VIII antibody followed by saline; a second control group given an inert material followed by endotoxin; and an experimental group given factor VIII antibody followed by endotoxin. The following parameters were measured: 125I-fibrinogen kinetics, fibrinogen levels, factor VIII, factor VII, factor V, WBC, platelets, and hematocrit. The kidneys were examined for deposition of fibrin. Mean values for factor VIII at the time of injection of the second test material and mean values for fibrinogen consumed in the 6 hr after the second injection were as follows: antibody-saline group, 8.5% and 11.0 mg/kg; control material-endotoxin group, 90% and 29.6 mg/kg; and antibody endotoxin group, 7.0% and 32.7 mg/kg. Factor V, factor VII, granulocytes, and platelets fell in both groups of animals given endotoxin. One animal in each group given endotoxin developed gross renal cortical necrosis. These data establish that selective impairment of the intrinsic clotting reactions does not reduce the amount of clotting induced by a single injection of endotoxin in the cortisone-treated rabbit.

Prothrombotic profile in multiple myeloma: Response to treatment and associated thrombotic complications: A prospective observational study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19531-e19531
Author(s):  
Dipanjan Panda ◽  
Atul Sharma ◽  
Vinod Raina ◽  
Lalit Kumar ◽  
Renu Saxena ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Observational Study ◽  
Factor Viii ◽  
Protein C ◽  
Prospective Observational Study ◽  
Indian Population ◽  
Protein S ◽  
Post Treatment ◽  
Factor Vii ◽  
Low Protein

e19531 Background: Venous thromboembolism (VTE) is a major complication of Multiple myeloma. The exact cause of thrombosis, role of anti myeloma drugs especially immunomodulators and steroids and the relation of thrombosis with alteration of thrombotic profile is not clear. While some available data is suggestive of low incidence of VTE in Asian population, true incidence and risk factors of VTE in Indian population is not known.So the present study was undertaken to have an evaluation of prothrombotic factors in Indian population. Methods: A prospective observational study was conducted from July 2008 to November 2009 at All India Institute of Medical Sciences (AIIMS), New Delhi, India. Thirty patients of newly diagnosed myeloma were recruited and were treated with thalidomide and dexamethasone for 4 months. Prothrombotic profile including protein Cand S, activated protein C resistance, plasma fibrinogen, factor VII and von Willebrand factor level was measured and Doppler study was done at baseline and after 4 months. Statistical analysis was done using SPSS 15 software. Frequency distribution, mean, median, range, standard deviation, Inter Quartile Range were calculated. To find out difference between pre and post treatment, Macnemar chi-square test (for proportion) and paired t test (mean) were done. Results: At the base line 4 patients (13%) had low protein C, 3 (10 %) had low protein S and 2 patients (6%) had high factor VIII. Post induction therapy 7 patients showed low protein C, 1 had low protein S and 1 had high factor VIII value. Rest of the factors was within normal limit both at baseline and post treatment in other patients. During the study period 2 subjects developed DVT. While one had low protein S, other patient had low protein C and low anti thrombin III which was done to find out the cause of DVT. Conclusions: Incidence of DVT in our patients seems to be less than western published data. Although thrombotic factors abnormalities are present in myeloma patients but the relation of coagulation factor abnormalities and development of DVT require further study. A larger prospective trial may be required to get a clear picture.

Abstract P357: Induction Of Soluble P-selectin And CD40 Ligand And, FXIII Deficiency Promote Aberrant Coagulation And Thromboembolism In Severe COVID-19

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Abaher O Al-Tamimi ◽  
Ayesha M Yusuf ◽  
Manju N Jayakumar ◽  
Abdul W Ansari ◽  
Mona Elhassan ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Thrombus Formation ◽  
Plasminogen Activator Inhibitor ◽  
Cd40 Ligand ◽  
Control Group ◽  
Soluble P ◽  
D Dimer ◽  
Fxiii Deficiency

Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19. However, the underlying pathomechanisms are largely undefined. Here, we sought to identify the potential underlying molecular mechanisms of SARS-CoV-2 mediated coagulopathy and thromboembolism. In this series, 30 hospitalized COVID-19 patients presenting elevated D-dimer with (severe cases that required intensive care) or without pneumonia (moderate cases) were included in the study. Patients with anticoagulant/ antiplatelet therapy or with a history of cardiovascular diseases were excluded. Phenotypic and molecular characterizations were carried out employing basic coagulation tests, flow cytometry-based multiplex assays, and ELISA. The findings revealed slightly higher prothrombin and activated partial thromboplastin times (aPTT) with normal platelet counts. Elevated levels of plasma P-selectin and CD40 ligand (CD40L), markers of platelet activation, were observed in the moderate COVID-19 cases which were significantly abolished with the progression of COVID-19 severity. Moreover, analysis of the coagulation pathways revealed comparable FIX, prothrombin, and anti-thrombin levels, and a significantly higher level of fibrinogen was observed in both the moderate and severe patients vs. control group. Interestingly, the levels of plasma tissue factor pathway inhibitor (TFPI) and FXIII, a regulator of stable thrombus formation, were significantly lower particularly in the severe COVID-19 cases. Moreover, a dysregulated fibrinolysis was indicated by elevated tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), and D-dimer levels in COVID-19 cases. In summary, SARS-CoV-2 infection-mediated endothelial cell lining damage potentially enhances soluble P-selectin and CD40L levels inducing platelet activation. Furthermore, in severe COVID-19, a decreased level of TFPI possibly contributes to additional thrombin generation through activation of the TF pathway and provides positive feedback to platelet activation and thrombus formation. FXIII deficiency plays a key role in thrombus instability which most likely promotes thromboembolism in the severe COVID-19.

Maintenance Therapy with Thalidomide/Prednisone Post Autologous Stem-Cell Transplant for Patients with Multiple Myeloma Elevates D-Dimer and Possibly Factor VIII Levels.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2561-2561 ◽  
Author(s):  
Michael J. Kovacs ◽  
Judy-Anne W. Chapman ◽  
Lois Shepherd ◽  
Ralph Meyer ◽  
Michael Keeney ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Factor Viii ◽  
Stem Cell Transplant ◽  
Clinical Laboratory ◽  
P Value ◽  
Cell Transplant ◽  
Increased Risk ◽  
D Dimer

Abstract Background: Thalidomide is commonly used for the treatment of multiple myeloma (MM). Several studies have observed that venous thromboembolism (VTE) is a complication for up to 10% of patients receiving thalidomide therapy, especially when used as combination chemotherapy as part of primary treatment. Elevated Factor VIII and D-dimer levels are well described markers of thrombin generation and for an increased risk of VTE. The purpose of this study was to assess whether MM patients allocated to receive maintenance therapy with thalidomide and prednisone (thal/pred) post stem cell transplant for MM have increased levels of Factor VIII and D-dimer as laboratory confirmation for the reported increased clinical occurrence of VTE with thalidomide therapy. Methods: This is a correlative sub-study of NCIC CTG MY.10 which is an open-label randomized multicentre trial assessing the efficacy (time to progression) of maintenance therapy with the combination of thalidomide 200mg/day and prednisone 50mg every other day compared to no maintenance therapy post stem cell transplant. No clinical outcomes are available at this time as the study is ongoing. This laboratory companion study was incorporated in MY.10 a priori. Eligible patients were registered and randomized 60–100 days post transplantation. All consenting patients had plasma samples collected and frozen at baseline and two months post study enrollment. An unmatched comparison by MY.10 treatment arm was performed to assess the change in D-dimer and Factor VIII from baseline to two months for the first 79 patients entered into the trial. Results: There were 37 patients allocated to thal/pred (28 males, 76%) and 42 on observation (29 males, 69%). The mean ages were 56.6 and 55.8 years respectively. Based on continuous log D-dimer and log Factor VIII using two-way ANOVA, the results are shown in Table 1. Since D-dimer is also reported as positive or negative (&lt;200 or =/&gt;200μg/l) this was also assessed and the results as shown in Table 2. D-dimer results were significantly different (Bonferroni, p = 0.05) at two months compared with baseline for patients allocated to thal/pred rather than observation alone. At two months there were also significantly more patients allocated to thal/pred who had elevated D-dimers, 13 (72%) versus 5 (28%), (Bonferroni p &lt; 0.05). There was a trend towards higher Factor VIII levels in patients allocated to thal/pred than on observation. Conclusion: These results provide clinical laboratory evidence of thrombin activation with the use of thal/pred post autologous transplant in patients with MM, and offer a potential mechanism, as well as, potential predictive markers for the clinical observations to date that patients receiving treatment with thalidomide for MM have an increased risk of VTE. Table 1 Mean Unadjusted Baseline 2 months p-value thal/pred Observation thal/pred Observaton (D-dimer μg/l) 119 101 137 75.6 0.03 FVIII (units/ml) 1.25 1.30 1.60 1.26 0.09 Table 2 D-dimer # ≥200(μg/l) Unadjusted p-value N thal/pred Observation Pearson Exact Chi-square Fisher Baseline 23 10 (43%) 13 (57%) 0.70 0.81 At 2 months 18 13 (72%) 5 (28%) 0.01 0.02

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