A Composite study of Coagulation Milieu in Covid-19: Experience from a Tertiary Care Centre from India

Author(s):  
Gopal Krishana Bohra ◽  
Abhishek Purohit ◽  
Deepak Kumar ◽  
Mahendra Kumar Garg ◽  
Naresh Kumar Midha ◽  
...  

Background:: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19. Methods: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive – C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease. Results: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, D-Dimer, and hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP). Conclusions: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, D dimer, and hs-CRP were significantly associated with poor outcomes.

2021 ◽  
Author(s):  
Shivkumar Gopalakrishnan ◽  
sangeetha kandasamy ◽  
S.Malini ◽  
S.Peer Mohamed ◽  
k.velmurugan

Abstract Background. Approximately 5% of COVID-19 patients suffer near fatal disease. Clinical and radiologic features may predict severe disease albeit with limited specificity and radiation hazard. Laboratory biomarkers are eyed as simple, specific and point of care triage tools to optimize management decisions.This study aimed to study the role of inflammatory markers in prognosticating COVID-19 patients.Methodology. A hospital based retrospective study was conducted on COVID-19 adult inpatients classified into three groups as mild disease-recovered [Group I], severe disease-recovered [Group II] and dead [Group III]. Categorical outcomes were compared using Chi square test. Univariate binary logistic regression analysis was performed to test the association between the explanatory and outcome variables. Unadjusted OR along with 95% CI was calculated. The utility of lab parameters (Ferritin, LDH, D dimer, N/L ratio and PLT/L ratio) in predicting severity of COVID-19 was assessed by Receiver Operative Curve (ROC) analysis. P value < 0.05 was considered statistically significant.Results. The mean age was 49.32 +/- 17.1 years. Among study population, 378 were Group I, 66 Group II, and 56 Group III. Median levels of Ferritin among the 3 groups were 62ng/mL, 388.50 ng/mL and 1199.50 ng/mL. Median value of LDH were 95U/L, 720 and 982.50(p <0.001). D-dimer values of 3 groups were 23.20ng/mL, 104.30 ng/mL and 197.10 ng/mL (p <0.001). CRP done qualitatively was positive in 2 (0.53%), 30 (45.45%) and 53 (94.64%) of patients. The odds of patients suffering severe COVID-19 rose with rising values of ferritin, LDH and D-dimer [unadjusted OR 1.007, 1.004 &1.020]Conclusion. One time measurement of serum ferritin, LDH, D-dimer and CRP is promising to predict outcomes for COVID 19 inpatients. Single qualitative CRP was equally good but more cost effective than quantitative CRP. The most specific combination was NLR, Lymphocyte percentage and D-dimer levels done between 7th – 10th day of symptoms.


2021 ◽  
Vol 9 (B) ◽  
pp. 692-697
Author(s):  
Arif Hanafi ◽  
Noorwati Soetandyo ◽  
Achmad Mulawarman Jayusman ◽  
Leovinna Widjaja ◽  
Fifi Dwijayanti ◽  
...  

Aim: To describe the clinical data and disease severity of thoracic malignancy patients with COVID-19 and its relation to the mitigation process at the Dharmais National Cancer Center, Indonesia. Methods: Total 5256 cancer patients registered from May 2020 to March 2021. There were 681 cancer patients diagnosed with COVID-19. Forty-five thoracic malignancy patients were enrolled. Data from medical records were obtained at the Dharmais Cancer Hospital, then analyzed using SPSS version 25. Comparative result was considered significant, as p-value < 0.05. Results: There were 12.9% of total patients registered infected by COVID-19, which 6% with thoracic malignancy dominated by Non-small cell lung carcinoma (57.8%). Patients who have asymptomatic (31.1%), mild (13.3%), and moderate COVID-19 disease (8.9%) were alive. Patient with severe disease (46.7%) tend to deteriorate. Neutrophilia (mean 78.0%), lymphopenia (mean 13.0%), high neutrophil to lymphocyte ratio (mean 13.1), hyperuricemia (mean 31.6 mg/dL), high fibrinogen (mean 521.7 mg/dL), and high d-dimer (mean 3821.6 ng/mL) were significantly associated with disease severity (p-value < 0.05). Conclusions: Only small number of cancer patients affected by COVID-19 and mostly do not progress to severe disease, showing the strict mitigation strategy was successful. Severe disease patients have a poor prognosis, with neutrophilia, lymphopenia, high neutrophil to lymphocyte ratio, hyperuricemia, high fibrinogen, and high d-dimer may be valuable for predicting poor prognosis.


2021 ◽  
Vol 27 ◽  
pp. 107602962110276
Author(s):  
Mehmet Gökhan Gönenli ◽  
Zeynep Komesli ◽  
Said İncir ◽  
Özlem Yalçın ◽  
Olga Meltem Akay

Identifying a hypercoagulable state in patients with COVID-19 may help identify those at risk for virus–induced thromboembolic events and improve clinical outcomes using personalized therapeutic approaches. Herein, we aimed to perform a global assessment of the patients’ hemostatic system with COVID-19 using rotational thromboelastometry (ROTEM) and to describe whether patients with different disease severities present different coagulation profiles. Together with 37 healthy volunteers, a total of 65 patients were included and then classified as having mild, moderate, and severe disease depending on clinical severity. Peripheral blood samples were collected and analyzed using a ROTEM Coagulation Analyzer. Also, complete blood count and coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels were measured at admission. EXTEM and INTEM MCF ( P < 0.001) values were significantly higher and the EXTEM CFT ( P = 0.002) value was significantly lower in patients with COVID-19 when compared with controls. In particular, patients with the severe disease showed a significant decrease in CFT ( P < 0.001) and an increase in MCF ( P < 0.001) in both INTEM and EXTEM assays compared with patients with the non-severe disease. Correlation analysis revealed significant correlations between ROTEM parameters and other coagulation parameters. There were significant positive correlations between fibrinogen, D-dimer, platelet count, and MCF in both EXTEM and INTEM assays. Our data demonstrate thromboelastographic signs of hypercoagulability in patients with COVID-19, which is more pronounced in patients with increased disease severity. Therefore, ROTEM analysis can classify subsets of patients with COVID-19 at significant thrombotic risk and assist in clinical decisions.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Mohsin Sheraz Mughal ◽  
Ikwinder Preet Kaur ◽  
Ali R. Jaffery ◽  
Chang Wang ◽  
Muhammad Asif ◽  
...  

Introduction:The underlying pathophysiology of severe COVID-19 involves cytokine storm syndrome that is associated with an elevation of immunoinflammatory cytokines [1]. This hyper-inflammatory state has been implicated with coagulopathy among severely sick patients with COVID-19. Inflammation and coagulopathy are interlinked processes [2]. Coagulopathy has been associated with high mortality in COVID-19 patients [3]. LMWH is traditionally used for its anticoagulant and antithrombotic properties, however, its anti-inflammatory effect has not been fully elucidated. A study done by Shastri et al. suggested that LMWH can inhibit the release of different cytokines (IL-4, IL-5, IL-13, and TNF-α) [4]. Recent retrospective studies on COVID-19 illustrated that the LMWH (40-60 mg, subcutaneously every day) was associated with better prognosis as measured by (28 days of survival) in severely sick patients meeting sepsis-induced coagulopathy (SIC≥4) criteria compared to nonusers [5]. The potential role of escalated/therapeutic LMWH (1mg/kg/subcutaneously every 12 hours) remains unclear. This study involves a retrospective analysis of the potential role of an escalated dose of LMWH to alter the hyper-inflammatory state in hospitalized patients with COVID-19 and compared outcomes to those patients who received a low dose (40-60 mg, subcutaneously every day) of LMWH. Methods:Adult patients with confirmed SARS-CoV-2 infection by nasopharyngeal (NP) polymerase chain reaction (PCR) who were hospitalized from March 1st to April 20, 2020, were included. They were divided into two cohorts based on the dose of LMWH; cohort 1 (40-60 mg, subcutaneously every day) and cohort 2 (1mg/kg/subcutaneously every 12 hours). Categorical variables were compared by conducting a chi-square test or Fisher's exact test while continuous ones were compared by conducting a median two-sample test. Results:The median values of PT, PTT, INR, CRPmax, LDHmax, ferritinmax, D-dimermax, are mentioned in table 1. Incidence of thrombotic events (deep venous thrombosis, ischemic stroke, pulmonary embolism) was higher in cohort 1 (n=3, 4.8%) compared to cohort 2 (n=1, 2.6%). Cohort 2 had a higher number of patients who received ICU level of care (n=24) compared to the 6 patients in cohort 1. Out of 24 patients in cohort 2, 18 patients received invasive mechanical ventilation. The median value of length of stay in the hospital (10.0 days) and all-cause mortality (31.6 %) were higher in cohort 2 as compared to cohort 1 (p&lt;0.05). Discussion:Infections have the ability to trigger systemic inflammation [6]. The interplay between the host system and its response to foreign pathogens can lead to the activation of coagulation pathways. SARS-CoV-2 entry via ACE-2 receptors on endothelial cells is likely associated with endothelial dysfunction. This endotheliopathy plays a significant role in COVID-19 related microcirculatory changes [7]. Severe COVID-19, a hyperinflammatory state, is marked by elevated inflammatory markers including D-dimer, ferritin, IL-6, LDH, and CRP levels. Elevated D-dimer levels have been correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 [8]. The incidence of VTE and pulmonary embolism among COVID-19 ICU patients was higher in a study from France [9]. The patient population who received the escalated dose of LMWH in our study either had SIC score ≥ 4 or D-dimer ≥ 2.2 (FEU). This data indicated that the median value of peak inflammatory markers in cohort 1 was lower (p&lt;0.05) when compared to cohort 2. Patients in cohort 2 were sicker than cohort 1, as evidenced by a statistically significant longer length of hospital stay and a higher rate of ICU admission. However, the potential dose-dependent anti-inflammatory effect of LMWH was not observed. Additional studies evaluating comorbidities and disease severity in both cohorts may yield different results. Conclusion:Aside from the known anticoagulant benefit of LMWH, there was no additional anti-inflammatory role with higher doses (1mg/kg/subcutaneously every 12 hours) of LMWH. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Nathanael Fillmore ◽  
Jennifer La ◽  
Chunlei Zheng ◽  
Shira Doron ◽  
Nhan Do ◽  
...  

Abstract Importance: Since the early days of the pandemic, COVID-19 hospitalizations have been used as a measure of pandemic severity. However, case definitions do not include assessments of disease severity, which may be impacted by prior vaccination.Objective: To measure how the severity of respiratory disease changed among inpatients with documented SARS-CoV-2 infection and to measure the impact of vaccination status on these trends, in order to evaluate the accuracy of the metric of “hospitalization plus a positive SARS-CoV-2 test” for tracking pandemic severity.Design: Retrospective cohort of inpatients with laboratory-confirmed SARS-CoV-2. All data were obtained from electronic health records.Setting: Multi-center, nationwide study conducted in the healthcare system of the US Department of Veterans Affairs (VA) from March 1, 2020, through June 30, 2021.Participants: All VA patients admitted to a VA hospital with a laboratory-confirmed SARS-CoV-2 infection within the 14-days prior to admission or during the hospital admission.Main Outcome: Moderate-to-severe COVID-19 disease, defined by use of any supplemental oxygen or documented SpO2 <94%, during an inpatient hospitalization between one day before and two weeks after a positive SARS-CoV-2 test.Exposure: SARS-CoV-2 vaccination status at the time of hospitalization. Patients were regarded as fully vaccinated starting 14 days after receiving the second of a 2-dose regimen or 14 days after receipt of a single-dose vaccine.Results: Among 47,742 admissions in 38,508 unique patients with laboratory-confirmed SARS-CoV-2, N=28,731 met the criteria for moderate-to-severe COVID-19. The proportion with moderate-to-severe disease prior to widespread vaccine availability was 64.0% (95% CI, 63.1-64.9%) versus 52.0% in the later period (95% CI, 50.9-53.2%), p-value for non-constant effect, <0.001. Disease severity in the vaccine era among hospitalized patients was lower among both unvaccinated (55.0%, 95% CI, 53.7-56.4%) and vaccinated patients (42.6%, 95% CI, 40.6-44.8%).Conclusions and Relevance: The proportion of hospitalizations that are due to severe COVID-19 has changed with vaccine availability, thus, increasing proportions of mild and asymptomatic cases are included in hospitalization reporting metrics. The addition of simple measures of disease severity to the case definition of a SARS-CoV-2 hospitalization is a straightforward and objective change that should improve the value of the metric for tracking SARS-CoV-2 disease burden.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2401-2401
Author(s):  
Emily Bontekoe ◽  
Matthew T. Rondina ◽  
Debra Hoppensteadt ◽  
Elizabeth Middleton ◽  
Antoinette Blair ◽  
...  

Background : Sepsis is characterized by a simultaneous activation of inflammation and hemostasis in response to microbial infection. This systemic inflammatory response is due to the release of pro-inflammatory cytokines, pro-coagulants and adhesion molecules from immune cells and/or damaged endothelial tissue. Simultaneous activation of coagulation and fibrinolysis leads to consumption coagulopathy and severe vascular dysfunction. Profiling of biomarkers of hemostatic activation and inflammation along with the measurement of coagulation parameters has provided useful data in the understanding of the pathogenesis of sepsis. This study was designed to profile biomarkers of hemostatic activation, inflammation and endothelial dysfunction along with the measurement of coagulation parameters in a defined clinically confirmed sepsis population in conjunction with an IRB approved clinical trial. Materials & Methods: Citrated blood samples were collected from sepsis patients with suspected or confirmed infection, and organ dysfunction as defined by a SOFA ³ baseline. Plasma samples from septic shock patients were collected in citrated tubes within 72 hours of ICU admission under an IRB approved protocol in conjunction with an ongoing trial at the University of Utah and Veteran's Affair FFC Health Care System VAMC. Normal controls were comprised of commercially available 25 male and 25 female citrated plasma samples (George King Biomedical, Overland Park, Kansas City). Such biomarkers as CRP, PAI-1, D-Dimer, vWF and microparticle tissue factor complex (MP-TF) were measured using a commercially available sandwich ELISA methods. Nitric oxide (NO) levels were measured using a commercially available Griess reaction based colorimetric method. PT/INR, aPTT and fibrinogen measurements were based on clot based assays. All results were compiled as mean ± SD and SEM. Correlation analysis was carried out to determine relevance between different parameters. Results: Most of the biomarkers of hemostatic activation and inflammation were elevated in patients with sepsis as shown on table 1a, CRP (66 fold) and D-Dimer (23 fold) showed the most pronounced increase in comparison to the control. Other parameters also showed increase levels including MP-TF (5.3 fold), PAI-1 (3.5 fold), vWF (3.1 fold) and NO (3.0 fold). Clotting parameters such as PT/INR (2.0 fold), aPTT (2.5 fold) and fibrinogen (2.0 fold) were also significantly elevated in the sepsis patients. These differences were significant (p value ≤0.0009) for all of the parameters except for NO (p value 0.0937) and fibrinogen (p value 0.4694). As shown on table 1b, there was no correlation between various biomarkers and fibrinogen in the sepsis patients. Summary & Conclusion: In comparison to the control group, the sepsis patients showed wide variations in all of the parameters investigated in this study. The marked prolongation of PT and aPTT are suggestive of both the extrinsic and intrinsic pathway defects and consumption of clotting factors. The aPTT data showed wider scatter in comparison to PT data. The fibrinogen levels were also elevated and nearly 1/3 of the patients showed >1000 mg/dL levels. The markedly higher level of CRP in the sepsis group are indicative of severe inflammatory response. Marked elevation of D-Dimer is indicative of endogenous fibrin formation and its consumption consistent with activation of secondary fibrinolysis. MP-TF, vWF and PAI-1 were also increased in the sepsis patients suggesting marked endothelial dysfunction. This is consistent with increased NO levels which may be due to induction of iNOS in the endothelial lining of sepsis patients. These results further underscore the multifactorial pathophysiology of sepsis which results in the dysregulation of hemostasis, upregulation of inflammatory responses and generalized endothelialopathy. Profiling of the biomarkers included in this study and coagulation parameters may be helpful in the risk stratification and clinical management of patients with sepsis and related disorders. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4959-4959
Author(s):  
Jitender Khunger ◽  
Monica Malhotra ◽  
Nitin Kumar ◽  
VPS Punia ◽  
Mohan Agarwal

Introduction: The metabolic syndrome is a complex disorder characterized by the presence of a clustering of metabolic risk factors usually in a single individual associated with the presence of central obesity and a strong association with diabetes and cardiovascular disease morbidity and mortality. It is a fast spreading global pandemic & emerging as a public health problem with poor outcome and Quality of life thus more predilection is towards preventive than curative treatment. According to WHO Clinical Criteria, Metabolic syndrome is defined as insulin resistance, identified by 1 of the following, Type 2 diabetes, fasting blood glucose more than 110 mg/dl plus any 2 of the following: antihypertensive medication and /or high blood pressure > 140 mm systolic or >90 mm diastolic, plasma triglyceride (TG) level more than 150 mg/dl (1.7 mmol/L), high-density lipoprotein (HDL) cholesterol level less than 35 mg/dl (0.9 mmol/L) in men or less than 39 (1.0 mmol/L)in women , BMI >30 kg/m2 and/or waist:hip ratio >0.9 in men, > 0.85 in women, Urinary albumen excretion rate > 20 mcg/min or albumin:creatinine ratio>30mg/g Aims & Objectives: To investigate the coagulation profile derangements in metabolic syndrome. To study the relationship of various components of metabolic syndrome with coagulation parameters. Material & Methods: This was a prospective cross-sectional study carried out in Haematology & Medicine Deptt of SafdarJang Hospital, New Delhi. After taking consent from the Hospital Ethics Committee, a total of 50 cases of metabolic syndrome presenting as outpatient or inpatient were included in the study. 50 age & sex matched controls were selected which did not satisfy the criteria for metabolic syndrome. Observation & Results: In our study we found that the cases with metabolic syndrome have significantly increased levels of Fibrinogen, Factor VIII and Plasminogen Activator Inhibitor1 (PAI1). PT & APTT were shorter in cases with metabolic syndrome. The mean value of fibrinogen in cases was 402.24 ± 66.92 mg/dl while that in control was 261.5 ± 41.95 mg/dl with a P value of <.0001 which was statistically significant. The mean value of Factor VIII in cases was 152.66 ± 7.54 IU/dl while that in control was 131.44 ± 6.24 IU/dl with a P value of <.0001 which was statistically significant. The mean value of Plasminogen Activator Inhibitor1 (PAI1) in cases was 49.99 ± 5.34 ng/ml while that in control was 36.75 ± 3.35 ng/ml with a P value of <.0001 which was statistically significant. Prothrombin Time (PT) values in cases were 9.79 ± 0.74 seconds and in controls were 12.04 ± 0.7 seconds & this difference was statistically significant (p<.0001). Activated partial Thromboplastin Time (APTT) values in cases were 28.96 ± 0.92 seconds and in controls were 32.6 ± 1.34 seconds & this difference was statistically significant (p<.0001). Conclusions: The coagulation parameters studied correlated significantly with the components of metabolic syndrome. The values varied significantly with increased number of features of metabolic syndrome. Thus we can conclude that metabolic syndrome is a hypercoagulable state and further studies are required for further evaluation of the consequences of this hypercoagulable state.. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 8 (4) ◽  
pp. 461-464
Author(s):  
Vineet Banga ◽  
Stuti Jain

Patients of Covid 19 infections present with different severity. Levels of D Dimer in these patients can be correlated with disease severity for management and prognosis. To evaluate the usefulness of D-Dimer levels in blood to correlate with disease severity in COVID 19 patients. Retrospective study was done in Department of Pathology of Secondary Care hospital that became designated covid hospital from May 2021 to June 2021 on 60 COVID 19 positive admitted patients. D dimer levels were analysed and correlated with clinical severity of disease. Out of total 60 patients, 33 were in mild, 23 in moderate and 4 were in severe category. In mild cases D Dimer varies from 43 ng/ml to 183 ng/ml. In moderate cases D Dimer varies from 270 ng/ml to 991 ng/ml. In severe cases D Dimer varies from 1043 ng/ml to 2463 ng/ml. The study suggests cut off levels for D Dimer as up to 200 ng/ml for mild, 200-1000 ng/ml for moderate and more than 1000 ng/ml for severe category in COVID 19 patients. D dimer helps in identifying severe disease and can be used as an essential biomarker in developing the management protocol for COVID 19 patients.


2021 ◽  
Author(s):  
Jing Li ◽  
Mingyang Tang ◽  
Didi Liu ◽  
Fengchao Wang ◽  
Yanqing Yang

Abstract Background: Coronavirus disease-2019 (COVID-19) has become a worldwide emergency and has had a severe impact on human health. Inflammatory factors have the potential to either enhance the efficiency of host immune responses or damage the host organs with immune overreaction in COVID-19. Therefore, there is an urgent need to investigate the functions of inflammatory factors and serum markers that participate in disease progression. Methods: In total, 54 COVID-19 patients were enrolled in this study. Disease severity was evaluated by clinical evaluation, laboratory tests, and computed tomography (CT) scans. Data were collected at: admission, 3–5 days after admission, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection became negative, and composite endpoint. Results: We found that the positive rate in sputum was three times higher than that in throat swabs. Higher levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (D-D), interleukin-6 (IL-6) and neutrophil-to-lymphocyte (NLR) or lower lymphocyte counts suggested more severe disease, and the levels of cytokines and serum markers were intrinsically correlated with disease progression. When SARS-CoV-2 RNA detection became negative, the receiver operating characteristic (ROC) curve demonstrated that LDH had the highest sensitivity independently, and four indicators (NLR, CRP, LDH, and D-D) when combined had the highest sensitivity in distinguishing critically ill patients from mild ones. Conclusions: Monitoring dynamic changes in NLR, CRP, LDH, IL-6, and D-D levels, combined with CT imaging and viral RNA detection in sputum, could aid in severity evaluation and prognosis prediction and facilitate COVID-19 treatment.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2561-2561 ◽  
Author(s):  
Michael J. Kovacs ◽  
Judy-Anne W. Chapman ◽  
Lois Shepherd ◽  
Ralph Meyer ◽  
Michael Keeney ◽  
...  

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


Sign in / Sign up

Export Citation Format

Share Document