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Biomedical subjects

Ajay K Kakkar

Publications and source records attributed to Ajay K Kakkar.

At least 19 recordsLinked to original sources
PubMed2006

A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement.

BACKGROUND: Rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders. METHODS AND RESULTS: This randomized, double-blind, double-dummy, active-comparator-controlled, multinational, dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement. Patients (n=873) were randomized to once-daily oral rivaroxaban doses of 5, 10, 20, 30, or 40 mg (initiated 6 to 8 hours after surgery) or a once-daily subcutaneous enoxaparin dose of 40 mg (given the evening before and > or = 6 hours after surgery). Study drugs were continued for an additional 5 to 9 days; mandatory bilateral venography was performed the following day. The primary end point (composite of any deep vein thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality) was observed in 14.9%, 10.6%, 8.5%, 13.5%, 6.4%, and 25.2% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=618, per-protocol population). No significant dose-response relationship was found for efficacy (P=0.0852). Major postoperative bleeding was observed in 2.3%, 0.7%, 4.3%, 4.9%, 5.1%, and 1.9% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=845, safety population), representing a significant dose-response relationship (P=0.0391). CONCLUSIONS: Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement, with the convenience of once-daily oral dosing and without the need for coagulation monitoring. When both efficacy and safety are considered, these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies.

Administration, Oral↗
PubMed2005

Retroperitoneal myolipoma.

BACKGROUND: Myolipoma is a benign tumour in which smooth muscle cells are mixed with adipocytes. CASE PRESENTATION: A 34-year old lady presented with a mass in the right iliac fossa detected on computerised tomographic (CT) scan. Wide excision of the retroperitoneal mass was done. Histopathology showed features of myolipoma. There was no recurrence or metastasis at three years. CONCLUSION: Myolipoma is a rare benign entity; hence a benign course and good prognosis are expected.

Journal Article↗
PubMed2005

Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.

PURPOSE: Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism. PATIENTS AND METHODS: Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups. RESULTS: During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02). CONCLUSION: The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.

Acute Disease↗
PubMed2005

Mechanisms of disease: the impact of antithrombotic therapy in cancer patients.

Venous thromboembolism is a common complication in patients with malignant disease. It is associated with a systemic hypercoagulable state that is secondary to tumor elaboration of tissue factor (the physiological initiator of blood coagulation), activation of other procoagulant mechanisms and downregulation of anticoagulant mechanisms. The consequent generation of activated coagulation serine protease in the peritumoral environment influences tumor growth, invasion, metastasis and angiogenesis. The use of antithrombotic agents, such as the low-molecular-weight heparins, might influence survival in cancer patients through several mechanisms. These mechanisms include a reduction in the frequency of overt and silent fatal thromboembolic events, interference with the activation of blood coagulation and generation of coagulation serine proteases that affect the tumor phenotype, and direct cellular effects of heparin on both epithelial and endothelial tumor elements.

Blood Coagulation↗
PubMed2005

Transdermal estradiol therapy for prostate cancer reduces thrombophilic activation and protects against thromboembolism.

PURPOSE: Oral estrogens were an effective treatment for prostate cancer but were abandoned because of an increased risk of cardiovascular toxicity and particularly thromboembolism. We have recently shown that transdermal estradiol produces an effective tumor response and negligible cardiovascular toxicity. Here we report the influence of transdermal estradiol therapy on the coagulation profile of men with advanced prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated using transdermal estradiol patches and the coagulation profile was assessed before and during 12 months therapy. Activation of coagulation was assessed by assaying the levels of activated factor VII (VIIa), activated factor XII (XIIa), prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin III (TAT III) complex and fibrinogen. Inhibition of the coagulation cascade was assayed by protein C, protein S and activated protein C resistance (APC-R). Fibrinolytic activity was determined by assaying tissue plasminogen activator (TPA) and plasminogen activation inhibitor type 1 (PAI-1). D-Dimer levels assessed both coagulation and fibrinolytic (thrombophilic) activity. Venous Duplex, color Doppler ultrasound and photoplethysmography were used to assess for thrombosis. RESULTS: Levels of VIIa and XIIa were unaffected by transdermal estradiol therapy. Although levels of TAT III were increased in some patients at 12 months, the increase was markedly less than that observed historically with equivalent doses of oral estrogens. Levels of the inhibitory and fibrinolytic factors including protein C, protein S, APC-R, TPA and PAI-1 remained stable. Reductions in F1+F2, fibrinogen and D-Dimer levels represented a normalization from increased levels to the physiological range. CONCLUSIONS: These results suggest that transdermal estradiol reduces thrombophilic activation in men with advanced prostate cancer, and protects against the risk of thrombosis.

Administration, Cutaneous↗
PubMed2005

Prevention of fatal pulmonary embolism and mortality in surgical patients: a randomized double-blind comparison of LMWH with unfractionated heparin.

The incidences of fatal pulmonary embolism and death in surgical patients receiving low-molecular-weight heparin thromboprophylaxis have not been previously determined in large, adequately designed clinical trials and information on the relative efficacy and safety of unfractionated and low-molecular-weight heparin in preventing these clinical endpoints is not available. In a double-blind study, 23078 surgical patients randomly received the low-molecular-weight heparin, certoparin (3000 anti Xa IU) subcutaneously once-daily, or unfractionated heparin (5000 IU) subcutaneously three-times daily, for a minimum of 5 days. The primary outcome measure, autopsy-proven fatal pulmonary embolism recorded up to 14 days after the end of prophylaxis, occurred in 0.152% (95% confidence interval (CI) 0.10, 0.20%; 35 of 23078 patients) of cases, with no significant difference between the certoparin-treated patients (0.147% (95% CI 0.077, 0.217%; 17 of 11542 patients) and patients treated with unfractionated heparin (0.156% (95% CI 0.084, 0.228%; 18 of 11,536 patients, P=0.868). The autopsy rate was 70.2%. Comparing mortality, there was no significant difference between the groups (1 .44% [166 of 11542 certoparin patients] versus 1.27% [146 of 11536 unfractionated heparin patients]; P=0.279). The safety profiles of both treatment groups were similar. Once-daily certoparin and three-times daily unfractionated heparin are equally effective and safe in reducing fatal pulmonary embolism and death to low levels in surgical patients and mirror the findings of comparative efficacy studies using surrogate endpoints.

Adult↗
PubMed2005

Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients: the MC-4 cancer substudy.

Cancer patients undergoing surgery are at a high risk of venous thromboembolism, but few studies have described the rate of autopsy-confirmed fatal pulmonary embolism after heparin thromboprophylaxis. In a post hoc analysis of a randomized study (MC-4), which compared the efficacy and safety of certoparin (3000 anti-Xa IU, subcutaneously, once-daily) with unfractionated heparin (5000 IU, subcutaneously, three-times daily) in 23078 patients undergoing surgery lasting more than 30 min, the incidence of autopsy-confirmed fatal pulmonary embolism, death and bleeding in the cancer patients (n=6124) was compared with non-cancer patients (n=16954). Fatal pulmonary embolism was significantly more frequent in cancer patients (0.33% [20/6124]) than in non-cancer patients (0.09% [15/16954], relative risk (RR), 3.7 [95% confidence intervals (CI), 1.80, 7.77], p=0.0001) at 14 days post-prophylaxis. Perioperative mortality was also significantly higher in cancer patients than in noncancer patients (3.14% [192/6124] vs. 0.71% [120/16954], RR, 4.54 [95% CI, 3.59, 5.76], p=0.0001), as were blood loss (p<0.0001), and transfusion requirements (p<0.0001). Prevention of venous thromboembolism in cancer surgical patients remains a clinical challenge.

Anticoagulants↗
PubMed2004

Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS).

PURPOSE: In experimental systems, interference with coagulation can affect tumor biology. Furthermore, it has been suggested that low molecular weight heparin therapy may prolong survival in patients with cancer. The primary aim of this study was to assess survival at 1 year of patients with advanced cancer. PATIENTS AND METHODS: Patients with advanced malignancy (N = 385) were randomly assigned to receive either a once-daily subcutaneous injection of dalteparin (5,000 IU), a low molecular weight heparin, or placebo for 1 year. RESULTS: The Kaplan-Meier survival estimates at 1, 2, and 3 years after randomization for patients receiving dalteparin were 46%, 27%, and 21%, respectively, compared with 41%, 18%, and 12%, respectively, for patients receiving placebo (P =.19). In an analysis not specified a priori, survival was examined in a subgroup of patients (dalteparin, n = 55; and placebo, n = 47) who had a better prognosis and who were alive 17 months after randomization. In these patients, Kaplan-Meier survival estimates at 2 and 3 years from randomization were significantly improved for patients receiving dalteparin versus placebo (78% v 55% and 60% v 36%, respectively, P =.03). The rates of symptomatic venous thromboembolism were 2.4% and 3.3% for dalteparin and placebo, respectively, with bleeding rates of 4.7% and 2.7%, respectively. CONCLUSION: Dalteparin administration did not significantly improve 1-year survival rates in patients with advanced malignancy. However, the observed improved survival in a subgroup of patients with a better prognosis suggests a potential modifying effect of dalteparin on tumor biology.

Aged↗
PubMed2004

Antithrombotic therapy with low molecular weight heparin in cancer patients.

Thrombosis is a common complication in patients with cancer. Low molecular weight heparins have been shown to be effective in both the prevention and treatment of venous thromboembolism in the cancer patient. More recently, studies have confirmed the benefits of extended duration of LMWH in the primary prevention of VTE after cancer surgery and for up to six months therapy for acute symptomatic VTE treatment. Beyond these well established uses for LMWH in the prevention and treatment of thrombosis in cancer patients, contemporary studies have demonstrated that LMWH therapy can prolong survival in patients with solid tumour malignant disease.

Anticoagulants↗
PubMed2004

Current status of pulmonary embolism in general surgery in Japan.

The true incidence of pulmonary embolism (PE) after general surgery in Japan is unknown. We searched the PubMed and Japana Centra Revuo Medicina 1985-2002 databases, entering "surgery" and "pulmonary embolism" or "thromboembolism", and reviewed the reported incidence of clinical PE associated with general surgery in Japan. The overall incidence of PE after general surgery was 0.33%. Fatal PE was reported in 0.08% of the surgical population and the mortality rate of patients with PE was 31%. The incidence of PE after cancer surgery ranged from 0.57% after colon malignancy to 3.85% after pancreatic cancer surgery, and was significantly higher than that after surgery for noncancerous conditions (0.20%). The incidence of PE after various cancer operations corresponded to a moderate or high risk, as defined by the 6th American College of Chest Physicians consensus recommendations. There was no significant difference in the incidence of PE after laparoscopic and open abdominal surgery. The incidence of PE was four to six times lower in patients who had received mechanical prophylaxis, although the difference was not significant. In conclusion, the incidence of PE in Japanese surgical patients is not as low as previously thought. Perioperative prophylaxis against venous thromboembolism is important, but its benefits need to be confirmed by prospective clinical studies.

Humans↗
PubMed2004

Low- and ultra-low-molecular-weight heparins.

Heparins and low-molecular-weight heparins (LMWHs) have been the mainstay for the prevention and management of venous and arterial thromboembolic disease. In particular, the LMWHs have become well established in the past 15 years for the prevention of thrombosis in medium- and high-risk surgical and medical patients and in the initial management of venous thromboembolism (VTE). They have also been widely evaluated and adopted in clinical practice in the management of patients with acute coronary syndromes. More recently, a variety of heparin-like drugs have been evaluated as potential antithrombotic agents, and the synthetic pentasaccharide (fondaparinux) has been developed and evaluated for the prevention and treatment of VTE.

Heparin↗
PubMed2004

Thrombosis and cancer.

Venous thromboembolism is a common problem in cancer patients. It complicates both the surgical management of those with cancer and has been associated with varying risk for the development of clinical thromboembolism in patients receiving chemotherapy. Unfractionated and low-molecular-weight heparin have been validated both in terms of their efficacy and safety, in the prevention of venous thromboembolic disease in cancer patients undergoing surgical intervention and for the primary treatment and secondary prevention of recurrent venous thromboembolism. Beyond their uses in the prevention and treatment of thrombosis, low-molecular-weight heparins have recently been shown to prolong survival in patients with solid tumour malignancy.

Anticoagulants↗
PubMed2003

Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

BACKGROUND: Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. METHODS: Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). RESULTS: During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. CONCLUSIONS: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.

Acenocoumarol↗
PubMed2003

An expanding role for antithrombotic therapy in cancer patients.

Thromboembolic disease has a negative impact on outcome in the cancer patient. Venous thromboembolism appears to be a more aggressive disease in patients with cancer who present with both a greater thrombus burden and more pronounced derangements of coagulation parameters with non-cancer patients with thrombosis. Restrospective analyses suggest that treatment of venous thromboembolism in cancer patients with low-molecular-weight heparin is associated with additional benefits in terms of their survival. The mechanism for this effect is unclear but may be attributed to a reduced incidence of recurrent thrombosis and fatal pulmonary embolism in those patients with underlying thrombosis. To investigate and potential of low-molecular-weight heparin to prolong survival in cancer patients without underlying thrombosis, a prospective trial (FAMOUS) has evaluated the effect of treatment with the low-molecular-weight heparin dalteparin for 1 year terms of survival of patients with advanced cancer and no underlying thrombosis.

Clinical Trials as Topic↗
PubMed2003

Low-molecular-weight heparins: beyond thrombosis in the management of the cancer patient.

Thrombosis is a common complication in patients with cancer and large, retrospective population-based studies indicate that cancer patients with clinical venous thromboembolism have a poorer prognosis than those without. The risk of thrombosis appears to differ between different tumor types. Beyond the important impact that fatal pulmonary embolism may have on cancer outcome, the activated coagulation serine proteases generated by cancer cells through the peritumor activation of blood coagulation pathways are able to interact with cell surface protease receptors. These, in turn, mediate several cellular events resulting in important phenotypic alterations in tumor cell behavior.

Anticoagulants↗
PubMed2003

Venous thromboembolism in laparoscopic surgery.

Currently there are limited randomized data regarding thromboprophylaxis in laparoscopic surgery. The aim of this article is to identify principles to guide safe practice with regard to prevention of venous thromboembolism. With the exception of laparoscopic cholecystectomy, there are no prospective, randomized studies comparing the incidence of venous thromboembolism between a conventional procedure and a laparoscopic procedure for the same operation. Surveys of surgical practice indicate that policies for venous thromboembolism prophylaxis in laparoscopic surgery are generally the same as those for conventional surgery. The increasing use of a minimal access approach for a variety of abdominal, pelvic, and thoracic procedures demands further prospective, randomized studies in this area. Current guidelines endorsed by The Society of American Gastrointestinal Endoscopic Surgeons recommend following the adoption of protocols used in conventional surgery for the equivalent laparoscopic operation, and the European Association for Endoscopic Surgery has recommended the use of intraoperative intermittent pneumatic compression of the lower extremities for all prolonged laparoscopic procedures. There is only limited evidence to support these recommendations. Venous thromboembolism is an important and preventable complication in surgical patients. Evidence does not exist to consider laparoscopic surgery patients to be at a substantially lower risk for venous thromboembolism than those undergoing conventional procedures. Currently there is a lack of data regarding the prophylaxis against venous thromboembolism in laparoscopic surgery, and the practice is thus opinion based. The authors recommend that the use of standard prophylactic regimens tailored to specific patient populations for conventional operations be adopted for laparoscopic surgery until prospective data are available.

Humans↗