Witold Tomkowski

Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial.

Abstract Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism. Design Double blind randomised placebo controlled trial. Setting 35 centres in eight countries. Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days. Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days. Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month. Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died. Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.

Vena Cava Filter Occlusion and Venous Thromboembolism Risk in Persistently Anticoagulated Patients: A Prospective, Observational Cohort Study

BACKGROUND Inferior vena cava (IVC) filter placement may be life-saving, but after contraindications to anticoagulation remit, patient management is uncertain. METHODS We followed patients who had venous thromboembolism, followed by treatment with permanent IVC filter placement, and were anticoagulated long-term as soon as safety allowed. We conducted annual physical examinations and ultrasound surveillance of the lower extremity deep veins and of the IVC filter site. Clot detected at the filter site was treated with graded intensities of anticoagulation, depending on the clot burden. RESULTS Symptomatic DVT occurred in 24 of 121 patients (20%; 95% CI, 14%-28%); symptomatic pulmonary embolism (one fatal) was diagnosed in six patients (5%; 95% CI, 2%-10%). There were 45 episodes of filter clot in 36 patients (30%; 95% CI, 22%-38%). The rate of major bleeding (6.6%) was similar to that of a concurrent persistently anticoagulated cohort without IVC filters (5.8%). CONCLUSIONS If therapeutic anticoagulation can be safely begun in patients with IVC filters inserted after venous thromboembolism, further management with clinical surveillance, including ultrasound examination of the IVC filter and graded degrees of anticoagulation therapy if filter clot is detected, has a favorable prognosis. This approach appears valid for patients with current IVC filter and can serve as a comparison standard in subsequent clinical trials to optimize clinical management of these patients.

Neoplastic pericardial disease in lung cancer: Impact on outcomes of different treatment strategies. A multicenter study

BACKGROUND Local (intrapericardial) chemotherapy has been reported to be useful for the treatment of neoplastic pericardial disease, but it has never been compared to systemic chemotherapy, a combination of the two and simple pericardial drainage or sclerosis. METHODS We analyzed the clinical and echocardiographic data of 119 patients, suffering of neoplastic pericarditis due to lung cancer (97 with non-small-cell), comparing the outcomes of four different treatment strategies (extended catheter drainage/sclerosis, systemic chemotherapy, local chemotherapy, and combined - local plus systemic - chemotherapy) at the last available follow-up or at the change of therapy after a treatment failure. The outcomes (based on semiquantitative evaluation of pericardial disease) were classified as complete, partial, no response and progressing disease. RESULTS A complete response was achieved in 37/53 of patients with combined, in 12/22 with local, in 5/27 with systemic chemotherapy, respectively, and in 4/17 after drainage/sclerosis (p<0.001). Overall response was achieved in 51/53 with combined, 18/22 and 16/27 with local or systemic chemotherapy, respectively, and in 5/17 with drainage/sclerosis only (p<0.001). Survival was significantly better after combined chemotherapy (p<0.001) and 12/53 patients (23%) in this subgroup survived more than 1 year. The overall response rate was higher with intrapericardial cisplatinum than with other agents (98% vs 80%, χ(2)=7.69, p<0.01). CONCLUSIONS Local chemotherapy, alone or with systemic chemotherapy, is effective in treating pericardial metastases from lung carcinoma, leading to a good control of pericardial effusion in 92% of cases, and to complete disappearance of effusion and masses in 65%. Combined therapy is significantly better than any other treatment. Pericardiocentesis and intrapericardial chemotherapy should be used whenever possible in lung cancer neoplastic pericardial disease, not only in case of tamponade.

2015 update on the diagnosis and management of neoplastic pericardial disease.

The best approach in diagnosis and treatment of neoplastic pericardial disease has not been defined yet. The authors report the most recent literature about the new diagnostic techniques that are useful to improve the diagnosis. The literature about the therapeutic options is critically reviewed, in order to give suggestions of use to the clinical practice. Pericardial effusion may require urgent drainage; the solid component, however, becomes predominant in some cases. Neoplastic pericardial disease should be assessed following oncologic criteria evaluation of the neoplastic burden; outcome classified as complete or partial response, stable or progressive disease and – in cases with progression – event-free survival. Systemic chemotherapy may be effective in lymphomas and possibly in breast carcinomas. Intrapericardial chemotherapy with systemic chemotherapy is the treatment of choice in lung cancer. Pericardial window with systemic chemotherapy is also effective in preventing the accumulation of large amount of fluid.

The inefficacy of enoxaparin prophylaxis in a patient with congenital antithrombin deficiency.

and hemoptysis complicated the course of PE. Secondary prophylaxis with OA and international normalized ratio maintenance between 2 and 3 are being successfully continued. The presented case report shows a poorly investigated problem, demonstrating the imperative for a better understanding of the efficacy of antithrombotic measures used in patients with trauma and documented AT deficiency. According to the existing guidelines, thromboprophylaxis with LMWH should be started, if possible, in patients with trauma and prolonged immobilization with at least 1 risk factor of venous thromboembolism like the AT deficiency. Enoxaparin appeared to be insufficient in producing its major anticoagulant effect by activating AT, even at higher than the recommended dosage. This case provides further evidence that enoxaparin and related drugs require AT for their clinical efficacy.

Pulmonary artery stenosis due to embryonal carcinoma with primary mediastinal location

A 29-year old man was admitted to the intensive care unit after losing consciousness. On physical examination, a loud systolic murmur over the heart was found. Echocardiography revealed narrowing of pulmonary artery with high pressure gradient. Computed tomography of the chest revealed the presence of large tumour localised in the upper anterior mediastinum. Due to the risk of total closure of the pulmonary artery, interventional mediastinotomy was performed and diagnosis of carcinoma embryonale was established. Subsequent chemotherapy (BEP regimen) has brought regression of tumour and significant improvement in haemodynamic parameters (relief of pressure gradient in pulmonary artery). During the second surgery, the resection of all accessible tumour mass together with marginal resection of the right upper lobe was performed. No signs of cardiac or great vessels infiltration was found. Histopathologic examination revealed the necrotic masses and neoplastic foci diagnosed as teratoma immaturum. In a four-month follow-up the patients condition remained good. The patient is still under the care of both oncological and cardiological specialists. Thus far he has not required further chemotherapy. Holter ECG monitoring revealed no arrhythmia, but the patient is still treated with mexiletine. The patient is planning to return to work.

Silent venous thromboembolism (VTE) in patients undergoing thoracic surgery in the course of lung cancer

Background: Venous thromboembolism often occurs after thoracic surgery but can even occur before surgery in patients with lung cancer. Aims: The aim of the study was the investigation of the incidence of silent deep vein thrombosis (DVT) and pulmonary embolism (PE), confirmed by objective imaging tests, before and after thoracic surgery in the course of lung cancer. Methods: Venous ultrasound (US) imaging was performed to detect DVT before and after thoracic surgery in patients with non-small cell lung cancer. Plasma D-dimer (DD) levels as well as Caprini and Khorana risk scores were examined in all patients. All cases with signs or symptoms of PE after surgery were examined by computed tomography pulmonary angiography (CTPA). Results: The study was perfomed in 200 patients (M:K = 122:88) with lung cancer and hospitalized for thoracic surgery. All patients received primary antithromobotic prophylaxis by low molecular weight heparins. DVT was detected by US in 3 patients before thoracic surgery. There was no symptoms od DVT and DD Level was elevated in one case. PE was diagnosed by CTPA in 2 patients after surgery; there was no DVT in these cases. DD levels were elevated in both cases. Conclusions: Silent or subclinical VTE may occur before surgical treatment in many patients with non-small lung cell cancer. Risk factors for VTE as well as elevated DD level before treatment might not be sufficient for identification silent DVT in thoracic surgery. PE represent potentially lethal postoperative complication despite pharmacological prevention of VTE.

Venous thromboembolism — recommendations on the prevention, diagnostic approach and management. The 2017 Polish Consensus Statement

The 2017 Polish Consensus Statement (PCS 2017) includes updated recommendations on the prevention, diagnostic approach, and management of venous thromboembolism (VTE). For VTE without cancer, the authors of PCS 2017 recommend apixaban, edoxaban, rivaroxaban, and dabigatran over vitamin K antagonists (VKA) as long-term anticoagulant therapy. For VTE with cancer, the authors of PCS 2017 recommend low molecular weight heparins (LMWH) over VKA, apixaban, edoxaban, rivaroxaban and dabigatran. For extended secondary prevention of deep venous thrombosis (DVT), PCS 2017 recommends apixaban, edoxaban, rivaroxaban, dabigatran, VKA, and sulodexide. For extended secondary prevention of pulmonary embolism (PE), PCS 2017 recommends apixaban, edoxaban, rivaroxaban, dabigatran and VKA. For extended secondary prevention in patients with idiopathic DVT and a high risk of bleeding complications, the authors of PCS 2017 recommend NOT to stop anticoagulation and use sulodexide. For extended secondary prevention in patients with idiopathic PE and a high risk of bleeding, the authors of PCS 2017 recommend NOT to stop anticoagulation and suggest treatment with apixaban, edoxaban, rivaroxaban, and dabigatran in reduced doses adjusted to the risk of bleeding. For VTE treated with anticoagulants, PCS 2017 recommends against insertion of a vena cava filter. For patients with DVT, PCS 2017 suggests USING compression stockings routinely to prevent postthrombotic syndrome. For subsegmental PE without proximal DVT, PCS 2017 suggests clinical surveillance over anticoagulation with a low risk of recurrent VTE, and anticoagulation over clinical surveillance with a high risk of recurrent VTE. The 2017 Polish Consensus Statement suggests thrombolytic therapy for PE with hypotension, and systemic therapy over catheter-directed thrombolysis. For recurrent VTE on a non-LMWH anticoagulant, PCS 2017 suggests LMWH, and for recurrent DVT and/or PE on LMWH, PCS 2017 suggests increasing the dose of LMWH.

РЕКОМЕНДАЦИИ ESC ПО ДИАГНОСТИКЕ И ВЕДЕНИЮ ПАЦИЕНТОВ С ЗАБОЛЕВАНИЯМИ ПЕРИКАРДА 2015

The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC) Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS)

Guidelines for the prevention and treatment of venous thromboembolism in non-surgically treated cancer patients

Guidelines for the prevention and treatment of venous thromboembolism (VTE) are aimed to improve patients’ safety and quality of life by appropriate prophylaxis and treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). These guidelines relate to adult cancer patients treated non-surgically. Recommendations included in those guidelines do not relate to paediatric patients. The guidelines presented here directed to physicians and other healthcare professionals taking care of mentioned patients: clinical oncologists, haematologists, radiotherapists, pulmonologists, oncological gynaecologists, internal medicine physicians, and GPs. Venous thromboembolism (VTE) comprises a serious problem in oncology because it is the most common complication as well as the second most common cause of cancer-related deaths. The term “venous thromboembolism” includes the cases of DVT and PE; however, the former is a primary event and the latter is a secondary result. Active malignant disease classifies patients to a group with at least moderate risk of VTE. D-dimer levels could be increased in cancer patients without concomitant VTE. D-dimer levels below cut-off value (negative D-dimer) do not exclude VTE in cancer patients. In patients with active malignant disease with clinical symptoms suggesting VTE ultrasound (US) examination of deep veins or computed tomography angiography (angio-CT) should be performed, depending on the symptoms. Low-molecular-weight heparins (LMWH) are the drugs of choice in prevention and treatment of VTE in cancer patients. Antithrombotic treatment in cancer patients with DVT does not differ from treatment of cancer patients with PE, except clear indications to thrombolytic therapy. Cancer patients with clinical symptoms suggesting PE (dyspnoea, chest pain or tachycardia) are per definition classified into the group of moderate or high clinical probability of PE. The majority of PE cases account for embolism, which do not warrant thrombolytic treatment and should be treated with LMWH, UFH, or fondaparinux; LMWHs are the treatment of choice in cancer patients with VTE. Cancer patients have increased risk of recurrence of VTE. Available evidence does not justify the use of antithrombotic drugs to prolong survival in cancer patients.