Israel Medical Association Journal

Background: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel.

Objectives: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence.

Methods: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events.

Results: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time.

Conclusions: Clinician training regarding discharge of VTE patients from the ED should continue.

Pulmonary embolism (PE) is very common in cancer patients and is a marker of increased mortality in these patients. Treatment is associated with increased rates of recurrent thrombosis and bleeding and has undergone significant change in the last years with the increasing use of direct oral anticoagulants. Diagnosis of PE and risk stratification is possible with minor changes to existing risk scores. Thrombolytic therapy should be considered in appropriate patients.

Background: Venous thromboembolism (VTE) is a serious disease, which demands a fast accurate diagnosis to begin suitable treatment. It presents a major problem in the emergency department (ED), and its confirmation requires adequate evaluation.

Objectives: To evaluate a potential role of mean platelet volume (MPV) in differentiating VTE from other potential diagnosis in patients with suspected VTE.

Methods: We conducted a retrospective case-controlled study of 440 consecutive patients who presented to the ED of our hospital with clinical VTE, but only 316 with proven VTE. A control group was composed of patients (124) who presented with clinical VTE but without proven VTE. We checked the MPV value in all 440 patients and the correlation with VTE occurrence in the study group vs. control group.

Results: Statistical analysis of the acquired results indicated that MPV value could not aid in determining the difference of real VTE vs. patients with VTE-like clinical picture presenting to the ED. We found an inverse correlation between MPV value and proven VTE, in contrast to most researchers who have studied the same issue.

Conclusions: Although MPV can be a useful diagnostic marker in many diseases, we found no definite association between low MPV and VTE

Background: Venous thromboembolism is a well-recognized and relatively frequent complication of malignancy, whereas tumor thrombosis is a rare complication of solid cancers. Correct diagnosis of tumor thrombosis and its differentiation from VTE[1] can alter patient management and prevent unnecessary long-term anticoagulation treatment.

Objectives: To evaluate the contribution of 18F-fluorodeoxyglucose positron emission tomography/computed tomography to the diagnosis of tumor thrombosis and its differentiation from VTE.

Methods: PET/CT[2] scans from 11 patients with suspected tumor thrombosis were retrospectively evaluated. Suspicion arose from positive PET/CT in eight cases, or from findings on contrast-enhanced CT in three patients. Criteria for positivity of PET/CT included increased focal or linear uptake of 18F-FDG[3] in the involved vessel. Findings were categorized as PET/CT positive, or PET/CT negative and compared to contrast-enhanced or ultrasound Doppler, pathology where available, and clinical follow-up.

Results: Eight occult tumor thromboses were identified by PET/CT-positive scans. Underlying pathologies included pancreatic, colorectal, renal cell, and head-neck squamous cell carcinoma, as well as lymphoma (4 patients). Three thrombotic lesions on contrast-enhanced CT were PET/CT negative, due to VTE (2 patients) and leiomyomatosis. Accuracy of PET/CT to differentiate between tumor thrombosis and benign VTE was 100% in this small study.

Conclusions: Contrast-enhanced CT defines the extent of thrombotic lesions, while the functional information from PET/CT characterizes the lesions. It appears that PET/CT may be helpful in the diagnosis of occult tumor thrombosis and its differentiation from VTE.

Objectives: To investigate and compare the epidemiologic, clinical and laboratory characteristics of cancer and non-cancer patients hospitalized with venous thromboembolism in a large referral medical center in Israel.

Methods: Between February 2002 and February 2003, patients diagnosed at the Rambam Medical Center as suffering from VTE[1] (deep vein thrombosis and/or pulmonary embolism), based on diagnostic findings on Doppler ultrasonography, spiral computed tomography scan or lung scan showing high probability for pulmonary embolism, were prospectively identified and evaluated. In addition, at the conclusion of the study period, the reports of spiral chest CT scans, performed during the aforementioned period in this hospital, were retrospectively reviewed to minimize the number of unidentified cases. Blood samples were drawn for evaluation of the coagulation profile.

Results: Altogether, 147 patients were identified and 153 VTE events diagnosed, accounting for 0.25% of all hospitalizations during the study period. The cancer group included 63 patients (43%), most of whom had advanced disease (63%). The most common malignancies were cancer of the lung (16%), breast (14%), colon (11%) and pancreas (10%). Of 121 venous thromboembolic events (with or without pulmonary embolism) there were 14 upper extremity thromboses (12%). The most common risk factors for VTE, except malignancy, were immobilization (33%), surgery/trauma (20%) and congestive heart failure (17%). There was no difference in prevalence of various risk factors between cancer and non-cancer patients. During an acute VTE event, D-dimer levels were higher in cancer patients than non-cancer patients (4.04 ± 4.27 vs. 2.58 ± 1.83 mg/L respectively, P = 0.0550). Relatively low values of activated protein C sensitivity ratio and normalized protein C activation time were observed in both cancer and non-cancer groups (2.05 ± 0.23 vs. 2.01 ± 0.33 and 0.75 ± 0.17vs. 0.71 ± 0.22, respectively). These values did not differ significantly between the groups.

Conclusion: The proportion of cancer patients among patients suffering from VTE was high. Their demographic, clinical and laboratory characteristics (during an acute event) were not different from those of non-cancer patients, except for higher D-dimer levels.

Background: Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.

Objectives: To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.

Methods: The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW[1] heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE[2]. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.

Results: Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.

Conclusion: These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

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[1] LMW = low molecular weight

[2] VTE = venous thromboembolism