Thromboembolic events are reported to occur with a high frequency in the setting of malignancy. However, reports on an association between cholangiocarcinoma and pulmonary thromboembolism, thus far, are almost lacking. We present here an unusual case of a 56-yr-old patient presenting cholangiocarcinoma and unexplained pulmonary thromboembolism. The patient had been quite healthy before the diagnosis. Coagulation tests showed elevated levels of fibrinogen, fibrinogen degradation product (FDP), D-dimer, and IgM anticardiolipin antibody (aCL Ab). The thromboemboli were resolved 3 weeks after anticoagulant therapy using low-molecular-weight-heparin. Then, follow-up coagulation tests showed a marked decrease to normal in aCL Ab titer as well as the normalization of FDP and D-dimer levels. In this case, we describe pulmonary thromboembolism caused by hypercoagulable state associated with cholangiocarcinoma and speculate that such a thrombotic phenomenon could be regressed by anticoagulant therapy.
Cholangiocarcinoma; Pulmonary Embolism; Heparin; Heparin, Low-Molecular-Weight
The GliaSite radiation therapy system (RTS) is an implantable balloon brachytherapy applicator used to deliver iodine-125 in the treatment of recurrent high-grade gliomas. Patients generally tolerate the procedure well, with only rare reports of adverse events such as wound infection, meningitis, and symptomatic radiation necrosis. Hemorrhagic complications have not been reported. We present a case report describing intracranial hemorrhage during GliaSite manipulation in a patient receiving long-term anticoagulation for a previously diagnosed pulmonary embolism. The GliaSite RTS and the management of venous thromboembolism in patients with brain tumors are reviewed. These events suggest that normalizing coagulation status during GliaSite balloon inflation and deflation should be considered.
Glioblastoma multiforme; Venous thromboembolism; Anticoagulation; Intracranial hemorrhage; GilaSite RTS; Brachytherapy
Cancer is an acquired thrombophilic condition manifested by increased incidence of venous and arterial thromboembolic complications. Despite progress that has been achieved in treatments over the recent years, thromboembolism remains a major complication in patients with breast cancer; it is accompanied by significant morbidity and mortality. Approximately, 1% of breast cancer patients develop venous thromboembolism within 2 years with the highest incidence occurring in the 6 months post diagnosis. Metastatic disease and their comorbidities are the strongest predictors of the development of thrombotic event. The diagnosis of venous thromboembolism is associated with a higher risk of death within 2 years of diagnosis. Thromboembolic events in cancer patients range from abnormal laboratory coagulation tests without specific symptoms to massive thomboembolism and disseminated intravascular coagulation. The underlying pathophysiology is complex and includes the prothrombotic properties of cancer cells, which can be enhanced by anticancer treatment modalities, such as surgery, hormonal agents, and chemotherapy. Primary thromboprophylaxis in cancer patients should be individualized according to risk. For secondary prevention, several clinical studies have shown that low molecular weight heparin has improved patients' compliance, cancer outcomes and overall survival. This review summarizes the available data on the pathogenesis and clinical approach of hemostatic changes in breast cancer.
Blood coagulation; Breast neoplasms; Hemostasis; Thrombosis
Thromboembolus can occur during endovascular coil embolization. The aim of our study was to show our experience of intraarterial (IA) tirofiban infusion for thromboembolism during coil embolization for ruptured intracranial aneurysms.
This retrospective analysis was conducted in 64 patients with ruptured aneurysms who had emergent endovascular coil embolization from May 2007 to April 2011 at a single institute. Thromboembolic events were found in ten patients (15.6%). Anticoagulation treatment with intravenous heparin was started after the first coil deployment in ruptured aneurysmal sac. When a thrombus or embolus was found during the procedure, we tried to resolve them without delay with an initial dosage of 0.3 mg of tirofiban up to 1.2 mg.
Three patients of four with total occlusion had recanalizations of thrombolysis in myocardial infarction (TIMI) grade III and five of six with partial occlusion had TIMI grade III recanalizations. Eight patients showed good recovery, with modified Rankin Scale (mRS) score of 0 and one showed poor outcome (mRS 3 and 6). There was no hemorrhagic or hematologic complication.
IA tirofiban can be feasible when thromboembolic clots are found during coil embolization in order to get prompt recanalization, even in patients with subarachnoid hemorrhage.
Aneurysm coiling; Thromboembolism; Tirofiban; Intracranial aneurysm
Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions concerning the duration of anticoagulant therapy.
In this exploratory study, we investigated whether whole blood gene expression data could distinguish subjects with single venous thromboembolism from subjects with recurrent venous thromboembolism.
40 adults with venous thromboembolism (23 with single event and 17 with recurrent events) on warfarin were recruited. Individuals with antiphospholipid syndrome or cancer were excluded. Plasma and serum samples were collected for biomarker testing, and PAXgene tubes were used to collect whole blood RNA samples.
D-dimer levels were significantly higher in patients with recurrent venous thromboembolism, but P-selectin and thrombin-antithrombin complex levels were similar in the two groups. Comparison of gene expression data from the two groups provided us with a 50 gene probe model that distinguished these two groups with good receiver operating curve characteristics (AUC 0.75). This model includes genes involved in mRNA splicing and platelet aggregation. Pathway analysis between subjects with single and recurrent venous thromboembolism revealed that the Akt pathway was up-regulated in the recurrent venous thromboembolism group compared to the single venous thromboembolism group.
In this exploratory study, gene expression profiles of whole blood appear to be a useful strategy to distinguish subjects with single venous thromboembolism from those with recurrent venous thromboembolism. Prospective studies with additional patients are needed to validate these results.
genomics; risk factors; deep vein thrombosis
We report on two patients with cerebral sinus venous thrombosis following chemotherapy with cisplatin, bleomycin and etoposide for non-seminomatous germ cell tumor. Headache and neurological deficits were the leading symptoms. Cancer and cisplatin chemotherapy are well-known risk factors for thromboembolic events. The therapeutic strategy is an anticoagulant therapy. Symptoms are usually reversible within weeks under this therapy. Therefore, in patients with testicular cancer and chemotherapy who present with neurological symptoms, cerebral sinus venous thrombosis should be considered in the differential diagnosis.
Germ cell tumor; Cisplatin; Cerebral sinus venous thrombosis
Venous thromboembolism (blood clots of the legs and lungs) is an important cause of hospital related morbidity and mortality. We describe the occurrence of this disease, the characteristics of affected patients, and associated outcomes in a typical New England community. A total of 587 Worcester residents developed venous thromboembolism in 1999 – approximately 128 events per 100,000 population. Three quarters of patients developed their venous thromboembolism in the outpatient setting – a substantial proportion of the patients had undergone recent surgery or had a recent prior hospitalization. Less than half of patients received anticoagulant prophylaxis to prevent venous thromboembolism during high-risk periods before their event. While most patients were treated with anticoagulants for their event, a second venous thromboembolism occurred in 5% of patients. The underutilization of prophylaxis prior to venous thromboembolism, and relatively high 30-day recurrence rates, suggest a continued need for the improvement of venous thromboembolism prophylaxis and management in the community.
On 169 occasions anticoagulant therapy for thromboembolic disease was stopped electively and patients were followed for 16 subsequent weeks. The records of those who remained well and those who suffered a relapse were compared in an attempt to identify factors that might affect liability to thromboembolic relapse.
During the follow-up period there were 37 thromboembolic recurrences, an incidence of 22 per cent. None occurred among the patients in whom the original diagnosis of thromboembolic disease was discarded or when a predisposing cause had ceased to be present. There was an inverse relation between liability to relapse and degree of prothrombin time prolongation.
No significant relation could be shown between liability to relapse and any of the following: sex and age; type and severity of the initiating thromboembolic episode; history of earlier thromboembolic disease or relapse after stopping earlier anticoagulant courses; presence of hypertension, hypercholesterolaemia, or diabetes mellitus; type of anticoagulant drug used, duration of therapy, and method of stopping treatment.
Patients with overt occlusive arterial disease at more than one site had a significantly increased liability to relapse when compared with patients with symptomatic disease at a single site. In the group of 134 subjects receiving anticoagulant therapy for coronary arterial disease, occurrence of a thromboembolic episode during the course of treatment and the presence of angina of effort in the months before it was discontinued were both associated with a significant increase in liability to relapse. It is suggested that, ideally, anticoagulant therapy should be continued indefinitely in any patient whose pattern of disease thus increases the likelihood of a thromboembolic recurrence.
Pulmonary thromboembolism is a very rare event in children, but the mortality rate is reported to be approximately 10%. The majority of children with thromboemboli have multiple risk factors, such as a catheter-related thrombosis, an infection, and a congenital prothrombotic disorder. Hypereosinophilia is very rarely associated with pulmonary emboli in adults; however, this condition has not been reported in children. We present a 12-year-old boy who had a pulmonary thromboembolism and deep vein thrombosis associated with hypereosinophilia and thrombocytopenia. The thromboembolism was managed with anticoagulant therapy and the hypereosinophilia resolved spontaneously.
Pulmonary thromboembolism; Child; Eosinophilia
AIM—To identify the
incidence of congenital thrombophilia in a cohort of children
presenting with symptomatic thromboembolism.
METHOD—A review of
children with thromboembolism investigated for thrombophilia over a 12 month period.
children with thromboembolic episodes and 16 of their family members.
MEASUREMENTS AND DATA
COLLECTION—Data were collected on age at
diagnosis, underlying diagnosis, site of thrombosis, associated
precipitating factors, occurrence of other thromboembolic events, and
family history. Investigations included measurement of protein C
activity, total and free protein S antigen, antithrombin III activity,
screening for factor V Leiden and prothrombin 20210A, urinary
homocysteine estimation, and a screen for lupus anticoagulant.
of 30 patients had one or more risk factors present at the time of
thromboembolism. Eighty three per cent had acquired precipitating
factors present, and 43% had underlying congenital thrombophilia.
a high incidence of congenital thrombophilia in this group of patients
with symptomatic thromboembolism. These findings emphasise the
importance of such defects in the pathogenesis of childhood thrombosis,
and suggest that full thrombophilia investigations should be performed
on all children presenting with thromboembolic disease.
Sticky platelets syndrome
Disease of unknown ethiology
Sticky platelets syndrome (SPS) is an inherited thrombophilia characterized by platelet hyperaggregability, which can lead to the higher risk of thrombosis. The etiology of SPS remains unclear, but several gene polymorphisms have been recently studied and autosomal dominant heredity is suspected. Although SPS is traditionally connected with arterial thrombosis, several cases of SPS as a cause of venous thromboembolism have been described.
We report the case of a 51-year-old apparently healthy woman with massive pulmonary embolism, who required thrombolytic therapy. In this patient SPS was identified as the only condition leading to higher risk of developing thromboembolic disease.
Although at present few physicians have practical experience with SPS, this syndrome may lead to serious health problems or even death. The presented case points to the benefit of SPS diagnostics in standard screening of inherited thrombophilia for effective prophylaxis and treatment in patients with venous thromboembolism.
sticky platelets syndrome; venous thromboembolism; inherited thrombophilia screening
With the rapidly developing applications of GDC endovascular aneurysm embolization, the recognition and treatment of potential intra-procedural complications is crucial to reducing the morbidity and mortality of this procedure. Thromboembolic complications occur with an incidence of 2-11 % with endovascular aneurysm coiling. We describe five cases in which the intraarterial use of thrombolytics was applied to disrupt a fresh clot and recanalize the occluded vessels with variable angiographic and clinical success.
Five cases are presented in which thromboembolic complications occurred during or shortly after GDC endovascular aneurysm occlusion. The complication was recognized while depositing coils in two cases, on post-embolization angiogram in one, and a few hours following embolization in two cases in which a new neurologic deficit developed in the ICU.
In those cases recognized while the microcatheter was near the aneurysm site, immediate thrombolysis was performed at the site of occlusion. The patients who developed a new neurologic deficit were returned to the endovascular suite and the site of occlusion was noted to be distal to the coiled aneurysm. Clot disruption was performed with the microcatheter before delivering intraarterial thrombolytics.
Thromboembolic complications of GDC aneurysm embolization are fortunately rare and can be managed with delivery of thrombolytic therapy at the site of occlusion. Intraarterial thrombolysis of fresh clot caused by GDC aneurysm occlusion can successfully open the occluded vessels but not without serious risk of hemorrhage.
intraarterial thrombolysis, coiling complications, thromboemboli
The treatment with antitumor necrosis factor agents has often been associated with the induction of autoantibodies (antinuclear antibodies, anti-double stranded DNA antibodies and antiphospholipid antibodies). The clinical significance of these antibodies remains unclear, but they may predispose to antiphospholipid syndrome with thromboembolic complications. The association of etanercept with thromboembolic events has not been reported previously in the literature.
We describe the cases of three patients with rheumatoid arthritis, psoriatic arthritis and seronegative inflammatory arthritis who were treated with etanercept. They developed deep vein thrombosis and/or pulmonary embolism one to three years after the initiation of etanercept therapy. All three patients had a prolonged activated partial thromboplastin time with a positive lupus anticoagulant that persisted even after 12 weeks.
Although the clinical significance of antiphospholipid antibodies during treatment with antitumor necrosis factor agents remains unclear, they may predispose patients to develop antiphospholipid syndrome when associated with prolonged activated partial thromboplastin time, lupus anticoagulant positivity, or the presence of anti-β2 glycoprotein I. Clinicians must keep this in mind during therapy with antitumor necrosis factor agents in order to prevent, detect and treat potential consequences such as deep vein thrombosis and pulmonary embolism.
Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events.
We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition.
Plasma factor (F) compositions (FII, V, VII, VIII, IX, X), antithrombin and free tissue factor pathway inhibitor (TFPI) from 46 consecutive RA patients with no cardiovascular events (39F, 7M, aged 57 [range, 23–75] years; DAS28 [Disease Activity Score] 5.2±1.1) were compared with those obtained in age- and sex-matched apparently healthy controls. Patients on anticoagulant therapy were excluded. Using each individual’s plasma coagulation protein composition, tissue factor-initiated thrombin generation was assessed both computationally and empirically.
RA patients had higher fibrinogen (4.18 [IQR 1.09] vs 2.56 [0.41] g/l, p<0.0001), FVIII (226±40 vs 113±15%, p<0.001), PC (107  vs 100 %, p<0.001), and free TFPI levels (22.3 [2.2] vs 14.7 [2.1] ng/ml, p<0.001). DAS28, but not age, RA duration, or C-reactive protein, was associated with FV, FVIII, FIX, FX, antithrombin, and free TFPI (r from 0.27 to 0.48, p<0.05). Intergroup comparison of computational thrombin generation profiles showed that in RA patients, maximum thrombin levels (p=0.01) and the rate of thrombin formation (p<0.0001) were higher, whereas the initiation phase of thrombin generation (p<0.0001) and the time to maximum thrombin levels (p<0.0001) were longer. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model.
Simulations of thrombin formation suggest that blood plasma composition, i.e. a marked increase in FVIII, somewhat counterbalanced by free TFPI, contributes to the prothrombotic phenotype in RA patients.
inflammation; plasma composition; prothrombotic phenotype; rheumatoid arthritis; tissue factor pathway inhibitor; thrombin generation
The alveolo-arterial gradient of Pco2 was measured and the percentage of ventilated but unperfused alveoli was derived from Severinghaus's formula in 312 patients divided into five groups according to clinical symptoms, biological, radiographic, scintigraphic or pathological data—87 patients with proved thromboembolic disease, 41 with probable thromboembolic disease, 67 with possible thromboembolic disease, 101 with non-embolic pulmonary disease, and 16 cases of miscellaneous cardiac diseases. After all capnographic curves without an alveolar plateau had been eliminated, 223 capnograms (71%) were examined.
In 59% of the patients with proved thromboembolic disease, the percentage of ventilated but unperfused alveoli was abnormal (>15%). In this group the mean percentage of ventilated but unperfused alveoli (16·3%) was significantly different from the value obtained in the remaining groups. This test was positive in 40% of the patients with probable thromboembolic disease but it was also positive in 22·5% of the cases of miscellaneous pulmonary and cardiac non-embolic diseases.
Compared to the lung scan, this method was less sensitive but also less equivocal in patients with preexisting cardiopulmonary disorders. Estimates of the pulmonary vascular defect by these two methods did not always correspond.
A 55-year-old man with massive pulmonary thromboembolism underwent thrombolysis, pulmonary artery embolectomy and tricuspid annuloplasty. Nine months later, a mobile echogenic intra-cardiac mass was found in the tricuspid valve. Because the patient had undergone annuloplasty, thrombosis was suspected as the most likely diagnosis and thrombolytic therapy was instituted. However, the size of the cardiac mass did not change and after surgical excision the mass was found to be a myxoma. Cardiac valvular tumors are uncommon and when they occur they are usually slow growing fibroelastomas. In this case, the rapid growing cardiac myxoma on the tricuspid valve was found after the occurrence of pulmonary thromboembolism. To our knowledge, this is first reported case of tricuspid valve myxoma in Korea.
Pulmonary thromboembolism; Thrombosis; Valvular myxoma
Venous thromboembolism is the most common preventable cause of death in surgical patients. Thromboprophylaxis, using mechanical methods to promote venous outflow from the legs and antithrombotic drugs, provides the most effective means of reducing morbidity and mortality in these patients. Despite the evidence supporting thromboprophylaxis, it remains underused because surgeons perceive that the risk of venous thromboembolism is not high enough to justify the potential hemorrhagic complications of anticoagulant use. The risk of venous thromboembolism is determined by patient characteristics and by the type of surgery that is performed. In this paper we identify the risk factors for venous thromboembolism and provide a scheme for stratifying surgical patients according to their risk. We describe the mechanism of action of the various forms of thromboprophylaxis and outline the evidence supporting thromboprophylaxis in different surgical settings. Finally, we recommend optimal forms of thromboprophylaxis in patients who undergo various types of surgery. Intermittent pneumatic compression, with or without elastic stockings, can be used for thromboprophylaxis in patients who undergo neurosurgical procedures; for patients who undergo vascular or cardiovascular procedures, long-term acetylsalicylic acid should be used for thromboprophylaxis. Low-molecular-weight heparin (LMWH) or warfarin is the choice for patients with spinal cord operations and all patients with major trauma who do not have contraindications to anticoagulation should receive thromboprophylaxis with LMWH.
Venous thromboembolism is a very common pathological process for which there are many well known (and less well-known) predisposing factors. Likewise, olanzapine is a commonly used anti-psychotic medication.
We present the case of a young Somali gentleman who developed venous thromboembolic disease after an overdose of olanzapine. The diagnosis was only made 48 hours after admission, due to the non-specific presentation of the pulmonary embolus and the fact that the link between olanzapine and pulmonary embolus was not previously widely described and therefore it did not immediately figure in the differential diagnosis. The patient made a full recovery.
There is an increasing body of circumstantial evidence linking olanzapine to pulmonary embolus. Clinicians should bear this possible association in mind when prescribing the drug and when faced with clinical situations where venous thromboembolism (VTE) is a possible diagnosis. VTE has occasionally been described in therapeutic dose olanzapine therapy, but never in the context of an acute overdose. Khat, a recreational drug, has been linked to arterial, but not venous thrombosis.
It is hoped that this case report will further encourage research into these associations, which remain to be proven and quantified.
In the context of changing population demographics and increasing global migration, a greater awareness of the potential effects of endemic practices and their potential consequences is essential to the modern-day doctor working in a multi-cultural society.
We investigated changes in the International Normalized Ratio (INR) and its measurement interval in patients with thromboembolic events who were treated by low intensity anticoagulation therapy after isolated mechanical aortic valve replacement.
Materials and Methods
Seventy-seven patients who underwent surgery from June 1990 to September 2006 were enrolled in the study and observed until August 2008. The patients were followed up at 4~8 week intervals and their warfarin (Coumadin)® dosage was adjusted aiming for a target range of INR 1.5~2.5. The rate of thromboembolic events was obtained. Changes in the mean INR and INR measurement interval were comparatively analyzed between the normal group (event free group, N=52) who had no anticoagulation-related complications and the thromboembolic group (N=10). Hospital records were reviewed retrospectively.
The observation period was 666.75 patient-years. Thromboembolic events occurred in 10 patients. The linearized occurrence rate of thromboembolism was 1.50%/patient-years. Actuarial thromboembolism-free rates were 97.10±2.02% at 5 years, 84.30±5.22% at 10 years, and 67.44±12.14% at 15 years. The percentages of INR within the target range and mean INR were not statistically significantly different for the normal and thromboembolic groups. However, the mean INR during the segmented period just before the events showed a significantly lower level in the thromboembolic group (during a 4 month period: normal group, 1.86±0.14 vs. thromboembolic group, 1.50±0.28, p<0.001). The mean intervals of INR measurement during the whole observation period showed no significant differences between groups, but in the segmented period just before the events, the interval was significantly longer in thromboembolic group (during a 6 month period: normal group, 49.04±9.47 days vs. thromboembolic group, 65.89±44.88 days, p<0.01).
To prevent the occurrence of thromboembolic events in patients who receive isolated aortic valve replacement and low intensity anticoagulation therapy, we suggest that it would be safe to maintain an INR level above 1.8 and to measure the INR at least every 7~8 weeks.
Mechanical heart valve; Thromboembolism; Anticoagulation; INR measurement interval
A retrospective review of premedication method and drug resistance of aspirin and clopidogrel in association with thromboembolic events during and after coil embolization of an unruptured intracranial aneurysm was conducted.
Our premedication policy for coil embolization of an unruptured intracranial aneurysm has changed from administration of the loading dose before the procedure (i.e. loading group) to repeated administration of the maintenance dose for several days (i.e. preparation group). The loading group (27 patients with 29 aneurysms) and the preparation group (30 patients with 35 aneurysms) were compared for identification of the effect of premedication method on periprocedural thromboembolic events. The results of drug response assays of the preparation group were analyzed with respect to periprocedural thromboembolic events.
No statistically significant difference in incidence of thromboembolic events was observed between the loading group and the preparation group. Analysis of the results of the drug response assay showed high prevalence (56.7%, 73.3%) of clopidogrel resistance and relatively low prevalence (6.7%) of aspirin resistance. Patients who had thromboembolic events tended to have lower responsiveness to both aspirin and clopidogrel than patients without it.
The method of antiplatelet premedication does not affect the rate of periprocedural thromboembolic events in coil embolization for treatment of an unruptured intracranial aneurysm. Nevertheless, considering the high prevalence of drug resistance, it is reasonable to premedicate antiplatelet agents in the preparation method for the drug response assay. Use of a higher dose of aspirin and clopidogrel or addition of an alternative drug (cilostazol or triflusal) can be applied against antiplatelet agent resistance. However, because the hemorrhagic risk associated with this supplementary use of antiplatelet agent has not been well-documented, the hemorrhagic risk and the preventive benefit must be weighed.
Antiplatelet agent premedication; Aspirin resistance; Clopidogrel resistance; Thromboembolic complication
Changes in the hemostatic system and chronic hemostatic activation are frequently observed in patients with cancer, even in the absence of venous thromboembolism (VTE). VTE is a leading cause of death among patients with cancer and contributes to long-term mortality in patients with early as well as advanced-stage cancer. Mounting evidence suggests that components of the clotting cascade and associated vascular factors play an integral part in tumor progression, invasion, angiogenesis, and metastasis formation. Furthermore, there are intriguing in vitro and animal findings that anticoagulants, in particular the low molecular weight heparins (LMWHs), exert an antineoplastic effect through multiple mechanisms, including interference with tumor cell adhesion, invasion, metastasis formation, angiogenesis, and the immune system. Several relatively small randomized controlled clinical trials of anticoagulation as cancer therapy in patients without a VTE diagnosis have been completed. These comprise studies with LMWH, unfractionated heparin, and vitamin K antagonists, with overall encouraging but nonconclusive results and some limitations. Meta-analyses performed for the American Society of Clinical Oncology VTE Guidelines Committee and the Cochrane Collaboration suggest overall favorable effects of anticoagulation on survival of patients with cancer, mainly with LMWH. However, definitive clinical trials have been elusive and questions remain regarding the importance of tumor type and stage on treatment efficacy, the impact of fatal thromboembolic events, optimal anticoagulation therapy, and safety with differing chemotherapy regimens. Although the LMWHs and related agents hold promise for improving outcomes in patients with cancer, additional studies of their efficacy and safety in this setting are needed.
Cancer and its therapies increase the risk of venous thromboembolism. Compared to patients without cancer, patients with cancer anticoagulated for venous thromboembolism are more likely to develop recurrent thrombotic events and major bleeding. Addressing all important outcomes including harm is of great importance to make evidence based health care decisions. The objective of this study was to compare low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism in patients with cancer.
A systematic review of the medical literature. We followed the Cochrane Collaboration methodology for conducting systematic reviews. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
Eight randomized controlled trials (RCTs) were eligible and reported data for patients with cancer. The quality of evidence was low for death and moderate for recurrent venous thromboembolism. LMWH, compared to VKA provided no statistically significant survival benefit (Hazard ratio (HR) = 0.96; 95% CI 0.81 to 1.14) but a statistically significant reduction in venous thromboembolism (HR = 0.47; 95% (Confidence Interval (CI) = 0.32 to 0.71). There was no statistically significant difference between LMWH and VKA in bleeding outcomes (RR = 0.91; 95% CI = 0.64 to 1.31) or thrombocytopenia (RR = 1.02; 95% CI = 0.60 to 1.74).
For the long term treatment of venous thromboembolism in patients with cancer, LMWH compared to VKA reduces venous thromboembolism but not death.
Whether to continue oral anticoagulant therapy beyond 6 months after an “unprovoked” venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants.
In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5–7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p < 0.10) with high interobserver reliability to derive a clinical decision rule.
We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%–11.3%). Men had a 13.7% (95% CI 10.8%–17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; D-dimer ≥ 250 μg/L while taking warfarin; body mass index ≥ 30 kg/m2; or age ≥ 65 years. These women had an annual risk of 1.6% (95% CI 0.3%–4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%–17.3%).
Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men. (http://Clinicaltrials.gov trial register number NCT00261014)
To assess the incidence of venous thromboembolism (VTE) and bleeding events with or without thromboprophylaxis and the associated costs in a cohort of medically ill patients in both in-hospital and outpatient settings.
A large hospital drug database and linked outpatient files were used to identify patients eligible for this analysis, based on demographic and clinical characteristics.
Among 11,135 patients identified, 1592 (14.30%) were admitted with chronic heart failure, 1684 (15.12%) with thromboembolic stroke, 3834 (34.43%) with severe lung disease, 1658 (14.89%) with acute infection, and 2367 (21.26%) with cancer. Of the 11,135 patients, 5932 received anticoagulant therapy at some point during their hospitalization and until 30 days after discharge. VTE events occurred in 1.30% of patients who received anticoagulant prophylaxis versus 2.99% of patients who did not. Risk-adjusted total healthcare costs for patients with a VTE or major or minor bleeding event were significantly higher than for those without events (VTE: $52,157 ± 24,389 vs $24,164 ± 11,418; major bleeding: $33,656 ± 18,196 vs $24,765 ± 11,974; minor bleeding: $33,690 ± 14,398 vs $23,610 ± 11,873). In a multivariate analysis, appropriate anticoagulant prophylaxis use was significantly associated with a reduced risk of clinical VTE, compared with no anticoagulant use (hazard ratio: 0.37). Patients admitted with thromboembolic stroke were less likely to have a VTE than patients admitted with cancer (hazard ratio: 0.42).
In this analysis, VTE and major bleeding event rates were lower for patients who received prophylaxis compared with those who did not. Prophylaxis use was associated with lower healthcare costs.
Extracorporeal membrane oxygenation (ECMO) after cardiac operations (postcardiotomy) is commonly used for the treatment of acute heart failure refractory to drug treatment. Bleeding and thromboembolic events are the most common complications of postcardiotomy ECMO. The present study is a retrospective comparison of the conventional heparin-based anticoagulation protocol with a bivalirudin-based, heparin-free protocol. Endpoints of this study are blood loss, allogeneic blood product use, and costs during the ECMO procedure.
A retrospective study was undertaken in the setting of cardiac surgery, anesthesia, and intensive care departments of a university research hospital. Twenty-one patients (12 adults and nine children) who underwent postcardiotomy ECMO from 2008 through 2011 were retrospectively analyzed. The first consecutive eight patients were treated with heparin-based anticoagulation (H-group) and the next 13 consecutive patients with bivalirudin-based anticoagulation (B-group). The following parameters were analyzed: standard coagulation profile, thromboelastographic parameters, blood loss, allogeneic blood products use, thromboembolic complications, and costs during the ECMO treatment.
Patients in the B-group had significantly longer activated clotting times, activated partial thromboplastin times, and reaction times at thromboelastography. The platelet count and antithrombin activity were not significantly different, but in the H-group a significantly higher amount of platelet concentrates, fresh frozen plasma, and purified antithrombin were administered. Blood loss was significantly lower in the B-group, and the daily cost of ECMO was significantly lower in pediatric patients treated with bivalirudin. Thromboembolic complications did not differ between groups.
Bivalirudin as the sole anticoagulant can be safely used for postcardiotomy ECMO, with a better coagulation profile, less bleeding, and allogeneic transfusions. No safety issues were raised by this study, and costs are reduced in bivalirudin-treated patients.