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Recurrent pulmonary embolism. A prospective study.

We have prospectively studied a series of 121 consecutive patients with venous thromboembolism (38 with pulmonary embolism, 83 with venous thrombosis of the lower extremities) searching for recurrences of pulmonary embolism despite adequate heparin therapy. A baseline ventilation-perfusion lung scan was obtained initially in every patient, whether the original diagnosis was pulmonary embolism or venous thrombosis. Repeat chest roentgenograms and lung scans were obtained routinely at eight days of heparin treatment. The primary trial endpoints were a finding of a clinically apparent recurrent pulmonary embolism, or laboratory evidence of subclinical pulmonary embolism. Eight items of clinical and laboratory information were recorded at admission and then correlated with the lung scan results. Recurrences were seen in seven of 38 patients with an original diagnosis of pulmonary embolism, and in five of 83 patients admitted because of venous thrombosis (p = 0.034). Recurrences were also more frequent in patients with a free-floating thrombus on venography (p = 0.014). The risk of new defects in patients with venous thrombosis and without free-floating thrombus was 3.05 percent, venous thrombosis with free-floating thrombus, 13.33 percent; patients with pulmonary embolism without free-floating thrombus, 11.42 percent; and with free-floating thrombus, 38.67 percent. Venography seems thus mandatory in patients with pulmonary embolism, as it recognizes a subgroup of patients at a high risk of recurrences.

Adult↗

[Chronic pulmonary hypertension caused by left axillary vein thrombosis. Report of a clinical case].

Deep venous thrombosis (DVT) of the upper extremity is infrequent, occurring with an incidence estimated at 1-3% of that of DVT of the lower extremity; acute pulmonary embolism following upper extremity DVT is very uncommon; thromboembolic chronic hypertension is quite rare. Therefore a case of chronic thromboembolic pulmonary hypertension due to a non-traumatic ("spontaneous") left axillary vein thrombosis is described: in this case only the double lung transplantation has been shown to be effective in the treatment of advanced cardiopulmonary disorder.

Adult↗

Diagnostic strategies in venous thromboembolism.

BACKGROUND AND OBJECTIVE: Diagnosis of acute deep vein thrombosis (DVT) and of pulmonary embolism (PE) is often difficult: symptomatic patients are usually investigated employing several diagnostic tests, which should be appropriately selected and sequenced, taking into account their sensitivity, specificity, safety and cost. The objective of this paper is to evaluate the performance of the new diagnostic tests and their combination in rational diagnostic strategies. DESIGN AND METHODS: A literature review was made using a Medline(R) database search for the period 1988-1998 on the following key words in various combinations: diagnosis, diagnostic strategy, venous thrombosis, pulmonary embolism, venous thromboembolism. Results of a new study by our group on diagnosis of DVT in hospitalized patients are also discussed. RESULTS: In patients with symptoms or signs suggestive of DVT, compression ultrasound (CUS) appears to be the diagnostic test of first choice, since it is a noninvasive test with high specificity and sensitivity for proximal DVT (about 97%). When CUS gives a negative result it is usually recommended that the test is repeated after one week, since its sensitivity for calf DVT is poor. The positive and negative predictive values (PPV and NPV) of CUS in symptomatic outpatients can be improved if adequate consideration is given to clinical diagnosis, using a standardized model (ref. #9), which allows symptomatic outpatients to be categorized as having a high, moderate or low probability of DVT. In case of agreement between clinical diagnosis and CUS results, no further testing is needed: patients with high or intermediate clinical probability and positive CUS results are treated, while in patients with low clinical probability and negative CUS results the diagnosis of DVT is excluded. In the case of discrepancy between clinical diagnosis and CUS results, D-dimer test and/or venography are requested. However in patients who develop signs or symptoms of DVT in the hospital the clinical model does not work, and diagnosis should be based on an appropriate mix of CUS, D-dimer (DD) test and venography. In patients presenting with signs or symptoms of pulmonary embolism, the ventilation/perfusion (V/P) lung scan remains a pivotal diagnostic test, and pulmonary angiography the reference standard, but both methods have limitations and in recent years other diagnostic tests such as echocardiography, helical (or spiral) computerized tomography, and magnetic resonance imaging have been introduced into clinical practice. Moreover, all four diagnostic tools mentioned for DVT diagnosis can be considered. Several diagnostic strategies have been proposed and evaluated in comparative studies but there is still debate over the most efficient test combination or sequence. INTERPRETATION AND CONCLUSIONS: Diagnostic strategies which include adequate consideration of clinical diagnosis using standardized models have the potential of being more efficient for outpatients (but not for inpatients) with symptoms or signs suggesting DVT of lower limbs. For patients with suspected PE, several diagnostic strategies have been assessed: V/P lung scan remains a pivotal diagnostic test, but its limitations have been increasingly recognized and newer non-invasive techniques are gaining credit. A consensus is still to be reached over the most appropriate combination of diagnostic tests.

Angiography↗

[Embolisms and thromboses in the lesser circulation and disseminated intravascular coagulation].

Investigations were carried out on 601 deceased with embolism and thrombosis in pulmonary circulation (ETPC), in 53 of the cases (8.82%) a generalized, in two or more organs, disseminated intravasal coagulation (DIC) was found. Generalized DIC develops most often in autochthon pulmonary thrombosis (in 30.91%) and more rarely in pulmonary embolism with additional autochthon thrombformation (in 15.19%). In a great part of pulmonary embolism with additional autochthon thromb-formation (96.62%) and autochthon pulmonary thrombosis (87.27%) DIC develops locally only in pulmonary microcirculation. The local DIC in lungs is characterized morphologically by the formation of multiple fibrin microthrombus (2--3 microthrombuses per square cm section) in the microcirculatory system of lungs. The development of local or generalized DIC aggravates the course of ETPC and could play an essential role in thrombogenesis, both by mechanic occlusion of pulmonary vessels and by serotonun elimination from the destroying thrombocytes.

Aged↗

[Pulmonary thromboembolism associated with glioblastoma multiforme: imaging diagnosis of a case and a review of the literature].

INTRODUCTION: The incidence of deep vein thrombosis and pulmonary embolism in patients with cerebral neoplasia has been estimated at 120/100,000 (the second highest rate for any kind of malignant neoplasia). A timely diagnosis is an indispensable requisite in the clinical evaluation of neurological patients. Patients suffering from glioblastoma multiforme present a generalized state of hypercoagulability with a deep vein thrombosis incidence after surgery of between 3 and 60%. The incidence with which pulmonary embolism occurs is 5% in patients following neurosurgical operations, with a mortality rate of between 9 and 50%. CASE REPORT: We report the case of a 64 year old male patient with a suspected diagnosis of pulmonary thromboembolism and thrombosis of the right lower limb. Clinical studies included a simple chest X ray, a Doppler ultrasound recording of the lower limbs, a spiral computed tomography (CAT) scan of the thorax, and a magnetic resonance (MR) scan of the head. The spiral CAT scan showed filling defects in the main pulmonary arteries, a tram track appearance and central filling defects. All these findings are compatible with an imaging diagnosis of pulmonary thromboembolism. CONCLUSIONS: The main aim of this study was to describe the use of spiral CAT scanning as a primary tool in the diagnosis of a case. The concurrence of the spiral scan image, the abnormal increase in D dimer and the clinical information left no doubts about the diagnosis. The clinical manifestations of pulmonary thromboembolism are not specific and therefore the patient s life is at risk. In addition, few reports have been published about the association between glioblastoma multiforme and the later appearance of pulmonary thromboembolism (a search was conducted in the medical literature from the last 10 years using MEDLINE), and hence we have presented a communication dealing with this pathological association together with a brief review of the clinical diagnosis of pulmonary thromboembolism and its physiopathogenic mechanisms.

Brain Neoplasms↗

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Septic atrial thrombosis. A potentially lethal complication of Broviac catheters in infants.

Even though the use of Silastic catheters for long-term parenteral nutrition has decreased the incidence of catheter-related thrombosis and infection, these serious complications still occur. We describe three infants with septic atrial thrombosis secondary to use of Broviac catheters. One of the infants had pulmonary embolism and Budd-Chiari syndrome. The use of echocardiography in the diagnosis of this potentially fatal complication and aggressive treatment--which included open heart removal of thrombi--are discussed. The three infants recovered fully from this complication.

Budd-Chiari Syndrome↗

Risk of thrombosis in patients with malignancy and heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a common immunological drug reaction. After exposure to heparin, some patients develop heparin dependent antibodies with no evidence of thrombosis, while others are at risk of thrombocytopenia, thrombosis, limb loss, and death. We conducted a retrospective chart review on all patients serologically positive for HIT by HPIA ELISA in a single tertiary-care hospital, to determine whether patients with malignancy had an increased risk of thrombotic complications. Medical records of 55 patients who tested positive for HIT and met clinical criteria for HIT were analyzed. All patients had been treated with unfractionated heparin. Malignancy was diagnosed in 11 patients, either at surgery or post-mortem examination. A higher rate of venous thrombosis and pulmonary embolism was observed in patients with HIT and malignant disease when compared to patients with no underlying malignancy (odds ratio 13.6, 95% CI 2.9-63.8).

Aged↗

[Venous thromboembolism prophylaxis].

Venous thromboembolism is a common and frequent complication of hospitalized patients. Some venous thromboembolisms may be subclinical, while others present as symptomatic deep vein thrombosis and/or pulmonary embolism. Venous thromboembolism and pulmonary embolism contribute significantly to inhospital morbidity and mortality. The risk of venous thromboembolism is aggravated by dispositional and/or expositional risk factors. In patients at intermediate or high risk of venous thromboembolism, additional pharmacological thromboembolism prophylaxis becomes mandatory.

Anesthesia↗

Low molecular weight heparin for deep vein thrombosis in glioma patients.

The treatment and secondary prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism, a common complication in patients with malignant glioma, has remained controversial. We treated 11 patients with malignant glioma and DVT prospectively with low molecular weight heparin (LMWH) at 175 IU/kg for 10 days and then for 3 months at 100 IU/kg. No patient developed bleeding complications or any other severe side effects of LMWH treatment. Two patients had a dose reduction of LMWH to 75 IU/kg because of chemotherapy-induced thrombocytopenia. One patient developed progressive DVT and nonlethal pulmonary embolism on day 14 of LMWH 100 IU/kg. After increasing the dose to 175 IU/kg he had no further recurrence. One patient had recurrence of DVT after a fracture of the leg affected by DVT at 8 months after the diagnosis of DVT and 5 months after the end of LMWH therapy. LMWH therapy may be safe and effective in the treatment and secondary prophylaxis of DVT in patients with malignant glioma.

Adult↗

Argatroban anticoagulation in patients with a history of heparin-induced thrombocytopenia.

INTRODUCTION: Heparin therapy is not recommended for patients with a history of heparin-induced thrombocytopenia (HIT), except in specialized situations, because this treatment can lead to severe reactions including thrombocytopenia and thrombosis. However, the optimal management of patients with a history of HIT requiring acute anticoagulation has not yet been clarified because of the lack of prospective studies. We evaluated the safety and efficacy of argatroban, a direct thrombin inhibitor, as an anticoagulant in patients with a history of HIT needing acute anticoagulation. METHODS: Thirty-six patients with a history of serologically confirmed HIT were treated prospectively with argatroban [median (5th-95th percentile) dose of 2.0 (1.0-4.3) microg/kg/min for 4.0 (0.7-8.4) days]. Prospectively defined endpoints included successful anticoagulation (therapeutic activated partial thromboplastin time), and bleeding, new thromboembolic events, or other adverse effects during therapy or within 30 days following its cessation. RESULTS: All patients required acute anticoagulation with the most common admission diagnoses being deep venous thrombosis or pulmonary embolism (n=13) and chest pain or acute coronary syndrome (n=12). Eleven patients had previously received argatroban therapy for HIT; one patient underwent two treatment courses of argatroban for a history of HIT. The median (5th-95th percentile) time between the past diagnosis of HIT and initiation of argatroban was 7.5 (0.4-114.6) months. All evaluable patients were successfully anticoagulated. No patient had major bleeding, new thromboembolic events, or other adverse effects. There were no adverse events related to reexposure. CONCLUSIONS: Argatroban can provide safe and effective anticoagulation, on initial or repeat exposure, in patients with a history of HIT.

Adult↗

Thromboembolic complications in patients with clear cell carcinoma of the ovary.

OBJECTIVE: The purpose of this study was to define the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients with clear cell carcinoma (CCC) of the ovary and to investigate the prognostic factors in such patients. METHODS: Between January 1987 and December 2003, 641 women with primary invasive epithelial ovarian cancer underwent treatment at the Royal Hospital for Women in Sydney, Australia. Sixty-six patients (10.3%) with CCC were identified from the data bank, and their data were compared with a matched-control group of 132 patients with non-clear cell epithelial ovarian carcinoma. RESULTS: A thromboembolic event (DVT or PE) was noted in 27.3% of patients with CCC, compared to 6.8% of patients with other epithelial ovarian cancers. PE was detected in 13.6% and 3.8% of patients, respectively. In patients with CCC, DVT was frequently observed before operation or at the time of recurrence. In a multivariate analysis of patients matched for age and stage, the occurrence of a DVT or the presence of endometriosis was significant predictors of clear cell histology. Within the clear cell group, no particular risk factor for DVT could be identified. Metastases of 50 mm or greater in diameter, ascites of 1000 ml or more, advanced FIGO stage, and the occurrence of DVT were poor prognostic factors for CCC in univariate analysis, but in a multivariate Cox regression analysis, only FIGO stage and occurrence of DVT remained significant. CONCLUSION: The incidence of venous thromboembolic events was found to be significantly higher in patients with CCC when compared to patients with other epithelial ovarian cancers.

Adenocarcinoma, Clear Cell↗

[Thrombotic accidents induced by thalidomide: two cases].

INTRODUCTION: First used as a sedative, thalidomide was taken out the market because of its teratogenicity. Despite other side effects, especially neuropathies, this drug is now again prescribed in various autoimmune and neoplasic diseases. Recently, venous or arterial thrombotic events have been described after the introduction of thalidomide. EXEGESIS: In this report, we describe two new venous thrombosis cases occurring during a treatment with thalidomide. The first case is a 37-year-old man treated for a discoid lupus, who developed three deep-vein thrombosis and a massive pulmonary embolism, with recurrent thrombosis even with an efficient anticoagulation therapy until the final stop of thalidomide. The second one is a 66-year-old woman treated with thalidomide for a multiple myeloma and a melanoma in therapeutic escape, who developed a deep-vein thrombosis two months after the beginning of her treatment. Published reports suggest that most thrombotic events appeared under three months after the introduction of the treatment and that thalidomide could have acted as a precipitating or as a starting factor in a patient population already at risk of thrombosis. Those complications should be particularly severe, but the mechanism underlying thrombosis with thalidomide is unknown. CONCLUSION: A complete coagulation check-up is advised before beginning a treatment with thalidomide.

Adult↗

D-dimer testing to determine the duration of anticoagulation therapy.

BACKGROUND: The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of D-dimer levels may play a role in the assessment of the need for prolonged anticoagulation. METHODS: We performed D-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal D-dimer level did not resume anticoagulation, whereas those with an abnormal D-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years. RESULTS: The D-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P=0.02). Thromboembolism recurred in 24 of 385 patients with a normal D-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal D-dimer level, as compared with those with a normal D-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P=0.02). CONCLUSIONS: Patients with an abnormal D-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal D-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277 [ClinicalTrials.gov].).

Acenocoumarol↗

Prolonged prophylaxis with unfractioned heparin is effective to reduce delayed deep vein thrombosis in total hip replacement.

The aim of this study was to assess the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) until 45 days after elective total hip replacement (THR) and the efficacy of prolonged unfractioned heparin (UH) prophylaxis up to postoperative day 30. To this end 79 of 96 patients admitted consecutively to the University Hospital of Pisa for THR were randomly assigned to short- or long-term UH prophylaxis. Sixty-one patients completed the study: 28 of them received short-term prophylaxis (subcutaneous UH 15,000 IU/24 h for 15 days) and 33 prolonged prophylaxis (subcutaneous UH 15,000 IU/24 h for 30 days). Lower limb phlebography was performed in all patients on day 45 after THR. DVT was demonstrated in 10 (16.3%) cases after hospital discharge. Among them, 2 patients also had symptomatic PE. The incidence of DVT was 21.4% in short- and 12.1% in long-term UH-treated patients. The incidence of only proximal DVT was 17.8% in short- and 3.0% in long-term UH-treated patients; although the difference was only close to significance (p = 0.085), the relative risk of developing proximal DVT was about six times greater in the former group of patients. We concluded that the risk for thromboembolism persists at least until 45 days after surgery in patients subjected to THR. Prophylaxis with UH given up to postoperative day 30 appears more effective and safer in reducing the delayed thromboembolic risk compared to prophylaxis with UH given up to discharge only.

Aged↗