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[Thromboembolic pulmonary arterial hypertension].

Thromboembolic pulmonary hypertension can occur in two different settings: either acute pulmonary embolism or chronic pulmonary thromboembolism. During acute pulmonary embolism, when the heart and lungs are normal, the mean pulmonary artery pressure never excesses 40 mmHg, this is the maximum pressure the right ventricle can stand. During chronic thromboembolism, the right ventricle can adapt to slowly increasing pulmonary artery pressure. The mean pulmonary artery pressure is usually very elevated and right heart failure is delayed. Diagnosis is difficult when an history of acute pulmonary embolism or phlebitis is lacking. At the beginning, the main differential is psychogenic dyspnea. A clue to the diagnosis is given by the pulmonary function test mainly arterial blood gases at rest and exercise and radionuclide perfusion scan. When the pulmonary hypertension is patent the main differential is primary pulmonary hypertension. No definitive clear cut can be made between multiple distal chronic thromboembolism and primary pulmonary hypertension.

Acute Disease↗

[Importance of risk factors in the extension of pulmonary thromboembolism].

The cases of pulmonary thromboembolism (PTE) diagnosed in the clinical autopsies performed in our hospital during a 15-year period were reviewed. The incidence was 2.7% (63 cases). The most common disease associated with thromboembolism was cancer (41%). In 30 cases, thromboembolism involved more than 60% of the pulmonary circulation (group I), between 40% and 60% in 18 cases (group II), and less than 40% in 15 cases (group III). 30% of the embolisms were recurrent. A statistically significant correlation between the extension of the involved pulmonary circulation and the condition associated with thromboembolism was found. Whereas in patients with neoplasia the extension of pulmonary circulation involved by PTE was quite variable, the patients with cardiovascular disease or thrombophlebitis had PTE with invariably severe compromise of pulmonary vasculature (groups I and II).

Acute Disease↗

[Chrono-risks in the episodes of fatal pulmonary thromboembolism].

A study on circadian and circannual rhythmicity in the episodes of fatal pulmonary thromboembolism has been conducted in 152 cases. The data demonstrate that the incidence in the episodes of pulmonary thromboembolism, evaluated as hour and day of onset in the clinical symptoms, presents a temporal, both circadian, and circannual distribution. The greater incidence occurs in the morning hours and in the winter season. The rhythmometric analysis by "cosinor" method showed a significant circadian and circannual rhythms in incidence of episodes of fatal pulmonary thromboembolism. The temporal distribution does not seem to be casual, but the effect of interrelationship between exogenous rhythms, such as those in the haemostatic system, endogenous rhythms, such as the cold temperature, and disease. These results demonstrate that the pulmonary thromboembolism is a disease with an high "chrono-risk", i.e. it is an expectable disease in its temporal recurrence.

Adult↗

[Anatomo-clinical correlations in pulmonary thromboembolism (observations on 258 cases)].

The authors studied 258 cases of deaths due to lung thromboembolization, totalling 13% of the necropsies. The patients' age ranged within 17-89 years, with the highest frequency between 70 and 75 years. The female sex was prevalent (56% of cases). According to the magnitude of the vessel occluded, the thromboembolisms were divided into: massive (35%), medium (50%) and small (15%). The lung infarctions were present in 42% of the cases investigated. The formation site of the thrombi was exactly established in 24% of the cases; the right side of the heart, the lung, the deep veins of the shank, periprostatic venous plexus, vena cava inferior, iliac veins. The lung thromboembolization was favoured by the cardiovascular affections (38.5%), neurologic affections (27%), malignant tumours (11.5%), postsurgery status (9%), lung diseases (9%), coma (3.5%), prostate affections (1.5%). The clinical diagnosis was established in 22% of cases. In the rest of them, thromboembolization was hidden or simulated by the coexisting affection.

Adolescent↗

Pulmonary thromboembolism associated with immune-mediated hemolytic anemia in dogs: ten cases (1982-1987).

Pulmonary thromboembolism was confirmed at necropsy in 10 (32.2%) of 31 dogs treated for immune-mediated hemolytic anemia. Radiographic findings associated with thromboembolism included pronounced interstitial lung pattern and small amounts of pleural effusion. Variables associated with significantly higher incidence of pulmonary thromboembolism included hyperbilirubinemia (P = 0.023), negative Coombs test result (P = 0.032), and presence of an indwelling catheter (P = 0.04). There was a tendency (P = 0.06) for association of higher number of whole blood transfusions with pulmonary thromboembolism.

Anemia, Hemolytic, Autoimmune↗

[Assessment of the pulmonary blood flow changes in thromboembolism of small branches of the pulmonary artery].

Patients with thromboembolism of small branches of the pulmonary artery (TESPA) were examined by rheopulmonography (RPG) for the pulmonary blood flow over the zones of thromboembolism and uninvolved parts of the lungs. The study was performed at the initial disease stage, on days 3-7 of the disease and before the patient's discharge from hospital. It was shown that pulmonary circulation undergoes some successive changes. During the first phase, the total vascular hypertension and arterial hypertension of the pulmonary circulation together with occlusion are noted. During the second phase, dilatation of the arterial bed in the healthy zones and normalization of arterial hypertension together with the reduced blood flow in the area of thromboembolism are observed. The convalescence phase is characterized by the recovery of the blood flow in the area of thromboembolism and return of the arterial tone in the pulmonary circulation to normal. RPG permits one to have an objective evaluation of the clinical picture of TESPA and therapy received by the patients.

Adult↗

Preoperative mini-heparin, prostatectomy and clinical pulmonary thromboembolism.

From February 1973 through May 1977, a selected group of 131 patients undergoing prostatectomy were given preoperative mini-heparin 6--8 hours prior to surgery. There were 17 retropubic prostatectomies, 1 subtotal suprapubic prostatectomy and 113 transurethral prostatic resections. Patients ages ranged from 35 to 108 years. There were 109 cases of benign prostatic hyperplasia, 13 cases of adenocarcinoma of the prostate and 9 cases of benign prostatic hyperplasia with foci of adenocarcinoma. There was one death from massive pulmonary thromboembolism and one case of non-fatal pulmonary thromboembolism. A retrospective review of 416 prostatectomies performed during the same period of time at the same hospital, in which mini-heparin was not administered preoperatively, revealed only one case of non-fatal pulmonary thromboembolism. Our study indicates that this preoperative mini-heparin regime did not effectively reduce the morbidity and mortality associated with clinical postoperative thromboembolic phenomena. There were no important side effects, such as prolonged bleeding or drug intolerance, associated with the administration of preoperative mini-heparin.

Adenocarcinoma↗

The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease.

Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C (PC). It has been clearly demonstrated that the anticoagulant and profibrinolytic functions of the PC system are important for the prevention of a thromboembolic disease. Patients with PC, protein S, or PC "'cofactor"' deficiency and/or dysfunction develop thromboembolic diseases. However, the molecular abnormality in at least 20% to 30% of thrombophilic patients cannot be identified by hitherto recognized defects. A putative pathologic lesion in the TM gene could be one of several candidates for these prothrombotic mutations. A directed search strategy for deletions, insertions, or point mutations in the TM gene has not been performed. Therefore, in the present study, we have analyzed the entire TM gene, including the promoter region, by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) in normal healthy volunteers and in patients presenting with a thromboembolic disease. We have identified a patient with a thromboembolic disease and a TM point mutation. In a 45-year-old Hispanic man with a documented pulmonary embolism, PCR-SSCP showed an aberrant band pattern and subsequent DNA sequence analysis showed a heterozygous substitution for G1456 to T. This substitution predicts an Asp468 to a Tyr change in the amino acid sequence that is located between the transmembrane domain and the sixth epidermal growth factor-like domain. The Asp468 to Tyr change would probably lead to significant structural changes not allowing the expression of the TM protein or to a conformational change that is not functional.

Adult↗

[Treatment with oral anticoagulants (acenocoumarol): influence of the initial doses in the incidence of hemorrhagic and thromboembolic episodes].

PURPOSE: To compare two initial doses of oral anticoagulant (acenocoumarin) studying the haemorrhagic and thromboembolic episodes occurred during the first month of treatment, the mean time and necessary controls until achievement of the desired level of anticoagulation. PATIENTS AND METHODS: From january 1992 to december 1993; a comparative study of two groups of patients was performed: group 1, compiling 129 patients chosen at random and retrospectively, who begun oral anticoagulant treatment with 4 daily mg of acenocoumarin; and group 2, compiling 129 patients chosen prospectively, who begun with 2 mg daily. In both groups the mean time and the number of controls performed until achieving the desired level of anticoagulation were analyzed, as well as the haemorrhagic episodes occurred during the first month of treatment, their severity (classified into major and minor ones), the level of anticoagulation when they occurred and their possible causes. In the same way the thromboembolic processes occurred during that period in both groups were studied. RESULTS: The mean time necessary to achieve the desired level of anticoagulation was 3.8 days in group 1 and 6.3 in group 2; the mean number of controls performed in group 1 was 1.2 and in group 2 it was 1.8. We have observed 19 haemorrhagic episodes, 15 in group 1 (4 minor and 11 major); and 4 in group 2 (2 minor and 2 major). We have found significant differences with respect to the mean time (p < 0.01), number of controls (p < 0.01) and incidence of hemorrhages (p = 0.017) between groups 1 and 2. One thromboembolic episode was registered in each group: in group 1 a deep venous thrombosis and in group 2 a stroke. CONCLUSION: The initial daily doses of acenocoumarin of 2 mg is as effective as the 4 mg one in the prevention of thromboembolic episodes, with a significant reduction in the number of haemorrhages observed during the first month of treatment. However this produces a prolongation in the necessary mean time and more number of controls performed until the achievement of the desired level of anticoagulation.

Acenocoumarol↗

[Surgical treatment of thromboembolism-induced pulmonary hypertension].

Non-resolved chronic pulmonary thromboembolism is a frequent cause of pulmonary hypertension. In long-standing disease hypertension is progressive due to intimal and medial changes in the perfused vessels. Non-resolution of thromboemboli is often associated with underlying coagulopathies; the presence of a lupus anticoagulant may pose a significant problem in the peri-operative management of these patients. Pulmonary thrombendarterectomy presents an efficient option of treatment which is feasible in the majority of patients. By means of pulmonary angiography and computed tomography operability is verified by the often difficult recognition of thromboembolic changes in the central pulmonary arteries. Patients with solely peripheral thromboembolic changes or primary pulmonary hypertension must be excluded. In presence of significant exertional dyspnea and/or pulmonary pressure elevation surgery is indicated. Mortality is high and mainly related to unrelieved pulmonary hypertension or pulmonary complications; pulmonary reperfusion edema, respiratory failure or pneumonia and sepsis. In all survivors the reduction of pulmonary hypertension is highly significant and persistent. Thromboembolic pulmonary hypertension may be treated curatively in most patients by thrombendarterectomy. Correct selection of surgical candidates is mandatory, and the patients should preferably be diagnosed and undergo surgery in an early stage of their disease.

Adolescent↗

Semiquantitative test for Dirofilaria immitis as a predictor of thromboembolic complications associated with heartworm treatment in dogs.

A semiquantitative heartworm test of antigen concentration was evaluated as a predictor of thromboembolism after adulticide treatment. Seventeen dogs with naturally acquired infections of Dirofilaria immitis (heartworms) were studied before and after thiacetarsamide treatment, using physical examinations, arterial blood gas analyses, thoracic radiography, and pulmonary hemodynamic and arteriographic tests. Eight dogs were considered to have a low burden of heartworms and 9 had a high burden. Dogs with a high worm burden had more severe pulmonary thromboembolism with pulmonary hypertension, dilated pulmonary arteries, flow obstruction of the caudal pulmonary arteries, and parenchymal lesions in the caudal lung lobes. Dogs with a low worm burden had minimal changes. Within each group of dogs, the severity of thromboembolism was less in some dogs in which all heartworms were not killed. Six of the 9 dogs with a high burden of heartworms had surviving heartworms, and 1 of these dogs had 38 live heartworms. Only 4 of the 8 dogs with a low worm burden had complete heartworm mortality, but only 1 dog had more than 3 surviving heartworms. We concluded that dogs with a high worm burden were more likely to have pulmonary thromboembolism after thiacetarsamide treatment and that dogs with a low worm burden were more likely to have minimal changes. A semiquantitative heartworm test of antigen concentration is recommended as part of the pretreatment evaluation of dogs infected with heartworms.

Animals↗

[Pulmonary thromboembolism--random analysis of autopsy material].

In the study an analysis of 13216 autopsy materials was performed to evaluate a frequency of pulmonary thromboembolism incidence including localisation of detected changes. Pulmonary thromboembolism was determined in 5.5% autopsies, with evident increase in older subjects (up to 31.3% in 70-79 years old group). The most frequently (67.8%) pulmonary thromboembolism was observed in lobar and segmental arteries in a course of atherosclerosis (28.6%), neoplasmas (20.8%) and septic diseases (15.5%). In 25% cases of pulmonary thromboembolism has been diagnosed during clinical observations and has been confirmed by autopsy procedure.

Adolescent↗

Risk factor profiles in patients with different clinical manifestations of venous thromboembolism: a focus on the factor V Leiden mutation.

BACKGROUND: Patients with venous thromboembolic disease may present with different clinical manifestations. Factor V Leiden mutation leading to resistance to activated protein C is associated with a sevenfold increased risk for presenting with deep-vein thrombosis. It is not yet established whether carriers of the mutation have a similarly increased risk for manifesting with pulmonary embolism. METHODS: From an Anticoagulation Clinic monitoring coumarin therapy, a consecutive series of patients with a first thromboembolic event (objectively proven by current radiological methods) were enrolled. All patients were interviewed and blood was drawn for genotyping. From the hospital charts and the personal interview, information was obtained on acquired risk factors and the signs and symptoms on hospital admission. RESULTS: 45 patients presented with symptoms of pulmonary embolism only, 211 had only symptoms of deep-vein thrombosis whereas 23 had clinical features of both. In about half of the patients acquired risk factors for venous thromboembolism were present which did not differ between the three groups of patients. Recent surgery had been performed more often in patients presenting with pulmonary embolism than in other patients (33.3% vs. 18.5%, p < 0.05). Factor V Leiden was present in 9% of the patients presenting with pulmonary embolism (relative risk: 3.3 95% CI: 1.0-10.6) and 17% of the patients presenting with deep-vein thrombosis (relative risk: 6.9 95% CI: 3.6-12.8). The prevalence of factor V Leiden was intermediate in patients with both clinical characteristics. CONCLUSION: These data suggest that patients with venous thromboembolism have different clinical presentation depending on the risk factor profile. Factor V Leiden may preferentially lead to manifest deep-vein thrombosis. Differences in structure of venous thrombi could underlie differences in embolic tendency.

Adult↗

Risk factors and prevention of venous thromboembolism.

In the last 20 years within the clinical research on venous thromboembolism a major objective was to identify and develop increasingly effective and safe methods of prevention. This trend is justified by the high incidence of thromboembolism as well as by the relevant mortality for acute pulmonary embolism and postphlebitic sequels of difficult treatment. A significant contribution to the rational application of methods of prevention was given by the knowledge of risk factors. Together with acquired risks, as surgery, age, malignant tumors, in the last 30 years some conditions of thrombophilia were identified. They are caused by deficiencies in coagulation inhibitors (antithrombin III, protein C, protein S) or other alteration of the anticoagulation system as resistance to activated protein C or antiphospholipid antibodies. The primary prophylaxis of venous thromboembolism is aimed at the prevention of thrombosis by pharmacologic methods able to oppose the procoagulant alterations while avoiding hemorrhagic complications. The physical methods tend to reduce the stasis in the veins of the lower extremities. Subcutaneous calcium heparin at the dose of 5000 U twice or three times a day is the most common pharmacologic method used. It was shown to be safe and effective especially in postoperative prophylaxis of venous thromboembolism in general surgery. More recently, low molecular weight heparin fractions have been introduced. As compared to standard heparin they have the advantage of a single daily dose and a better efficacy in some groups of patients, as those undergoing hip replacement. Among the substances under clinical experimentation, dermatan sulfate seems promising. Most common physical prevention methods consist in the use of elastic graduated compression stockings and systems of intermittent pneumatic calf compression. The former can be used also in presence of a hemorrhagic risk as in neurosurgery. The latter have shown a good efficacy in increasing flow velocity and probably also in enhancing the fibrinolytic activity. The combination of physical and pharmacologic methods seems to be able of enhancing the efficacy of prophylaxis.

Anticoagulants↗

Hyperhomocysteinemia and venous thromboembolic disease.

BACKGROUND AND OBJECTIVE: In spite of the large number of reports showing that hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and arterial occlusive disease, this metabolite of the methionine pathway is measured in relatively few laboratories and its importance is not fully appreciated. Recent data strongly suggest that mild HHcy is also involved in the pathogenesis of venous thromboembolic disease. The aim of this paper is to analyze the most recent advances in this field. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. In addition the authors of the present article have been working in the field of mild HHcy as cause of venous thromboembolic disease. STATE OF ART AND PERSPECTIVES: The studies examined provide very strong evidence supporting the role of moderate HHcy in the development of premature and/or recurrent venous thromboembolic disease. High plasma homocysteine levels are also a risk factor for deep vein thrombosis in the general population. Folic acid fortification of food has been proposed as a major tool for reducing coronary artery disease mortality in the United States. Vitamin supplementation may also reduce recurrence of venous thromboembolic disease in patients with HHcy. At the present time, however, the clinical efficacy of this approach has not been tested. In addition, the bulk of evidence indicates that fasting total homocysteine determinations can identify up to 50% of the total population of hyperhomocysteinemic subjects. Patients with isolated methionine intolerance may benefit from vitamin B6 supplementation. Homocysteine-lowering vascular disease prevention trials are urgently needed. Such controlled studies, however, should not focus exclusively on fasting homocysteine determinations and folic acid monotherapy.

Homocysteine↗

The cumulative incidence of venous thromboembolism during pregnancy and puerperium--an 11 year Danish population-based study of 63,300 pregnancies.

OBJECTIVES: The aim of the study was to estimate the cumulative incidence of venous thromboembolism during pregnancy and the puerperium. METHODS: All diagnoses concerning venous thromboembolism in the Hospital Discharge Registry from a Danish County in women less than 49 years of age from 1984 to 1994 were included. The number of deliveries in the County during this period was obtained from The Medical Registry of Birth. RESULTS: The cumulative incidence of venous thromboembolism during pregnancy and puerperium was 0.85 (95% CI: 0.64-1.11) per 1000 deliveries. The cumulative incidence was 0.49 (95% CI: 0.28-04).80) in 1984-89 but increased to 1.23 (95% CI: 0.87-1.69) after the introduction of ultrasound. CONCLUSION: The risk of diagnosed venous thromboembolism is low but estimates of the incidence are probably procedure dependent.

Denmark↗

Thromboembolic events associated with the treatment of cerebral aneurysms with Guglielmi detachable coils.

BACKGROUND AND PURPOSE: The purpose of this study was to document the prevalence, radiologic appearance, and treatment of thromboembolic events related to GDC embolization of cerebral aneurysms. METHODS: The clinical and radiologic records of all patients undergoing GDC treatment of intracranial aneurysms at our institution were reviewed. All cases in which unexpected complications occurred were selected. Those complications related to presumed thromboembolic events were analyzed. RESULTS: Of 59 patients (60 aneurysms) treated with GDCs, 17 (28%) experienced thromboembolic events. Seven patients had transient ischemic attacks and 10 had strokes. In 10 patients, the deficits occurred during or immediately after the procedure; in the rest, the complications were delayed. In six patients, all radiologic investigations were negative for infarction and in seven patients, CT scans showed new ischemic lesions. In four patients, MR imaging alone showed infarcts, and in four of nine patients who underwent subsequent angiography, acute ischemic findings were demonstrated. Eight patients were treated with volume expansion, eight with full heparinization, and one patient underwent intraarterial thrombolysis. Clinical outcome was excellent or good in 14 of 17 patients, with only three patients (5%) incurring permanent neurologic deficits. CONCLUSION: Thromboembolic events related to GDC treatment may be more common than has been reported in the literature. In our experience, this rate was 28%, with persisting deficits in 5%. These events can occur after uncomplicated procedures and may be unaccompanied by radiologic findings. Clinical outcome is usually favorable.

Adult↗

[Potential role of primary hypercoagulability and antiphospholipid antibody as a risk factor of acute pulmonary thromboembolism].

To examine whether primary hypercoagulable states, such as protein C and protein S deficiencies and antiphospholipid antibody, are associated with an increased risk, severity and recurrence of acute pulmonary thromboembolism, the blood levels of antithrombin III, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies were measured in 23 patients with acute pulmonary thromboembolism, 7 men and 16 women (mean age +/- SD, 52 +/- 5 years), admitted to Nippon Medical School Hospital from January, 1990 through December, 1997. Four patients (17.4%) had protein C deficiency, one had protein S deficiency (4.3%), 10 had lupus anticoagulant (43.5%), and 2 had anticardiolipin antibodies (8.7%). Hemodynamic evaluation by Swan-Ganz catheter and venography of the lower extremity to detect deep venous thrombi were carried out in 20 and 21 patients, respectively. There were no differences between the patients with and without primary hypercoagulable states in age (52 +/- 14 vs 52 +/- 19 years), gender, or percentage of patients with deep venous thrombi in the lower extremity (91.7% vs 88.9%). Mean pulmonary arterial pressure (38 +/- 9 vs 26 +/- 4 mmHg, p < 0.05) and total pulmonary vascular resistance (10 +/- 5 vs 6 +/- 2 Wood unit, p < 0.1) were higher in the 13 patients with primary hypercoagulable states compared with the 10 patients without primary hypercoagulable states. Recurrence of pulmonary thromboembolism tended to be higher in the 13 patients with primary hypercoagulable states compared with the 10 patients without primary hypercoagulable states (46.2% vs 10.0%, p < 0.1). These findings suggest that primary hypercoagulable states, such as protein C and S deficiencies and antiphospholipid antibody, are associated with the severity and increased risk and recurrence of acute pulmonary thromboembolism.

Acute Disease↗