Search  in
NUMBER 2-3 YEAR 2006
Cardiogenic Shock in a 71-Year-Old Man with Recurrent Syncopes
1 Cardiology Clinic, Timisoara Municipal Hospital
2 Institute of Cardiovascular Medicine, Timisoara
3 Haematology Clinic, Timisoara Municipal Hospital

Correspondence to:
Mirela Tomescu, Cardiology Clinic ASCAR, Municipal Hospital, 12 Revolutiei Blvd., Timisoara, Tel/Fax: +40 256 220 636
Embolia pulmonara este o boala frecvent subdiagnosticata, potential letala, ce apare in serviciile de medicina interna si chirurgie. Suspiciunea clinica de embolie pulmonara se bazeaza pe anamneza, examenul obiectiv, masurarea gazelor pulmonare, electrocardiograma si radiografia toracica. Diagnosticul este confirmat de o scintigrama de ventilatie-perfuzie patologica, de examenul computer-tomografic al toracelui cu substanta de contrast sau de angiografia pulmonara. Ultrasonografia venoasa este utila putind demonstra prezenta trombozei venoase profunde. Tratamentul anticoagulant ramine cel mai important mijloc terapeutic, in prezent fiind dezvoltate metode noi, indreptate fie spre reducerea riscului de recurenta, fie spre minimalizarea riscului de singerare la anumiti pacienti (filtre venoase, heparine cu greutate moleculara mica, medicamente anticoagulante noi). Articolul de fata descrie cazul unui pacient de 71 de ani spitalizat pentru soc cardiogenic. Nu s-a putut face distinctia clara intre embolia pulmonara si sindromul coronarian acut utilizind doar testele neinvazive disponibile. Diagnosticul de embolie pulmonara masiva ce a complicat o tromboza venoasa profunda a fost stabilit dupa efectuarea angiografiei pulmonare. Pacientul a avut o evolutie favorabila dupa tratamentul medical (anticoagulante: heparina si antivitamine K) si interventional (plasarea unui filtru venos). Episodul de hemoragie gastrica in cantitate mare survenit in cursul internarii si cauzat de trombocitopenia indusa de heparina a fost contracarat prin transfuzii de masa trombocitara si eritrocitara.

Pulmonary embolism is a frequently under diagnosed, potentially lethal condition in medical and surgical services. Clinical suspicion of pulmonary embolism rests upon history taking, physical examination, arterial blood gases determination, 12-lead ECG and chest X-ray. The diagnosis can be affirmed on abnormal ventilation / perfusion scan, spiral CT scan of the chest with contrast medium or contrast pulmonary angiography. Venous ultrasonography may be useful in documenting the presence of a deep venous thrombosis. Anticoagulant therapy remains the cornerstone of the therapy, newer techniques being developed in order either to minimize the risk of recurrent pulmonary embolism or the risk of hemorrhage in selected patients (venous filters, low molecular weight heparins, newer anticoagulant agents). The present case report concerns a 71-year old man hospitalized for cardiogenic shock. A definite distinction between pulmonary embolism and acute coronary syndromes couldn't be made using available non-invasive tests. The diagnosis of massive pulmonary embolism complicating a deep venous thrombosis was established after pulmonary angiography. The patient had a favorable outcome after medical (anticoagulants - heparin and vitamin K antagonists) and interventional (venous filter) therapy. A major episode of gastric hemorrhage due to heparin-induced thrombocytopenia complicating the patients' hospital course was overcome by platelet and red blood cell transfusions.

A 71-year-old man was admitted to the emergency department of the city hospital in cardiogenic shock. The patient had been in stable health until two weeks before admission, when he was admitted to another hospital with prolonged chest pain, lasting for several hours, palpitations, sweating and recurrent syncope.
Symptoms were interpreted as an acute coronary syndrome and persisted under treatment with nitrates, heparin, aspirin and beta blockers.
The patient had a history of deep venous thromboses of the left calf. He followed oral anticoagulant treatment with a vitamin K antagonist for one year and stopped this treatment a few months before the onset of symptoms.
The family history indicated a chronic venous insufficiency of the legs in his mother and a fatal myocardial infarction at the age of 60 years in his brother. The patient was retired. He had never smoked and had drunk alcohol occasionally.
In the emergency department, the hemodynamic condition of the patient was unstable. The patient was pale and perspired. The systolic blood pressure was 60 mm Hg, the heart rate was 90 beats per min. Auscultation of the heart sounds revealed the presence of a 3rd sound. The patient had tachypnea (26 breaths/min) without pulmonary rales, bulging of the neck veins, hepatomegaly and a painful swelling of the left calf, with a positive Homans sign. Neurological examination was normal.
Figure 1. Electrocardiogram obtained on admission.
Figure 2. Anteroposterior chest radiogram showing focal oligemia at the level of the upper left lung lobe, upper and middle right lung lobe (ar [...]
The electrocardiogram on admission showed a regular sinus rhythm with a ventricular rate of 90 beats per minute, a QRS axis at + 70o, a 1st degree atrioventricular block (PR interval = 0.24 sec), an incomplete right bundle branch block and non-specific ST-segment abnormalities: 1 mm ST elevations in DI, DII and aVL. (Fig. 1)
The chest radiography showed: normal heart size (cardio-thoracic ratio = 0.48), focal oligemia at the level of the upper left lung lobe, upper and middle right lung lobe, enlarged left descending pulmonary artery and elevation of the left hemidiaphragm. (Fig. 2). Transthoracic 2D-Doppler echocardiography showed normal size and function of the left ventricle, with an ejection fraction (LVEF) of 48%. The right ventricle was dilated (40 mm), with paradoxical septal motion. No thrombus was detected within the right ventricle. (Fig. 3) There was evidence of severe pulmonary hypertension (mean pulmonary arterial pressure = 50 mmHg).
Table 1. Laboratory values on admission.
Figure 3. Transthoracic echocardiogram. An apical four-chamber view of the heart shows dilatation of the right ventricle.
An ultrasonographic examination of the abdomen revealed a diffusely increased echographic texture of the liver. The gallbladder, common bile duct, pancreas, kidneys and spleen appeared to be normal.
Laboratory studies were performed. (Table 1) They showed leukocytosis (27.200/ml) with neutrophilia (84%), increased liver enzyme levels (ASAT = 117 U/l, ALAT = 60 U/l), increased total and indirect bilirubin levels, moderately increased levels of plasmatic creatinine (1.6 mg/dl) and BUN (50 mg/dl). CPK and CPK-MB levels remained normal. The number of platelets on admission was normal. The urinary volume was reduced (500 ml/24 hours). Arterial blood gases determination showed hypoxemia: arterial saturation in oxygen 90%. Pulmonary ventilation / perfusion scanning could not be performed due to technical reasons.
The presumptive diagnosis was pulmonary thromboembolism complicating a deep venous thrombosis of the left limb.
Two litres of normal saline were administered, and infusion of dopamine and dobutamine was started at a dose of 4-5 μg per kilogram per minute. Anticoagulant treatment was given, starting with a bolus of 5000 IU of unfractionated heparin, followed by a continuous infusion at a dose of 1200 units per hour, under the control of the partial-thromboplastin time. Oxygen was administered through a face mask.
The evolution of the patient was initially favorable, the blood pressure and the urinary volume increased to normal levels, dyspnea was regressive.
On the 3rd day of hospitalization, the patient complained of prolonged retrosternal pain, with new ECG changes: there was a deep S wave in lead I, with narrow Q waves in leads III, and aVF; a 1 mm ST-segment elevation in leads II, III and aVF; and T waves were inverted in leads I, II, III, aVF, and in V1 through V6. (Fig. 4)
Figure 4. Electrocardiogram obtained on the 3rd day after admission.
Figure 5. Coronary angiogram showing 25-50% stenosis of the left anterior descending artery.

Figure 6. Left pulmonary artery angiogram.
Figure 7. Optease venous filter inserted in the inferior vena cava (arrow).
The patient was addressed to the Institute of Cardiovascular Medicine, for invasive examination. Coronary angiography showed normal coronary arteries, except for a 25-50% stenosis in the middle segment of the left descending anterior artery. (Fig. 5) Pulmonary angiography revealed multiple embolic occlusions of the lobar arteries and severe pulmonary hypertension (systolic pulmonary artery pressure = 80 mm Hg). (Fig. 6)
Thrombolytic treatment was administered: 15 mg of alteplase (a recombinant tissue plasminogen activator) were given as an intravenous bolus, and then 85 mg were infused over a period of 90 minutes. After thrombolysis, systolic pressure in the pulmonary artery decreased to 50 mmHg and arterial saturation in oxygen increased to 96%.
An OPTEASE filter was placed in the inferior vena cava, in order to prevent further pulmonary embolism. (Fig. 7)
Anticoagulant treatment was continued with fractionated heparin (Enoxaparine, 100 mg bid), followed by oral anticoagulation with a vitamin K antagonist. The two anticoagulant therapies were associated for three days, until INR values became higher than 2 for two consecutive days.
The patient’s hospital course was complicated by the development of heparin-induced thrombocytopenia (platelet number decreased to 25,000/ml), and a major gastric haemorrhage with acute anemia (Hb = 9 g/dl, Hct = 27%).
Six units of platelets and one unit of packed red cells were transfused, in order to correct these abnormalities. A repeated platelet count was 180,000 per cubic millimeter, with a hematocrit of 28.9%. Gastric endoscopy revealed erosive gastritis.
Further evolution was favorable, with significant regression of dyspnea, chest discomfort and complete recovery of the renal and liver function tests. A moderate swelling persisted at the level of the left leg.
The patient was discharged with instructions to continue taking lifelong oral anticoagulant therapy, with a target international normalized ratio (INR) of 2.5 to 3.5.
His condition will be evaluated after a few months, in order to establish the severity of the residual arterial pulmonary hypertension and the usefulness of an open surgical embolectomy.


Differential diagnosis
The clinical probability of pulmonary embolism was intermediate (6 points).1,2 (Table 2)
The patient was at risk for coronary artery disease because of age, sex, clinical symptoms (chest pain associated with dyspnea), and dynamic ECG changes. But CPK-MB levels remained normal and echocardiography showed normal left ventricular wall motion, right ventricular dilatation and severe pulmonary arterial hypertension.
The accurate detection of pulmonary embolism remains difficult and differential diagnosis is extensive.2,3 (Tables 3, 4) Pulmonary embolism can accompany as well as mimic other cardiopulmonary illnesses. Overdiagnosis is as likely as underdiagnosis. The optimal strategy is an integrated diagnostic approach that includes a methodical history taking and physical examination, supplemented by selective testing when appropriate.
Table 2. Rules for predicting the probability of embolism.
Table 3. Symptoms, signs and findings in suspected pulmonary embolism (PE).

Table 4. Differential diagnosis of pulmonary embolism.
Table 5. Risk factors for venous thromboembolism.
Details should be sought regarding the patient’s history, family history of venous thrombosis, as well as coexisting conditions, environmental risk factors, and hormonal influences.4,5 (Table 5)
Dyspnea is the most frequent symptom of pulmonary embolism, and tachypnea is the most frequent sign.6 Whereas the presence of dyspnea, syncope, or cyanosis usually indicates massive pulmonary embolism, findings of pleuritic pain, cough, or hemoptysis often suggest a small embolism near the pleura.
On physical examination, findings of right ventricular dysfunction include bulging neck veins with prominent v waves, a left parasternal lift, an accentuated pulmonic component of the second heart sound, and a systolic murmur at the left lower sternal border that increases in intensity during inspiration. These signs may be obscured by obesity or by a barrel chest with increased anteroposterior diameter. Bulging neck veins may be replaced by profound hypoxemia when right-to-left shunting occurs through a patent foramen ovale.
Electrocardiography and chest radiography should usually be incorporated into the diagnostic workup. The most frequent electrocardiographic abnormality is the inversion of T waves in the anterior leads, especially leads V1 to V4. These are probably reciprocal changes reflecting inferoposterior ischemia due to compression of the right coronary artery by the right ventricle as a result of pressure overload. New-onset right-bundle branch block or atrial fibrillation is uncommon.
Abnormal findings on the chest film may include focal oligemia (Westermark’s sign), a peripheral wedge-shaped density above the diaphragm (Hampton’s hump), and an enlarged right descending pulmonary artery (Palla’s sign).6
If the clinical likelihood is low, however, a D -dimer enzyme-linked immunosorbent assay (ELISA) and venous ultrasonography may be useful. Because the D dimer ELISA lacks specificity and levels of D dimer may be elevated in patients with myocardial infarction, pneumonia, heart failure, or cancer and in those who have undergone surgery, the assay is best suited for patients who present to the emergency department or physician’s office without other systemic illnesses.1
The sensitivity and specificity of compression ultrasonography are more than 95% for proximal deep-vein thrombosis and lower (70-80%) for isolated deep vein thrombosis of the calf. Venography may be useful to confirm the diagnosis when ultrasonography suggests isolated distal thrombosis.
Findings of hypoxemia or hypocapnia may increase physician’s level of diagnostic suspicion, but these findings are not specific for pulmonary embolism.
Transthoracic echocardiography is particularly useful in critically ill patients suspected of having pulmonary emboli and can help identify right ventricular pressure overload as well as myocardial infarction, dissection of the aorta, or pericardial tamponade, which may mimic pulmonary embolism. The McConnell sign of pulmonary embolism is a pattern of regional right ventricular dysfunction in which apical wall motion remains normal despite hypokinesia of the free wall.7
Perfusion lung scanning remains the most useful screening test to rule out clinically important acute pulmonary embolism. Whereas normal results or results indicating a high probability of disease are extremely helpful, non diagnostic results are difficult to interpret. Only rarely does ventilation scanning clarify the interpretation of perfusion lung scans.8
An alternative to lung scanning or conventional pulmonary angiography is spiral computed tomography (CT) of the chest with contrast medium. This approach is best suited for identifying pulmonary embolism in the proximal pulmonary vascular tree.9
However, if CT findings are normal in the presence of a high index of clinical suspicion, contrast pulmonary angiography that focuses on the distal pulmonary vasculature should be performed. It is important to identify small distal pulmonary emboli that may not be detected by spiral CT of the chest, because a major pulmonary embolism may ensue unless adequate anticoagulation is initiated. For patients with renal insufficiency and high probability of pulmonary embolism, the exposure to contrast medium will be minimized if one forgoes CT and proceeds directly to conventional pulmonary angiography.
Another promising new technique is gadolinium-enhanced magnetic resonance pulmonary angiography, which reveals anatomical features as well as assesses right ventricular wall motion.10
Combining non-invasive diagnostic tests may be especially useful. For instance, a normal D – dimer ELISA and venous ultrasonographic examination can help rule out pulmonary embolism, whereas an echocardiogram showing right ventricular hypokinesis combined with positive findings on ultrasonography of the legs is virtually pathognomonic of pulmonary embolism.
Contrast pulmonary angiography remains the gold standard. It can generally be performed safely and may pinpoint the diagnosis in cases in which there is a high index of clinical suspicion despite nondiagnostic findings on lung scanning and normal results on venous ultrasonography and echocardiography.11 Occasionally, pulmonary angiography is used when the clinical suspicion is low despite the fact that other test results indicate pulmonary embolism.

Heparin represents the cornerstone of management of deep venous thrombosis. It accelerates the action of antithrombin III, thereby preventing an additional thrombus from forming and permitting endogenous fibrinolysis to dissolve some of the clot. Initial therapy with an oral anticoagulant and no heparin may paradoxically intensify hypercoagulability and increase the frequency of recurrent venous thromboembolism. In the absence of overt contraindications such as active gastrointestinal hemorrhage, patients with a moderate or high clinical likelihood of pulmonary embolism should receive intensive anticoagulation with heparin during the diagnostic workup. A bolus of unfractionated heparin (usually 5,000 to 10,000 IU) followed by a continuous infusion (initiated at a dose of 18 IU/kg/hour, not exceeding 1600 IU per hour, in otherwise healthy patients) usually rapidly results in a therapeutic partial-thromboplastin time of 60 to 80 seconds (ratio of 1.5-2.5 between the patient`s value and the control value). The use of heparin nomograms facilitates proper dosing, but there is a risk of variable degree of anticoagulation, due to different degrees of responsiveness among patients.12 Ideally, the therapeutic range of activated partial-thromboplastin times for each patient should correspond to ex vivo plasma levels of activity against activated factor X (anti-factor Xa) of 0.3-0.7 U/ml. In patients who appear to have a resistance to heparin, arbitrarily defined as a requirement for more than 50,000 IU of heparin per 24 hours, measurement of the plasma heparin level rather than the partial-thromboplastin time may avoid unnecessary dose escalation. Plasma heparin levels are also useful for titrating heparin concentrations in the presence of a prolonged partial-thromboplastin time at base line due to lupus anticoagulants. Heparin without oral anticoagulation is used throughout pregnancy to manage pulmonary embolism. Heparin is also used as short-term or long-term therapy in some patients with venous thrombosis associated with metastatic cancer, because oral anticoagulation usually fails to prevent recurrent thrombosis. Hemorrhage occurs in up to 7% of patients during initial treatment; the risk is affected by the heparin dose, the patient’s age, and the concomitant use of thrombolytic and antiplatelet agents. Long-term use of heparin (longer than one month) can cause osteoporosis. Heparin-induced thrombocytopenia is immune-mediated and in 30%-50% of cases is associated with venous thrombosis more often than arterial thrombosis.13 Although rapid loading of warfarin used to be recommended, this strategy may precipitate venous gangrene of the limbs, possibly as a result of a precipitous warfarin-mediated decline in protein C levels. Appropriate treatment approaches include use of a heparinoid or direct thrombin inhibitor. Patients with previous heparin-induced thrombocytopenia should receive alternative anticoagulant agents, such as danaparoid, lepirudin or argatroban.
Recently, inpatient administration of low-molecular-weight heparin has been shown to be as safe and effective as unfractionated heparin to treat pulmonary embolism in hemodinamically stable patients and they cause less bleeding.14 These heparin products show less non-specific binding, have improved bioavailability and elicit more predictable responses than unfractionated heparin. They are administered subcutaneously once or twice daily in weight adjusted doses, generally without monitoring. Although heparin-induced thrombocytopenia develops less frequently with low-molecular-weight heparins than it does with unfractionated heparin, these agents often cross-react with the antibody that causes heparin-induced thrombocytopenia and are therefore contraindicated in patients with a history of this condition. Low-molecular-weight heparins also cause less osteoporosis than does unfractioned heparin. They are more expensive than is unfractionated heparin, but they cut costs by reducing the need for laboratory monitoring and reducing the nursing time.
Warfarin or another coumarin can be safely started once a therapeutic partial-thromboplastin time or heparin level has been achieved. Loading of warfarin does not shorten the five-day period needed to achieve adequate oral anticoagulation, and an initial daily dose of 5 mg (rather than 10 mg) is often sufficient.15 Factor VII, the main coagulation factor affecting the prothrombin time, has a half-life of about six hours. However, true anticoagulation requires the depletion of factor II (thrombin), which takes about five days. Therefore, at least five days heparin therapy is overlapped with oral anticoagulation. Heparin therapy can be discontinued after 5 days, when therapy with the two drugs is started on the same day and the INR (international normalized ratio) has been at a therapeutic level for two consecutive days. Patients with massive thrombosis often receive an extended course (7 to 14 days) of heparin. The initial target INR should be 3.0, because concomitant administration of unfractionated heparin usually prolongs the INR by an additional 0.5, thus yielding an effective INR due to warfarin alone of 2.5. After hospital discharge, a target INR of 2.0 to 3.0 is used for secondary prophylaxis. The risk of bleeding complications and thromboembolic events can be minimized by having a centralized anticoagulation clinic to monitor the patient. Patients with the antiphospholipid antibody syndrome who are being treated for pulmonary embolism appear to require more intensive anticoagulation than other patients with pulmonary embolism. Patients with cancer also have a substantial risk for recurrent venous thromboembolism, even when they are treated with warfarin.16 The optimal duration of anticoagulation after pulmonary embolism remains uncertain. A treatment period of six months prevents far more recurrences than a period of six weeks among patients with a first episode of pulmonary embolism. An indefinite (lifelong) period of anticoagulation should be considered in patients with recurrent pulmonary embolism, if the risk of major bleeding is low (less than 5% per year).17 For patients with deficiencies of antithrombin III, protein C, or protein S, several years rather than lifelong anticoagulation may suffice. Whether patients with factor V Leiden and pulmonary embolism should receive prolonged courses of anticoagulation remains sharply debated.18
Table 6. Contraindications for anticoagulant therapy.
Inferior caval venous filters should be inserted in patients with contraindications to anticoagulation and in those who require urgent surgery that precludes anticoagulation.19 (Table 6) Temporary filters should be used if anticoagulation is likely to be safe within 14 days after the bleeding event. Although the insertion of venous filters can usually prevent major pulmonary embolism, filters appear to offer no advantage in patients with proximal deep venous thrombosis with free-floating thrombi.20 Filters do not halt the thrombotic process; large venous collateral vessels may develop; and in rare cases, caval thrombosis accompanied by massive oedema of the legs may ensue. Furthermore, in a randomized, controlled trial of 400 patients with deep venous thrombosis, inferior caval venous filters plus anticoagulation did not reduce the two-year mortality rate, as compared with anticoagulation alone. However, a venous filter is warranted in patients with pulmonary embolism in the presence of active haemorrhage or recurrent pulmonary embolism despite intensive and prolonged anticoagulation.
Thrombolysis can be lifesaving in patients with massive pulmonary embolism, cardiogenic shock, or overt hemodynamic instability.21 There appears to be a 14-day window for its effective administration. Controversy persists regarding the use of thrombolytic therapy in patients with stable systemic arterial pressure and right ventricular dysfunction (usually documented by echocardiography). In this population, rapid improvement of right ventricular function and pulmonary perfusion, accomplished with thrombolytic therapy in addition to heparin, may lead to a lower rate of recurrent pulmonary embolism than with heparin alone.
Multivariate analysis of the patients in the MAPPET registry suggested that those who were initially treated with thrombolysis plus anticoagulation had better clinical outcomes than those who were initially treated with anticoagulation alone. However, the potential benefit must be weighed against the risk of major haemorrhage, which rises with increasing age and body-mass index.
If aggressive intervention is warranted in patients in whom thrombolysis is contraindicated or unsuccessful, transvenous catheter embolectomy, or open surgical embolectomy, should be considered.22,23 Thrombectomy can be accomplished with the use of a newly developed catheter that delivers high-velocity jets of saline that draw thrombus toward the catheter tip and subsequently pulverize the clot.
Another interventional approach combines mechanical fragmentation with pharmacologic thrombolysis. During the treatment of such critically ill patients, norepinephrine or dobutamine may be required to maintain the mean arterial pressure and thus ensure adequate perfusion of the right coronary artery.
Patients with chronic thrombotic involvement of large pulmonary arteries and cor pulmonale may be candidates for pulmonary thromboendarterectomy. After the institution of cardiopulmonary bypass and deep hypothermia, incisions are made in both pulmonary arteries to remove organized thrombi. When this approach is successful, pulmonary hypertension will abate during the first few postoperative months and the quality of life will improve. Among properly selected patients at experienced centers, the mortality rate ranges from 5 to 10 percent.
The inability to remove sufficient thrombotic material at surgery (resulting in persistent postoperative pulmonary hypertension and right ventricular dysfunction) and severe reperfusion-associated lung injury are the two major causes of death.

Prevention of pulmonary embolism is of paramount importance because the disorder is difficult to detect, and treatment of established pulmonary embolism is not universally successful. The specific regimen that is chosen is less important than ensuring that all hospitalized patients are evaluated and stratified according to the risk of pulmonary embolism and that appropriate prophylaxis is implemented.
Mechanical approaches to prevention include the use of graduated-compression stockings, devices that provide intermittent pneumatic compression and inferior caval venous filters alone or in combination.
In addition to increasing venous blood flow in the legs, intermittent pneumatic compression increases endogenous fibrinolysis by stimulating the vascular endothelial wall.24 This approach also had the highest rate of compliance among patients in an intensive care unit. Among less critically ill patients, however, compliance may not be adequate.
Foot pumps, which compress the plantar venous plexus, have also been used as prophylaxis, but they have not been investigated extensively in randomized, controlled studies.
Fixed, low doses of subcutaneous unfractionated heparin have been used for perioperative laboratory monitoring and reduce the rate of fatal pulmonary embolism by two thirds.25 The initial injection is administered two hours before the skin is incised. Heparin is continued until the patient is discharged.
Patients in intensive care units are often poor candidates for pharmacologic prophylaxis because of overt bleeding or thrombocytopenia. Leg ulcers, wounds, or peripheral arterial occlusive disease may preclude the use of intermittent pneumatic compression.
The limitations of traditional anticoagulants have prompted the development of new agents. Drugs that are in an advanced stage of development but have not yet received the approval from the Food and Drug Administration include parenteral synthetic pentasaccharide analogues (e.g., fondaparinux and irdaparinux) and oral direct thrombin inhibitors (e.g., ximelagatran).
Large, randomized trials comparing fondaparinux, respectively ximelagatran, with enoxaparin for the initial treatment of deep vein thrombosis, rates of symptomatic, recurrent venous thromboembolism and major bleeding were not statistically different between the groups.26
In contrast to warfarin, ximelagatran does not require monitoring of the degree of anticoagulation, but may induce elevations in liver enzyme levels in 5% to 10% of patients receiving long- term therapy. Further studies are required to define the appropriate role of these new agents.


We have recently gained a better understanding of environmental and inherited risk factors for venous thromboembolism. A wide array of diagnostic tools maximizes our ability to detect or rule out pulmonary embolism. Finally, the expansion of options for prophylaxis facilitates the prevention of this potentially serious disorder.

1. Wells PS, Anderson DR, Rodger M et al. Derivation of a simple clinical model to categorize patients’ probability of pulmonary embolism: increasing the model’s utility with the SimpliRED D-dimer. Thromb Haemost 2000;83:416-20.
2. Wicki J, Perneger TV, Junod AF et al. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001;161:92-7.
3. Palla A, Petruzelli S, Donnamaria V, et al. The role of suspicion in the diagnosis of pulmonary embolism. Chest 1995;107:21S-24S.
4. Goldhaber SZ. Pulmonary embolism. N Engl J Med 1998;339:93-104.
5. Miniati M, Monti S, Bottai M. A structured clinical model for predicting the probability of pulmonary embolism. Am J Med 2003;114:173-9.
6. Stein PD, Terrin ML, Hales CA, et al. Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 1991;100:598-603.
7. Jardin F, Dubourg O, Bourdarias JP. Echocardiographic pattern of acute cor pulmonale. Chest 1997;111:209-17.
8. Stein PD, Terrin ML, Gottschalk A, et al. Value of ventilation / perfusion scans versus perfusion scans alone in acute pulmonary embolism. Am J Cardiol 1992;69:1239-41.
9. Remy-Jardin M, Remy J, Deschildre F, et al. Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy. Radiology 1996;200:699-706.
10. Meaney JFM, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med 1997;336:1422-7.
11. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992;85:462-8.
12. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism: a statement for healthcare professionals. Circulation 1996;93:2212-45.
13. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996;101:502-7.
14. Simonneau G, Sors H, Charbonnier B, et al. A comparison of low molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997;337:663-9.
15. Bate S.M., Ginsberg J. Treatment of deep-vein thrombosis. New Engl J Med 2004;351:268-77
16. Lee AYY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003;349:146-53.
17. Schulman S, Rhedin AS, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995;332:1661-5.
18. Hirsh J, Kearon C, Ginsberg J. Duration of anticoagulant therapy after first episode of venous thrombosis in patients with inherited thrombophilia. Arch Intern Med 1997; 157: 2174-7.
19. Abrams J, Frishman WH, Bates SM, et al. Pharmacologic options for treatment of ischemic disease. In: Antman EM, editor, Cardiovascular therapeutics: a companion to Braunwald’s Heart Disease, 2nd ed., Philadelphia: W.B. Saunders, 2002, p. 97-153.
20. Becker DM, Philbrick JT, Selby JB. Inferior vena cava filters: indications, safety, effectiveness. Arch Intern Med 1992; 152: 1985-1994.
21. Daniels LB, Parker JA, Patel SR, et al. Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. Am J Cardiol 1997;80:184-8.
22. Greenfield LJ, Proctor MC, Williams DM, Wakefield TW. Long-term experience with transvenous catheter pulmonary embolectomy. J Vasc Surg 1993;18:450-7.
23. Gulba DC, Schmid C, Borst HG, et al. Medical compared with surgical treatment for massive pulmonary embolism. Lancet 1994;343:576-7.
Kessler CM, Hirsch DR, Jacobs H, et al. Intermittent pneumatic compression in chronic venous insufficiency favourably affects fibrinolytic potential and platelet activation. Blood Coagul Fibrinolysis 1996;7:437-46.
25. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin: overview of results of randomized trials in general, orthopaedic, and urologic surgery. N Engl J Med 1988;318:1162-73.
26. The MATISSE Investigators. The MATISSE-DVT trial, a randomized, double-blind study comparing once-daily fondaparinux (Arixtra) with low-molecular-weight heparin (LMWH) enoxaparin, twice daily, in the initial treatment of symptomatic deep vein thrombosis (DVT). In: Program and abstracts of the XIX Congress of the International Society on Thrombosis and Haemostasis, Birmingham, England, July 12–18, 2003. Malden, Mass.: Blackwell publishing, 2003, Abstract.

"Victor Babes" Publishing House "Victor Babes" University of Medicine and Pharmacy Romanian Academy of Medical Sciences National Council of Scientific Research in Higher Education (B+) Index Copernicus
Journals Master List
Embase Journal List Timisoara Medical Scientific Association
ISSN: 1583-526X (Online Edition)
Copyright © 2002-2019 Timisoara Medical Journal. All rights reserved.