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Thromboembolic pulmonary hypertension due to disseminated fibromuscular dysplasia.

We present two patients with thromboembolic pulmonary hypertension associated with unusual complications probably caused by disseminated fibromuscular dysplasia (FMD) or FMD-like vascular lesions. Intimal fibroplasia, which is typical of the vascular lesions associated with FMD, was observed in both patients. The presence of such intimal lesions suggests that there was a systemic factor that caused the formation of recurrent thrombi in the systemic vessels in these patients. These cases are the first ones reported in which an association between FMD and pulmonary hypertension has been observed. The pathogenesis of the thrombi in our patients was thought to be recurrent pulmonary thromboembolisms resulting from FMD.

Adolescent↗

Abdominoplasty: thromboembolic risks for both sexes.

During surgical procedures, coagulation complications may occur. Discriminating factors are multiple and may vary because of the anatomical regions involved and because of preexisting diseases. The aim of this study was to analyze changes in such hematological parameters of patients undergoing conventional abdominoplasty with standard surgical procedures under general anaesthesia. For the study, 40 patients (20 men and 20 women) 30 to 60 years with normal coagulation assessments, no previous or current history of hemorrhagic or thrombotic disease, and no primary family history of such problems were selected. All the patients underwent conventional abdominoplasty surgical procedures. Analysis of the results suggests that immediately after surgery, in the absence of any preexisting hypo- or hypercoagulability state, there was no circumstantial modification in coagulation factors considered predictive for thromboembolic risk. However, an interesting difference between male and female patients was noted. In the male group, there was an insignificant uniform downward trend of all values immediately after surgery. In conclusion, women are less hypercoagulative than men in the postoperative period, suggesting that women have limited protection from the development of thromboembolic complications immediately after surgical procedures.

Abdomen↗

Low-molecular-weight heparins and Daflon for prevention of postoperative thromboembolism.

The efficacy of low-molecular-weight heparins (LMWH) alone versus a combination of Daflon 500 mg with LMWH in preventing postoperative symptomatic thromboembolism was investigated. A total of 1372 patients aged 40 years or older undergoing major abdominal, pelvic, or abdominal wall surgery were randomized into four groups. Group A (n = 591) received enoxoparin 20 mg or fraxiparin 0.3 ml. Group B (n = 595) received the regimens of group A plus Daflon 500 mg. Group C (n = 93) received enoxoparin 40 mg or fraxiparin 0.6 ml. Group D (n = 93) received the regimens of group C plus Daflon 500 mg. Each LMWH was given subcutaneously once a day during the hospitalization and continued in groups C and D for 15 days after discharge (high risk patients). Daflon 500 mg was given as two tablets every 8 hours during the day before surgery, two tablets 6 hours before surgery, and two tablets once a day on postoperative days 4 to 15. Daily clinical examination was performed; and phlebography or perfusion lung scanning (or both) were used in symptomatic patients to confirm deep vein thrombosis (DVT) or pulmonary embolism (PE). The wound was examined on a daily basis for hematomas. The diagnosis of PE was established in two patients of group A and in three patients of group C; symptomatic DVT was established in one patient in group A and three patients of group C. Neither DVT nor PE were established in Daflon 500 mg groups. These data suggest that the combination of Daflon 500 mg and LMWH is more effective than LMWH alone for preventing symptomatic thromboembolism.

Adult↗

Evaluation of enoxaparin given before and after operation to prevent venous thromboembolism during digestive surgery: play-the-winner designed study.

A total of 316 patients were included in a play-the-winner (PTW) designed study comparing the safety of enoxaparin started preoperatively versus postoperatively as prophylaxis against venous thromboembolism for digestive surgery. In a PTW-designed study the treatment of any next patient depends on the outcome of the previous patient. If successful, the next patient receives the same treatment, if not, the comparative regimen is given. Excessive bleeding according to specified criteria, severe adverse reactions, clinically detected deep venous thrombosis (DVT), or pulmonary embolism (PE) were criteria for classification as "loser." The PTW design allocates most patients to the superior treatment. The main variable in PTW studies is the number of consecutive patients receiving the same treatment. In this study 163 patients were allocated to postoperatively started and 153 to preoperatively started prophylaxis with enoxaparin. The frequency of "winners" was found to be 82.8% and 78.4% in the post- and preoperatively treated groups, respectively. No significant differences were found between the groups with regard to frequency of "winners" or the number of consecutive patients before change of treatment. The percentile of survival distribution did not detect superiority of any group. Prophylaxis against postoperative venous thromboembolism for digestive surgery using enoxaparin can safely be started preoperatively.

Adolescent↗

[Risk of thromboembolism and arteriosclerosis in women].

Young women are at a 3-fold higher risk of experiencing venous thromboembolism compared to young men. This risk is further increased by oral contraceptives, smoking, hereditary thrombophilia and/or low socioeconomic status. There are also hints for gender-specific differences in the arterial system. Coronary heart disease which is particularly important, develops in women 10-15 years later than in men. However, the clinical course in women is often more complicated. In women, thrombophilic predispositions play a more important role before menopause and metabolic risk factors after menopause compared to men. Thrombus formation needs to be initiated by disturbances of at least one element of the Virchow trias. There is principally no difference between men and women. However, all three elements are influenced by estrogen, resulting in gender-specific differences. There is a favorable influence on blood flow by the inhibition of atherogenesis and on the endothelial function by increased NO release, and the unfavorable influence on hemostasis resulting in hypercoagibility. Thus, particularly non-selective hormone replacement therapy for the inhibition of atherogenesis may be questionable due to increased thrombogenicity. The solution may be more selective estrogen receptor modulators. Clinical trials are still needed for both hormone replacement therapy and the therapy of venous and arterial thromboembolism, which have been studied in predominantly male patient cohorts so far.

Adult↗

Thromboembolic complications related to indwelling central venous catheters in children with oncological/haematological diseases: a retrospective study of 362 catheters.

Indwelling central venous catheters (CVC) are essential devices in the management of children with oncological/haematological diseases being treated with chemotherapy or undergoing bone marrow transplantation. Our study was aimed at detecting the incidence of important thrombotic events caused by CVC in children, and the coexistence of coagulation disorders in children affected with thromboembolic disease related to CVC. Therefore, we describe some antithrombotic strategies which have been successfully applied to solve functioning problems of correctly inserted CVC. We retrospectively evaluated the clinical records of 308 children (age range 2 months to 14 years) with oncological/haematological diseases undergoing insertion of 362 indwelling CVC from January 1994 to December 1998 at the Gaslini Children's Hospital. We collected data on seven serious asymptomatic thrombotic episodes diagnosed between 1994 and 1998 following catheter malfunctioning and one case of suspected lung embolism with symptoms. Coagulation tests allowed us to identify one case of probable heterozygosis of Protein C deficiency and one case of G20210A prothrombotic prothrombin mutation. This finding suggests the need for further evaluation for thrombophilia in all patients presenting with thrombotic complications of CVC. We therefore emphasise the importance of prophylaxis with low-dose heparin in children with malignancies receiving CVC. A prospective study, which has already been started, should identify the exact role of thromboembolic complications in children with indwelling CVC for oncological/ haematological malignancies.

Adolescent↗

Revascularization to prevent postoperative bowel infarction after surgery for acute superior mesenteric artery thromboembolism.

PURPOSE: Postoperative bowel infarction is a major contributing factor to the high mortality rate associated with acute thromboembolism of the superior mesenteric artery (SMA). This study was conducted to evaluate the prophylactic role of thrombectomy to prevent postoperative mesenteric infarction. METHODS: An autologous fibrin clot (1 cm3) was implanted into the SMA of beagle dogs. The animals in group I (n = 7) underwent only resection of the ischemic intestine 120 min after insertion of the thrombus. In group IIa (n = 6), the intestine was removed before thrombectomy of the SMA, and revascularization was performed 30 min prior to resection in group IIb (n = 6). The postoperative outcomes were compared among the three groups. RESULTS: Postoperative bowel infarction developed in four (57.1%) of the group I dogs, three (42.8%) of which died within 5 days postoperatively. The SMA was patent in the group IIa and IIb dogs, none of which died throughout the observation period. Performing thrombectomy before the resection reduced the length of resected intestine. CONCLUSION: Arterial revascularization is not only an essential procedure for mesenteric infarction due to SMA thromboembolism, but it also prevents the postoperative bowel infarction caused by the extension of thrombus in the mesentery.

Animals↗

Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation.

We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-beta(2)-glycoprotein-1 (beta(2)GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.

Administration, Oral↗

Low intensity warfarin anticoagulation is safe and effective as a long-term venous thromboembolism prevention strategy.

Longitudinal studies indicate a high rate of recurrence of venous thromboembolism after an episode of deep venous thrombosis or pulmonary embolism. Extended anticoagulant therapy will decrease the recurrence rate, but there is controversy as to the optimal intensity of therapy that will be effective, yet safe. The PREVENT trial addresses the question of whether long-term low intensity therapy (INR 1.5-2.0) will effectively prevent recurrence compared to placebo treatment, yet be safe without a significant increase in major bleeding. The results of this trial show a significant reduction in recurrent venous thromboembolism with a major bleeding rate that is no different than the placebo arm of the study (0.9 vs 0.4 per 100 patient years; p = 0.25). Although the ELATE trial showed greater effectiveness with no increase in bleeding in the standard intensity arm vs the low intensity arm, the question remains whether such safety can be obtained in the real world management of oral anticoagulation.

Anticoagulants↗

The standard is still the standard or why an INR of 2-3 is still the optimal intensity for secondary prevention of venous thromboembolism.

The optimal intensity of warfarin anticoagulation for secondary prevention of venous thromboembolism is debatable. Recent studies have shed light on the issue. The two pivotal studies, ELATE and PREVENT, are reviewed and discussed. Although the ELATE and PREVENT studies offer different conclusions, the results of the two studies are consistent with each other. Low intensity warfarin is more efficacious than placebo, although it is less efficacious than standard intensity and offers no safety advantage. For long term secondary prophylaxis of spontaneous venous thromboembolism, the optimal INR intensity of warfarin remains 2.0-3.0.

Anticoagulants↗

The genetics of venous and arterial thromboembolism.

There is substantial evidence to indicate that the pathologic processes of venous and arterial thromboembolism involve both genetic and environmental influences. Scientific progress over the past decade has revealed a growing number of genetic factors, such as factor V Leiden and the prothrombin gene variant, that are present in more than 1% of the population and increase the relative risk of venous thrombosis between two- and sevenfold. Furthermore, several of these factors have been demonstrated to interact adversely with environmental influences, such as oral contraceptives and smoking. Although these traits are present at relatively high prevalence in the population, the magnitude of the increased thrombotic risk associated with these factors is substantially less than that related to inherited deficiency of the natural anticoagulant protein antithrombin, and somewhat less than the elevated risk with protein C and protein S deficiencies. In contrast to the progress that has been made in understanding the genetic contributions to venous thromboembolism, much still remains to be learned about the genetic basis of arterial thrombosis. Despite the documentation of associations between several genetic polymorphisms with plasma procoagulant levels, consistent associations with arterial thrombotic disease have not been found.

Arterial Occlusive Diseases↗

Efficacy and safety of early versus late initiation of warfarin during heparin therapy in acute thromboembolism.

There is no universally accepted approach to the initiation of systemic anticoagulant therapy. In an open, randomized study, two anticoagulant regimens that differed only in the timing of warfarin therapy after the start of heparin were compared. We randomized 119 patients with acute thromboembolic events to receive warfarin either within 48 hours of the start of heparin (early group, n = 63) or 96 hours or later after the start of heparin (late group, n = 56). Heparin was given as a 5000 IU bolus as a constant infusion titrated to maintain the activated partial thromboplastin time at 1.5 to 2 times control values. Warfarin was started at 10 mg daily for 3 days and the dose was titrated to maintain the prothrombin time at 1.2 to 1.5 times control values. There were no significant differences between the early and late warfarin groups with regard to age, sex, indication for anticoagulation, heparin dose, mean activated partial thromboplastin time during heparin, warfarin dose at discharge, length of warfarin therapy before discharge, bleeding, recurrent thromboembolic events, or mortality rates. Time to the start of warfarin after heparin was 31 hours and 108 hours in the early and late groups, respectively. Length of hospitalization, hospital costs, and the incidence of heparin-induced infusion phlebitis and thrombocytopenia were significantly less in the early group compared with the late group. Early initiation of warfarin after heparin is safer, less expensive, and as effective as the late initiation of warfarin.

Aged↗

Ventricular thrombi and thromboembolism in dilated cardiomyopathy: a prospective follow-up study.

To determine the prevalence and natural history of left ventricular thrombus in dilated cardiomyopathy, we prospectively performed two-dimensional echocardiograms in 25 patients with nonischemic dilated cardiomyopathy who were not receiving anticoagulation. Eighty-five echocardiograms were performed serially over a 9- to 30-month period (mean follow-up 21.5 months). A left ventricular thrombus was present on initial echocardiogram in 11 (44%) patients, became present during follow-up in an additional four, and disappeared in two. Thrombus was significantly more common in patients with fractional shortening of less than or equal to 10% (12 of 15) than in those with a fractional shortening 11% to 25% (3 of 10) (p less than 0.02). Five embolic events (four cerebral) occurred over the follow-up period, four of which were associated with a previously visualized left ventricular thrombus. Three of five thrombi that protruded into the left ventricular cavity subsequently embolized. We conclude that in nonanticoagulated patients with dilated cardiomyopathy left ventricular thrombus and thromboembolism are common. Echocardiography may be helpful in predicting which patients are at risk of thromboembolism.

Adult↗

Bedside coagulation monitoring in heparin-treated patients with active thromboembolic disease: a coronary care unit experience.

Patients with active venous and arterial thromboembolic disorders are known to benefit from systemic anticoagulation with heparin. Clinical studies have shown, however, that therapeutic anticoagulation is rarely achieved rapidly and often is not maintained over time. Prolonged laboratory turnaround time of the activated partial thromboplastin time (aPTT) may contribute directly to these common problems. A total of 272 aPTT determinations were performed on 120 heparin-treated patients admitted to the coronary care unit. The time from sample collection to data availability was 126 +/- 84 minutes with standard laboratory aPTT testing. In contrast, a bedside coagulation device provided an aPTT within 3 minutes (p < 0.001). Subtherapeutic aPTT values (< 65 seconds) were documented in 21% of all patients; in each, the heparin dose was changed and a repeat aPTT was required. In a separate study of 33 heparinized patients randomized to either bedside or central laboratory aPTT testing (264 aPTT determinations), the time to achieve a therapeutic state of systemic anticoagulation was 8.2 hours and 18.1 hours, respectively (p < 0.005). The time from aPTT determination to a decision regarding heparin titration adjustments was 14.5 minutes and 3 hours with bedside and laboratory testing, respectively (p < 0.001). Thus bedside coagulation monitoring provides a convenient, rapid, and accurate assessment of systemic anticoagulation among heparin-treated patients with active thromboembolic disease in the coronary care unit. This technology warrants further clinical investigation.

Coronary Care Units↗

Resolution of left atrial spontaneous echocardiographic contrast after percutaneous mitral valvuloplasty: implications for thromboembolic risk.

Left atrial spontaneous echocardiographic contrast (SEC) is an important marker of increased thromboembolic risk in patients with mitral stenosis. To evaluate the effect of percutaneous transseptal mitral valvuloplasty (PTMV) on SEC, we performed transesophageal echocardiography 1 day before and 3 months after PTMV on 88 consecutive patients. SEC was present in 65 (74%) patients before PTMV and was associated with absence of moderate or severe mitral regurgitation (p = 0.01), a smaller valve area (p = 0.02), an older age (p = 0.04), and atrial fibrillation (p = 0.05). At 3 months, PTMV resulted in a mean absolute and relative increase in valve area of 0.54 +/- 0.36 cm2 and 53% +/- 43%, respectively. SEC resolved in 37 patients but persisted in 28 (32%) patients at the 3-month study. The absolute and relative increase of valve area and worsened mitral regurgitation after PTMV were predictors of resolution of SEC, with the relative increase in valve area being the only significant predictor on multivariate analysis. PTMV frequently results in resolution of SEC, which may have important implications in reducing the thromboembolic risk in these patients.

Adult↗

Risk of patent foramen ovale for thromboembolic events in all age groups.

The association between a patent foramen ovale (PFO) and thromboembolic events in young patients has been reported. Autopsy data suggest that a PFO may be present in 20 to 35% of the population. To further assess the role of a PFO in patients with possible thromboembolic events, precordial and transesophageal contrast echocardiography was performed in 104 consecutive patients (age range 16 to 84 years) presenting with a stroke, transient ischemic attack or peripheral artery embolus (group I). These patients were compared with 94 consecutive patients (age range 23 to 82 years) undergoing transesophageal echocardiography for other reasons (group II). A PFO was found in 22 patients; 9 of 35 (26%) with an event but no risk factor (group Ia), 10 of 69 (14%) with an event but a recognized risk factor (group Ib), and 3 of 94 control patients (3.2%) (group II) (group Ia vs II: relative odds 10:1, p less than 0.001; group Ib vs II: relative odds 5:1, p less than 0.01; and group Ia vs Ib: p = not significant). The detection of a PFO was not related to age. The relatively low prevalence of a PFO in this study may reflect patient selection, but other explanations include: (1) Transesophageal contrast echocardiography may be relatively insensitive for its detection; (2) the prevalence in the general population may have been overestimated; and (3) most PFOs are very small, clinically insignificant and undetectable with this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Vascular plasminogen activator levels and thromboembolic disease in patients with gynecologic malignancies.

Vascular plasminogen activator levels were measured preoperatively in 66 women with gynecologic malignancies. These levels were compared to levels in a matched control group of 84 women and to the incidence of postoperative venous thromboembolic disease in the patient group. Significantly lower levels of plasminogen activator were measured in patients who developed thrombotic complications (p = 0.0014). When results were stratified according to tumor location, patients with ovarian carcinoma had significantly higher activator levels than those found in control subjects (p = 0.0072), and significantly lower levels were associated with endometrial malignancy (p = 0.0140). Measurement of releasable plasminogen activator before operation may be an effective, noninvasive means of identifying patients potentially at risk for venous thromboembolic disease. Postoperative measurement of plasminogen activator may eventually find a role in monitoring tumor therapy and recurrence.

Female↗