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A 18-year old woman was hospitalized because of vena cava inferior thrombosis, renal vein thrombosis and pulmonary embolism due to inherited protein C deficiency and three months of contraceptive treatment with oestrogen hormones. Protein deficiency was detected in 12 other members of the family. The father had had a pulmonary embolism 12 years earlier, and two other members may have died of thromboembolism.
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To determine the incidence of thromboembolism in relation to thoracotomy, 77 patients undergoing pulmonary resection were prospectively studied up to 30 days postoperatively for deep venous thrombosis and pulmonary embolism. Overall, 20 of 77 patients (26%) had thromboembolic events during their hospitalization. Four deep venous thromboses and 1 pulmonary embolism were detected in 5 of 77 patients preoperatively for an incidence of 6%. Postoperative thromboembolism was detected in 15 of 77 (19%): deep venous thrombosis in 11 (14%) and pulmonary embolism in 4 (5%). No postoperative thromboembolisms occurred in the 17 patients receiving preoperative aspirin or ibuprofen, whereas they did occur in 25% of the remainder (15/60). Thromboembolism after pulmonary resection was more frequent with bronchogenic carcinoma than with metastatic cancer or benign disease (15/59 [25%] versus 0/18 [0%]; p < 0.01), adenocarcinoma compared with other types of carcinoma (11/25 [44%] versus 4/34 [12%]; p < 0.0004), large primary lung cancer (> 3 cm in diameter) compared with smaller lesions (9/19 [47%] versus 6/40 [15%]; p < 0.0001), stage II compared with stage I (7/14 [50%] versus 7/34 [21%]; p < 0.04), and pneumonectomy or lobectomy compared with segmentectomy and wedge resection (14/49 [29%] versus 1/28 [4%]; p < 0.005). Three of 4 patients with thromboembolism detected preoperatively had operation within the previous year. Postoperative pulmonary embolism was fatal in 1 of 4 (25%) and accounted for the one death. These results suggest patients undergoing thoracotomy for lung cancer, especially adenocarcinoma, should be considered for thromboembolic prophylaxis.
Venous thrombosis and pulmonary embolism are major clinical problems that result in significant morbidity and mortality. It is estimated that 600,000 cases of pulmonary embolism occur each year in the United States, resulting in the death of approximately 100,000 patients. Most of these pulmonary emboli arise from deep venous thrombosis (DVT). The clinical diagnosis of DVT is unreliable. Only a third of patients with a clinical suspicion of DVT have objective evidence of the disease, and half of patients with proven DVT do not have any clinical symptoms. Although ascending contrast venography is the present standard for the diagnosis of DVT, duplex ultrasonography, which is increasingly used in combination with color Doppler flow imaging, is accepted as a useful clinical afternative to contrast venography. Both contrast venography and ultrasonography are imaging procedures that detect changes in venous anatomy that are caused by the presence of an intraluminal thrombus that is sufficiently formed either to reduce vascular filling with contrast medium or to resist compression. However, these imaging procedures do not reflect the metabolic activity of the clot, and therefore, they may overestimate the presence of active clots. The sensitivity of ultrasonography is also limited by various disease-related and technical factors. An alternative approach to the diagnosis of acute DVT is to detect a molecular marker of acute DVT that is not present in old, organized DVT. Recent advances in biotechnology permit the use of highly specific synthetic peptide or small molecular markers, which are involved in the acute stages of DVT formation and can be labeled efficiently with 99mTc. 99mTc-apcitide, a glycoprotein (GP IIb/IIIa) receptor antagonist previously known as 99mTc-P280, has been approved recently by the Food and Drug Administration for the clinical detection of acute DVT. Two other agents are currently under clinical investigation: 99mTc-DMP 444, which is another GP IIb/IIIa receptor antagonist, and 99mTc-Fibrin-Binding Domain (FBD), a radio-labeled fibrin-binding domain of fibronectin. Different clinical studies have shown a high diagnostic accuracy with these synthetic 99mTc-labeled peptides in the detection of acute DVT. Although further studies are needed to fully appreciate all of the diagnostic potential of these radiopharmaceuticals, the clinical introduction of 99mTcapcitide scintigraphy will certainly be helpful in expanding the use of nuclear medicine in a specific field in which it used to play a relatively marginal role.
The authors describe a case of venous thrombosis of the legs, complicated by pulmonary embolism, in a 71 year-old man, following desmopressin therapy for hypothalamic diabetes insipidus. They suggest a role of desmopressin in stimulating the release of Von Willebrand's factor (VWF) from endothelial cells. VWF facilitates platelet adhesion by forming a bridge between platelet membrane and vascular subendothelium, followed by development of a large thrombus.
Ventilation and perfusion lung scans were performed preoperatively and postoperatively in 169 patients and classified blindly according to preset criteria. Perfusion lung scan abnormalities were present in 25 (15%) of the preoperative scans and 42 (25%) of the postoperative scans; 16 (38%) of the 42 abnormal postoperative scans were identical to the preoperative scans. Perfusion defects indicating a "high probability" of pulmonary embolism (lobar or segmental defects) were present in 5 preoperative scans and 10 postoperative scans; the 10 postoperative scans were classified as showing "definite" (5), "possible" (1) or "no" (4) pulmonary embolism on the basis of the preoperative scan and the ventilation scan; none of the 10 patients had clinical evidence of pulmonary embolism. Venous thrombosis was present in 12 patients, including 4 of the patients whose lung scans showed definite pulmonary embolism. Thus, postoperative perfusion lung scan defects are potentially misleading even when large.
PURPOSE: We evaluated the Gunther Tulip (GT) retrievable inferior vena cava (IVC) filter with regard to indications, filtration efficacy, complications, retrieval window, and use of anticoagulation. METHOD: A retrospective study was performed of 147 patients (64 men, 83 women; mean age 58.8 years) who underwent retrievable GT filter insertion between 2001 and 2005. The indications for placement included a diagnosis of pulmonary embolism or deep venous thrombosis with a contraindication to anticoagulation (n = 68), pulmonary embolism or deep venous thrombosis while on anticoagulation (n = 49), prophylactic filter placement for high-risk surgical patients with a past history of pulmonary embolism or deep venous thrombosis (n = 20), and a high risk of pulmonary embolism or deep venous thrombosis (n = 10). Forty-nine of the 147 patients did not receive anticoagulation (33.7%) while 96 of 147 patients did, 82 of these receiving warfarin (56.5%), 11 receiving low-molecular weight heparins (7.58%), and 3 receiving antiplatelet agents alone (2.06%). RESULTS: Filter placement was successful in 147 patients (100%). Two patients had two filters inserted. Of the 147 patients, filter deployment was on a permanent basis in 102 and with an intention to retrieve in 45 patients. There were 36 (80%) successful retrievals and 9 (20%) failed retrievals. The mean time to retrieval was 33.6 days. The reasons for failed retrieval included filter struts tightly adherent to the IVC wall (5/9), extreme filter tilt (2/9), and extensive filter thrombus (2/9). Complications included pneumothorax (n = 4), failure of filter expansion (n = 1), and breakthrough pulmonary embolism (n = 1). No IVC thrombotic episodes were recorded. DISCUSSION: The Gunther Tulip retrievable filter can be used as a permanent or a retrievable filter. It is safe and efficacious. GT filters can be safely retrieved at a mean time interval of 33.6 days. The newly developed Celect filter may extend the retrieval interval.
UNLABELLED: Technetium-99m-labeled anti-fibrin DD-3B6/22 Fab' monoclonal antibody fragments, which specifically target human cross-linked fibrin with high affinity, were evaluated in humans for safety and their capacity to detect deep vein thrombi and pulmonary embolism. METHODS: Twenty patients with proven deep-vein thrombosis, documented by contrast venography, or venous duplex scan, were injected with a 600 MBq (0.5 mg) dose of antibody. Planar images of the lower limbs were recorded at 0, 2, 6 and 24 hr and chest scintigrams were recorded at 6 and 24 hr. RESULTS: All venography documented thrombus sites, calves, popliteal and femoral, were detected with the radioimmunoconjugate. For the venous duplex scan-proven thrombus sites, all except two calf thrombi in two patients with bilateral disease and other positive sites were detected. Five patients had bilateral deep-vein thrombosis with multiple sites being visualized with the radioimmunoconjugate in the calf, popliteal and femoral regions. One case of pulmonary embolus was also definitively demonstrated. Documented thrombus sites were detected at 2 and 6 hr postinjection. Nineteen patients were on heparin. No adverse reactions to the injected dose were observed and one low titer human anti-mouse antibody response may have occurred. CONCLUSION: The results indicate that 99mTc-DD-3B6/22 Fab' has potential for noninvasive detection of deep-vein thrombosis and pulmonary embolism.
A series of 400 consecutive patients subjected to reconstructive arterial surgery were randomly allocated into four equal groups in order to study the effect of dipyridamole and acetylsalicylic acid (ASA) in the prevention of deep venous thrombosis and pulmonary embolism. There were 11 drop-outs. In the dipyridamole-ASA group there were no thrombotic complications while in the control group without antithrombotic therapy five cases of deep venous thrombosis and two cases of fatal pulmonary embolism were encountered (p < 0.05). In the groups receiving either dipyridamole or ASA alone two and four cases of deep venous thrombosis, respectively, were found. It is concluded that treatment with dipyridamole and ASA combined is useful in preventing postoperative thrombotic complication after peripheral vascular reconstructive surgery.
Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule Factor Xa inhibitors and thrombin inhibitors. The most advanced drugs reviewed include DPC-423, DPC-602, razaxaban, GSK's 813893, Portola's Xa inhibitors (formerly Millennium), otamixaban, DU-176b, KFA-1982, BAY-59-7939, DX-9065a, YM-150, LY-517717, Exanta, 3DP's thrombin inhibitors, SSR-182289, LB-30057, LB-30870, BIBR-1048 and Merck's thrombin inhibitors. With their potentially consistent and predictable pharmacological profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management.
Protein C and S are important factors in blood coagulation reported in many papers about people who suffered from thromboembolic diseases related to inherited or acquired deficiencies. Homozygous protein C/S deficiency is lethal in most cases without therapy. Heterozygous deficiency is moderate and complications occur between the 20.-50. year of age. Acquired protein C/S deficiency is a strong parameter for liver function. The typical clinical manifestations of protein C/S deficiencies are superficial and deep leg vein thrombosis, thrombosis of the mesenterial, cerebral, renal and axillary veins, portal vein thrombosis and pulmonary embolism. Most of the affected people live disease free over a longer period and develop thromboembolic complications during and after trauma, surgical interventions, pregnancy and puerperium. We report our experience with a 60 years old male who had developed a severe bilateral iliofemoral vein thrombosis with signs of pulmonary embolism after total hip replacement. An extended functional protein C deficiency (type II) was investigated by coagulation tests (Protein C Reagent, coagulometric from Behring Institute). A second female patient developed a descending iliofemoral vein thrombosis during pregnancy. Venous thrombectomy with arteriovenous fistula was performed, but reocclusion occurred after delivery. Redo-surgery was undertaken and a second reocclusion took place 10 days later. Further lysis therapy was not able to reopen the venous system. Whereas immunological and functional protein C levels showed normal ranges, the functional protein S level was markedly reduced (IL-Instrumentation Laboratory Protein S-Test).
BACKGROUND: Deep vein thrombosis is common in patients undergoing major knee surgery. Static graduated compression stockings effectively prevent venous thrombosis in general surgery. Because of the demonstrated prophylactic efficacy of pneumatic compression in knee surgery, the similar efficacy of static graduated compression and pneumatic compression in neurosurgery, and the easier use of static graduated compression in knee surgery, graduated static compression stockings were used as the control arm in our clinical trial. Although low-molecular-weight heparin had been shown to be effective in general surgery and hip replacement, its efficacy was unproved in knee surgery. METHODS: A double-blind, randomized trial compared the combination of low-molecular-weight heparin and graduated compression stockings with graduated compression stockings alone in patients undergoing major knee surgery. Patients received either ardeparin (Normiflo) (low-molecular-weight heparin), 0.005 mL/kg (50 anti-Xa U/Kg), or placebo. Both were administered subcutaneously twice daily commencing 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. Both study groups wore graduated compression stockings. Bilateral venography was performed on day 14, or sooner if the patient was ready for discharge. RESULTS: One hundred twenty-two patients were allocated to receive ardeparin and 124 received placebo. Ninety-six patients in the ardeparin group and 103 in the placebo group had evaluable venograms. Deep vein thrombosis was detected in 28 patients in the ardeparin group and in 60 in the placebo group. Proximal deep vein thrombosis was detected in two patients who received ardeparin and 16 who received placebo. One patient in each group, both of whom did not have venography, experienced pulmonary embolism. Thus, deep vein thrombosis or pulmonary embolism was detected in 29 (29.9%) of the 97 patients in the ardeparin group and in 61 (58.7%) of the 104 patients in the placebo group, a relative risk reduction of 49% (P < 00.1). The rate of major bleeding in the ardeparin group was 2.5%, compared with 2.4% in the placebo group. CONCLUSION: Ardeparin administered postoperatively twice daily is effective and safe for the prevention of venous thrombosis in patients undergoing major knee surgery. Whereas graduated compression stockings have been shown to be effective prophylactic agents in general surgery and neurosurgery, they have little effect in knee surgery.
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AIM: Venous thromboembolism remains a frequent complication after total hip or knee replacement surgery despite routine prophylaxis. However, the ability of pharmacologic thromboprophylaxis to prevent major venous thromboembolism, defined as proximal deep vein thrombosis, and/or pulmonary embolism, and/or death, has not been previously validated. METHODS: In a double-blind randomized study, 2018 patients, undergoing either total hip or knee replacement surgery, were allocated to receive subcutaneous preoperative reviparin (4,200 anti Xa IU) once daily or 7,500 IU unfractionated heparin twice daily, for a minimum of 11 days. The primary efficacy outcome was major venous thromboembolism, defined as the composite of venographically confirmed proximal deep vein thrombosis, and/or symptomatic pulmonary embolism and death, recorded up to day 14. RESULTS: The primary efficacy outcome was assessed in 1,628 patients and demonstrated a significant reduction in the reviparin group (3.4% [28 of 813 patients] compared with unfractionated heparin (5.5% [45 of 815]) (odds ratio, 0.61; 95% confidence interval, 0.38 to 0.99, P=0.04) by day 11 to 14. A significant reduction in venous thromboembolism was maintained up to 6-8 weeks (3.4% [28 of 813 reviparin patients] versus 5.6% [46 of 815 unfractionated heparin patients]) (odds ratio, 0.6; 95% confidence interval, 0.37 to 0.97, P=0.03). Major bleeding events occurred in 9 reviparin-treated patients (0.9%) and in 12 unfractionated heparin-treated patients (1.2%). CONCLUSIONS: Prophylaxis with reviparin significantly reduces the risk of major venous thromboembolism compared with unfractionated heparin in patients undergoing elective hip or knee replacement without increasing the risk of bleeding.