defibrotide and Postoperative-Complications

Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) is a rare complication characterized by hepatomegaly, right-upper quadrant pain, jaundice, and ascites, occurring after high-dose chemotherapy, hematopoietic stem cell transplantation (HSCT) and, less commonly, other conditions. We review pathogenesis, clinical appearance and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD occurring post-HSCT. The injury of the sinusoidal endothelial cells with loss of wall integrity and sinusoidal obstruction is the basis of development of postsinusoidal portal hypertension responsible for clinical syndrome. Risk factors associated with the onset of VOD and diagnostic tools have been recently updated both in the pediatric and adult settings and here are reported. Treatment includes supportive care, intensive management, and specific drug therapy with defibrotide. Because of its severity, particularly in VOD with associated multiorgan disease, prophylaxis approaches are under investigation. During the last years, decreased mortality associated to VOD/SOS has been reported being it attributable to a better intensive and multidisciplinary approach.

Topics: Animals; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Palliative Care; Polydeoxyribonucleotides; Postoperative Complications; Risk Factors; Transplantation, Homologous

The efficacy of postoperative DVT prophylaxis of defibrotide and heparin calcium was evaluated in a group of 47 patients undergoing general surgery for oncological pathologies. A sub-group (24 patients) received defibrotide treatment, 400 mg b.i.d. i.m.; the second subgroup (23 patients) was treated with heparin calcium, 5000 IU b.i.d. s.c., from the day before operation until the 7th postoperative day. No postoperative thrombotic symptoms were observed in either group of patients.

Topics: Fibrinolytic Agents; Heparin; Humans; Neoplasms; Polydeoxyribonucleotides; Postoperative Complications; Premedication; Thrombophlebitis

Twenty patients, submitted to internal arteriovenous fistula procedure, were randomly assigned to one of the following treatments: defibrotide 400 mg b.i.d. IM (starting the day before surgery and continuing for the following 7 days); calcium heparin 5,000 IU t.i.d. SC (since the day of surgery and for the following 7 days). No deep venous thrombosis or thrombosis of the fistula were noticed during both treatments and no side effects were observed. In the defibrotide group, ELT showed a significant decrease (-40%) attesting an improvement of fibrinolysis without a plasminogen abatement. These findings indicate that defibrotide represent an effective alternative to calcium heparin for antithrombotic prophylaxis of A-V fistula in uremic patients.

Topics: Arteriovenous Shunt, Surgical; Drug Tolerance; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Thrombophlebitis; Uremia

With the aim of preventing deep vein thrombosis after radical or modified mastectomy, 100 patients were randomly assigned to one of two different groups: the first group was treated with defibrotide (400 mg b.i.d. e.v.) starting from the day before the operation and continuing for the following seven days. The second group was given calcium heparin (5,000 IU b.i.d. by s.c. route) from day 0 to the 7th post-operative day. Neither side effects nor DVT or PE were observed. The quantity of fluids from the drainages rapidly decreased in both groups from the first day to the third one, while the quantity of blood cells was negligible starting from the second post-operative day. On this basis defibrotide may be considered an effective and well tolerated drug for the prevention of DVT.

Topics: Female; Fibrinolytic Agents; Heparin; Humans; Mastectomy, Modified Radical; Mastectomy, Radical; Middle Aged; Polydeoxyribonucleotides; Postoperative Care; Postoperative Complications; Premedication; Thrombophlebitis

The efficacy of defibrotide and calcium heparin in the prevention of Deep Vein Thrombosis (DVT) in gynecological surgery were compared in a randomized study. Seventy patients candidate to gynecological surgery (for benign conditions) and 50 candidate to surgery for malignancies were randomly allocated either to defibrotide (400 mg b.i.d. IM from the day before operation to the 7th postoperative day, n = 60) or to calcium heparin (5000 IU t.i.d. SC from the operation to the 7th postoperative day, n = 70). The diagnosis of DVT was made with impedance plethysmography and if necessary confirmed with phlebography. No patient developed established DVT in either groups and no adverse reactions were observed. These results indicate that defibrotide may be considered as an alternative to heparin in the DVT prophylaxis in gynecological surgery.

Topics: Female; Fibrinolytic Agents; Genital Diseases, Female; Heparin; Humans; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Randomized Controlled Trials as Topic; Thrombophlebitis

Topics: Abdomen; Adult; Drug Tolerance; Fibrinolytic Agents; Heparin; Humans; Polydeoxyribonucleotides; Postoperative Complications; Thrombophlebitis

Forty-one surgical patients at risk of deep venous thrombosis (DVT) were treated with defibrotide (400 mg/b.i.d./i.v.) or with heparin (5000 UI/t.i.d./s.c.). Neither DVT nor pulmonary embolism was evidenced. In the heparin group the healing rate was longer and during the first three days bleeding from the surgical wound was more pronounced. In particular one patient of the heparin group had to interrupt the treatment for haemorrhage.

Topics: Adolescent; Adult; Aged; Drug Tolerance; Fibrinolytic Agents; Heparin; Humans; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Risk Factors; Thrombophlebitis

Deep venous thrombosis (DVT) can be a significant complication of the postoperative course in gynaecological surgery, because of traumatism and compression to which the vascular pelvic structures are subjected. A protocol was therefore designed to evaluate the effectiveness and tolerability of defibrotide, a new antithrombotic and profibrinolytic drug, compared with low-dose heparin. The study was conducted on 102 women, undergoing major gynaecological surgery for benign and malignant affections, randomly assigned to the following two treatment groups. A) defibrotide (400 mg i.v./i.m. b.i.d., starting the day before the surgery for 8 days); B) calcium heparin (5000 IU s.c. b.i.d., starting on the day of surgery, for/days). Clinical, haematological and instrumental (Doppler ultrasound) parameters were assessed and no major events were noted in either of the two treatment groups though in the calcium heparin group, 2 patients showed clinical signs of DVT (not confirmed by Doppler ultrasound) and no side effects were noticed, except for a cutaneous rash in one defibrotide patient and an episode of bleeding on the third postoperative day in a patient treated with calcium heparin. Defibrotide proved as effective as calcium heparin in the prevention of DVT in gynaecological surgery.

Topics: Clinical Trials as Topic; Drug Tolerance; Female; Fibrinolytic Agents; Genital Neoplasms, Female; Heparin; Humans; Polydeoxyribonucleotides; Postoperative Complications; Random Allocation; Thrombophlebitis; Time Factors; Ultrasonography

In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide and calcium heparin in the prophylaxis of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) an evaluation has been made on 4810 patients. 2810 patients received defibrotide (800 mg/die: 400 mg b.i.d. or 200 mg q.i.d. by IV route); 2000 patients received calcium heparin (500 IU b.i.d. or t.i.d. by SC route) till the 7th post-operative day. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routine criteria. The incidence of DVT has been 33/2810 (1.17%) in the defibrotide group and 47/2000 (2.35%) in the heparin group (chi 2 p = 0.002), while the cases of suspected or ascertained PE have been respectively 15/2810 (0.53%) and 23/2000 (1.15%) (p = 0.025). The post-operative course was totally normal in both groups; no significant adverse reactions were noticed. The obtained results suggest the effectiveness of defibrotide as an alternative to heparin in the prevention of post-operative DVT.

Topics: Adult; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Polydeoxyribonucleotides; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis

In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide in the prophylaxis of postsurgical deep vein thromboses (DVT) an ad interim evaluation has been made on 2626 patients thus far enrolled. 1323 had received defibrotide (200 mg q.i.d. by IV route from day -1 to day +7th postoperative), 941 calcium heparin (5000 IU b.i.d. or t.i.d. by SC route from day 0 to day +7 postoperative) and 362 other treatments (antiaggregating agents, placebo or no therapy). This group has not been included in the final evaluation, due to its limited size. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routinary criteria. The incidence of DTV has been 15/1323 (1.13%) in the defibrotide group and 21/941 (2.23%) in the heparin group (chi-square, p = 0.056) while the cases of suspected or ascertained PE have been respectively 3/1323 (0.22%) and 10/941 (1.06%) (p = 0.02). The incidence of adverse effects with defibrotide was less than 1%; occasional cases of increased serum transaminase levels were seen with heparin. These preliminary results supports the effectiveness of defibrotide in the prevention of post-surgery DVT, its effects being similar or more prominent than those of calcium heparin, currently regarded as the standard medication.

Topics: Adult; Aged; Clinical Trials as Topic; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Pulmonary Embolism; Thrombosis

The efficacy and tolerability of defibrotide (800 mg/i.v.) and calcium heparin (15,000 UI/s.c.) in the prophylaxis of post-surgical deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared in a multicentre trial involving 60 Italian surgical institutions (general surgery, obstetrics and gynecology, urology). Total enrollment was 2,250 patients (defibrotide: 1.194; calcium heparin 1.056). According to the protocol, the clinical suspicion of DVT and/or PE led to in-depth diagnostic evaluations (DVT: Doppler ultrasound velocimetry; PE: chest X-rays; ECG, pulmonary scintigraphic scanning). The incidence of post-surgical DVT was similar in the two groups (defibrotide: 8 patients; calcium heparin: 10 patients). A trend towards a lower incidence of DVT in the defibrotide group no PE; calcium heparin: 4 cases (chi 2 = 4.530, p less than 0.05). The local and systemic tolerability of both treatment was excellent. This trial, carried out in routine surgical practice, establishes the profibrinolytic approach to DVT prophylaxis as a sound and effective alternative to the traditional interference with the coagulation cascade.

Topics: Analysis of Variance; Clinical Trials as Topic; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Polydeoxyribonucleotides; Postoperative Complications; Pulmonary Embolism; Random Allocation; Thrombophlebitis

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Random Allocation; Thrombophlebitis

The effectiveness of defibrotide was compared with that of calcium heparin and acetylsalicylic acid (ASA) in the prevention of deep venous thrombosis (DVT) resulting from orthopedic surgery. Sixty-three patients scheduled for elective or traumatological surgery, for the most part involving the hip joint, were recruited. The patients were randomly assigned to one of the following treatment groups: defibrotide (400 mg twice daily), administered intramuscularly (n = 19); calcium heparin (5,000 IU thrice daily), administered subcutaneously (n = 25); and ASA (100 mg on alternate days), administered orally (n = 19). Administration of the drug was started one day before surgery and continued until the seventh day after surgery. Each patient was monitored daily by means of the fibrinogen uptake test. The incidence of increased uptake did not differ significantly in the three groups (defibrotide, ten out of 19; calcium heparin, ten out of 25; ASA, seven out of 19). Conversely, a trend in favor of defibrotide was noted in cases of symptomatic DVT (defibrotide, one out of 19; calcium heparin, two out of 25; ASA, four out of 19) and pulmonary embolism (defibrotide, no cases; calcium heparin, one case; ASA two cases). On the strength of these findings, defibrotide therapy qualifies as a valid alternative to conventional DVT prophylaxis in orthopedic surgery.

Topics: Aged; Aspirin; Female; Fibrinolytic Agents; Heparin; Hip Joint; Humans; Male; Orthopedics; Polydeoxyribonucleotides; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Thrombophlebitis

The latest research into the prevention of peri- and postoperative thromboembolic disease has found orthopaedic surgery patients to be most at risk. As the genesis of deep venous thrombosis (DVT) is due to haemodynamic, hemorheologic and parietal factors, various prophylactic measures have been considered in the past, measures which have not proved able to provide satisfactory protection in orthopaedics. The results obtained with Defibrotide in a random and controlled clinical study versus calcium heparin involving 211 patients of both sexes candidates to receive total hip arthroplasty and presenting at least one major thromboembolic risk factor are reported. The patients were assigned at random to one of the following treatments: 1) Defibrotide at a dose of 400 mg b.i.d. i.v. in 50 ml phleboclysis in 5 minutes (n = 108); 2) calcium heparin at a dose of 5000 IU t.i.d. subcutaneously (n = 103). The treatment began the day before operation and continued on average up to the eighth day for the Defibrotide group. With the control group it continued until discharge (usually on the 15th day) and at home for about three weeks until the completion of the physiotherapy cycle. In the 108 patients treated with Defibrotide only one case of DVT was reported and in none of these patients were symptoms or signs of pulmonary embolism encountered. In the group treated with calcium heparin 2 cases of clinically and radiologically diagnosed pulmonary embolism and 4 cases of DVT were observed. Although the differences were not statistically significant, the tendency favours Defibrotide. Statistically significant (p less than 0.01) was the difference in postoperative bleeding evaluated with particular attention in patients of advanced age. Further, in the Defibrotide group, scarring was considered excellent in 96% of cases while in the heparin group scarring was excellent in 85% (p less than 0.05). To conclude, the sure clinical effectiveness, tolerance, handiness and lack of interference with clotting functions make Defibrotide a really useful drug for the prevention of thromboembolic episodes in patients undergoing major orthopaedic surgery.

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hip Prosthesis; Humans; Male; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Premedication; Random Allocation; Thromboembolism; Wound Healing

The prophylactic activity of defibrotide, a new extractive antithrombotic-thrombolytic agent of mammalian origin, was assessed by detection of deep venous thrombosis (DVT) in patients who underwent general elective surgery. 120 patients (aged 25-85 years, mean 55.6) were randomly assigned to defibrotide (60 patients) or to placebo (60 patients). The two groups were homogeneous for age, sex and risk factors for DVT. The active drug was given intravenously 200 mg four times a day, starting the day before the operation and then for the following 7 days. To detect DVT, 125I-fibrinogen was used, by conventional methods. Defibrotide reduced the frequency of DVT to 4/60 (7%) from 16/60 (27%) in the placebo group. The difference was highly significant (p less than 0.01). Neither side effects nor anticoagulant activity were observed. On the basis of this evidence, defibrotide may be considered an effective and well-tolerated drug for prevention of DVT.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Partial Thromboplastin Time; Polydeoxyribonucleotides; Postoperative Complications; Prothrombin Time; Thrombophlebitis

In transplanted patients graft rejection is the most frequent complication in the first year after surgery. Vascular lesions (necrosis, intimal proliferation, thrombosis) are signs of poor prognosis and lead to irreversible loss of renal function and graft removal in most cases. The problem of vascular rejection is still not solved and the results of therapy unsatisfactory, both because of inadequacy of diagnosis and/or inadequacy of available therapy. The role of prevention, very likely the best approach, is still sub judice. In an attempt to explore the validity of prevention, 22 transplanted patients (group A) were given a new antithrombotic agent (defibrotide) immediately after surgery, and the results were compared with those of a well-matched group of 30 patients on dipyridamole (group B). Follow-up lasted 6-19 months (mean 9.9) for group A; 5-21 months (mean 12) for group B. In group A, 8 patients (36%) had rejection episodes. Antirejection therapy was followed by recovery of renal function in all cases. In group B, 9 patients (29%) had rejection crises and graft removal was necessary in 7 instances due to severe vascular lesions. At the end of follow-up, all patients treated with defibrotide had normally functioning grafts: among the 30 patients on dipyridamole, 22 (73%) had satisfactory graft function.

Topics: Clinical Trials as Topic; Dipyridamole; Fibrinolytic Agents; Graft Rejection; HLA Antigens; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Polydeoxyribonucleotides; Postoperative Complications; Random Allocation; Thrombosis

Defibrotide, a new antithrombotic compound without anticoagulant activity, has been tested for prevention of deep venous thrombosis (DVT) in patients undergoing gynecological surgery (mainly hysterectomy). Eighty-nine women (mean age 48.5) were randomly allocated to defibrotide (44 patients) or placebo (45 patients). 800 mg defibrotide was given daily (200 mg intravenously 4 times a day), starting on the day before operation and then for the next 7 days. DVT were detected by the conventional 125I-fibrinogen test. The two groups were homogeneous for known risk factors (age, varicosities, obesity, neoplasia and previous thromboembolic episodes). The results showed a statistically significant reduction of DVT incidence in patients on defibrotide, as compared with those on placebo: 4/44 = 9% vs. 13/45 = 28.8% (p less than 0.05). There were no side effects, including hemorrhagic complications. The numbers of units transfused were comparable for the 2 groups. In conclusion, the trial shows that defibrotide is an effective and safe drug for the prevention of DVT in gynecological surgery.

Topics: Double-Blind Method; Female; Fibrinogen; Fibrinolytic Agents; Genital Diseases, Female; Humans; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Random Allocation; Thrombophlebitis; Uterine Neoplasms; Varicose Veins

Severe hepatic veno-occlusive disease (VOD) is a recognized complication of autologous and allogeneic stem cell transplantation (SCT) that is often fatal. Defibrotide (DF) is a polydeoxyribonucleotide that has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anticoagulation. Preliminary studies have demonstrated activity for DF in the treatment of VOD, with minimal associated toxicity. In the present study, 40 patients who fulfilled established criteria for VOD were treated with DF on compassionate grounds in 19 European centres; 28 patients met risk criteria predicting progression of VOD and fatality or had evidence of multiorgan failure (MOF), and were defined as 'poor-risk'. DF was commenced intravenously at a median of 14 d (range, -2 d to 53 d) post SCT at doses ranging from 10 to 40 mg/kg. The median duration of therapy was 18 d (range, 2--71 d). Twenty-two patients showed a complete response (CR) (bilirubin < 34.2 micromol/l and resolution of signs/symptoms of VOD and end-organ dysfunction) [CR = 55%, confidence interval (CI) 40--70%] and 17 patients (43%) are alive beyond d +100. Ten poor-risk patients showed a complete response (CR = 36%, CI 21--51%). These results demonstrate that DF is an active treatment for VOD following SCT and a randomized trial is now underway in order to further evaluate its role.

Topics: Acute Disease; Adolescent; Adult; Bilirubin; Breast Neoplasms; Child; Child, Preschool; Female; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Hodgkin Disease; Humans; Infant; Leukemia, Myeloid; Male; Middle Aged; Multiple Myeloma; Polydeoxyribonucleotides; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

Primary deep venous insufficiency (PDVI) represents an important cause of chronic venous insufficiency (CVI). The clinical picture is generally related to a congenital weakness of the vein wall at the level of the valvular ring which may dilate its diameter with consequent lengthening and prolapse of the valvular cusps. However, in an initial stage of PDVI the leaflets are normally formed and may undergo restorative surgery. In this condition an external banding valvuloplasty (EBV) with a Dacron sleeve around the incompetent valve may restore the competence. The authors report 54 cases of superficial femoral vein EBV performed over a period of 1986 to 1991. The patients were affected by signs of CVI and/or relapsing, complicated or atypical varices in which descending venography showed a grade II, III or IV primary deep reflux. In a mean follow-up of 38 months (4 to 63 months) deep reflux had disappeared in 41 patients (76%), had significantly decreased in 8 (14.8%) and was completely unmodified in 5 (9.2%). According to the experience of other authors, these results suggest the therapeutic validity of EBV in the initial stage of PDVI.

Topics: Adolescent; Adult; Chronic Disease; Female; Femoral Vein; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Male; Phlebography; Polydeoxyribonucleotides; Postoperative Complications; Treatment Outcome; Venous Insufficiency

Defibrotide, a new anti-thrombotic and profibrinolytic agent, has been experimented in the prophylaxis of thromboembolic disease in 99 women subjected to obstetrico-gynaecological operations. The drug's effectiveness, lack of changes in the clotting set-up and good tolerance were demonstrated. In conclusion, it is hoped that the good results obtained will promote more regular use of this drug in the prophylaxis of deep venous thrombosis in obstetrico-gynaecological surgery.

Topics: Adult; Aged; Aged, 80 and over; Drug Evaluation; Female; Fibrinolytic Agents; Genitalia, Female; Humans; Middle Aged; Polydeoxyribonucleotides; Postoperative Complications; Pregnancy; Pregnancy Complications; Thromboembolism

Topics: Aged; Dihydroergotamine; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Postoperative Complications; Pulmonary Embolism; Risk Factors; Thromboembolism; Thrombophlebitis

Topics: Abdomen; Female; Fibrinolytic Agents; Heparin; Humans; Male; Polydeoxyribonucleotides; Postoperative Complications; Thrombophlebitis