scholarly journals Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial [see comments]

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2834-2840 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
A Huynh ◽  
JP Charlet ◽  
...  

Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2834-2840 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
A Huynh ◽  
JP Charlet ◽  
...  

Abstract Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.


1987 ◽  
Author(s):  
C CARON ◽  
J P JOUET ◽  
J HIMPENS ◽  
P HIVES ◽  
H GRUSON ◽  
...  

Decrease of factor VII (F VII) and protein C (PC) has been said to allow an early detection of hepatic veno-occlusive disease (VOD) (VILMER, Path. Biol. 1986, 34 : 79), that represents a serious complication of bone marrow transplantation (BMT). In this purpose, F VII (activity) and PC (antigen) have been measured in 18 patients (aged 9 to 45 yr- m : 26 yr) who underwent allogeneic bone marrow graft for chronic myelogenous leukemia (9 cases), acute lymphocytic leukemia (7 cases) acute myelogenous leukemia (2 cases). All patients received as preparation for BMT total body irradiation (mean dose = 10 Gy) along with cyclophosphamide (120 mg/Kg). All were given low dose heparin (100 UI/Kg/24 hr) from days -7 to +30. None of the patients developed VOD but graft-versus-host disease occurred in 13 out of them between days 18 and 52. Moreover, coagulation studies performed from days 1 to 28 detected a moderate decrease of F VII and PC (maximum on day 11). These parameters were normalized on day 28. The level of the other vitamin K-dependent factors was not significantly changed.So the moderate decrease of F VII and PC found in the post-graft period was not associated with hepatic VOD. However, as none of the patients developed this complication, these results do not exclude that a major decrease of these parameters could serve as an early diagnosis of VOD. On the other hand, a prophylactic effect of low dose heparin cannot be ruled out.


1987 ◽  
Author(s):  
G G Neri Semeri ◽  
F Rovelli ◽  
G F Gensini ◽  
S Pirelli ◽  
M Carnovali ◽  
...  

The effectiveness of low dose heparin in the prevention of myocardial reinfarction was investigated in a multi centric randomized controlled study. After having given their, informed consent to undergo daily subcutaneous heparin adninistratian, 728 patients of both sex aged 50-75 years, who had suffered frcm a transmural myocardial infarction 6-18 months before the enrollment and were in the I or II NYHA class were randomized. 365 patients (control group) were an the therapy usually performed by the 21 experimental canters participating in the study and 363 (heparin group) were treated with subcutaneous calcium heparin (Calciparina®) 12,500 IU daily in addition to the usual therapy of the centers. Curing enrollment the balancement of the two grcups was periodically checked for age, sex, serum cholesterol, cigarette smoking, blood pressure, site of infarction, arrhythmias and drug regimen. The prospect!vely established end-points were: transmural reinfarctioi as primary end-point; general mortality and mortality for cardiovascular events as accessory end-points over a mean follow-up period of 24 nxnths. Statistical analysis was foreseen both on drug efficacy (EE) and intention to treat (IT) basis. Patients of both groups underwent periodical examinations during the study. Acherence to the therapy and bone mineral content (bone density by double isotope technique) were also checked. At the end of the study the balancement for the factors considered was satisfactory and the drop-outs were 7.7% in heparin group and 6.3% in control group (ns). In heparin group the re infarction rate was lcwer by 62.92% than in control group. At life table analysis the difference was statistically significant (p<0.05 DE and p=0.05 IT). Mortality rate was reduced by 47.61% (DE) in heparin group (p<0.05 at life table analysis). Cardiovascular mortality was not significantly reduced (−33.06%), but the mortality attributable to thromboembolism was reduced in heparin group (p<0.05). Sixty patients (16.5%) discontinued heparin treatment, but only in 23 patients (6.3%) suspension was due to side effects.


Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 732-736 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
JP Charlet ◽  
D Schlaifer ◽  
...  

Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.


2012 ◽  
Vol 19 (02) ◽  
pp. 246-250
Author(s):  
ABID NAEEM ◽  
TAHIRA JABBAR

Objective: To evaluate the therapeutic benefit of low dose heparin in cerebral venous thrombosis, occurring during period ofperpeurum. Study design: Descriptive study. Setting: Department of Medicine DHQ Hospital Mirpur (Department of Obs/Gynae DHQ HospitalMirpur(AK). Period: January 2010 to November 2011. Method: This study was carried on 100 patients with history of postpartum cerebralvenous thrombosis. Out of which 48 on heparin and 52 formed the control group. The ages of all patients were between 20 to 30 years.Parameter recorded included history. Blood pressure.,the diagnosis was supported by cranial computed tomography. The secondary causeswere ruled out on the basis of history and physical examination. The data and results were analyzed in SPSS. Results: Out of 48 patients inheparin group 30 with non-heamorrhage lesion and 18 with haemorrhagic infarction). 52 in control group. 34 non-haemorriagic lesion and 18with haemorragic infarct .in non-haemorrhagic CVT, there is no death in heparin group as compared to 5 deaths in control group. In patients withhaemorriagic lesions, there were 5 deaths in heparin group as compared to 7 deaths in the control group. Heparin faed better than the controlgroup, both in patients with haemorrhagic as well as non-haemorrhagic lesions. Conclusions: Low molecular weight (LMWH) at low doses issafe and effective for both non-haemorrhage and haemorrhgic infarct of postpartum cvt with regard to recovery and outcome as compared tocontrol group.


1979 ◽  
Author(s):  
G. Lahnborg ◽  
B. Beerman

The favourable effect of low-dose heparin prophylaxis in preventing postoperative deep-vain thrombosis (DVT) in patients undergoing surgical treume has bean shown in several investigations. However, there are still some patients sustaining DVT in spite of heparin prophylaxis. In an attempt to improve the prophylaxis, dihydroergotamine (DHE) has been added to the heparin.In a prospective trial the effect of low-dose heparin and DHE prophylaxis was studied in 190 patients undergoing nailing of fractured femoral neck. The patients were divided into 3 groups and were randomly given heparin or a combination of heparin and DHE and the third group was given only saline.The frequency of DVT, detected by the 125-I-fibrinogen method was 167. in the group given heparin and DHE, 20%, in the heparin group and 39% in the control group.Preliminary results. Completed evaluation will be presented during the congress.


1991 ◽  
Vol 9 (5) ◽  
pp. 865-870 ◽  
Author(s):  
M Attal ◽  
D Schlaifer ◽  
H Rubie ◽  
F Huguet ◽  
J P Charlet ◽  
...  

Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.


1975 ◽  
Author(s):  
V. V. Kakkar ◽  
T. P. Corrigan

Several controlled trials have shown that low-dose heparin is effective in reducing the incidence of deep vein thrombosis without increasing the risk of bleeding. However its effectiveness in preventing fatal pulmonary embolism has yet to be determined and, for this, a multicentre tiral was organised in which 31 centres took part; patients over the age of 40, undergoing only major elective abdominal, thoracic or orthopaedic surgery were included. They were randomly allocated to a control or heparin group and, for each patient entered in the trial, essential information was recorded in a proforma designed for computer analysis. The incidence of fatal pulmonary embolism was determined by autopsy examination. 4,121 patients were admitted to the trial – 2,076 in the control group and 2,045 in the heparin group. 16 patients in the control group died due to acute massive pulmonary embolism confirmed at autopsy, but only 2 in the heparin group. The difference is statistically significant (P < 0.01). There was no evidence of excessive blood loss during or after surgery. These results will be presented in detail. Low-dose heparin prophylaxis can now be recommended as the method of choice for preventing postoperative fatal pulmonary embolism.


Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 732-736 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
JP Charlet ◽  
D Schlaifer ◽  
...  

Abstract Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.


1978 ◽  
Vol 49 (3) ◽  
pp. 378-381 ◽  
Author(s):  
Dario Cerrato ◽  
Cesare Ariano ◽  
Folco Fiacchino

✓ By the use of 125I-labeled fibrinogen test, the incidence of postoperative deep vein thrombosis (DVT) and the effectiveness of prophylactic low-dose heparin treatment were investigated in 110 patients who underwent elective neurosurgical procedures. Fifty patients were appointed randomly to a control group and 50 to a heparin group (10 patients were excluded since they had DVT before surgery). The incidence of DVT was reduced from 34% in the control group to 6% in the heparin group (p < 0.005). No statistically significant differences were observed in transfusion requirements, postoperative hemoglobin concentration, and the occurrence of postoperative hematomas between the two groups. Positive correlation was observed between DVT and motor deficit (p < 0.05). Preoperative assessment of patients' sensitivity to the standard 5000-unit dose of heparin was performed in all treated patients and is thought an important factor in improving the safety of heparin prophylaxis.


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