A comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (... more A comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/g bw), LMWH in 2 doses (2 XaI U/g or 0.4 XaI U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis ...
To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-m... more To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-molecular-weight heparin (LMWH) 24 patients undergoing elective cholecystectomy received one subcutaneous injection of the LMWH Fragmin. Each group of eight patients received either 2,500 or 5,000 XaI U 2 h before operation or 5,000 XaI U 10 h before surgery. For comparison an additional eight patients received 5,000 IU unfragmented heparin (UH) before operation. Laboratory analyses included amidolytically measured XaI- and IIaI-activities and direct measurements of heparin. Dose-dependent increase in the XaI- and IIaI-activity with maximal levels about 3-4 h after injection was seen. Patients given the LMWH 2 h before operation had lower levels of XaI-activity 2 h after injection than those receiving it 10 h before surgery, despite the same dose given. This correlated with the heparin concentrations, where the highest concentration was measured in patients given the LMWH 10 h before surgery. In conclusion, the surgical trauma of a cholecystectomy does not seem to have any major influence on the XaI- or IIaI-activity after administration of the studied LMWH. Alterations of the absorption and/or elimination rates cannot, however, be ruled out, but are related to factors other than the operative trauma per se, such as effects of premedication or circadian rhythmic variations.
An experimental model based on the combination of endothelial damage and flow reduction was used ... more An experimental model based on the combination of endothelial damage and flow reduction was used to induce jugular vein thrombosis in rabbits. The effect on thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70, placebo and their combination was studied in a double-blind fashion with actual doses used in clinical thromboprophylaxis. Saline and polygeline were used as placebo in the control group. Four groups with 120 isolated vein segments in 60 animals were studied for presence of thrombus formation, occlusive thrombi and thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when compared with the placebo control group. Similarly, LMWH reduced the thrombus weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi (p = 0.0001). Compared with the LMWH group the group treated with the combination of LMWH and dextran was found to reduce the frequenc...
With the advent of ventriculo-peritoneal shunting and improved medical therapies, patients with h... more With the advent of ventriculo-peritoneal shunting and improved medical therapies, patients with hydrocephalus are living longer and presenting with unrelated medical problems. It can be disconcerting to discover that the patient who needs a routine laparoscopic procedure also has a ventriculoperitoneal (VP) shunt. Although the literature is limited there is a small body of evidence indicating that it is safe to perform laparoscopic surgery on these patients with routine anesthetic monitoring. The authors report the case of a laparoscopic cholecystectomy in a patient with a VP shunt.
Awareness of cost-effectiveness aspects has become increasingly important within the health care ... more Awareness of cost-effectiveness aspects has become increasingly important within the health care sector in times of constrained resources. Health economics deal with methods of making choices under conditions of uncertainty and provide models for decision making. A key question is to compare alternative strategies. Within the field of prophylaxis against venous thromboembolism general thromboprophylaxis is cost-effective provided that the frequency of deep vein thrombosis is higher than 10%. Diagnostic screening and selective treatment of detected thrombosis is always the least cost-effective alternative. Although detailed analyses are still lacking it seems as if the use of low molecular weight heparins is more cost-effective than unfractionated low dose heparin. Besides saving lives by preventing fatal pulmonary embolism an adequate thromboprophylaxis also will provide monetary savings.
An experimental model based on the combination of endothelial damage and flow reduction was used ... more An experimental model based on the combination of endothelial damage and flow reduction was used to induce jugular vein thrombosis in rabbits. The effect on thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70, placebo and their combination was studied in a double-blind fashion with actual doses used in clinical thromboprophylaxis. Saline and polygeline were used as placebo in the control group. Four groups with 120 isolated vein segments in 60 animals were studied for presence of thrombus formation, occlusive thrombi and thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when compared with the placebo control group. Similarly, LMWH reduced the thrombus weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi (p = 0.0001). Compared with the LMWH group the group treated with the combination of LMWH and dextran was found to reduce the frequency of occlusive thrombi (p = 0.03) and numerically, but not significantly, further reduce the overall frequency of thrombosis (p = 0.18) and thrombus weights (p = 0.11). The results are consistent with an augmentation of the antithrombotic effect of LMWH by dextran 70. The need for further evaluation of the combined efficacy of LMWH and dextran is apparent from this study.
The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in do... more The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 ml i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-h period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 h and AUC0-24 h in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. Our findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.
In this prospective randomized double-blind study the thromboprophylactic effect of postoperative... more In this prospective randomized double-blind study the thromboprophylactic effect of postoperative low molecular weight heparin (tinzaparin) was compared with placebo in 80 patients undergoing emergency abdominal surgery. The fibrinogen uptake test was used but because of withdrawal of the labelled fibrinogen from the market the calculated number of patients was not reached. However, this is one of the few studies in emergency abdominal surgery we thought it important to report. The frequency of deep vein thrombosis was reduced with prophylaxis from 22% (95% conf. intervall 11-38%) to 8% (2-21%), a risk reduction of 65%, which is however not significant. Together with data from the few previously published studies it can be concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis, which should be instituted either before operation or at latest 24 hours after. The exact prophylactic relation between pre- and post-operative start would, however, require a separate, randomized study.
The International journal of risk & safety in medicine, 1996
The aim of the study was to determine the long-term survival in patients undergoing total hip art... more The aim of the study was to determine the long-term survival in patients undergoing total hip arthroplasty in relation to type of perioperatively administered thromboprophylaxis. Patients from seven randomized controlled trials of the effect of thromboprophylaxis on development of early thromboembolic complications after total hip arthroplasty were included in a follow-up analysis with death as the end-point. There was no difference in survival between groups receiving active thromboprophylaxis, but there was a general trend towards a better survival in the 3 placebo groups compared with low molecular weight heparin (LMWH), (RR: 1.53; C.I.: 1.04-2.25). There was a significant excess of cardiovascular deaths in the LMWH groups (RR: 2.48; CI: 1.45-4.24). Long-term prospective studies should be performed to assess the long-term effect of various thromboprophylactic regimens on morbidity and mortality after total hip arthoplasty.
The International journal of risk & safety in medicine, 1997
The aim of the study was to determine the effect on long-term survival of the location of DVT in ... more The aim of the study was to determine the effect on long-term survival of the location of DVT in relation to age groups and side of operation. 1310 patients undergoing total hip arthroplasty and who participated in one of 7 randomized, prospective clinical trials with thromboprophylaxis were included in this analysis. A trend analysis showed that the incidence of proximal and distal DVT increased significantly with age (p<0.05). In patients older than 64 years of age the relative risk of death was non-significantly higher when proximal DVT was present compared to patients without DVT and the relative risk of death was non-significantly higher in patients older than 74 years of age when distal thrombi was present compared to patients without DVT. The test for trend showed an increase with age in the incidence of both ipsi- and contralateral DVT; the increase was significant in patients with contralateral DVT (p<0.05). The relative risk of death was higher (of borderline significance) in patients older than 74 years of age with contralateral DVT.In conclusion, the pattern of location of asymptomatic deep vein thrombosis changes with increasing age. The location of asymptomatic and treated DVT has no significant influence on long-term survival.
The estimated degree of carotid stenosis is decisive for the selection of patients who would bene... more The estimated degree of carotid stenosis is decisive for the selection of patients who would benefit from surgical treatment. Carotid thrombendarterectomy is recommended in patients with symptomatic > or = 80 procent internal carotid artery stenosis (ECST method). Many vascular centers now often rely entirely on duplex ultrasonography to select the patients for carotid surgery. The results of a recently published Swedish multicenter study (Jogestrand et al., Eur J Vasc Endovasc Surg 2002; 23:510-8) demonstrate that certain technical aspects of the ultrasound examination are of importance for the estimation of the degree of stenosis. Based on these results, the Swedish Quality Board for Carotid Surgery recommends the use of Doppler angle range specific cut off points for the peak systolic velocity in the internal carotid artery for identification of high-grade internal carotid artery stenosis: These cut off points are > or = 2.1 m/s for insonation angles of 0-49 degrees and > or = 3.2 m/s for angles 50-60 degrees. The angle of insonation should be kept as small as possible and should always be stated in the investigators report.
Indications for and the results of carotid endarterectomy in symptomatic and asymptomatic carotid... more Indications for and the results of carotid endarterectomy in symptomatic and asymptomatic carotid artery stenosis are reviewed. The main indication for carotid endarterectomy is symptomatic stenosis of a carotid artery with > 70 percent lumen reduction according to the NASCET method, or > 85 percent lumen reduction according to the ECST method. The operation should ideally be performed within two weeks after the onset of symptoms. Preliminary results from the ACST study, indicating significant beneficial effects of carotid endarterectomy also in asymptomatic carotid artery stenosis have been orally presented. Assessment of and surgery upon Swedish patients with significant carotid artery stenosis should be performed in specialised multidisciplinary "carotid artery centers". Endovascular treatment of carotid artery stenosis should at the present stage only be performed within clinical trials.
A comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (... more A comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/g bw), LMWH in 2 doses (2 XaI U/g or 0.4 XaI U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis ...
To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-m... more To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-molecular-weight heparin (LMWH) 24 patients undergoing elective cholecystectomy received one subcutaneous injection of the LMWH Fragmin. Each group of eight patients received either 2,500 or 5,000 XaI U 2 h before operation or 5,000 XaI U 10 h before surgery. For comparison an additional eight patients received 5,000 IU unfragmented heparin (UH) before operation. Laboratory analyses included amidolytically measured XaI- and IIaI-activities and direct measurements of heparin. Dose-dependent increase in the XaI- and IIaI-activity with maximal levels about 3-4 h after injection was seen. Patients given the LMWH 2 h before operation had lower levels of XaI-activity 2 h after injection than those receiving it 10 h before surgery, despite the same dose given. This correlated with the heparin concentrations, where the highest concentration was measured in patients given the LMWH 10 h before surgery. In conclusion, the surgical trauma of a cholecystectomy does not seem to have any major influence on the XaI- or IIaI-activity after administration of the studied LMWH. Alterations of the absorption and/or elimination rates cannot, however, be ruled out, but are related to factors other than the operative trauma per se, such as effects of premedication or circadian rhythmic variations.
An experimental model based on the combination of endothelial damage and flow reduction was used ... more An experimental model based on the combination of endothelial damage and flow reduction was used to induce jugular vein thrombosis in rabbits. The effect on thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70, placebo and their combination was studied in a double-blind fashion with actual doses used in clinical thromboprophylaxis. Saline and polygeline were used as placebo in the control group. Four groups with 120 isolated vein segments in 60 animals were studied for presence of thrombus formation, occlusive thrombi and thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when compared with the placebo control group. Similarly, LMWH reduced the thrombus weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi (p = 0.0001). Compared with the LMWH group the group treated with the combination of LMWH and dextran was found to reduce the frequenc...
With the advent of ventriculo-peritoneal shunting and improved medical therapies, patients with h... more With the advent of ventriculo-peritoneal shunting and improved medical therapies, patients with hydrocephalus are living longer and presenting with unrelated medical problems. It can be disconcerting to discover that the patient who needs a routine laparoscopic procedure also has a ventriculoperitoneal (VP) shunt. Although the literature is limited there is a small body of evidence indicating that it is safe to perform laparoscopic surgery on these patients with routine anesthetic monitoring. The authors report the case of a laparoscopic cholecystectomy in a patient with a VP shunt.
Awareness of cost-effectiveness aspects has become increasingly important within the health care ... more Awareness of cost-effectiveness aspects has become increasingly important within the health care sector in times of constrained resources. Health economics deal with methods of making choices under conditions of uncertainty and provide models for decision making. A key question is to compare alternative strategies. Within the field of prophylaxis against venous thromboembolism general thromboprophylaxis is cost-effective provided that the frequency of deep vein thrombosis is higher than 10%. Diagnostic screening and selective treatment of detected thrombosis is always the least cost-effective alternative. Although detailed analyses are still lacking it seems as if the use of low molecular weight heparins is more cost-effective than unfractionated low dose heparin. Besides saving lives by preventing fatal pulmonary embolism an adequate thromboprophylaxis also will provide monetary savings.
An experimental model based on the combination of endothelial damage and flow reduction was used ... more An experimental model based on the combination of endothelial damage and flow reduction was used to induce jugular vein thrombosis in rabbits. The effect on thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70, placebo and their combination was studied in a double-blind fashion with actual doses used in clinical thromboprophylaxis. Saline and polygeline were used as placebo in the control group. Four groups with 120 isolated vein segments in 60 animals were studied for presence of thrombus formation, occlusive thrombi and thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when compared with the placebo control group. Similarly, LMWH reduced the thrombus weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi (p = 0.0001). Compared with the LMWH group the group treated with the combination of LMWH and dextran was found to reduce the frequency of occlusive thrombi (p = 0.03) and numerically, but not significantly, further reduce the overall frequency of thrombosis (p = 0.18) and thrombus weights (p = 0.11). The results are consistent with an augmentation of the antithrombotic effect of LMWH by dextran 70. The need for further evaluation of the combined efficacy of LMWH and dextran is apparent from this study.
The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in do... more The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 ml i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-h period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 h and AUC0-24 h in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. Our findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.
In this prospective randomized double-blind study the thromboprophylactic effect of postoperative... more In this prospective randomized double-blind study the thromboprophylactic effect of postoperative low molecular weight heparin (tinzaparin) was compared with placebo in 80 patients undergoing emergency abdominal surgery. The fibrinogen uptake test was used but because of withdrawal of the labelled fibrinogen from the market the calculated number of patients was not reached. However, this is one of the few studies in emergency abdominal surgery we thought it important to report. The frequency of deep vein thrombosis was reduced with prophylaxis from 22% (95% conf. intervall 11-38%) to 8% (2-21%), a risk reduction of 65%, which is however not significant. Together with data from the few previously published studies it can be concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis, which should be instituted either before operation or at latest 24 hours after. The exact prophylactic relation between pre- and post-operative start would, however, require a separate, randomized study.
The International journal of risk & safety in medicine, 1996
The aim of the study was to determine the long-term survival in patients undergoing total hip art... more The aim of the study was to determine the long-term survival in patients undergoing total hip arthroplasty in relation to type of perioperatively administered thromboprophylaxis. Patients from seven randomized controlled trials of the effect of thromboprophylaxis on development of early thromboembolic complications after total hip arthroplasty were included in a follow-up analysis with death as the end-point. There was no difference in survival between groups receiving active thromboprophylaxis, but there was a general trend towards a better survival in the 3 placebo groups compared with low molecular weight heparin (LMWH), (RR: 1.53; C.I.: 1.04-2.25). There was a significant excess of cardiovascular deaths in the LMWH groups (RR: 2.48; CI: 1.45-4.24). Long-term prospective studies should be performed to assess the long-term effect of various thromboprophylactic regimens on morbidity and mortality after total hip arthoplasty.
The International journal of risk & safety in medicine, 1997
The aim of the study was to determine the effect on long-term survival of the location of DVT in ... more The aim of the study was to determine the effect on long-term survival of the location of DVT in relation to age groups and side of operation. 1310 patients undergoing total hip arthroplasty and who participated in one of 7 randomized, prospective clinical trials with thromboprophylaxis were included in this analysis. A trend analysis showed that the incidence of proximal and distal DVT increased significantly with age (p<0.05). In patients older than 64 years of age the relative risk of death was non-significantly higher when proximal DVT was present compared to patients without DVT and the relative risk of death was non-significantly higher in patients older than 74 years of age when distal thrombi was present compared to patients without DVT. The test for trend showed an increase with age in the incidence of both ipsi- and contralateral DVT; the increase was significant in patients with contralateral DVT (p<0.05). The relative risk of death was higher (of borderline significance) in patients older than 74 years of age with contralateral DVT.In conclusion, the pattern of location of asymptomatic deep vein thrombosis changes with increasing age. The location of asymptomatic and treated DVT has no significant influence on long-term survival.
The estimated degree of carotid stenosis is decisive for the selection of patients who would bene... more The estimated degree of carotid stenosis is decisive for the selection of patients who would benefit from surgical treatment. Carotid thrombendarterectomy is recommended in patients with symptomatic > or = 80 procent internal carotid artery stenosis (ECST method). Many vascular centers now often rely entirely on duplex ultrasonography to select the patients for carotid surgery. The results of a recently published Swedish multicenter study (Jogestrand et al., Eur J Vasc Endovasc Surg 2002; 23:510-8) demonstrate that certain technical aspects of the ultrasound examination are of importance for the estimation of the degree of stenosis. Based on these results, the Swedish Quality Board for Carotid Surgery recommends the use of Doppler angle range specific cut off points for the peak systolic velocity in the internal carotid artery for identification of high-grade internal carotid artery stenosis: These cut off points are > or = 2.1 m/s for insonation angles of 0-49 degrees and > or = 3.2 m/s for angles 50-60 degrees. The angle of insonation should be kept as small as possible and should always be stated in the investigators report.
Indications for and the results of carotid endarterectomy in symptomatic and asymptomatic carotid... more Indications for and the results of carotid endarterectomy in symptomatic and asymptomatic carotid artery stenosis are reviewed. The main indication for carotid endarterectomy is symptomatic stenosis of a carotid artery with > 70 percent lumen reduction according to the NASCET method, or > 85 percent lumen reduction according to the ECST method. The operation should ideally be performed within two weeks after the onset of symptoms. Preliminary results from the ACST study, indicating significant beneficial effects of carotid endarterectomy also in asymptomatic carotid artery stenosis have been orally presented. Assessment of and surgery upon Swedish patients with significant carotid artery stenosis should be performed in specialised multidisciplinary "carotid artery centers". Endovascular treatment of carotid artery stenosis should at the present stage only be performed within clinical trials.
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Papers by Thomas Mätzsch