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Low Molecular Weight Heparin impairs tendon repair
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
2008 (English)In: Journal of Bone and Joint Surgery, ISSN 0301-620X, E-ISSN 2044-5377, Vol. 90-B, no 3, 388-392 p.Article in journal (Refereed) Published
Abstract [en]

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair.

Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed.

Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections.

Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

Place, publisher, year, edition, pages
2008. Vol. 90-B, no 3, 388-392 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13015DOI: 10.1302/0301-620X.90B3.19493OAI: oai:DiVA.org:liu-13015DiVA: diva2:17673
Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2017-12-13
In thesis
1. Stimulation of tendon repair by platelet concentrate, CDMP-2 and mechanical loading in animal models
Open this publication in new window or tab >>Stimulation of tendon repair by platelet concentrate, CDMP-2 and mechanical loading in animal models
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Growth factor delivery may be useful to accelerate the rate of tendon healing. We studied Platelet Concentrate, which in effect can be regarded as a cocktail of growth factors relevant for tendon healing. In a rat Achilles tendon transection model, one postoperative injection of Platelet Concentrate resulted in increased strength even 3 weeks later.

Mechanical stimulation improves the repair of ruptured tendons. We studied the effects of platelets upon Achilles tendon regenerates in rats 3, 5 and 14 days after transection, either unloaded or mechanically stimulated. At 14 days, physical activity and platelets increased repair independently. Unloading decreased the mechanical properties of the repair tissue to less than half of normal. Moreover, the platelets had no effect without loading.

Thrombin, which we used for platelet activation, improved healing of the rat Achilles tendon by itself. Conversely, continuous inhibition of thrombin by low molecular weight heparin (LMWH) inhibited tendon repair. However, intermittent inhibition, similar to clinical thromboprophylaxis, had no effect on tendon healing.

Cartilage Derived Morphogenetic Protein-2 (CDMP-2) can improve tendon healing in loaded defect models. We now studied unloaded repair in a rabbit patellar tendon model. Two hours postoperative, the rabbits received CDMP-2 injected into the haematoma. The healing tendon became 65 % stronger than controls. We then studied Achilles tendon healing with CDMP-2 injections in sheep, to get a bigger animal model. There was an unexpectedly high variation of repair in these animals, and the study turned out to be underpowered. Spontaneous ruptures in humans have a more variable geometry than in our sheep model, so humans can also be expected to vary a lot in mechanical characteristics of Achilles tendon repair. This accentuates the importance of individualized rehabilitation programs.

In conclusion, both platelet concentrate and CDMP-2 injections might be of interest for clinical use as a complement to surgical or conservative treatment of tendon ruptures. Platelet treatment for tendon ruptures should probably be combined with early physiotherapy.

Place, publisher, year, edition, pages
Institutionen för nervsystem och rörelseorgan, 2007. 34 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1005
Keyword
Achilles tendon, injuries, physiology, Blood platelets, tendon injuries, physiopathology, therapy, wound healing
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-11264 (URN)978-91-85831-88-3 (ISBN)
Public defence
2007-06-07, Aulan, Hälsans Hus, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2009-08-22

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Virchenko, OlenaLindahl, TomasAspenberg, Per

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