Abstract Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60–70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency. 

/pdf/the-impact-of-acquired-coagulation-factor-xiii-deficiency-in-1e58due1.pdf

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing

The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia. In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM. The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group. Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.

/pdf/effects-of-coagulation-factor-xiii-on-intestinal-functional-fpgc4ye9u7.pdf

Effects of coagulation factor XIII on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation in experimental endotoxemia

The present study investigated the suitability of three different absorbable biocomposites for the repair of critical sized bone defects created at the mandibular angle of adult sheep. Each biocomposite was composed of a three-dimensional individualized polylactide scaffold, containing a tricalcium phosphate biomaterial (chronOS). Either autologous bone marrow (chOS/BoneMarrow) or coagulation factor XIII (chOS/FactorXIII) was added to the biomaterial for osteopromotion. Venous whole blood (chOS/Blood) added to the biomaterial served as a control. A total of 18 adult sheep were used for implantation studies, subdivided into three groups of six animals each. After 12 weeks of observation, the animals were sacrificed and the mandibles were retrieved for qualitative and quantitative histologic assessment within three regions of interest (transitional zone, center, and periphery) throughout the biocomposites. Successful bone regeneration was defined by the absence of scaffold deformation and the presence of new bone formation within the biocomposites. In histomorphometry, only chOS/BoneMarrow showed elevated area fractions of newly formed bone in all regions of interest (transitional zone 50.7 ± 7.5, center 31.9 ± 9.3, periphery 23.1 ± 13.5). This led to preservation of the macroscopic scaffold structure in all specimens. Zero hurdle regression confirmed this by validating the factor biocomposite as significant (p < 0.001) for regeneration success. In our experiment, chOS/BoneMarrow was the only biocomposite passing the hurdle of regeneration in all three regions of interest. In contrast, bone formation was less pronounced and uniform in chOS/FactorXIII and chOS/blood-containing specimens. In these groups, scaffolds showed obvious to significant deformation. Overall, autologous bone marrow showed the most promising results in our experimental setting. As opposed to reports in the literature, we could not confirm the suitability of coagulation factor XIII to promote bone formation, since bone formation rates were comparable only to those of the control venous blood.

Tricalcium phosphate-based biocomposites for mandibular bone regeneration--A histological study in sheep.

We investigated the osteopromotive properties of plasmatransglutaminase (F XIII), bone marrow and venous blood on a resorbable β-tricalcium phosphate (β-TCP) scaffold. A baseline binding and release study of F XIII from the scaffold showed a continuous release of 18% of the total dose after 48 h. The main study consisted of 18 adult sheep with cylindrical defects in both tibiae. The defects were filled with a β-TCP cylinder impregnated either with bone marrow, venous blood, F XIII or sheep were treated with 1250 IU F XIII intravenously over 14 days (n = 4 in each group). The defects were left open in two sheep. QCT and histology was performed after 6 and 12 weeks. The best bone ingrowth was seen after 6 weeks in the bone marrow group and after 12 weeks in the local F XIII group. The highest ingrowth on the inside of the cylinder proving the osteopromoting potential of F XIII was found in the local F XIII group. In our opinion F XIII is a good and readily available osteopromoting agent which can be used with β-TCP in cases of bone deficit to promote bone regeneration.

Osteopromotion with a plasmatransglutaminase on a β-TCP ceramic

Heterotopic ossification (HO) is widely recognized as a common occurrence among patients suffering from traumatic spinal cord injuries (SCI). The exact etiology of HO formation remains unknown. Published medical and surgical management strategies are often plagued with questionable effectiveness and frequent complications. There are minimal publications regarding the management strategies of HO in SCI patients as it pertains to plastic surgery. We present a case series of patients treated at our institution who underwent treatment for pressure ulcers with underlying HO to highlight the vast spectrum of clinical phenotypes present in this population. The pathophysiology, diagnostic tools, methods of prevention, and surgical management of HO are discussed here. We believe that there are two clinically relevant patterns of HO in SCI patients. A neurogenic process that occurs early after injury is usually bilateral and involves uninjured hip joints. Pressure sores that occur are related to poor joint mobility and subsequent development of pressure points. An infection-driven process in which HO development is associated with either pressure sores or septic hip joints is generally unilateral and not always associated with hip contractures. They present different challenges and reconstructive options to plastic surgeons. Although complications such as infection and HO recurrence are common, the functional and psychological benefits of restoring hip flexion are usually worthwhile.

Pressure ulcer reconstruction in patients with heterotopic ossification after spinal cord injury: A case series and review of literature.

The role of plasma transglutaminase (F XIII) in wound healing of complicated pressure sores after spinal cord injury

The role of plasma transglutaminase (F XIII) in wound healing of complicated pressure sores after spinal cord injury.

Study design: Clinical study. Objectives: To evaluate indications of hip endoprosthesis in periarticular ossifications. Setting: A Spinal Cord Injury Centre in Germany. Methods: Clinical examination, X-ray control. Results: Surgery of periarticular ossification (paraosteoarthropathy, POA) either involves simple resection of the ossification or removal of the hip. The latter has an impact on the sitting posture with concomitant increased pressure sore risk. Nevertheless the hip is biomechanically important in paraplegics. We are investigating the outcome of total hip replacement (THR) in patients with ankylosis due to periarticular ossification. Six hip replacement cases seen in follow-up of up to 24 months showed no loosening, with good mobility of the joint. We follow a strict perioperative POA prophylaxis, which resulted in each case reporting only a slight recurrence (Brooker 1–2) without any loss of functional mobility. Conclusion: In ankylotic hips with mobility/social/hygenic problems we favour a hip replacement in cases with osteoarthritis or high risk of osteoporotic fracture. A replacement of the joint should be preferred to a Girdlestone operation.

/pdf/endoprosthesis-in-paraplegics-with-periarticular-1wlu8j9mit.pdf

Endoprosthesis in paraplegics with periarticular ossification of the hip

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The role of plasma transglutaminase (F XIII) in wound healing of complicated pressure sores after spinal cord injury.

Endoprosthesis in paraplegics with periarticular ossification of the hip