The contribution of the individual blood elements to the variability of thromboelastographic measures

BACKGROUND

Thromboelastography (TEG) is widely advocated as a rapid method for obtaining critical blood coagulation data to guide resuscitation, but the method suffers well‐known limits in sensitivity, repeatability, and interpretability.

STUDY DESIGN AND METHODS

Mixtures of fresh human blood components were prepared that represent the range of blood element concentrations seen in health and disease and after injury. These mixtures were tested in a TEG device after kaolin, tissue factor and phospholipid, or tissue factor and phospholipid with abciximab activation. The results were measured as reproducibility and nonlinear effects in regression analysis and evaluated for interpretability.

RESULTS

Clot strength was associated with increased platelet (PLT) content and plasma fibrinogen concentration and content. Increasing hematocrit (Hct) reduced while increasing PLT or plasma concentration increased TEG clot strength. The abciximab dose used to block PLT activity did not fully inhibit the PLT contribution to clot strength. Clot strength is logarithmically correlated in the absence and linearly correlated to PLT concentration in the presence of abciximab. TEG clot strength with or without abciximab is dependent on Hct, PLT, and plasma (fibrinogen) concentrations in complex patterns.

CONCLUSION

Interpretation of TEG variables is limited without knowledge of the concentration of the blood components present. When “normal” TEG values are known for a certain PLT‐plasma‐red blood cell concentration, the assay can be used to assess PLT and plasma function in coagulation. The TEG “functional fibrinogen” assay should be used only as a gross estimate of the fibrinogen concentration in whole blood.     

Degradation of tissue-type plasminogen activator by human monocyte- derived macrophages is mediated by the mannose receptor and by the low- density lipoprotein receptor-related protein

The balance of tissue-type plasminogen activator (t-PA) production and degradation determines its concentration in blood and tissues. Disturbance of this balance may result in either increased or decreased proteolysis. In the present study, we identified the receptor systems involved in the degradation of t-PA by human monocytes/macrophages in culture. Monocytes were cultured and became macrophages within 2 days. At 4 degrees C, 125I-t-PA bound to macrophages with high (apparent dissociation constant [kd], 1 to 5 nmol/L) and low affinity (kd > 350 nmol/L). At 37 degrees C, the cells internalized and degraded t-PA via the high affinity binding sites, which were partially inhibited by mannan. The low affinity binding sites were 6-aminohexanoic acid- inhibitable and not involved in t-PA degradation. Degradation of t-PA was upregulated during differentiation of monocytes to macrophages. Dexamethasone further upregulated the mannan-inhibitable t-PA degradation. Lipopolysaccharide downregulated both mannan-inhibitable and non-mannan-inhibitable t-PA degradation. Non-mannan-inhibitable degradation was completely blocked by recombinant 39-kD receptor- associated protein (RAP, inhibitor of lipoprotein receptor-related protein [LRP]), whereas mannan-inhibitable degradation was blocked by the addition of a monoclonal antibody against the mannose receptor. No differences between the degradation of t-PA and functionally inactivated t-PA were observed. We conclude that human monocyte-derived macrophages are able to bind, internalize, and degrade t-PA. Degradation of t-PA does not require complex formation with plasminogen activator inhibitors. The macrophages use two independently regulated receptors, namely, the mannose receptor and LRP, for the uptake and degradation of t-PA.     

Frozen for combat: Quality of deep-frozen thrombocytes,produced and used by The Netherlands Armed Forces 2001–2021

Background

The Netherlands Armed Forces (NLAF) are using −80°C deep-frozen thrombocyte concentrate (DTC) since 2001. The aim of this study is to investigate the effect of storage duration and alterations in production/measurement techniques on DTC quality. It is expected that DTC quality is unaffected by storage duration and in compliance with the European guidelines for fresh and cryopreserved platelets.

Study Design and Methods

Pre-freeze and post-thaw product platelet content and recovery were collected to analyze the effects of dimethyl sulfoxide (DMSO) type, duration of frozen storage (DMSO-1 max 12 years and DMSO-2 frozen DTC max 4 years at −80°C) and type of plasma used to suspend DTC. Coagulation characteristics of thawed DTC, plasma and supernatant of DTC (2× 2500 G) were measured with Kaolin thromboelastography (TEG) and phospholipid (PPL) activity assay.

Results

Platelet content and recovery of DTC is ±10%–15% lower in short-stored products and remained stable when stored beyond 0.5 years. Thawed DTC (n = 1724) were compliant to the European guidelines (98.1% post-thaw product recovery ≥50% from original product, 98.3% ≥200 × 10⁹ platelets/unit). Compared to DMSO-1, products frozen with DMSO-2 showed ±8% reduced thaw–freeze recovery, a higher TEG clot strength (MA 58 [6] vs. 64 [8] mm) and same ±11 s PPL clotting time. The use of cold-stored thawed plasma instead of fresh thawed plasma did not influence product recovery or TEG-MA.

Discussion

Regardless of alterations, product quality was in compliance with European guidelines and unaffected by storage duration up to 12 years of −80°C frozen storage.     

Anwendung von Dermatographie als Behandlungsmethode in verschiedenen medizinischen Fachbereichen

Zusammenfassung Dermatographie ist die Anwendung von T?towierungstechniken in der Medizin. In der Vergangenheit konnten hiermit keine erfolgreichen und reproduzierbaren Resultate erzielt werden. Doch in den letzten 10 Jahren hat sich die Dermatographie zu einer allgemein anwendbaren und reproduzierbaren Technik entwickelt. Diese Technik wird heutzutage verwendet, um Hautverf?rbungen und Narben auf Dauer zu camouflieren. In diesem Artikel werden die technischen und medizinischen Aspekte der Dermatographie beschrieben. Au?erdem wird eine übersicht über die Anwendungsm?glichkeiten der Dermatographie gegeben. Eingegangen am 15. September 1995 Angenommen am 20. Februar 1996     

Fractures of the extremely atrophic mandible

Fracture treatment of the extremely atrophic mandible is a challenge to the surgeon because of the special problems and complications. A reliable method is the internal fixation technique with multiple split rib grafts. By use of immediate split rib bone grafting secondary revisions and reconstructions may be avoided. The technique and rationale are discussed.     

Cardiac cell-cell junctions in health and disease: Electrical versus mechanical coupling

Intercalated discs are the membrane sites where individual cardiomyocytes are connected to each other. Adherens-, desmosomal-, and gap junctions are situated in the intercalated disc and ensure mechanical coupling between cells and enable propagation of electrical impulses throughout the heart. A number of cardiac disorders, for example arrhythmogenic right ventricular dysplasia/cardiomyopathy, have been described in which an impaired mechanical coupling leads to electrical dysfunction, with occurrence of fatal arrhythmias.In this article the interaction between electrical and mechanical coupling is explored by reviewing studies performed in patients, animals, and in vitro. In these studies the effect of changes in protein composition of a mechanical junction on the electrical junction, and vice versa were investigated. It is shown that impaired electrical coupling does not change mechanical coupling. However, impaired mechanical coupling largely affects electrical coupling.     

Utilization of the pedicle of the temporal-forehead-flap to close defects in the maxilla after tumour surgery

The forehead flap can be used to close defects in the cheek and floor of the mouth, its pedicle can be used to close defects in the maxilla. This method was successfully applied in six patients.