chondroitin-sulfates and Necrosis

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis.

Topics: Administration, Oral; Anticoagulants; Arginine; Blood Coagulation; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Hirudins; Humans; Ischemia; Leg; Necrosis; Pipecolic Acids; Recombinant Proteins; Skin; Sulfonamides; Thrombocytopenia; Thrombosis; Warfarin

There are three distinct syndromes of heparin-induced thrombocytopenia: an acute reversible from seen immediately after intravenous bolus injection, a delayed-onset antibody-mediated form seen several days after the initiation of therapy, and an intermediate type characterized by mild thrombocytopenia developing just a few days after starting therapy. Delayed-onset heparin-induced thrombocytopenia, clinically the most important form, results from the formation of heparin-dependent antibodies that are directed against the platelet membrane. In the presence of heparin, these antibodies may induce in vitro or in vivo platelet aggregation. Consequently, the course may be complicated by arterial thromboses. Treatment of this syndrome includes the prompt cessation of heparin. Since continued or future anticoagulation is usually necessary, alternative means of anticoagulation have been explored. Oral anticoagulation is often started but requires several days to take effect. Other options include low-molecular-weight heparins, antiplatelet agents, prostacyclin analogues, and low-molecular-weight dextran. In vitro laboratory tests may be helpful in guiding alternative therapy in some, but not all cases. Unfortunately, none of these agents have proved to be uniformly effective and additional agents and clinical investigation are needed before a definitive option becomes available.

Topics: Aspirin; Cardiopulmonary Bypass; Chondroitin Sulfates; Dermatan Sulfate; Epoprostenol; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Iloprost; Necrosis; Platelet Aggregation Inhibitors; Skin; Skin Diseases; Thrombocytopenia; Thrombosis

Topics: Aged; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Toxins; Chondroitin Sulfates; Collagen; Debridement; Diabetic Ketoacidosis; Drainage; Enterotoxins; Exotoxins; Hand; Humans; Knee Joint; Leukocidins; Male; Necrosis; Negative-Pressure Wound Therapy; Skin Transplantation; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Synovectomy

Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.. The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.. In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings.. Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux.. Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Hospital Mortality; Hospitalization; Humans; Male; Necrosis; Off-Label Use; Partial Thromboplastin Time; Patient Safety; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Registries; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism; Treatment Outcome

Topics: Accidents, Traffic; Adult; Aged, 80 and over; Burns; Cellulitis; Chondroitin Sulfates; Collagen; Debridement; Diabetic Foot; Elastin; Female; Foot Injuries; Humans; Leg Injuries; Male; Middle Aged; Necrosis; Skin, Artificial

The reconstruction of large full-thickness scalp defects remains a challenge, particularly when dura is exposed. Various reconstructive methods have been described in the past. Dermal Regeneration Templates (DRTs) are becoming increasingly popular in the management of acute wounds as well as the reconstruction of burn scars, oncological defects and various other complex reconstructive problems. We describe a case where Integra® was successfully used together with a Vacuum-Assisted Closure (VAC) dressing to reconstruct a full-thickness scalp defect with exposed dura. Surgical technique is discussed as well as problems encountered during the case and possible solutions.

Topics: Chondroitin Sulfates; Collagen; Craniotomy; Debridement; Decompressive Craniectomy; Dura Mater; Female; Humans; Intracranial Hemorrhages; Middle Aged; Necrosis; Negative-Pressure Wound Therapy; Plastic Surgery Procedures; Scalp; Skin Transplantation; Skin, Artificial

Dying cells, such as apoptotic and necrotic cells, are cleared rapidly from the site of cell death to prevent the exposure of intracellular antigenic and immunostimulatory molecules that may cause tissue injury or facilitate the development of autoimmune diseases. For the immune system to recognize and remove dying cells efficiently, professional phagocytes use a variety of mechanisms that distinguish healthy cells from dying cells. HRG, a relatively abundant heparin/HS-binding protein in human plasma, has been shown recently to tether IgG specifically to necrotic cells and aid the phagocytic uptake of necrotic cells via a FcgammaRI-dependent pathway. In this study, we provide direct evidence that HRG can function cooperatively with cell surface HS on the monocytic cell line THP-1 to promote necrotic cell removal. In addition, we found that the presence of heparin can markedly inhibit HRG-enhanced necrotic cell clearance by THP-1 cells, possibly by blocking the ability of HRG to interact with necrotic cells as well as THP-1 cells. Thus, these data suggest that HRG can aid the phagocytosis of necrotic cells via a HS-dependent pathway, and this process can be regulated by the presence of certain HRG ligands, such as heparin.

Topics: Animals; Cell Communication; Cell Line; Cell Membrane; Cell Survival; Chondroitin Sulfates; Dermatan Sulfate; Hemin; Heparin; Heparitin Sulfate; Humans; Models, Immunological; Necrosis; Phagocytes; Phagocytosis; Protein Binding; Proteins; T-Lymphocytes; Zinc

We present the case of a 58-year-old lady who developed radionecrosis following irradiation of the chest wall following mastectomy. The ensuing radionecrosis of the soft tissue and bony rib cage on the left side of the chest wall progressed to advanced ischaemia with secondary infection and abscess formation. Initially the patient underwent left-sided chest wall reconstruction using a right-sided pedicled TRAM flap. The flap eventually became ischaemic and necrosed over a period of 3 weeks leaving the pleura and ribs exposed. The patient underwent VAC Therapy in order to promote the formation of granulation tissue. Several weeks later the greater Omentum was harvested as a pedicled flap and transposed into the defect which was then in turn covered with Integra and a split-skin graft. Complete wound closure was obtained with this Integra-omental flap reconstructive technique.

Topics: Breast Neoplasms; Chondroitin Sulfates; Collagen; Female; Humans; Mastectomy; Middle Aged; Necrosis; Omentum; Radiodermatitis; Skin Ulcer; Surgical Flaps; Thoracic Wall; Tissue and Organ Harvesting; Treatment Outcome; Wound Healing

Reconstruction was performed on the back of a hand following a poorly managed septic hand injury leading to skin and extensor apparatus necrosis using a reverse radial forearm fasciocutaneous flap and a bilayer artificial skin substitute.. Authors report on the first Hungarian case using Integra dermal regeneration template. Integra was placed on the back of the hand on an area left uncovered by the reverse radial forearm fasciocutaneous flap as well as on the flap harvest area. After biointegration of the regeneration template, the outer silicon layer was removed and a split thickness skin graft was applied.. The take-rate on the donor area was 100% for Integra and 99% for the skin graft, and 90% for both Integra and the skin graft on the back of the hand, providing a good functional and aesthetic result.

Topics: Chondroitin Sulfates; Collagen; Dermatologic Surgical Procedures; Hand Injuries; Humans; Male; Middle Aged; Necrosis; Plastic Surgery Procedures; Skin; Skin, Artificial; Surgical Flaps

Meningococcal sepsis leading to purpura fulminans leaves survivors with extensive areas of skin and soft-tissue necrosis. Soft-tissue loss in the limbs may result in large areas of exposed bone, leaving a choice between free tissue transfer and amputation. We present a case of meningococcal sepsis where the entire medial and lateral surfaces of the tibiae were exposed with loss of anterior muscle compartments on each side. Faced with the possibility of bilateral above-knee amputation, these were instead covered using the dermal replacement Integra (Integra LifeSciences Corp.), in conjunction with an antimicrobial dressing, topical negative pressure dressing and subsequent skin grafting. This management decision achieved rapid wound closure avoiding amputation. Additional secondary reconstruction with microvascular free flaps was performed to preserve joint function.

Topics: Adult; Bacteremia; Chondroitin Sulfates; Collagen; Female; Humans; IgA Vasculitis; Limb Salvage; Meningococcal Infections; Necrosis; Plastic Surgery Procedures; Skin

Topics: Adult; Biocompatible Materials; Burns, Chemical; Chondroitin Sulfates; Collagen; Facial Injuries; Female; Humans; Necrosis; Occlusive Dressings; Plastic Surgery Procedures; Skin Transplantation; Sulfuric Acids

To evaluate cell death in human donor corneas stored at 4 degrees C, to determine whether terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labeling (TUNEL) discriminates between apoptosis and necrosis in corneas stored at 4 degrees C.. Ten human corneas were stored in Optisol (Chiron Ophthalmics, Irvine, CA) at 4 degrees C for periods ranging from 0 to 21 days and then fixed for histologic examination. Central corneal sections from each cornea were examined by transmission electron microscopy (TEM) and by the TUNEL assay. Electron micrographs of at least 15 keratocytes each from the anterior, middle, and posterior stroma were examined by three masked observers who graded each cell as normal, apoptotic, or necrotic. Central sections from the same corneas were processed by the TUNEL assay and evaluated with a laser scanning confocal microscope to determine the percentage of apoptotic cells.. By TEM, apoptosis occurred in 23% of the keratocytes and necrosis in 12%. By TUNEL assay, apoptosis occurred in 11% of the keratocytes, with the results in individual corneas being similar to the findings by TEM for apoptosis, rather than for necrosis. By TUNEL assay, apoptosis occurred in 13% of the epithelial cells and in 8% of the endothelial cells. The percentage of apoptotic cells and storage time correlated significantly for the epithelium, but not for the keratocytes or endothelium in this small sample.. Both apoptosis and necrosis occur in cells during corneal storage at 4 degrees C, with apoptosis appearing to predominate. The TUNEL assay identifies cells undergoing apoptosis, but not necrosis, in corneal tissue. Inhibition of apoptosis in corneas stored at 4 degrees C may prolong acceptable storage times.

Topics: Adult; Apoptosis; Child, Preschool; Chondroitin Sulfates; Complex Mixtures; Cornea; Cryopreservation; Culture Media, Serum-Free; Dextrans; Gentamicins; Humans; In Situ Nick-End Labeling; Middle Aged; Necrosis; Organ Preservation

A 52-year-old man had been in terminal renal failure for 6 years. On haemodialysis under heparin without complications, acral skin necroses occurred. Even with low-molecular heparin anticoagulation further lesions developed. Within 12 weeks of haemodialysis being performed without heparin the necroses healed, but they recurred when heparin was again added for dialysis. On admission the patient was in poor general condition, with a weight of 55 kg (height 175 cm). LABORATORY INVESTIGATIONS: The heparin-induced platelet aggregation (HIPA) test was positive in the absence of thrombocytopenia. Na-heparin reacted positively in three out of four tests, but Danaparoid did not react.. The skin necroses once again healed after the heparinoid Danaparoid, which had not reacted in the HIPA test, had been substituted for heparin.. This case illustrates that skin necroses, thrombocytopenia and thromboembolism can be independent signs of immunologically induced platelet aggregation.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Foot Dermatoses; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Necrosis; Platelet Aggregation; Renal Dialysis; Skin; Skin Diseases

Previous experimental studies concerning morphological changes of corneal endothelium after cryopreservation have been performed directly or within hours after thawing. The purpose of this study was to investigate morphological alterations of corneal endothelium up to 1 week after thawing in organ culture. We evaluated (1) pig corneas that were cryopreserved within 4 h of death, (2) pig corneas that had been stored in cryopreservation medium at 31 degrees C for 4 h before cryopreservation, and (3) as a control, corneas that were preserved in organ culture until the specific time of evaluation. Corneas were frozen to -196 degrees C in an automated freezing chamber in a cryopreservation medium containing chondroitin sulfate. Morphologic evaluation after trypan blue and alizarin red staining was performed after 1 day and after 1 week of organ culture preservation after thawing. One day after thawing, computer-assisted morphometric analysis of endothelial cell density and necrotic areas revealed endothelial cell loss of 25.7% in group 1 (8% necrosis), 48.7% in group 2 (17.4% necrosis) and 0% in group 3 (0% necrosis) compared to freshly dissected corneas. After 1 week, endothelial cell density had decreased by another 29% in groups 1 and 2 and by 11% in group 3 compared to results 1 day after thawing. However, necrotic areas could no longer be detected in any of the groups. We conclude that the highest decrease in endothelial cell density can be expected within 1 day after thawing. Further cell loss seems to be due to non-mitotic wound healing resulting in a confluent endothelial monolayer.

Topics: Animals; Cell Count; Cell Survival; Chondroitin Sulfates; Cryopreservation; Endothelium, Corneal; Necrosis; Organ Culture Techniques; Swine; Wound Healing