heparitin-sulfate and Skin-Diseases

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

Heparan sulfate (HS) is a glycosaminoglycan that is anchored to the outside of cell membranes. Under ordinary circumstances, it is not present in the interstitium, but under certain circumstances, mainly in the setting of inflammation and tissue repair, HS can be shed from the cell surface into the interstitium in a regulated fashion. Under these circumstances, interstitial HS seems to have an immunomodulatory function because of its binding of many cytokines. However, it is not known which cell types present at an inflammatory site are responsible for this shedding.. We have investigated the presence of interstitial HS by immunohistochemistry in various inflammatory skin diseases characterized by different compositions of the inflammatory infiltrate.. Strong interstitial HS immunoreactivity was present only in diseases with a predominantly histiocytic infiltrate but not in diseases with a predominantly lymphocytic or neutrophilic infiltrate.. This indicates that histiocytes have a direct or indirect role in the HS shedding process. In the well-formed granulomas of sarcoidosis, interstitial HS immunoreactivity was spatially associated with the fibrotic ring at the periphery of the granulomas, but not with the center harboring the histiocytes. This suggests that histiocytes can stimulate fibroblasts to shed HS into the interstitium.

Topics: Cell Communication; Fibroblasts; Granuloma; Heparitin Sulfate; Histiocytes; Humans; Immunohistochemistry; Inflammation; Retrospective Studies; Skin Diseases

Topics: Anticoagulants; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Combinations; Drug Hypersensitivity; Drug Monitoring; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Injections, Subcutaneous; Risk Factors; Skin Diseases; Thromboembolism

We present a case of Hunter syndrome diagnosed because of skin eruption. A 4-year-old Japanese boy presented with a 3-4-months history of papular lesions on the back and extremities. His growth and development were almost normal. His face was not of coarse appearance. He had multiple, whitish to skin-coloured, papules and nodules symmetrically distributed on the scapular regions and the extensor aspects of the upper arms and thighs. There was no family history of similar symptoms. Skin biopsy showed the deposition of a considerable amount of mucin in the dermis. Although physical examinations failed to detect any other signs of Hunter syndrome, X-rays showed the characteristic features of mucopolysaccharidosis: deformities of the vertebral bone, ribs, and pelvis. Mucopolysaccharide analysis of the urine revealed a marked increase in dermatan sulphate and heparan sulphate. The activity of iduronate sulphatase in the lymphocytes was deficient, which was diagnostic for Hunter syndrome. We emphasize that the skin eruption can be the earliest sign of Hunter syndrome, particularly in the mild form presenting with normal development and growth.

Topics: Child, Preschool; Dermatan Sulfate; Facies; Heparitin Sulfate; Humans; Iduronate Sulfatase; Male; Mucopolysaccharidosis II; Pelvic Bones; Radiography; Ribs; Skin Diseases; Spine

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

Heparan sulfate proteoglycans have pleiotropic functions in the normal vasculature. Autoimmunity to heparan sulfate may play a role in vascular injury. In this study, monoclonal antibody (mb) 28C3-1 to heparan sulfate derived from autoimmune Tight skin (TSK) mice was investigated for its reactivity with endothelial cells. Mb 28C3-1 was previously demonstrated to inhibit the heparin-accelerated formation of antithrombin III-thrombin complexes. In the current studies it is shown that mAb 28C3-1 bound to heparan sulfate proteoglycan with the highest affinity in direct binding solid phase radioimmunoassay. Binding to the heparan sulfate was stronger than binding to the protein core, indicating that the primary epitope of 28C3-1 is the polysaccharide component. Using confocal fluorescent microscopy, mAb 28C3-1 was demonstrated to bind to the endothelial cell surface. Furthermore, treatment of endothelial cells with heparitinase abolished mAb 28C3-1 binding. These studies support the hypothesis that naturally occurring anti-heparan sulfate autoantibodies from autoimmune mice may cause vascular injury by initial interaction with endothelial cell surface heparan sulfate.

Topics: Animals; Antibodies, Monoclonal; Autoantibodies; Autoimmune Diseases; Cattle; Cells, Cultured; Endothelium; Heparitin Sulfate; Mice; Mice, Mutant Strains; Polysaccharide-Lyases; Radioimmunoassay; Skin Diseases

Recent cell biologic studies have emphasized the importance of the basement membrane (BM) and its molecular components in angiogenesis. We immunostained 60 angioproliferative lesions (angiosarcoma, sclerosing hemangioma of skin, pyogenic granuloma, capillary hemangioma, lymphangioma, glomangioma and granulation tissue) and 23 cases of Kaposi's sarcoma (KS) for the major macromolecular components laminin, collagen type IV, fibronectin and heparan sulfate proteoglycan (HSPG). Normal structures served as aggregate controls in each group, and semiquantitative scoring reflected the degree of consistency of staining about blood and lymphatic endothelium and vascular sheath (pericyte/smooth muscle) within and peripheral to each lesion. Benign and reactive vasoproliferations consistently maintained immunoreactivity for each BM component around endothelium and sheath components of blood vessels. Angiosarcoma showed from 20 to more than 60% less consistent immunoreactivity by comparison, although the score variances were greater than for non-malignant lesions. Staining about blood vessel endothelium was both strong and consistent among histologic stages in KS with the exception of HSPG, which was weakly immunoreactive in all stages. Marked selective HSPG loss was characteristic only of KS and normal lymphendothelium, and in the light of evidence for a role for HSPG in the assembly and maintenance of BM, suggests that reduced HSPG may be responsible for the loss of ultrastructural integrity of perivascular BM in both.

Topics: Basement Membrane; Collagen; Fibronectins; Granuloma, Pyogenic; Hemangiosarcoma; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Immunohistochemistry; Laminin; Proteoglycans; Sarcoma, Kaposi; Skin Diseases; Skin Neoplasms

From three patients with pretibial myxedema (PTM) of Graves' disease, a portion of the skin involved was biopsied, analyzed for proteoglycans and the results were compared with those obtained with euthyroid and hyperthyroid subjects without PTM. The tissue specimen was extracted with 4 M guanidine HCl and subjected to subsequent CsCl density gradient centrifugation. Glycosaminoglycan and protein were recovered in the heaviest density fraction in the three specimens obtained from patients with PTM and not from subjects without PTM. From the analysis by Sepharose CL-6B column, glycosaminoglycan was present as a form of proteoglycan because alkaline borohydride treatment released single chain glycosaminoglycan with a molecular weight of 77,000 or 66,000. The digestion with chondroitin ABC lyase revealed that the majority of proteoglycan in the skin tissue was chondroitin sulfate or dermatan sulfate, and heparan sulfate comprised the minor component (14-34%). The rate of proteoglycan biosynthesis was examined by 35S incorporation into glycosaminoglycan's by cultured fibroblasts from PTM and normal skin. Incorporation of 35S into both proteoglycan and single chain glycosaminoglycan was observed in the fibroblasts of PTM patients as well as of those of subjects without PTM, although the rate of synthesis was more pronounced in the former. The rate of synthesis was influenced neither by normal serum or serum from a pretibial myxedema patient. Since proteoglycan accumulation was detected only in the affected skin of PTM patients, the impairment of local degradation and the proteoglycan clearance mechanism may also be involved.

Topics: Centrifugation, Isopycnic; Chondroitin Sulfates; Graves Disease; Heparitin Sulfate; Humans; Molecular Weight; Myxedema; Proteoglycans; Skin Diseases

A case of localized cutaneous amyloidosis which developed after a lichen planus-like skin reaction is reported. The amyloid consisted of amyloid fibrils enveloped by heparan sulphate granules. These amyloid fibrils reacted to anti-human keratin antibody, indicating an epidermal origin for the fibrils.

Topics: Aged; Amyloid; Amyloidosis; Antibodies; Heparitin Sulfate; Humans; Keratins; Male; Skin; Skin Diseases