Alopecia following Treatment with Dextran Sulphate and Other Anticoagulant Drugs

Tudhope, G. R.; Cohen, Harold P.; Meikle, R. W.

doi:10.1136/bmj.1.5078.1034

Cited by 18 publications

(9 citation statements)

References 15 publications

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“…The delayed alopecia seen with parenteral dextran sulfate was noted previously when this drug was used as an anticoagulant and has been observed in up to 60% of patients receiving parenteral heparin (29). Hair loss was not seen until 4 to 6 weeks after discontinuing dextran sulfate and was always reversible, consistent with induction of a telogen effluvium (hair follicle phase shift; see reference 19).…”

Section: Discussionmentioning

confidence: 69%

“…Five of the eight subjects who received drug for more than 3 days developed extensive but reversible alopecia. Scalp hair loss was reported beginning 4 to 6 weeks after the discontinuation of dextran sulfate, consistent with telogen effluvium induction, as reported previously in patients receiving parenteral heparin or dextran sulfate (29). One female subject experienced total loss of scalp hair over a 24-h period 30 haloperidol.…”

mentioning

confidence: 61%

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Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection

Flexner

Barditch‐Crovo

Kornhauser

et al. 1991

Antimicrob Agents Chemother

143

103

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Polysulfated polysaccharides are attractive candidates for antiviral drug development because of their potent in vitro activities against human immunodeficiency virus (HIV), herpesviruses, and other enveloped viruses. To determine the potential anti-HIV activity of a prototypical polysulfated polysaccharide, we administered the maximally tolerated dose of dextran sulfate by continuous intravenous infusion to 10 subjects with symptomatic HIV infection for up to 14 days. Since parenteral dextran sulfate is an anticoagulant, the infusion was adjusted to produce the greatest acceptable increase in activated partial thromboplastin time. Drug concentrations in plasma achieved with this protocol were up to 200-fold greater than the 50% inhibitory concentration for free HIV infectivity in vitro. Despite this, circulating HIV antigen (p24) levels increased in all eight subjects who received the drug for more than 3 days (median proportional increase, 73.5%; range, 32 to 130%); this increase was highly significant when it was compared with that in a large cohort of untreated historical controls (Fisher's exact test, P < 0.001). Frequent decreases in infusion rate were required in all subjects to maintain a constant activated partial thromboplastin time; plasma dextran sulfate levels did not fail as the infusion rate decreased, suggesting a decline in estimated drug clearance over time. Continuous intravenous dextran sulfate was toxic, producing profound but reversible thrombocytopenia in all eight subjects who received drug for more than 3 days and extensive but reversible alopecia in five of these subjects. Because of its toxicity and lack of beneficial effect on surrogate markers, dextran sulfate is unlikely to have a practical role in the treatment of symptomatic HIV infection.Polysulfated polyanions, including heparin, pentosan polysulfate, and dextran sulfate, are potent inhibitors of human immunodeficiency virus (HIV) infectivity and syncytium formation in vitro (2,13,23,30). In addition, these compounds inhibit other retroviruses, herpes simplex viruses, cytomegalovirus, and paramyxoviruses (4). These compounds are believed to block virus binding and penetration into target cells (3, 23) and, specifically, to block the binding of the HIV envelope protein to the CD4 receptor (25). They may also exert activity at a second step in infectivity, such as membrane fusion (8, 28).Potential advantages of polysulfated polysaccharides as antiviral agents include their broad-spectrum activity and simple chemical structure, which allows production costs to be low compared with those of the available nucleoside analogs or synthetic polypeptides. Clinical trials of oral dextran sulfate in HIV-infected patients (1) were terminated soon after the drug was shown to be poorly absorbed (21) In order to assess the potential anti-HIV activity of parenteral polysulfated polysaccharides, we selected dextran sulfate as a prototypical agent for study in patients with AIDS or AIDS-related complex (ARC). We chose dextran sulfate because it is...

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Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 61%

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection

Flexner

Barditch‐Crovo

Kornhauser

et al. 1991

Antimicrob Agents Chemother

143

103

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“…Alopecia during anticoagulation has been described, with heparins and vitamin K antagonists (VKAs) being the most common offenders. Reported incidences range from 30% to 40% with VKAs and 54‐66% with unfractionated heparin although these numbers seem quite high compared to our center's adult and pediatric clinical experience. Another report describes diffuse alopecia, principally involving the scalp, in 40% of patients on warfarin .…”

Section: Discussionmentioning

confidence: 73%

Agent specific effects of anticoagulant induced alopecia

Weyand

Shavit

2017

Research and Practice in Thrombosis and Haemostasis

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Summary Alopecia has been observed with many anticoagulants although the mechanism is unclear. A 20 year old female with recurrent DVTs developed alopecia with multiple anticoagulants, including heparin derivatives and the new oral anticoagulants. This resolved with discontinuation of the agents. The patient was ultimately able to be anticoagulated with fondaparinux long term without any alopecia. This case addresses the key clinical question of management and recognition of anticoagulant induced alopecia. This side effect can result from almost any of the available agents and is quickly reversible, underlining the importance of tailoring treatment to the individual and their experiences.

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“…In the chronic phase, the major evidences of toxicity after either intramuscular or intravenous administration were diarrhea, nausea, vomiting, and thrombocytopenia. These results have occurred with other heparinoids which have been tested for lipolytic or anticoagulant ac-tivity22, 26,36,51,58,60,63,64,71,97,112,116,130 in human patients or in laboratory animals. In an earlier study of polyethylene sulfonate, Kuo, Hopkins, and Wurzel13 reported diarrhea in 1 of 2 patients who received 1 mg. per kilogram intramuscularly every 8 hours.…”

Section: Clinical Pharmacologymentioning

confidence: 84%

Effect of an anionic polyelectrolyte (polyethylene sulfonate) in patients with cancer Clinical pharmacology of a macromolecule

Regelson

Holland

1962

Clin Pharma and Therapeutics

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Polyethylene sulfonate, an anionic polymer of average molecular weight (13,000) Department of Medicine A, Roswell Park Memorial InstituteThe anionic polyelectrolyte polyethylene sulfonate, in the form of the sodium salt of polymeric ethylene sulfonic acid, has been shown by us to be an active inhibitor of seven transplanted solid tumors in mice. 103 ,105 Polyethylene sulfonate, of an average molecular weight of 13,000, has been reported to be a less potent anticoagulant than native heparin but to have similar lipolytic activity. 26,37,38,42,73 Like heparin, polyethylene sulfonate showed no bone marrow depression on chronic administration to animals but produced pathologic fracture as well as evidence of ulceration of the gastrointestinal tract.26 Earlier clinical study of its lipolytic activity in man was uneventful. 37, 38, 73 Because of its tumor-inhibiting activity in mice, a trial against advanced cancer in man was undertaken.

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Alopecia following Treatment with Dextran Sulphate and Other Anticoagulant Drugs

Cited by 18 publications

References 15 publications

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection

Agent specific effects of anticoagulant induced alopecia

Effect of an anionic polyelectrolyte (polyethylene sulfonate) in patients with cancer Clinical pharmacology of a macromolecule

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