Warfarin treatment of chronic idiopathic urticaria and angio‐oedema

Parslew, Richard; Pryce, D.W.; Ashworth, J.; Friedmann, Peter S.

doi:10.1046/j.1365-2222.2000.00857.x

Cited by 85 publications

(49 citation statements)

References 11 publications

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“…However, the fact that such an activation parallels the activity of CU may provide the rationale for an anticoagulant and antifibrinolytic therapy in patients with severe CU. The effectiveness of anticoagulant therapy in some patients with refractory CU was observed more than a decade ago (90) by the use of oral anticoagulants and more recently by the use of heparin (14,91,92). The use of heparin can be effective in patients with urticaria who have high levels of D-dimer and poor response to antihistamines (14,85).…”

Section: Discussionmentioning

confidence: 99%

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Tedeschi

Kolkhir

Asero³

et al. 2014

Allergy

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Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.Chronic urticaria (CU) is a widespread skin disease characterized by the recurrence of transient wheals and itch for more than 6 weeks. It is believed that over 50% of CU cases are accompanied by a deep subcutaneous and/or submucosal edema, called angioedema (AE; 1).It is well known that the characteristic symptoms of urticaria appear following the activation of mast cells (MCs) and basophils in the skin by various stimuli. These cells release several biologically active substances, the most important of which is histamine. Histamine induces vasodilation, increases vascular permeability and stimulates sensory nerve endings. These effects lead to the appearance of erythema, wheals and itch (2). It is supposed that other biologically active substances may have similar effects. These include serotonin, C3a and C5a anaphylatoxins, platelet-activating factor (PAF), neuropeptides, and arachidonic acid metabolites (prostaglandin D2, leukotrienes C4, D4 and E4; 3).Activation and degranulation of basophils and MCs may occur by immunological (formation of immune complexes, complement activation, IgE cross-linking), nonimmunological (pseudoallergy, infection, or direct effect of agents on MCs), or mixed mechanisms. The mechanism and cause of urticaria remain unclear in many patients with CU.In recent years, attention was paid to several important aspects of the disease pathogenesis. It is believed that about 30-50% of patients have CU symptoms associated with autoimmune reactions and synthesis of autoantibodies against IgE (4) and/or the FceRI a-subunit on MCs and basophils (autoimmune/autoreactive urticaria; 5). Furthermore, these patients show an increased frequency of HLA DRB1*04 (DR4) as it occurs in other autoimmune diseases (6). The role of coagulation casc...

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Section: Discussionmentioning

confidence: 99%

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Tedeschi

Kolkhir

Asero³

et al. 2014

Allergy

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“…In effect, there have already been scattered reports, and 1 double-blind placebo-controlled study as well, suggesting that anticoagulants (either heparin or warfarin) may be effective in the treatment of CU [19,20,21,22,23], although the efficacy of warfarin has not been confirmed by other authors [24], possibly due to the heterogeneity of the pathomechanisms involved in this disease. Further, we and others have previously shown that heparin is able to turn a markedly positive intradermal autologous serum skin test negative [25,26], and that heparin inhibits the histamine release activity of sera from CU patients on cultured basophils [26].…”

Section: Discussionmentioning

confidence: 99%

Heparin and Tranexamic Acid Therapy May Be Effective in Treatment-Resistant Chronic Urticaria with Elevated D-Dimer: A Pilot Study

Asero

Tedeschi

Cugno

2010

Int Arch Allergy Immunol

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Background: Chronic urticaria (CU) patients often present activation of the coagulation cascade and fibrinolysis whose markers correlate with disease severity. Aim: We evaluated whether CU patients with elevated plasma D-dimer have a poor response to antihistamines, and anticoagulation and inhibition of fibrinolysis may be beneficial in these patients. Methods: Sixty-eight consecutive patients with CU were prescribed cetirizine 10 mg daily for 2 weeks; plasma D-dimer was measured. Non-responders were given cetirizine 30 mg daily for 1 week and subsequently, in case of failure, systemic steroids. Patients with persistent uncontrolled CU and elevated D-dimer plasma levels were offered subcutaneous nadroparin 11,400 IU once a day and oral tranexamic acid 1 g three times a day for 2 weeks. Results: D-dimer levels were elevated in 14/68 (20.6%) patients (range 306–7,317 ng/ml; normal values <278 ng/ml) and were associated with a more severe disease. Twelve of 14 patients with elevated D-dimer levels did not respond to antihistamine treatment (p = 0.0001). On the whole, 14 patients reported a poor or absent response to cetirizine 10 mg daily and only 1 of these responded satisfactorily to cetirizine 30 mg daily. Eight patients with elevated D-dimer and whose disease was not satisfactorily controlled by prednisone received nadroparin and tranexamic acid. A marked improvement of symptoms was observed in 5/8 cases. Conclusion: Our findings indicate that CU patients with elevated D-dimer often present a more severe disease with reduced response to antihistamines. Based on this short pilot study, some of these patients may benefit from treatment with nadroparin and tranexamic acid.

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“…A small double-blind, placebo-controlled study carried out about 15 years ago first detected the effectiveness of oral anticoagulant therapy in some patients with refractory CSU [48]. After an attempt carried out more than 60 years ago [49], in some more recent studies, heparin also has been effective in patients with severe disease [50,51] and elevated D-dimer plasma levels [52].…”

Section: Anticoagulants/antifibrinolytics In Chronic Spontaneous Urtimentioning

confidence: 99%