warfarin and Anaphylaxis

Topics: Aged; Anaphylaxis; Anticoagulants; Enoxaparin; Female; Fibrinolytic Agents; Glucocorticoids; Humans; Injections, Intravenous; Male; Middle Aged; Tissue Plasminogen Activator; Venous Thrombosis; Warfarin; Young Adult

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.

Topics: Adult; Anaphylaxis; Anticoagulants; Autoantibodies; Autoantigens; Blood Platelets; Drug Therapy, Combination; False Negative Reactions; Female; Heart Arrest; Heparin; Humans; Immunoenzyme Techniques; Immunoglobulin G; Immunoglobulin M; Medical Errors; Obesity; Platelet Activation; Platelet Factor 4; Pulmonary Embolism; Recurrence; Sensitivity and Specificity; Serotonin; Thrombocytopenia; Venous Thrombosis; Warfarin

Vitamin K is used as a correction factor to avert the risk of bleeding due to warfarin overdose. Among the reported complications of this therapy, the most serious one is the anaphylactic cardiovascular collapse caused by intravenous infusion of the drug. We report herein a patient with over-anticoagulation from warfarin use and a subcapsular renal bleeding who developed a fatal anaphylactic shock after vitamin K administration via slow intravenous infusion. Vigilance with the intravenous formulation of this agent should always be sought in order to prevent fatal outcomes, especially in patients with severe comorbidities.

Topics: Aged, 80 and over; Anaphylaxis; Antifibrinolytic Agents; Hemorrhage; Humans; Infusions, Intravenous; Male; Vitamin K; Warfarin

Warfarin hypersensitivity is exceedingly rare. A 59-year-old male with acute renal infarction and a history of allergy to warfarin underwent evaluation, confirming presence of warfarin hypersensitivity. Induction of tolerance to warfarin was successfully completed using an oral desensitization protocol, which has not previously been reported.

Topics: Administration, Oral; Anaphylaxis; Anticoagulants; Desensitization, Immunologic; Drug Eruptions; Humans; Immune Tolerance; Infarction; Kidney; Male; Middle Aged; Risk Factors; Thromboembolism; Warfarin

Over-anticoagulation from warfarin is a common occurrence, and these patients are often referred to the Emergency Department for further treatment. Unfortunately, there is little guidance in the Emergency Medicine literature for the management of such patients. The American College of Chest Physicians (ACCP) issued guidelines in 1998 that address the use of vitamin K for patients with over-anticoagulation. However, there is still debate as to the optimal dose and route of vitamin K administration. This case report describes a patient who was treated with intravenous vitamin K within the scope of these guidelines at a very low dose (1 mg) and had a fatal anaphylactic reaction. This article will further discuss this patient, the 1998 ACCP guidelines, and the data supporting the alternative of subcutaneously administered vitamin K for patients with over-anticoagulation with no active bleeding.

Topics: Aged; Anaphylaxis; Anticoagulants; Fatal Outcome; Female; Guideline Adherence; Humans; Infusions, Intravenous; International Normalized Ratio; Vitamin K; Warfarin

In an attempt to improve the reporting rate of adverse drug reactions the Adverse Drug Reaction Advisory Committee approached the Australian Council on Healthcare Standards Care Evaluation Program to develop a set of indicators to improve healthcare standards by heightening awareness amongst clinical staff of the morbidity, mortality and financial implications of adverse drug reactions. Ten clinical indicators addressing: (i) reporting of adverse drug reactions; (ii) adherence to treatment protocols for anaphylaxis; (iii) monitoring of warfarin; and (iv) monitoring of streptokinase, were field tested in ten Australian health-care organizations, to determine that the data were available, that the indicators were relevant to clinical practice and that the measures were achievable. Based on the results of this field test, six adverse drug reaction clinical indicators will be introduced into the Australian Council on Healthcare Standards Evaluation and Quality Improvement Program from January 1999.

Topics: Adverse Drug Reaction Reporting Systems; Anaphylaxis; Anticoagulants; Australia; Clinical Protocols; Drug Monitoring; Fibrinolytic Agents; Guideline Adherence; Humans; Quality Indicators, Health Care; Streptokinase; Warfarin