Adverse events induced by ceftriaxone: a 10-year review of reported cases to Iranian Pharmacovigilance Centre

What is known and Objectives: Ceftriaxone, a third‐generation cephalosporin antibiotic, is used for a vast variety of infectious diseases. Different types of adverse reactions are reported to be induced by ceftriaxone; however, there is limited published information on spontaneous adverse reactions collected by a national pharmacovigilance centre. This study was conducted to evaluate ceftriaxone‐induced adverse drug events, registered in the Iranian pharmacovigilance database during a 10‐year period, and to identify preventive measures for reducing ceftriaxone‐induced adverse events. Method: All adverse events registered in the Iranian pharmacovigilance database from 1998 through 2009 were screened for ceftriaxone‐related adverse events. The extracted data were categorized based on patients’ demographics and previous history of allergic reactions to antibiotics. Assessment of system–organ classes, seriousness and causality of reactions was performed according to World Health Organization scale. The preventability was analysed based on Schumock questionnaire. Results and Discussion: Ceftriaxone was responsible for the highest number of deaths in our database (49 cases). Of 20 877 reports, 1205 (5·8%) were related to ceftriaxone; 357 reports (30%) are categorized as serious including cardiac arrest, anaphylactic and anaphylactoid reactions. The high number of serious cases makes it necessary to develop preventive measures for reducing those adverse events. Unlabelled use of the drug (2·9%) is identified as one of the risk factors for adverse events. Evaluation of the 1030 intravenous injections of the drug shows that rapid intravenous injection of ceftriaxone is another risk factor. One hundred and sixteen patients (9·6%) had a previous history of allergic reaction to ceftriaxone, penicillin or both. We recommend an alternative antibiotic, if possible, in the case of a positive history of allergic reaction to cephalosporins, penicillins and/or other beta‐lactam antibiotics. What is new and Conclusion: Severe and life‐threatening adverse reactions induced by ceftriaxone are of great concern. Rapid intravenous injection, unlabelled use and previous patient history of allergic reactions to cephalosporins or penicillins are risk factors that should be guarded against.     

Heparin‐induced non‐necrotizing skin lesions: rarely associated with heparin‐induced thrombocytopenia

See also Warkentin TE, Linkins L‐A. Non‐necrotizing heparin‐induced skin lesions and the 4T’s score. This issue, pp 1483–. Summary. Background: Recently, there has been an increasing number of reports regarding adverse skin reactions to subcutaneous heparin administration. Case series have implied that heparin‐induced skin lesions are predominantly associated with life‐threatening heparin‐induced thrombocytopenia (HIT) in at least 22% of patients. Skin lesions, therefore, have been included in clinical scores for HIT. Objectives: To determine the association of heparin‐induced skin lesions with HIT. This would have a pivotal impact on further anticoagulatory management in patients with heparin‐induced skin lesions. Patients/Methods: In our observational cohort study, 87 consecutive patients with heparin‐induced skin lesions (85 occurring during low‐molecular‐weight heparin administration) were evaluated using a standardized internal protocol, including HIT diagnostics (heparin‐platelet factor 4‐ELISA, heparin‐induced platelet activation assay), platelet count monitoring, clinical/sonographical screening for thrombosis, skin allergy testing and, if necessary, histology. Results: None of the observed heparin‐induced skin lesions was due to HIT; all lesions were caused by delayed‐type IV‐hypersensitivity reactions (DTH) instead. Even the cutaneous reaction in one patient with concomitant HIT could be classified histologically as DTH reaction, amounting to an association of heparin‐induced skin lesions and HIT in 1.2% (1/87; 95% confidence interval, 0.00–0.06). Conclusion: Heparin‐induced skin lesions associated with use of low‐molecular‐weight heparins do not seem to be strongly associated with a systemic immunologic reaction in terms of HIT and might rather be due to DTH reactions than due to microvascular thrombosis. Hence, we propose refining existing pretest probability scores for HIT, unless underlying causes have been clarified.     

Fondaparinux treatment of acute heparin‐induced thrombocytopenia confirmed by the serotonin‐release assay: a 30‐month, 16‐patient case series

See also Greinacher A. Immunogenic but effective: the HIT‐fondaparinux brain puzzler. This issue, pp 2386–8; Goldfarb MJ, Blostein MD. Fondaparinux in acute heparin‐induced thrombocytopenia: a case series. This issue, pp 2501–3. Summary. Background: Fondaparinux is theoretically an attractive agent for the treatment of immune heparin‐induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet‐activating anti‐platelet factor 4/heparin antibodies. Although reports of the use of fondaparinux for this indication have thus far been favorable, the diagnosis of HIT in most cases was not based on definitive laboratory confirmation of heparin‐dependent, platelet‐activating antibodies. Objectives: To report thrombotic and major bleeding outcomes with fondaparinux in patients with a high likelihood of having acute HIT based on clinical features and a positive result in the confirmatory platelet serotonin‐release assay (SRA), a sensitive and specific test for platelet‐activating HIT antibodies. Methods/Patients: We reviewed consecutive eligible patients with SRA‐positive HIT (mean peak serotonin release, 91% [normal, < 20%]; mean IgG‐specific PF4/heparin enzyme immunoassay result, 2.53 optical density units [normal, < 0.45 units]) in one medical center over a 30‐month period who received fondaparinux for anticoagulation during acute HIT (platelet count, < 150 × 10⁹ L^?1). Where available, plasma samples were used to measure thrombin–antithrombin (TAT) complex levels. Results: Sixteen patients with SRA‐positive HIT received fondaparinux: 14 surgical (11 after cardiac surgery; three after vascular surgery) and two medical (acute stroke). Fifty‐six per cent of patients had HIT‐associated thrombosis at the time of diagnosis. No patient developed new, recurrent or progressive thrombosis; one patient developed a major bleed (calf hematoma). One patient judged to have irreversible tissue necrosis before receiving fondaparinux therapy ultimately required limb amputation. TAT complex levels were reduced within 24 h of starting fondaparinux, and 13 of 13 patients were successfully switched to warfarin. Conclusion: Fondaparinux shows promise for the treatment of patients with SRA‐positive acute HIT.     

Adverse events in acute care: an integrative literature review

An integrative literature review was conducted to investigate studies on adverse events reported in medical, health services, and nursing literature. The review was guided by the method proposed by Jackson ( 1980 ) and Ganong (1987). Three questions shaped the review: (a) What terms are used to denote adverse events? (b) What purposes drive adverse events research? and (c) What data sources are used to study adverse events? Adverse events was the dominant term, the study of adverse events as an outcome variable was the prevailing research purpose, and monitoring or screening the patient clinical record and self‐reported incidents by health care professionals were the main data sources. Future research is recommended to conceptualize and study adverse events. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:398–408, 2003     

A patient's perspective: the impact of adverse drug reactions on patients and their views on reporting

What is known and objective: Adverse drug reactions to prescribed medication are relatively common events. However, the impact such reactions have on patients and their attitude to reporting such events have only been poorly explored. Previous studies relying on self‐reporting patients indicate that altruism is an important factor. In the United Kingdom, patient reporting started in 2005; though, numbers of serious reports remain low. Method: A purposive sample of fifteen patients who had been admitted to an inner city hospital with an adverse drug reaction were interviewed using a semi‐structured questionnaire. Patients were asked to relate in their own words their experience of an adverse drug reaction. Patient’s reactions to the information leaflet, adherence to treatment and use of other sources of information on medication were assessed. Interviews were recorded, and a thematic analysis of patients’ responses was performed. Results and discussion: Analysis of the patient interviews demonstrated the reality of being admitted to hospital is often a frightening process with a significant emotional cost. Anger, isolation, resentment and blame were common factors, particularly when medicines had been prescribed for acute conditions. For patients with chronic conditions, a more phlegmatic approach was seen especially with conditions with a strong support networks. Patients felt that communication and information should have been more readily available from the health care professional who prescribed the medication, although few had read the patient information leaflet. Only a minority of patients linked the medication they had taken to the adverse event, although some had received false reassurance that the drug was not related to their illness creating additional barriers. In contrast to previous studies, many patients felt that adverse drug reporting was not their concern, particularly as they obtained little direct benefit from it. The majority of patients were unaware of the Yellow Card Scheme in the UK for patient reporting. Even when explained, the scheme was felt too cold and impersonal and not a patient’s ‘job’. What is new and conclusion: Patients having a severe adverse drug reaction following an acute illness felt negative emotions towards their health care provider. Those with a chronic condition rationalized the event and coped better with its impact. Neither group felt that reporting the adverse reaction was their responsibility. Encouraging patients to report remains important but expecting patients to report solely for altruistic purposes may be unrealistic.     

Gastrointestinal tolerability of aspirin and the choice of over‐the‐counter analgesia for short‐lasting acute pain

Rationale: For the management of common disorders producing short‐lasting pain, there is very good evidence of the efficacy of aspirin. Yet paracetamol is often preferred, despite that evidence of its efficacy is much less sound. The reason for this appears to be a concern over gastrointestinal (GI) toxicity. If this concern is misplaced, so may be the preference for paracetamol, with the consequence of widespread sub‐optimal treatment. Our purpose in this analysis of pooled individual patient data from clinical studies of aspirin is to adduce the evidence that will show whether or not this is so, for the benefit of consumers and health‐care professionals who advise them. Methods: The frequencies of all and GI adverse events (AEs) and adverse drug reactions (ADRs) were calculated from the pooled individual patient data of nine similar randomized, double‐blind, placebo controlled clinical trials of single‐doses of aspirin 1000 mg in the treatment of acute migraine attacks, episodic tension‐type headache and dental pain. Absolute differences between active and placebo AE and ADR rates, and numbers‐needed‐to‐harm (NNH), were calculated. Results: Of 2852 patients included in the analysis, 1581 were treated with aspirin and 1271 with placebo. Reported AE rates were 14·9% and 11·1% amongst patients allocated to aspirin and placebo respectively (NNH: 26), with the GI system most frequently affected (aspirin: 5·9%; placebo: 3·5%; NNH: 42). Reported ADR rates were much lower (aspirin: 6·3%; placebo: 3·9%; NNH: 42), especially for the GI system (aspirin: 3·1%; placebo: 2·0%; NNH: 91). Most of the AEs and ADRs were mild or moderate, and none was serious. Conclusions: The GI ADR differences between aspirin and placebo are not great enough to support decision choices for short‐lasting acute pain based on tolerability: these are better based on efficacy.     

Investigation of heparin-related hypotensive adverse events during photopheresis: utility of a patient care database

BACKGROUND: Extracorporeal photopheresis (ECP) is a procedure in which leukocytes are harvested from a patient's whole blood, treated with a DNA binding dye and ultraviolet light to inactivate lymphocytes, and then returned into the patient's circulation. In January 2008, we observed moderately severe anaphylactoid reactions in eight of 16 patients undergoing ECP. CASE STUDY: Each affected individual exhibited hypotension of sudden onset, usually with tachycardia, during the return of heparin‐anticoagulated blood at the end of the first cycle of collection of leukocytes. A systematic investigation of possible contributing factors revealed that all reactions were associated with administration of a single new lot of heparin. RESULTS: Changing to a different manufacturer of heparin eliminated the occurrence of further such hypotensive reactions during ECP. Although the symptoms were initially attributed to vasovagal reactions or dehydration, their temporal association with exposure to a new lot of heparin suggested a procedure‐related phenomenon. Of particular note, was the finding that of the eight patients who had reactions at any time, six had initial exposures without reactions, suggesting a process of sensitization. CONCLUSION: This study demonstrated the value of a patient database listing lot numbers of all medications and components used in each routine ECP procedure for facilitating rapid determination of common patient exposures, making it easier to determine the cause of adverse events, in this case, a particular lot of heparin responsible for the hypotensive adverse events.     

Severe ranitidine-induced anaphylaxis: a case report and literature review

What is known and Objective: Ranitidine is a generally well‐tolerated drug, and serious side effects are rare. However, ranitidine‐induced anaphylaxis has been reported on rare occasions. We report on such a case and review other cases reported in the literature. Case summary: A 36‐year‐old man with no history of other medications, illnesses or allergic diseases, especially to drugs, consulted our emergency department because of renal colic and epigastric discomfort. He was given 50 mg of ranitidine as a slow intravenous bolus and 20 mg of piroxicam intramuscularly. Within the first minute, the patient developed a cold sweat, trembling, dyspnoea and deterioration of his consciousness. The condition was considered as an anaphylactic shock, and cardiopulmonary resuscitation and inotropic support were immediately commenced. Two days later, he was weaned off the ventilator as he was haemodynamically stable. He was discharged after 7 days. Four weeks later, skin prick tests to ranitidine and piroxicam were performed on the forearm of the patient. He reacted strongly to ranitidine about 10 min later but not to piroxicam. To assess cross‐reactivity to other H2‐ and H1‐receptor antagonists in our patient, we subsequently performed prick tests to famotidine, cimetidine and desloratadine and all were negative. What is new and Conclusion: We re‐emphasize a potentially serious, albeit very rare, adverse effect of ranitidine and summarize other reported cases. This case demonstrates that commonly used, generally safe drugs may on occasions cause serious adverse effects.     

Anaphylaxis during the first course of high-dose methotrexate: a case report and literature review

What is known and Objective: Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high‐dose MTX in a paediatric patient and review the literature for similar cases. Case summary: An 11‐year‐old boy with small‐cell osteoblastic osteosarcoma in the lower limb experienced a case of life‐threatening anaphylaxis during the first course of high‐dose MTX. The adverse event occurred during the first course, likely due to an immune‐mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. What is new and Conclusion: Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this ‘signal alarm’ for serious MTX‐related hypersensitivity reactions.     

Apixaban used for the management of heparin‐induced thrombocytopenia in a 72‐year‐old woman with lung cancer

Heparin‐induced thrombocytopenia (HIT) is a serious adverse reaction to heparin treatment with a high risk of thrombosis. Heparin must be discontinued immediately and replaced with alternative anticoagulants that do not interact with HIT antibodies. In this case, a lung cancer patient, diagnosed with HIT was successfully treated with apixaban.     

Experience in adverse events detection in an emergency department: nature of events

Objective: The study was performed to determine the nature of adverse events in an ED. Methods: The methodology has been described in the accompanying paper. Two by two tables were analysed using the two‐tailed Fisher’s exact test. A P‐value of ≤0.05 was considered significant. Statistical analysis was performed using MINITAB. Results: One hundred and ninety‐four events were detected, from a sample of 3222 patients. Except where specified, events with management causation ≤3 were excluded. This excluded 24 events (12.4%) leaving 170 for analysis. Errors of commission occurred in 55% and omission in 45%. Errors of commission were significantly associated with prior events, errors of omission with ED events (P ≤ 0.0001, respectively). The most common cause of events was drug reactions. 1.35% had a Naranjo score ≥ 1, 0.54% ≥ 4. Prior events were significantly associated with adverse drug reactions (P ≤ 0.0001). Drug reactions were associated with a lower preventability score (P ≤ 0.0001). Diagnostic issues were present in 1.2%. All three categories, that is diagnosis not considered, diagnosis within the differential and seriousness not appreciated were associated preventability ≥4 (P ≤ 0.0001, P ≤ 0.02 and P ≤ 0.004, respectively). Diagnostic problems were significantly associated with ED events (P ≤ 0.0001). Conclusion: In conclusion, the data demonstrate that events fall into two sets: prior events which are associated with errors of commission, drug reactions and lower preventability; and ED events which are associated with errors of omission, diagnostic issues and high preventability.     

Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost‐effectiveness analysis

Summary. Background: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. Objectives: We aimed to evaluate the cost‐effectiveness of a CYP2C19*2 genotype‐guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two ‘no testing’ strategies (empiric clopidogrel or prasugrel). Methods: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet‐related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis‐related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. Results: Base case analyses demonstrated little difference between treatment strategies. The genetic testing‐guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype‐guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild‐type individuals treated with clopidogrel. Above a 47% increased risk, a genotype‐guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost‐effective. Conclusions: Among ACS patients undergoing PCI, a genotype‐guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective.     

Flash pulmonary oedema during anidulafungin administration

What is known and Objective: Anidulafungin is an echinocandin antifungal used to treat invasive fungal infections caused by Candida or Aspergillus species. While the echinocandins are generally well tolerated, novel adverse reactions may occur. Specifically, echinocandins have been associated with histamine‐mediated infusion reactions. We describe a novel case of flash pulmonary oedema associated with anidulafungin administration, which may be related to histamine release. Case summary: A 52‐year‐old male developed flash pulmonary oedema after the first dose of anidulafungin, which was characterized by acute onset of spasmodic cough with shortness of breath and chest tightness with subsequent new bilateral perihilar and interstitial oedema visualized on chest X‐ray. The patient was treated appropriately with diphenhydramine, hydrocortisone and albuterol with complete recovery and a normal follow‐up chest X‐ray the following day. What is new and Conclusion: This is the first report of pulmonary oedema attributable to an echinocandin antifungal agent. While such infusion‐related adverse events including pulmonary oedema appear uncommon, it is important for clinicians to be aware of this possibility and maintain the drug’s infusion rate to <1·1 mg/min and monitor for signs and symptoms of pulmonary oedema.     

Risk factors for sedation‐related events during procedural sedation in the emergency department

Objective: To determine the nature, incidence and risk factors for sedation‐related events during ED procedural sedation, with particular focus on the drugs administered. Methods: Eleven Australian EDs enrolled consecutive adult and paediatric patients between January 2006 and December 2008. Patients were included if a sedative drug was administered for an ED procedure. Data collection was prospective and employed a specifically designed form. Multivariate logistic regression was employed to determine risk factors for sedation‐related events. Results: Two thousand, six hundred and twenty‐three patients were enrolled (60.3% male, mean age 39.2 years). Reductions of fracture/dislocations of shoulders, wrists and ankles were most common. Four hundred and sixty‐one (17.6%) cases experienced at least one airway event that required intervention. Airway obstruction, hypoventilation and desaturation occurred in 12.7%, 6.4% and 3.7% of all patients, respectively. Two thousand, one hundred and forty‐six cases had complete datasets for further analyses. Increasing age and level of sedation, pre‐medication with fentanyl, and sedation with propofol, midazolam or fentanyl were risk factors for an airway event (P < 0.05). Ketamine was a protective factor. Hypotension (systolic pressure <80 mmHg) occurred in 34 (1.6%) cases with midazolam being a significant risk factor (P < 0.001). Vomiting also occurred in 34 (1.6%) cases, 12 of whom required an intervention. One patient aspirated. Vomiting occurred after administration of all drugs but was not associated with fasting status. Other events were rare. Conclusions: Sedation‐related events, especially airway events, are common but very rarely have an adverse outcome. Elderly patients, deeply sedated with short‐acting agents, are at particular risk. The results will help tailor sedation to individual patients.     

Heparin‐induced thrombocytopenia: towards standardization of platelet factor 4/heparin antigen tests

Summary. Background: Laboratory confirmation of heparin‐induced thrombocytopenia (HIT) is based on detection of heparin‐dependent platelet‐activating antibodies. Platelet factor 4 (PF4)/heparin enzyme‐immunoassays (EIA) are a widely available surrogate for platelet‐activating antibodies. Objective: Defining the optical density (OD) reactivity profiles of a PF4/heparin EIA in reference subject and patient populations and the correlation of the EIA results (expressed in OD units) with the prevalence of platelet‐activating antibodies. Patients/methods: Using quantile regression we determined the 97.5th percentile of PF4/heparin‐immunoglobulin G (IgG) EIA reactivities in non‐heparin‐treated individuals [blood donors (n = 935)] and patients before heparin therapy (n = 1207). In patients with suspected HIT, we compared the correlation of EIA‐IgG reactivities (Greifswald laboratory; n = 2821) and the heparin‐induced platelet activation assay (HIPA) with the correlation of reactivities of another EIA‐IgG (McMaster laboratory; n = 1956) with the serotonin‐release assay (SRA). Results: PF4/heparin‐IgG EIA OD reactivities had a lower OD 97.5th percentile in blood donors compared with patient groups before heparin treatment (P < 0.001). The percentage of sera testing positive in the functional assays strongly correlated with PF4/heparin‐IgG EIA OD reactivities in both laboratories with very similar results (correlation coefficient > 0.9) when normalized OD ranges (maximum OD divided by 10) were used instead of absolute OD values. Conclusions: Results of PF4/heparin‐IgG EIA should not be reported as only positive or negative as there is no single acceptable cut‐off value. Instead, reporting PF4/heparin‐IgG EIA OD results in ranges allows for risk‐stratified prediction for presence of platelet‐activating antibodies. Use of normalized OD ranges permits a standardized approach for inter‐laboratory comparisons.     

Polymorphism of ITPA 94C>A and risk of adverse effects among patients with acute lymphoblastic leukaemia treated with 6-mercaptopurine

What is known and Objective: Genetic polymorphisms of thiopurine S‐methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6‐mercaptopurine (6‐MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6‐MP. Methods: Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated. Results and Discussion: Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6‐MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected. What is new and Conclusion: Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6‐MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.     

Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry.

BACKGROUND: Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective surgical or an invasive procedure. Heparin bridging therapy has been used in these situations, although the optimal method has not been established. No large prospective studies have compared unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for the perioperative management of patients at risk of thromboembolism requiring temporary interruption of long-term OAC therapy. PATIENTS/METHODS: This multicenter, observational, prospective registry conducted in North America enrolled 901 eligible patients on long-term OAC who required heparin bridging therapy for an elective surgical or invasive procedure. Practice patterns and clinical outcomes were compared between patients who received either UFH alone (n = 180) or LMWH alone (n = 721). RESULTS: Overall, the majority of patients (74.5%) requiring heparin bridging therapy had arterial indications for OAC. LMWH, in mostly twice-daily treatment doses, represented approximately 80% of the study population. LMWH-bridged patients had significantly fewer arterial indications for OAC, a lower mean Charlson comorbidity score, and were less likely to undergo major or cardiothoracic surgery, receive intraprocedural anticoagulants or thrombolytics, or receive general anesthesia than UFH-bridged patients (all P < 0.05). The LMWH group had significantly more bridging therapy completed in an outpatient setting or with a < 24-h hospital stay vs. the UFH group (63.6% vs. 6.1%, P < 0.001). In the LMWH and UFH groups, similar rates of overall adverse events (16.2% vs. 17.1%, respectively, P = 0.81), major composite adverse events (arterial/venous thromboembolism, major bleed, and death; 4.2% vs. 7.9%, respectively, P = 0.07) and major bleeds (3.3% vs. 5.5%, respectively, P = 0.25) were observed. The thromboembolic event rates were 2.4% for UFH and 0.9% for LMWH. Logistic regression analysis revealed that for postoperative heparin use a Charlson comorbidity score > 1 was an independent predictor of a major bleed and that vascular, general, and major surgery were associated with non-significant trends towards an increased risk of major bleed. CONCLUSIONS: Treatment-dose LMWH, mostly in the outpatient setting, is used substantially more often than UFH as bridging therapy in patients with predominately arterial indications for OAC. Overall adverse events, including thromboembolism and bleeding, are similar for patients treated with LMWH or UFH. Postoperative heparin bridging should be used with caution in patients with multiple comorbidities and those undergoing vascular, general, and major surgery. These findings need to be confirmed using large randomized trials for specific patient groups undergoing specific procedures.     

A preliminary audit investigating remedy reactions including adverse events in routine homeopathic practice

Homeopathic medicines are regarded as safe but practitioners report several types of healing or remedy reactions including aggravations, new symptoms and recurrence of old symptoms, some of which could be regarded as side effects or unwanted effects. Some remedy reactions may be regarded as adverse events. AUDIT QUESTIONS: Do such reactions occur within our unit, and if so, how frequently? Do patients regard these events as "adverse"? METHODS: The audit was carried out in the Bristol Homeopathic Hospital Outpatient Department. All patients were given a questionnaire to complete when at their first follow-up consultation approx 6-10 weeks after their first appointment. One hundred and sixteen patients were sampled over a 2-month period. RESULTS: Reactions were frequent: 28 out of the 116 (24%) patients, experienced an aggravation. Thirteen patients (11%) reported an adverse event even though 5 of those were patients who also reported an aggravation followed by an overall improvement of their symptoms. Thirty-one patients described new symptoms (27%) and 21(18%), a return of old symptoms. Those experiencing the latter appeared to have better outcomes. CONCLUSIONS: Remedy reactions are common in clinical practice; some patients experience them as adverse events. Systematically recording side effects would facilitate our understanding of these reactions and would enable standards to be set for audit of information and patient care.     

Management of heparin resistance due to antithrombin deficiency in a Chinese pregnant woman: a case report

Untreated individuals with antithrombin (AT) deficiency are at higher risk of thrombosis and adverse pregnancy outcomes. The present recommendations are mostly empirical for treating patients with AT deficiency during pregnancy because of the absence of guidelines. We report a rare case of heparin resistance due to AT deficiency in a pregnant 32-year-old Chinese woman. We also reviewed the English medical literature for AT deficiency and its association with thromboembolism and treatment. This patient suffered two early miscarriages because of thrombosis due to AT deficiency. The patient was administered the combination of adequate low molecular weight heparin with fresh frozen plasma and warfarin because of her heparin resistance. She delivered a healthy female newborn without any adverse effects of the anticoagulation therapy. Our findings suggest that the combination of adequate low molecular weight heparin with fresh frozen plasma and warfarin is effective for preventing thrombus during pregnancy.