Heparin-induced skin necrosis and low molecular weight heparins

Heparin-induced skin necrosis is a rare but potentially devastating side-effect of low molecular weight heparins. These agents are widely used in surgical practice and doctors prescribing them should be aware of the condition, as failure to recognise it may increase morbidity. An unusually severe case is presented with a review of the literature.     

Anticoagulant Reversal in Gastrointestinal Bleeding: Review of Treatment Guidelines

Background

Patients receiving anticoagulant therapies, such as vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), commonly experience gastrointestinal (GI) bleeding as a complication and may require anticoagulant reversal prior to endoscopic treatment. Anticoagulant reversal agents include prothrombin complex concentrates (PCCs; including 3 or 4 coagulation factors), plasma, vitamin K, and target-specific DOAC reversal agents (e.g., idarucizumab and andexanet alfa).

Aim

To review current US, as well as international, guidelines for anticoagulant reversal agents in patients on VKAs or DOACs presenting with GI bleeding prior to endoscopy, guideline-based management of coagulation defects, timing of endoscopy, and recommendations for resumption of anticoagulant therapy following hemostasis. Supporting clinical data were also reviewed.

Methods

This is a narrative review, based on PubMed and Internet searches reporting GI guidelines and supporting clinical data.

Results

GI-specific guidelines state that use of reversal agents should be considered in patients with life-threatening GI bleeding. For VKA patients presenting with an international normalized ratio >?2.5, guidelines recommend PCCs (specifically 4F-PCC), as they may exhibit greater efficacy/safety compared with fresh frozen plasma in reversal of VKA-associated GI bleeding. For DOAC patients, most guidelines recommend targeted specific reversal agents in the setting of GI bleeding; however, PCCs (primarily 4F-PCC) are often listed as another option. Resumption of anticoagulant therapy following cessation of GI bleeding is also recommended to reduce risks of future thromboembolic complications.

Conclusions

The utility of anticoagulant reversal agents in GI bleeding is recognized in guidelines; however, such agents should be reserved for use in truly life-threatening scenarios.

     

Cyclooxygenase enzyme expression and E series prostaglandin receptor signalling are enhanced in heavy menstruation

BACKGROUND: Although the mechanisms underlying the causes of heavy menstrualblood loss (MBL) remain to be elucidated, prostaglandins havebeen previously implicated. This study was initiated to elucidatea pattern of expression of the various components of the cyclooxygenase(COX)–prostaglandin signalling pathways present in theendometrium of women with normal and heavy MBLs. METHODS: Endometrial biopsies were collected at different stages of themenstrual cycle from women who underwent measurement of MBL.Tissue was divided for either examination of gene expressionby quantitative RT–PCR analysis or in vitro culture experimentation. RESULTS: Analysis of gene expression demonstrated a significant elevationin expression of COX-1 and COX-2 mRNA in endometrium obtainedfrom women with heavy MBL when compared with endometrium obtainedfrom women with normal MBL. Tissue culture with PGE₂ stimulationcaused a significantly elevated production of cyclic AMP (cAMP)by endometrium of women with heavy MBL when compared with normalMBL. Expression of phosphodiesterase 4B, an enzyme involvedin cAMP breakdown, was reduced in these same endometrial samplesobtained from women with heavy MBL. CONCLUSIONS: These data identify the E series prostaglandin receptors andtheir signalling pathways as potential therapeutic targets inthe treatment of heavy menstruation.     

From functions to mechanisms of the prototypic complement C5 antibody BB5.1

Antibodies that bind complement components were first identified over 30 years ago. Investigations into their functions in animal models motivated clinical studies that have now generated licensed products and a strong pipeline of future therapeutics. Despite this, the mechanisms of action of one of the first effective C5-binding antibodies, BB5.1, were not known. Here, we report a new study that reveals these mechanisms, enabling new approaches for designing C5-binding molecules for therapeutic use.     

Brief modification of suggestibility and hypnotic analgesia: Too good to be true?

A 10-minute training procedure, based on the Carleton Skill Training Program, has previously been reported to produce substantial increments in responsiveness to hypnotic suggestion. The authors attempted to replicate this effect and also assessed the impact of the training procedure on hypnotically suggested analgesia. Ninety-eight students who had been preselected for high, medium, and low levels of initial suggestibility were randomly assigned to experimental and control groups. Training failed to increase overall suggestibility scores or to enhance the effects of a suggestion for pain reduction. Suggested pain reduction was more highly correlated with posttreatment suggestibility scores than with pretreatment suggestibility and, in a regression analysis, only posttreatment suggestibility predicted pain reduction uniquely.     

Participation in social activities: maternal ratings of maltreated and nonmaltreated children

Using the Achenbach Child Behavior Checklist (T. M. Achenbach, 1991), 192 mothers of maltreated children and 179 mothers of nonmaltreated children rated children's participation in social activities. Maltreated children were reported as belonging to fewer organizations and were judged less proficient at sports than nonmaltreated children. Regarding specific types of activities, maltreated children were rated as less likely to take part in team sports and to belong to sports organizations. Psychosocial disadvantage may reduce opportunities for maltreated children to participate in social activities.