Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Isolated superior mesenteric artery dissection in the emergency department: A rare cause of abdominal pain

Acute onset abdominal pain constitutes a significant proportion of emergency department visits, but only a small fraction of these cases are attributable to vascular pathologies (Bauersfeld, 1947 [1]). In this case, report, we present an incidental diagnosis of Spontaneous Isolated Superior Mesenteric Artery Dissection (SISMAD). A 69-year-old man was admitted to the emergency department complaining of fever, loss of appetite, vague epigastric pain, dysuria, and a productive cough for several days. A lower extremity venous Doppler ultrasound was performed, and a deep venous thrombosis (DVT) was identified in the left main femoral vein and in the proximal segment of the superficial vein. The patient also had no blood flow in the distal part of left external iliac vein. A contrast-enhanced computerized tomography angiography of the thorax and abdomen was performed to detect pulmonary embolism and the etiology of the abdominal pain. No pulmonary embolism was found; however, multiple metastatic nodules were identified in both lungs, as well as infiltration on the posterobasal field of the right lung, metastases on the liver, focal dilatation, and an intimal flap on the middle-distal part of the superior mesenteric artery (SMA) at 2?cm, with a segment that was compatible with isolated dissection. There was a contrast passage on the distal part of SMA, and no sign of bowel ischemia.     

Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.     

Patient preference for triptan formulations: a prospective study with zolmitriptan

OBJECTIVES: To investigate patterns of patient preference for 3 formulations of zolmitriptan, in a primary care study utilizing a naturalistic longitudinal design. BACKGROUND: Although differences in efficacy between individual triptans tend to be small, migraine patients show clear preferences for individual triptans and formulations. The groups of patients suitable for the different triptan formulations, and the reasons underlying individual preferences, are not clearly understood. METHODS: Migraine patients entered a prospective, randomized, open, crossover, longitudinal design study, with patients receiving zolmitriptan formulations according to UK prescribing recommendations. Patients na?ve to zolmitriptan received zolmitriptan 2.5-mg film-coated tablets or 2.5-mg Orally Disintegrating Tablets (ODT) for 1 month, before being crossed over to receive the alternative formulation for Month 2. All patients then received zolmitriptan nasal spray 5 mg for Month 3. Patients could then choose the formulation(s) of their choice for a further 7 months. Patients recorded their preferences for individual formulations, the reasons for their preferences, and also the headache-related disability (measured by the Migraine Disability Assessment [MIDAS] score) at clinic visits. Primary endpoints were the individual preferences and changes in MIDAS scores. Adverse events were also recorded. RESULTS: Forty-eight patients took part in the study. At baseline, most patients expressed a preference for conventional tablets. After 4 months, 46.9% of patients preferred zolmitriptan ODT, 43.8% zolmitriptan nasal spray, and 6.3% the conventional tablet. The most common reasons given for preferring conventional tablets were personal reasons: for zolmitriptan ODT, convenience and, to a lesser extent, speed of onset: for zolmitriptan nasal spray, speed of onset, and overall efficacy. MIDAS scores decreased significantly following treatment with zolmitriptan. Zolmitriptan was well tolerated. CONCLUSIONS: Patient experience of newer zolmitriptan formulations influenced a change in preference away from conventional tablets. Speed and efficacy were the key drivers of preference for zolmitriptan nasal spray, while convenience mostly drove preference for the ODT formulation. Open, longitudinal, naturalistic studies may, allowing for biases, sometimes be an appropriate way of conducting migraine studies in primary care.     

Physiotherapists’ use of suprascapular nerve blocks: an online survey

BackgroundThere is some evidence to support the use of suprascapular nerve blocks (SSNBs) to manage shoulder pain. Although many patients with shoulder pain are referred to physiotherapy, there are no data describing whether physiotherapists currently use SSNBs for these patients.ObjectiveTo explore if physiotherapists who manage musculoskeletal shoulder pain are using SSNBs and identify, of those who responded to an online questionnaire, how commonplace this practice is in the United Kingdom (UK)DesignAn online, cross-sectional, questionnaire survey was developed for physiotherapists involved in the management of patients with shoulder pain.MethodsA snowball sampling method was used to invite physiotherapists to complete the online survey, using email, research advertisements in a professional magazine and via social media. The questionnaire captured respondents’ demographic and professional practice characteristics, their knowledge and use of SSNBs and their views and experiences regarding SSNBs as a treatment for shoulder pain.ResultsIn total, there were 529 responders to the survey. Of these, 492 were eligible and formed the sample for analyses. The majority of responders (290/474; 61%) were from the UK. Of these, the majority (259/282; 92%) were familiar with SSNBs as a method of treatment for shoulder pain, although few (9/149; 6%) reported regularly using SSNBs in their clinical practice. Only 8 of 287 responders from the UK (3%) reported delivering SSNBs to patients.ConclusionsThis survey provides preliminary evidence that the use and delivery of SSNBs by UK physiotherapists is uncommon. Future research is required to investigate the potential value of physiotherapists using this treatment option for their patients with shoulder pain.     

Is chronic synovitis an example of reperfusion injury?

In an attempt to define why the joint synovial cavity is prone to develop persistent synovial inflammation we show that hypoxia is induced by pressure changes caused by exercise in the presence of an inflammatory effusion. On resting 'reperfusion injury' may take place. The biochemistry of reperfusion injury has only recently been defined and perhaps surprisingly for an insult that has hypoxia as its central ingredient involves the subsequent production of oxygen derived free radical species. We apply the reaction sequences that are believed to occur during hypoxic/reperfusion injury to the joint synovial cavity and, on the basis of reported 'in vivo' observations, suggest novel therapeutic approaches that we believe are applicable to the treatment of persistent synovial inflammation.     

Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation

After lethal irradiation of C57BL mice followed by the injection of 10(7) marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 hr after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.     

The use of an animal drawing test in the assessment and disposition of transsexualism

Reported results of a study that compared two projective techniques for a group of 19 transsexuals who were seeking sex reassignment surgery. The Draw-A-Person Test (DAP), widely used in clinical settings, was contrasted to the Animal and Opposite Drawing Technique (AODT), which is a relatively new and little-examined variation of the DAP. Discussion focuses on the use of both measures as predictors of those transsexuals to be recommended for surgery. Use of the AODT as an effective measure in the assessment of transsexualism is investigated.