Fatal ovarian hyperstimulation syndrome in an anonymous egg donor

Ovarian hyperstimulation syndrome is a rare, but potentially life-threatening iatrogenic disorder arising from ovulation induction or ovarian hyperstimulation for assisted reproduction techniques. We report a case of a 26-year-old multiparous woman, an anonymous egg donor, who died a few hours after undergoing a procedure to donate eggs at an in vitro fertilization clinic. Her husband alleged that medical negligence had led to her death. The autopsy confirmed death due to ovarian hyperstimulation syndrome. We know of no previous descriptions of fatal ovarian hyperstimulation syndrome in an anonymous egg donor in medico-legal literature.

Defining the Role of Monocytes in Heparin-Induced Thrombocytopenia (HIT): Insights from a Murine HIT Model.

Heparin-induced thrombocytopenia (HIT) is an iatrogenic disorder seen in 1–5% of patients exposed to unfractionated heparin. One unusual feature of HIT is that affected patients often have only moderate thrombocytopenia yet suffer severe, life-threatening thrombosis. We have previously defined the importance of PF4:glycosaminoglycan (GAG) antigenic complexes on the surface of circulating platelets in the development of thrombocytopenia using mice that express varying levels of human PF4 (hPF4+/+) as well as Fc γRIIA on the platelet surface after infusing the animals with a monoclonal antibody (KKO) that demonstrates HIT-like properties. Because HIT antibodies have been reported to activate monocytes to produce tissue factor in vitro, we further examined their role both in vitro and in vivo in the murine HIT model. Monocytes bind PF4 onto their surface forming antigenic PF4:GAG complexes recognized by KKO. Monocytes express antigenic complexes at low levels of PF4, a setting in which none can be demonstrated on platelets. Furthermore, monocytes express antigenic complexes at heparin concentrations that completely dissociate antigen from the surface of platelets. We then investigated the role of monocytes in a murine model of HIT. Monocytes were depleted by IV injection of 200 μL of clodronate-containing liposomes (Encapsula Nano Sciences) 12 hrs prior to IP injection of 200 μg of KKO. Over 92% of circulating monocytes were depleted for >24 hrs with a return to near baseline by 72 hrs. In co-transgenic hPF4+/+/FcγRIIA mice, clodronate did not cause a significant fall in platelet count at 4 hrs, but counts fell to 30 ± 14% of baseline by 24 hrs vs. 70 ± 23% of baseline after injection of control liposomes or no liposomes (p<0.001), thrombocytopenia persisted for 72 hrs. Nevertheless, monocyte depletion inhibited thrombosis in the HIT model. Rose Bengal (500 mg/kg) was injected and the right carotid artery injury was exposed to 3 mW green (540 nm) light for 5 min followed by an IV injection of KKO (500 μg/kg). 4 of 5 mice that did not receive liposomes and 4 of 5 mice that received control liposomes 16–24 hrs prior to KKO developed thrombosis, in contrast to 1 of 5 clodronate liposome-treated mice (p<0.01 vs. all controls) in spite of having platelet counts of 860,000 ± 185,000/μL. These studies show that antibody mediated activation of monocytes contributes to the initiation of HIT, while intravascular activation of platelets contributes to the development of thrombocytopenia. These studies also suggest that depletion of monocytes may be a novel target for therapeutic intervention in the early stages of the disease.

Tardive Dyskinesia: A Review

Objective: To review recent research findings on tardive dyskinesia (TD) with relevance to clinical practice. Method: TD is a syndrome of involuntary movements that can occur in association with chronic neuroleptic use. It is of unknown pathophysiology. It can be irreversible, is cosmetically disfiguring, and can be functionally disabling. Results: There is as yet no treatment of demonstrated efficacy for TD. It is an iatrogenic disorder whose incidence is increased by age and total cumulative dose of typical neuroleptics. It has been the source of successful litigation in some jurisdictions but, until very recently, there has been no effective antipsychotic agent without this effect. Conclusion: This litigation in some jurisdictions has been a major impetus to the development of novel antipsychotic agents. It is less well known that a similar, possibly identical, movement disorder occurs spontaneously particularly in the elderly and inpatients with schizophrenia, and that TD is often reversible.

Review: Drug Induced Akathisia in Medical and Surgical Patients

Drug-induced akathisia is a significant and common iatrogenic disorder. It involves both a subjective component of a disturbing sense of compulsion to move and an objective component of motor restlessness. Akathisia is being seen with increasing frequency in medical and surgical patients. This is due to the increased use of anti-emetics or novel adjuncts to pain control as well as more widespread use of the major psychoactive drugs throughout medicine. This review focuses on diagnostic features of the disorder as well as on possible treatment approaches. In addition, the disorder demonstrates the close anatomic and functional relationship between cortical and subcortical dopaminergic pathways. Akathisia is thus both an increasingly significant clinical problem and a fascinating glimpse at the relationship between brain function and behavior.