Fatal Blood Research Articles

Chemical Shift Artifact on Steady-State MRI Sequences for Detection of Vesical Wall Invasion in Placenta Percreta.

Antenatal diagnosis of the invasiveness of a placenta percreta helps in planning the surgical approach, reducing blood loss and morbidity. Doppler sonography is the mainstay diagnostic modality with a sensitivity of 80-95%. With the advent of high magnetic field MRI techniques, there has been recent interest in evaluation of placenta by MRI. On an extensive PUBMED search, we could not find any citations describing imaging, ultrasound, or MRI features to evaluate vesical wall invasion by placenta percreta. We attempt to evaluate transmyometrial vesical wall invasion by placenta percreta using chemical shift artifact as a marker of intact bladder-myometrial interface on steady-state MRI sequences. This is a prospective observational study, conducted at a university hospital. We have compiled clinico-radiological criteria for diagnosis of invasive placentae based on the existing body of evidences, in four patients. We further go on to analyze a specific proposed sign on a newly introduced MR imaging sequence i.e., loss of chemical shift artifact (India ink line) on steady-state GRE sequence (TrueFISP), to diagnose transmyometrial vesical invasion in placenta percreta. Though the sample size is small, the sensitivity, specificity, positive, and negative predictive value of the proposed sign for the purpose was 100 %. Loss of chemical shift artifact (India ink line) on steady-state GRE sequences at the vesico-myometrial junction in case of invasive placentae confirms vesical wall invasion, a prospective diagnoses of which can help in planning the surgical protocol and preventing potentially fatal blood loss.

"Surgically created" excision of the back mimicking homicide: report of an unusual case.

Fatalities due to sharp force trauma, with respect to manner of death, may be homicidal, self-inflicted, or accidental in nature. This article presents a case of an unusual sharp force injury inflicted under very specific and seemingly obscured circumstances, initially suggestive of homicidal origin. A 69-year-old, socially isolated male was found dead with a strange, heavily blood-stained excision-like lesion on the right subscapular area. The autopsy confirmed that the wound led to fatal external blood loss. Toxicological analysis of the blood and urine revealed severe alcohol intoxication. The police investigation turned up that the man had suffered from a painful skin furuncle of the right upper back. As he was worried about receiving medical treatment, he voluntarily asked his two acquaintances for "surgical" assistance to remove the skin affection. Based on the circumstances surrounding death and findings at autopsy, it was concluded that the injury was inflicted without the intent to harm or cause death, as a result of simple negligence. Consequently, the manner of death was ultimately certified as an involuntary manslaughter. Our case has clearly illustrated that even highly suspicious and atypically shaped wounds created by sharp-edged instruments with localization in non-accessible body areas does not exclusively indicate homicidal activity, hence, the accidental, suicidal or even iatrogenic origin of the wounding mechanism must be taken into consideration.

Sedative and hypnotic drugs—Fatal and non-fatal reference blood concentrations

In postmortem investigations of fatal intoxications it is often challenging to determine which drug/s caused the death. To improve the interpretation of postmortem blood concentrations of sedative and hypnotic drugs and/or clonazepam, all medico-legal autopsies in Sweden – where these drugs had been detected in femoral vein blood during 1992–2006 – were identified in the databases of the National Board of Forensic Medicine. For each drug, concentrations in postmortem control cases – where the cause of death was not intoxication and where incapacitation by drugs could be excluded – were compiled as well as the levels found in living subjects; drugged driving cases and therapeutic drug monitoring cases. Subsequently, fatal intoxications were assessed with regards to the primary substances contributing to death, and blood levels were compiled for single and multiple drug intoxications. The postmortem femoral blood levels are reported for 16 sedative and hypnotic drugs, based on findings in 3560 autopsy cases. The cases were classified as single substance intoxications (N=498), multiple substance intoxications (N=1555) and postmortem controls (N=1507). Each autopsy case could be represented more than once in the group of multiple intoxications and among the postmortem controls if more than one of the included substances were detected. The concentration ranges for all groups are provided. Overlap in concentrations between fatal intoxications and reference groups was seen for most substances. However, the concentrations found in single and multiple intoxications were significantly higher than concentrations found in postmortem controls for all substances except alprazolam and triazolam. Concentrations observed among drugged drivers were similar to the concentrations observed among the therapeutic drug monitoring cases. Flunitrazepam was the substance with the highest number of single intoxications, when related to sales. In summary, this study provides reference drug concentrations primarily to be used for improving interpretation of postmortem drug levels in obscure cases, but which also may assist in drug safety work and in pharmacovigilance efforts.

Haematopoietic cell transplantation – from its birth to the twenty-first century

After more than 60 years of investigations into the use of allogeneic haematopoietic cell transplantation for treatment of otherwise fatal malignant and non-malignant blood disorders, this procedure has been transformed from one that was thought to be plagued with insurmountable difficulties to a standard therapy for many haematological diseases. How have these problems been overcome and how was this procedure extended to include patients who were too old or medically unfit to tolerate conventional, high-intensity transplant approaches?

Improving The Efficacy And Availability Of Stem Cell Transplant Therapies For Hematopoietic Stem Cell Transplantation

Over a million hematopoietic stem cell transplants (HSCTs) have been performed around the world for treatment of a range of cancers and hematological indications. A significant increase in transplants and transplant centers has been seen in many parts of the world, with the highest relative increase of transplant centers occurring in the Asia Pacific region, specifically in countries like China, India, Singapore and Thailand. The Bone Marrow Donors Worldwide (BMDW) register has grown to include over 20 million donors by 2013 with consequent greater ease in finding an unrelated donor for transplant. The availability of donors have been further enhanced through the use of alternate stem cell sources like cord blood and haploidentical donors. To protect donors while serving the needs of patients who are urgently seeking histocompatible donors in around the world, the World Marrow Donor Association (WMDA) has helped in establishing standards, accreditation, safety measures, shared processes and global monitoring systems for stem cell registries. Recent developments in pre-transplant preparative regimens as well as post-transplant care have made incremental but definite improvements in post-transplant survival. Graft engineering has also helped to facilitate the removal of cells which cause graft-versus-host disease (GVHD), the eradication of cells which might cause relapse, the expansion of donor cells when there is an inadequate cell dose, and the addition of selected cells to improve graft function with augmented anti-tumor or anti-infective properties. These advances help enhance the safety, efficacy and availability of HSCT, ensuring that this modality of treatment remains an important part of the continuum of care of patients of potentially fatal cancers and blood diseases.

Black esophagus - case report

Diseases of the gastrointestinal system, and especially diseases of esophagus, are a rare cause of sudden unexpected death in any age group. Black esophagus is an acute necrotizing inflammation of the mucosa of the lower parts of esophagus, diffusely affecting its entire circumference. This inflammation could be a source of profuse bleeding and cause sudden unexpected death. A case of 76-year-old male was presented herein. He has been treated for hypertension and diabetes for several years. As a consequence of stroke, which happened several months prior to death, he had been hemiplegic and immobilized. He died in hospital, suddenly and unexpectedly. The autopsy showed the acute necrotizing esophagitis, as well as the acute gastric and duodenal erosions of mucosa. These were the causes of fatal blood loss. Acute necrotizing esophagitis should be recognized during autopsy and related to the immediate cause of death as well as to concomitant diseases of other organs, which either potentiate or facilitate presentation of this disease.

Current concepts in the pathophysiology and treatment of aplastic anemia

Historically viewed in isolation as an odd, rare, and invariably fatal blood disease, aplastic anemia is now of substantial interest for its immune pathophysiology, its relationship to constitutional BM failure syndromes and leukemia, and the success of both stem cell transplantation and immunosuppressive therapies in dramatically improving survival of patients. Once relegated to a few presentations in the red cell and anemia sessions of the ASH, the Society now sponsors multiple simultaneous sessions and plenary and scientific committee presentations on these topics. This update emphasizes developments in our understanding of immune mechanisms and hematopoietic stem cell biology and new clinical approaches to stem cell stimulation as a therapy, alone and in combination with conventional suppression of the aberrant immune system.

Paper-based device for rapid typing of secondary human blood groups

We report the use of bioactive paper for typing of secondary human blood groups. Our recent work on using bioactive paper for human blood typing has led to the discovery of a new method for identifying haemagglutination of red blood cells. The primary human blood groups, i.e., ABO and RhD groups, have been successfully typed with this method. Clinically, however, many secondary blood groups can also cause fatal blood transfusion accidents, despite the fact that the haemagglutination reactions of secondary blood groups are generally weaker than those of the primary blood groups. We describe the design of a user-friendly sensor for rapid typing of secondary blood groups using bioactive paper. We also present mechanistic insights into interactions between secondary blood group antibodies and red blood cells obtained using confocal microscopy. Haemagglutination patterns under different conditions are revealed for optimization of the assay conditions.

P.3.d.053 Olanzapine concentrations collected postmortem in patients treated with olanzapine long-acting injection

In post-mortem investigations of fatal intoxication, it is challenging to determine which drug(s) were responsible for the death, and which drugs did not. This study aims to provide post-mortem femoral blood drug levels in lethal intoxication and in post-mortem control cases, where the cause of death was other than intoxication. The reference values could assist in the interpretation of toxicological results in the routine casework.To this end, all post-mortem toxicological results in femoral blood from 2011 to 2017 in Western Switzerland were considered. A full autopsy with systematic toxicological analysis (STA) was conducted in all cases. Results take into account the cause of death classified into one of four categories (as published by Druid and colleagues): I) certified intoxication by one substance alone, IIa) certified intoxication by more than one substance, IIb) certified other causes of death with incapacitation due to drugs, and III) certified other causes of death without incapacitation due to drugs.This study includes 1 990 post-mortem cases where femoral blood was analysed. The material comprised 619 women (31%) and 1 371 men (69%) with a median age of 50 years. The concentrations of the 32 most frequently recorded substances as well as alcohol are discussed. These include 6 opioids and opiates, 3 antidepressants, 6 neuroleptics and hypnotics, 1 barbiturate, 11 benzodiazepines (and related drugs), 2 amphetamine-type stimulants, cocaine, paracetamol, and tetrahydrocannabinol (THC).The most common substances that caused intoxication alone were morphine, methadone, ethanol, tramadol, and cocaine. The post-mortem concentration ranges for all substance are categorized as I, IIa, IIb, or III. Statistical post-mortem reference concentrations for drugs are discussed and compared with previously published concentrations. This study shows that recording and classifying cases is time-consuming, but it is rewarding in a long-term perspective to achieve a more reliable information about fatal and non-fatal blood concentrations.

Case reports in forensic toxicology

Case reports in forensic toxicology

The unusual appearance of black esophagus in a case of fatal hypothermia: a possible underlying mechanism

Acute esophageal necrosis is characterized by a full length, circumferential black discoloration of the entire mucosa of the esophagus that ends abruptly at the esophagogastric junction [1]. The clinical presentation of cases is almost universally related to upper gastrointestinal bleeding [2]. Although unclear, the etiology is likely to be multifactorial [1, 2]. Case history: A 61-year-old male, alcoholic with liver cirrhosis was found lying unconscious on a cold bathroom floor. The patient was in a deep coma, hypotensive with accompanying metabolic acidosis, slight hyperglycemia, significantly elevated urea, creatinine, and liver enzymes levels, and had progressing secondary anemia. The patient died approximately 46 h after he was initially found in his house. The autopsy found that the distal third of the esophagus contained blackish necrotic mucosa, which ended abruptly at the esophagogastric junction. The stomach mucosa had numerous red-brownish erosions— Wischnewski spots (Fig. 1). The entire length of the intestine was filled with dark-red blood. Microscopic examination revealed an acute full-thickness necrosis of the esophagus mucosa in which the epithelium was almost completely consumed, and acute inflammatory cells in the submucosa and mucosa. The cause of death was fatal blood loss from the upper gastrointestinal tract. Hypothermia stimulates profound vasoconstriction, especially in the splanchnic region, and alterations in microcirculation, which leads to ischemic organ damage [3]. A somewhat atypical presentation of a black esophagus as seen in this case, where only the lower third of the organ is affected, is most likely related to its segmental vascular supply. The distal esophagus receives its blood flow from branches of the left gastric artery or left inferior phrenic artery, and is the least vascularized section of the esophagus. Therefore, the first signs of an ischemic injury to the esophagus typically appear in the distal section [2]. Although the black esophagus in this case could perhaps be related to acute alcohol intoxication, or liver cirrhosis, the most probable cause has been considered to be the vasoconstriction of the common arteries of the stomach and the distal section of the esophagus due to hypothermia. Wischnewski spots would seem to occur more frequently in the elderly after having been exposed to cold stress for an extended period of time [4, 5]. The presence of them in this case indicates that the cooling of the body was not rapid, that is, the patient had most probably been lying on the cold ceramic floor for some time before being found, loosing body heat via conduction during that time. The microscopic appearance of acute esophagitis with a sharp demarcation of mucosal necrosis by predominantly neutrophilic granulocytes places the noxious mucosal injury within a time frame of approximately 24–72 h prior to death [1]. The microscopic picture of the black esophagus in this case is consistent with this finding, as the patient died approximately 46 h after he was admitted to hospital. The cause of death in this case has been attributed to fatal exsanguination from the upper gastrointestinal tract. All other potential sources of bleeding from the gastrointestinal tract were excluded by autopsy. The fatal blood loss was facilitated by coagulopathy due to the preexisting alcoholic liver cirrhosis, as well as liver failure caused by re-warming [3]. The mucosal necrosis of the distal section of the esophagus may represent a delayed complication of V. Živkovic S. Nikolic (&) Institute of Forensic Medicine, University of Belgrade School of Medicine, 31a Deligradska str., 11000 Belgrade, Serbia e-mail: bobanvladislav@yahoo.com; slobodan.nikolic@mfub.bg.ac.rs

Biosafe alternative to xylene: A comparative study

Background:Xylene in one of the non-substitutable chemical used in histology laboratories. However, it is known to have many toxic effects. The toxic effects of xylene include heart and kidney injuries, some fatal blood dyscrasia and other less dangerous problems, such as skin erythema, drying, scaling and secondary infections. The exposure and handling of xylene is maximum during deparaffinizing tissue sections.Aims:The aim of this study was to evaluate the efficacy of 1.7% dishwashing soap (DWS) solution as a deparaffinizing agent for hematoxylin and eosin (H and E) staining and compare it with xylene.Materials and Methods:Sixty sections of 4 μm were obtained from 30 formalin-fixed paraffin-embedded (FFPE) tissues and were considered in two different groups, groups A and B. Slides in group A were stained with routine H and E staining procedure; whereas, slides in group B were stained using 1.7% DWS as a deparaffinizing agent.Statistical Analysis Used:Wilcoxon matched-pairs signed rank test was used to calculate the test of significance (P-value significant at ≤0.05).Results and Conclusion:1.7% DWS was found to be an effective alternative deparaffinizing agent to xylene and meanwhile facilitating as less biohazardous, economical and a faster deparaffinizing agent.

Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector

Anopheles mosquitoes are vectors of malaria, a potentially fatal blood disease affecting half a billion humans worldwide. These blood-feeding insects include in their antihemostatic arsenal a potent thrombin inhibitor, the flexible and cysteine-less anophelin. Here, we present a thorough structure-and-function analysis of thrombin inhibition by anophelin, including the 2.3-Å crystal structure of the human thrombin·anophelin complex. Anophelin residues 32-61 are well-defined by electron density, completely occupying the long cleft between the active site and exosite I. However, in striking contrast to substrates, the D50-R53 anophelin tetrapeptide occupies the active site cleft of the enzyme, whereas the upstream residues A35-P45 shield the regulatory exosite I, defining a unique reverse-binding mode of an inhibitor to the target proteinase. The extensive interactions established, the disruption of thrombin's active site charge-relay system, and the insertion of residue R53 into the proteinase S(1) pocket in an orientation opposed to productive substrates explain anophelin's remarkable specificity and resistance to proteolysis by thrombin. Complementary biophysical and functional characterization of point mutants and truncated versions of anophelin unambiguously establish the molecular mechanism of action of this family of serine proteinase inhibitors (I77). These findings have implications for the design of novel antithrombotics.

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India

BackgroundHIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance.ResultsA comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.); ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd.) gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd.), Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd.) did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100%) except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.). The kit efficiency didn’t vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p < 0.01) among three kit types.ConclusionsELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful for further detection of false positive samples. ELISA seems the appropriate assay in blood bank. For availability of quality commercial diagnostic assays, evaluation of kit may be helpful.

Playing with danger

Young people who sit still for hours playing computer games can double their risk of potentially fatal blood clots. The charity Lifeblood is alerting nurses to 'e-thrombosis'. It is calling on them to ensure young people are aware of the risks of prolonged immobility and the need to take regular breaks from gaming or using a computer.

Health care utilization of patients diagnosed with idiopathic thrombotic thrombocytopenic purpura in a commercially insured population in the United States

Incident idiopathic thrombotic thrombocytopenic purpura (TTP) is an uncommon, potentially fatal blood disorder for which there are little or no data on health care costs. Patients satisfying a validated claims-based algorithm including an inpatient diagnosis of TTP and plasma exchange (PE) procedure during the period January 1, 2001 to May 31, 2008 were identified in the HealthCore Integrated Research Database. To characterize patterns of treatment and payments, a quantitative evaluation of comorbidities and treatments, health care utilization, and payments among this population of patients was conducted. All patients were followed until death, end of health plan enrollment, or 365 days after the TTP hospitalization, whichever occurred first. One hundred fifty-one patients met the claims coding algorithm. Mean total health care payments for the TTP hospitalization were $56,347 (standard deviation [SD] $80,230). Ten patients (6.6%) died during the hospitalization for TTP. Mean payments for PE services in the month following discharge were $9127 (SD $20,840). Several patients required prolonged PE during the acute TTP phase (up to 116 separate exchanges over a period of 365 days), prolonging required treatment and skewing payments and resource utilization during the 365-day period following discharge from the index TTP hospitalization. These data document the health care resource utilization by patients with idiopathic TTP, demonstrating that management of these patients is not only expensive but also skewed, with some patients requiring prolonged treatment. These data can contribute to cost-effectiveness models when new treatments for TTP become available.

Therapeutic and postmortem opioids levels

BackgroundThe range of opioid dose in patients receiving palliative care is wide and not directly related to response. The levels of opioids in therapeutic and postmortem, population group studies and...

Personalized medicine for acute myelogenous leukemia—At the entrance gate

With the advent of molecularly targeted therapies in the oncology clinic, previously fatal blood cancers have now become chronic diseases. Imatinib, a small molecule tyrosine kinase inhibitor that targets the BCR-ABL fusion protein, dramatically extends survival for patients with chronic myelogenous leukemia and has opened the flood gates for modern ‘‘personalized cancer medicine’’. Rituximab, a monoclonal antibody with affinity for the CD20 antigen of B-lymphocytes, in an analogous fashion has revolutionized treatment for patients with B-cell lymphomas. Does this paradigm, a rather commonplace approach for the treatment of hematologic malignancies, apply also to acute myelogenous leukemia (AML)? This is an exciting time to be involved in AML research, and an explosion of new basic science discoveries has formed a springboard for some brand new personalized treatment concepts that this commentary will serve to outline. Targeted Therapy

Lipid solubility of a series of drugs and its relevance to fatal poisoning.

For 11 commonly used drugs, the n-octanol/water partition coefficient (pH 7.4 temperature 37 degrees C) and solubility in n-octanol were determined. The drugs tested were chlorpromazine, amitriptyline, trazodone, dextropropoxyphene, diltiazem, dibucaine, amethocaine, procaine, quinidine, acetylsalicylic acid and paracetamol. For eight of the drugs, the relative lipid saturation corresponding to a fatal plasma concentration was estimated from the two parameters determined above and the median fatal blood concentrations reported in the literature. For five of those eight drugs, the estimated relative saturation in the lipid phase fell within the range 0.001-0.004 which is close to relative saturation figures in aqueous and vapour phases already published for chemicals possessing a non-specific or physical mechanism of toxicity. Since this is determined largely by their lipid solubility, it is probable that accumulation in the lipid phase is an important determinant of the lethal toxicity of drugs and chemicals with a non-specific mechanism of toxicity.

Spontaneous haemothorax and haemoperitoneum inPlasmodium vivaxmalaria

Although patients with Plasmodium vivax malaria usually recover from the disease without any sequelae, several complications do occasionally occur and these may need urgent invasive procedures, including surgery, and/or lead to fatal blood loss (Jacobs et al., 2005; Gockel et al., 2006; Maguire and Baird, 2010). Worryingly, the incidence of complications in P. vivax malaria, such as acute respiratory-distress syndrome or splenic rupture, appears to be increasing (Kasliwal et al., 2009). A case of P. vivax malaria complicated by spontaneous haemothorax (perhaps the first ever reported) is described below.