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Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies. [ABSTRACT FROM AUTHOR]

Hereditary thrombotic thrombocytopenic purpura (hTTP), also known as Upshaw–Schulman syndrome, is a rare genetic disorder caused by mutations in the ADAMTS13 gene that leads to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. The result is circulating ultra-large multimers of VWF that can cause microthrombi, intravascular occlusion and organ damage, especially at times of turbulent circulation. Patients with hTTP may have many overt or clinically silent manifestations, and a high index of suspicion is required for diagnosis. For the treatment of hTTP, the goal is simply replacement of ADAMTS13. The primary treatment is prophylaxis with plasma infusions or plasma-derived factor VIII products, providing sufficient ADAMTS13 to prevent acute episodes. When acute episodes occur, prophylaxis is intensified. Recombinant ADAMTS13, which is near to approval, will immediately be the most effective and also the most convenient treatment. In this review, we discuss the possible clinical manifestations of this rare disease and the relevant differential diagnoses in different age groups. An extensive discussion on prophylaxis and treatment strategies is also presented. Unique real patient cases have been added to highlight critical aspects of hTTP manifestations, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder secondary to development of antibodies against prothrombin protein, in the presence of antiphospholipid antibodies. We describe the case of a 13-year-old girl who presented with severe menorrhagia and symptomatic anemia. Labs indicated anemia, thrombocytopenia, elevated PT and aPTT, high-titer inhibitor on mixing studies, positive ANA and anti-dsDNA antibodies, along with a triple-positive antiphospholipid antibody panel. Given additional systemic manifestations, systemic lupus erythematosus was diagnosed. High dose steroids and hydroxychloroquine subsequently started. Her clinical course was complicated by femoral deep venous thrombosis and post renal biopsy retroperitoneal hematoma. Further workup revealed low prothrombin level and the diagnosis of lupus anticoagulant hypoprothrombinemia syndrome. In view of suboptimal response to initial immunosuppressive therapy, rituximab was added to her regimen, leading to an improvement in clinical symptoms and resolution of hypoprothrombinemia. She remains recurrence free 5 years from the event. Highlights: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare acquired disorder caused by the formation of prothrombin antibodies in patients with antiphospholipid antibodies. No standard of care exists due to paucity of data; treatment largely relies on supportive transfusions and immunosuppressive therapy. We discuss the case of a 13-year-old girl with LAHPS who was successfully treated with rituximab after proven to be steroid-refractory. LAHPS patients who demonstrate poor response to high-dose corticosteroids can potentially be treated with rituximab with good outcomes. [ABSTRACT FROM AUTHOR]

Management of multiple sclerosis (MS) has shifted from supportive to disease modifying therapy. Considering the increasingly widespread adoption of this approach in managing MS patients, we hypothesized that hospitalizations and surrogates of disease-related complications should have declined during the last decade. Methods. Using the Nationwide Inpatient Sample, hospitalizations for MS and associated secondary diagnoses and procedures as well as discharge status were examined. Time trends were examined for different age cohorts focusing on the period from 2001 to 2010. Results. During the preceding decade, annual hospitalizations for MS increased by 40%, with stable rates in all age groups except geriatric patients, who accounted for a significantly higher fraction of admissions. Nursing home transfers as a surrogate marker of disability remained unchanged for all age groups. Similarly, urinary tract infections, the need for skin debridement, or gastrostomy tube placement did not vary during the decade. Conclusion. During a time of increased adoption of disease modifying therapy, MS-related hospitalizations continued to increase and surrogate measures of disability in admitted patients remained stable, demonstrating the still significant impact of the disease on affected individuals. [ABSTRACT FROM AUTHOR]

Constipation and fecal incontinence are common in patients with neuromuscular diseases. Despite their high prevalence and potential impact on overall quality of life, few studies have addressed anorectal dysfunction in patients with multiple sclerosis (MS). The goal of this paper is to define the prevalence, pathophysiology, impact, and potential treatment of constipation and incontinence in MS patients. Methods. The PubMed database was searched for English language publications between January 1973 and December 2011. Articles were reviewed to assess the definition of the study population, duration, type and severity of MS, sex distribution, prevalence, impact, results of physiologic testing, and treatments. Results. The reported prevalence of constipation and fecal incontinence ranged around 40%. Anorectal dysfunction significantly affected patients with nearly 1 in 6 patients limiting social activities or even quitting work due to symptoms. Caregivers listed toileting as a common and significant burden. The only randomized controlled trial showed a marginal improvement of constipation with abdominal massage. All other reports lacked control interventions and only demonstrated improvement in individuals with milder symptoms. Conclusion. Anorectal dysfunction is a common manifestation in MS that significantly affects quality of life. Therapies are at best moderately effective and often cumbersome, highlighting the need for simple and more helpful interventions. [ABSTRACT FROM AUTHOR]

Constipation and fecal incontinence are common in patients with neuromuscular diseases. Despite their high prevalence and potential impact on overall quality of life, few studies have addressed anorectal dysfunction in patients with multiple sclerosis (MS). The goal of this paper is to define the prevalence, pathophysiology, impact, and potential treatment of constipation and incontinence in MS patients. Methods. The PubMed database was searched for English language publications between January 1973 and December 2011. Articles were reviewed to assess the definition of the study population, duration, type and severity of MS, sex distribution, prevalence, impact, results of physiologic testing, and treatments. Results. The reported prevalence of constipation and fecal incontinence ranged around 40%. Anorectal dysfunction significantly affected patients with nearly 1 in 6 patients limiting social activities or even quitting work due to symptoms. Caregivers listed toileting as a common and significant burden. The only randomized controlled trial showed a marginal improvement of constipation with abdominal massage. All other reports lacked control interventions and only demonstrated improvement in individuals with milder symptoms. Conclusion. Anorectal dysfunction is a common manifestation in MS that significantly affects quality of life. Therapies are at best moderately effective and often cumbersome, highlighting the need for simple and more helpful interventions. [ABSTRACT FROM AUTHOR]