Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing, humorally-mediated autoimmune disorder characterized by unpredictable episodes of microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with neurologic dysfunction, kidney injury, and fever. Episodes are caused by immune destruction or inhibition of the von Willebrand Factor (vWF) cleaving protease ADAMTS13. Currently, the standard of care is therapeutic plasma exchange (TPE), and most add immunosuppression with corticosteroids - a standard that is unchanged for nearly 30 years. There are multiple strategies for adding corticosteroids to TPE and the limited data available suggests that corticosteroids reduce the duration of ADAMTS13 deficiency in iTTP. Rituximab is also frequently used in the treatment of iTTP and evidence suggests that while it may not reduce the number TPE procedures required to induce remission, it likely increases relapse-free survival. Novel approaches to immunosuppression that have been reported include low-dose rituximab (also currently in clinical trials) and proteasome inhibition. A more targeted approach includes the anti-vWF nanobody, caplacizumab, recently approved for iTTP in Europe and United States, which in two large randomized controlled trials significantly shortened the time to normalization of platelet count, appreciably lowered the 30-day recurrence rate, and decreased the rate of the composite endpoint of death, recurrence, and major thromboembolic events. Recombinant ADAMTS13 has been tested in congenital TTP and could be tested in iTTP as well, along with novel approaches of modifying the enzyme to avoid the immune response or leveraging other vWF cleaving proteases such as plasmin to bypass ADAMTS13. Also, therapies that target preformed antibodies that are currently being tested in other humorally-mediated disorders could cross over to iTTP. Finally, progress has long been hampered in iTTP due to difficulty with accrual and disagreement about trial design. A good surrogate endpoint for relapse-free survival is also needed. Despite these challenges, a new era of precision medicine is likely soon emerging for treatment of iTTP, and with it comes the opportunity to further improve outcomes in this rare and deadly disease.
 ...
PMID:Taking Empiricism out of Immune Thrombotic Thrombocytopenic Purpura: Current and Future Treatment Strategies. 3164 75

This case describes an uncommon acute complication of diffuse thrombotic angiopathy and associated aHUS/TTP in an 11-year-old girl with Danon disease who underwent orthotopic heart transplant. Shortly after transplant, despite an uncomplicated operative course, the patient developed severe kidney injury and progressive altered mental status, culminating in cerebral edema, brain herniation, and death. She had received a single dose of tacrolimus (FK506) and a single dose of antithymocyte globulin. Sources of progressive somnolence, including oversedation from impaired renal clearance of opiates, and severe myopathy as has been previously described in Danon disease, were ruled out, and the patient continued to decline. Initial brain CT scan early after transplant showed no signs of cerebral edema, but repeat CT indicated severe cerebral edema. Based on autopsy, diffuse thrombotic angiopathy, with signs of hemolytic anemia with schistocytes, was likely responsible for her deterioration in the broader condition of aHUS/TTP.
 ...
PMID:Thrombotic microangiopathy following heart transplant in pediatric Danon disease. 3206 23

Thrombotic Microangiopathy (TMA) is a heterogeneous collection of syndromes that encompasses TTP, HUS, and other processes characterized by thrombocytopenia, microangiopathic hemolytic anemia, and, if untreated, organ failure and death. Novel therapies have recently been approved for the management of certain thrombotic microangiopathies, including caplacizumab for immune-mediated TTP, and eculizumab for atypical HUS. These options have complicated the standard workflow, which includes initiation of plasma exchange until ADAMTS13 testing can be resulted. Given such results may take several days, there is indecision regarding the appropriate initial management of TMA. Decisions regarding caplacizumab and eculizumab are complex, and include considerations over costs, side effects, and efficacy. In the following forum, we discuss the current data and pose possible management strategies in patients with TMA before final diagnosis can be obtained.
 ...
PMID:When to consider targeted therapies in thrombotic microangiopathies in the modern era: walking the tightrope between cost, safety, and efficacy. 3221 21


<< Previous 1 2 3 4 5