Chiefs’ Inquiry Corner – 1/24/22

January 24, 2022

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 Thrombocytopenia is commonly observed as a complication of underlying liver disease, typically defined as either moderate (<100K) or severe (<50K). The pathophysiology of thrombocytopenia is actually quite multifactorial – while we often discuss the role of splenic sequestration, other factors include reduced activity of the hematopoietic growth factor thrombopoietin (TPO) as well as potential bone marrow suppression by chronic hepatitis infections or chronic alcohol use. Of these factors, platelet sequestration and decreased TPO production by the liver predominate. While platelet sequestration is seen in patients with cirrhosis-induced portal hypertension and congestive splenomegaly, we do see thrombocytopenia in patients without splenomegaly. In those cases, it is likely a combination of decreased TPO production (plus some of the other potential factors).

References: Management of thrombocytopenia due to liver cirrhosis: A review
  Chronic myeloid leukemia (CML) is a myeloproliferative disorder with the classic Philadelphia chromosome translocation between chromosomes 9 and 22. CML usually presents in a chronic phase with characteristic clonal expansion of mature myeloid cells. All untreated patients will eventually progress to a blast phase; however, recent treatment advances in tyrosine kinase inhibitors has allowed the life expectancy for patients diagnosed with CML to reach that of the general healthy population. Prior to the use of agents such as imatinib, rates of progression were estimated around 1.5-3.5% yearly, now down to an estimated 0.3-2% annual risk. Diagnosis in an advanced or accelerated phase is rare. In contrast, the myelodysplastic syndromes (MDS) are characterized by one or more cytopenias and abnormal cellular maturation and have numerous subtypes. These patients are at risk for transformation to AML, but the incidence varies widely across the subtypes. For this reason, low risk patients are managed with supportive therapy, while high risk patients are managed with more targeted therapies depending on their age and underlying health status.

References: Management of Chronic Myeloid Leukemia in Advanced Phase
 IgA nephropathy is one of the most common glomerulonephritides. It is mediated by the deposition of IgA1 immune complexes. Glomerular IgA1 deposits trigger the local production of cytokines and growth factors, leading to the activation of mesangial cells and the complement system. While it is frequently asymptomatic with a benign course, roughly 5-10% of patients can present as rapidly progressive crescentic glomerulonephritis. Current management of IgA nephropathy consists of management of hypertension and proteinuria using ACE inhibitors or angiotensin receptor blockers, and management of dyslipidemia using HMG-CoA inhibitors and omega-3 fatty acids. The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 guidelines also suggest the use of glucocorticoids and cyclophosphamide for the treatment of rapidly progressive IgA nephropathy. According to the 2019 guidelines from the American Society for Apheresis, the use of plasmapheresis in patients with rapidly progressive IgA nephropathy may be attempted, but this is a grade 2B recommendation based on the limited available data (weak recommendation, best actions may differ depending on circumstances). The rationale for plasmapheresis in IgA nephropathy is for the removal of circulating immune complexes and complement products. In one study including 12 patients with rapidly progressive IgA nephropathy compared with 12 historical controls, Xie et al. showed that the use of plasmapheresis as adjunctive therapy to routine steroid and cyclophosphamide was associated with decreased proteinuria, decreased serum creatinine levels, decreased dialysis dependency, decreased plasma and urinary complement product levels, and higher kidney survival. The efficacy and safety of plasmapheresis in IgA nephropathy warrants further assessment in large randomized controlled trials.

References: Plasma Exchange as an Adjunctive Therapy for Crescentic IgA Nephropathy