Table 1.
Causes and/or superimposed factors of hyponatremia in hematological patients.
| Type of Hyponatremia | Causes | Associated Conditions |
|---|---|---|
| Pseudohyponatremia (isotonic hyponatremia: serum osmolality 280–295 mOsm/kg) | Hyperglobulinemia | MM, other paraproteinemias, POEMS syndrome, Castleman’s disease, post-transplant monoclonal gammopathies, NHL, CLL, cryoglobulinemia, cold agglutinin disease, Gaucher disease, HCV or HIV infection, cirrhosis drugs: IVIG, interferon. |
| Hypertriglyceridemia | HLH, uncontrolled diabetes mellitus drugs: L-asparaginase, ATRA. Interferon. |
|
| Hypercholesterolemia | Allogeneic stem cell transplantation, MM, NHL. | |
| Mixed dyslipidemia | Nephrotic syndrome (secondary causes include: HL, monoclonal gammopathy, cryoglobulinemia, POEMS syndrome, leukemia, glycogen storage diseases, sickle cell disease, MDS, GVHD, infections). | |
| Hypertonic hyponatremia: (serum osmolality >295 mOsm/kg) | Hyperglycemia | Diabetes mellitus: preexisting or related to hemochromatosis, thalassemia, and HSCT. Infections. Drugs: glucocorticoids, interferon, tacrolimus, immune checkpoint inhibitors. |
| Hypotonic hyponatremia (serum osmolality <280 mOsm/kg) | Hypervolemic (edematous hyponatremia) | Cirrhosis. Nephrotic syndrome. Renal insufficiency: chemotherapy, contrast media, NSAIDs, infections, post-HSCT, PNH, sickle cell disease and other hemoglobinopathies, MM, lymphomas, paraproteinemia, TTP, HUS, TLS Heart failure: cardiomyopathy due to hemochromatosis, hemoglobinopathies, amyloidosis, or paraproteinemias. Drug-induced heart failure (e.g., anthracyclines, alkylating agents, fluopyrimidines, TKIs), CAR T- cell therapy, thoracic radiation therapy, immune checkpoint inhibitors-induced myocarditis. POEMS syndrome. (Extravascular volume overload is among the minor criteria of the syndrome). |
| Euvolemic hyponatremia | SIADH: lymphomas, paraproteinemias, HLH, post-HSCT, sickle cell disease, porphyria. Pain and nausea. Pulmonary and CNS infections. Drugs: vinca alkaloids, cyclophosphamide, platinum compound drugs, melphalan, busulfan, interferon, bortezomib, TKIs, methotrexate, tacrolimus, cyclosporine A, CAR T-cells therapy, carbamazepine, SSRIs. |
|
| Hypovolemic hyponatremia | Adrenal insufficiency: adrenal metastases or CNS invasion by lymphomas, AML, ALL, hemoglobinopathies. Infections: CNS infections (e.g., tuberculosis), systemic fungal infections. Bilateral cranial radiation therapy. Drugs: steroids, immune checkpoint inhibitors. Extra-renal salt loss: infection mediated. Renal salt loss: myeloproliferative diseases, LAHS, sickle cell disease. Post-HSCT with CNS complications. Drugs: methotrexate, hydroxyurea, platinum compounds, etc. Adrenal hemorrhage: e.g., coagulopathy. |
ALL: acute lymphoblastic leukemia, ATRA: all trans retinoic acid, AML: acute myeloid leukemia, CAR: chimeric antigen receptor, CML: chronic myeloid leukemia, CLL: chronic lymphocytic leukemia, CNS: central nervous system, GVHD: graft versus host disease, HCV: hepatitis C virus, HIV: human immunodeficiency virus, HL: Hodgkin’s lymphoma, HLH: hemophagocytic lymphohistiocytosis, HSCT: hematopoietic stem cell transplantation, HUS: hemolytic uremic syndrome, IVIG: intravenous immunoglobulin, LAHS: lymphoma-associated hemophagocytic syndrome, MDS: myelodysplastic syndrome, MM: multiple myeloma, NHL: non Hodgkin, POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes, SSRIs: selective serotonin reuptake inhibitors.