Thrombosis in Paroxysmal Nocturnal Hemoglobinuria (PNH): From Pathogenesis to Treatment

Paroxysmal Nocturnal Hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH) constitutes a rare bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… syndrome characterized by hemolytic anemia hemolytic anemia: Anemia due primarily to the excessive hemolysis or destruction of red blood cells , thrombotic events (TEs), and bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. aplasia of variable degrees. Thrombosis Thrombosis: (throm-BOE-suss) A blood clot (thrombus) that develops and attaches to a blood vessel. is one of the major clinical manifestations of the disease, affecting up to 40% of individuals with PNH. Venous thrombosis Venous thrombosis: Blood clot in a vein is more prevalent, affecting mainly unusual sites, such as intrabdominal and hepatic veins. TEs might be the first clinical manifestation of PNH. Complement activation, endothelial dysfunction, hemolysis hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. , impaired bioavailability of nitric oxide nitric oxide: (NIGH-trik OK-side) A molecule that helps muscles stay smooth and relaxed. A shortage of nitric oxide can occur in paroxysmal nocturnal hemoglobinuria (PNH), causing muscle spasms in certain parts of the body. , and activation of platelets and neutrophils are implicated in the pathogenesis of TEs in PNH patients. Moreover, a vicious cycle involving the coagulation cascade, complement system complement system: A group of proteins that move freely in the bloodstream. These proteins support (complement) the work of white blood cells by fighting infections. , and inflammation cytokines, such as interleukin-6, is established. Complement inhibitors, such as eculizumab eculizumab: Eculizumab (Soliris ®) is given as an IV into a vein at the doctor’s office or at a special center. The procedure usually takes about 35 minutes. You will probably get an IV once a week for the first 4 weeks. Starting in the 5th week, you will get a slightly higher dose of Soliris every 2 weeks. … and ravulizumab (C5 inhibitors), have revolutionized the care of patients with PNH. C5 inhibitors should be initiated in patients with PNH and thrombosis, while they constitute a great prophylactic prophylactic: Something that prevents or protects. Blood thinners may be given as a prophylactic to prevent blood clots in high risk patients. measure for TEs in those individuals. Anticoagulants, such as warfarin warfarin: It is used to prevent blood clots from forming. Warfarin is a tablet that is taken by mouth. and low-molecular-weight heparin heparin: Heparin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood. Heparin is also used to stop the growth of clots that have already formed in the blood vessels, but it cannot be used to decrease the size of clots that have… , and, in selected cases, direct oral anticoagulants (DOACs) should be used in combination with C5 inhibitors in patients who develop TEs. Novel complement inhibitors are considered an alternative treatment option, especially for those who develop extravascular or breakthrough hemolysis when terminal inhibitors are administered.