Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder that results in the production of defective red blood cells. Premature destruction of the blood cells via complement activation occurs in patients with PNH, which may result in the presence of hemoglobin in the urine.1

The symptoms experienced by patients with PNH derive from the defective blood cells, the associated chronic hemolysis, and the low production of blood cells from the bone marrow. All patients with PNH present with bone marrow dysfunction, and the severity of the reported symptoms may vary according to the severity of this dysfunction.1 

Patients with PNH can present with other disorders that may be related to PNH, such as acquired aplastic anemia and myelodysplasia. The connection between both diseases and PNH remains uncertain, but PNH is most likely derived from autoimmune bone marrow failure, which is the main cause of acquired aplastic anemia and the cause of some cases of myelodysplasia.1 Patients with PNH may present with comorbidities of acquired aplastic anemia or a myelodysplastic syndrome.1 In a recent study, the presence of PNH clones was shown in a study population with aplastic anemia and myelodysplastic syndromes.2

Acquired Aplastic Anemia

Acquired aplastic anemia is a rare blood disease that results from failure of the bone marrow to produce blood cells. Because there are virtually no hematopoietic stem cells present in the bone marrow, it causes very low levels of red blood cells, white blood cells, and platelets (pancytopenia). Most cases of acquired aplastic anemia originate from autoimmunity.3

The most common symptoms of acquired aplastic anemia are consequences of the insufficient production of blood cells by the bone marrow, including fatigue, weakness, dizziness, headaches, excessive bleeding, and recurrent infections.1

Patients with acquired aplastic anemia can present with PNH, as it is believed that both the autoimmunity and bone marrow failure scenarios observed predispose patients to developing PNH.3 Having aplastic anemia is a known risk factor for the development of PNH, with more than 10% of patients with aplastic anemia developing PNH.4

Read more about PNH risk factors

Myelodysplastic Syndromes

Myelodysplastic syndromes (or myelodysplasias) represent a group of blood diseases derived from an incorrect development of blood cells in the bone marrow. The three blood cell types may be affected in these syndromes, therefore patients with myelodysplasia typically have a low blood count. Patients experience symptoms such as fatigue, weakness, dizziness, headaches, bleeding, and bruising.5

The causes underlying myelodysplasia are not fully understood but most commonly include somatic genetic abnormalities in the cells that are present in the bone marrow.1 Contrary to acquired aplastic anemia in which patients present with almost no blood-producing cells in the bone marrow, in patients with myelodysplasia, the bone marrow has cells, but they are defective.5 On average, 2 in every 100 individuals with PNH develop a myelodysplastic syndrome.4

Read more about PNH pathophysiology

Acute Leukemia

In rare cases, PNH may develop into acute leukemia. However, the mechanism underlying this association is still to be determined.1 Some patients with myelodysplasia can also present with this disease.3

Acute leukemia is a form of cancer marked by the accumulation of immature blood cells, which affects the bone marrow and the blood. Acute leukemia can result in pancytopenia or leukocytosis.1

Read more about PNH diagnosis

Budd-Chiari Syndrome

Budd-Chiari Syndrome (BCS) is a rare disease characterized by the obstruction of the hepatic venous outflow tract. PNH has been related to BCS as more than one-third of the thrombotic events observed in patients with PNH are reported in the hepatic veins or inferior vena cava. Patients with PNH are, therefore, at a higher risk of developing BCS.6

Symptoms associated with BCS include pain in the upper right abdomen, hepatomegaly, and ascites.1

Read more about PNH signs and symptoms


1. Paroxysmal nocturnal hemoglobinuria. National Organization for Rare Disorders (NORD). Accessed November 29, 2022.

2. Fattizzo B, Ireland R, Dunlop A, et al. Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia. Leukemia. 2021;35(11):3223-3231. doi:10.1038/s41375-021-01190-9

3. Acquired aplastic anemia. National Organization for Rare Disorders (NORD). Accessed November 29, 2022.

4. PNH – paroxysmal nocturnal hemoglobinuria. The Aplastic Anemia and MDS International Foundation. Accessed November 29, 2022.

5. Myelodysplastic syndromes. National Organization for Rare Disorders (NORD). Accessed November 29, 2022.

6. Hoekstra J, Leebeek FWG, Plessier A, et al; European Network for Vascular Disorders of the Liver. Paroxysmal nocturnal hemoglobinuria in Budd-Chiari syndrome: findings from a cohort study. J Hepatol. 2009;51(4):696-706. doi:10.1016/j.jhep.2009.06.019

Reviewed by Harshi Dhingra, MD, on 11/30/2022.