Symptoms of Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH presents with three cardinal manifestations: complement-mediated hemolytic anemia, bone marrow failure, and thrombosis, with thrombotic complications being the most life-threatening feature, particularly in unusual venous sites like hepatic veins (Budd-Chiari syndrome). 1, 2
Core Clinical Manifestations
Hemolytic Anemia Symptoms
- Chronic intravascular hemolysis causing fatigue, weakness, and exercise intolerance 1, 2
- Hemoglobinuria (dark or cola-colored urine), classically occurring in the morning but can occur at any time despite the "nocturnal" name 2
- Anemia-related symptoms including pallor, dyspnea, and tachycardia 3
- Jaundice from elevated indirect bilirubin due to hemolysis 1
Thrombotic Complications (Affecting up to 40% of Patients)
- Budd-Chiari syndrome (hepatic vein thrombosis) presenting with abdominal pain, abdominal distention, ascites, and progressive liver dysfunction 4, 3
- Cerebral venous thrombosis manifesting as severe headache, confusion, seizures, or focal neurological deficits 4, 3
- Portal vein thrombosis causing abdominal pain and portal hypertension 4
- Mesenteric vein thrombosis presenting with severe abdominal pain 4
- Splenic vein thrombosis 4
- Thrombosis may be the first clinical manifestation of PNH, occurring before hemolytic symptoms are recognized 1
Bone Marrow Failure Manifestations
- Thrombocytopenia causing easy bruising, petechiae, or bleeding 3
- Leukopenia increasing infection risk 2
- Pancytopenia in severe cases 2
Additional Clinical Features
- Severe headaches from smooth muscle dystonia due to nitric oxide depletion 1
- Abdominal pain (both from thrombosis and smooth muscle spasm) 3
- Dysphagia and odynophagia from esophageal spasm 1
- Erectile dysfunction in males from impaired nitric oxide bioavailability 1
- Renal dysfunction from chronic hemosiderosis and thrombotic microangiopathy 1
- Pulmonary hypertension in chronic cases 1
Context-Specific Considerations for This Patient
With Budd-Chiari Syndrome History
- Hepatomegaly (present in 67% of Budd-Chiari patients) 5
- Intractable ascites (present in 83% at diagnosis) 5
- Progressive liver failure with elevated transaminases and bilirubin 5, 3
- Esophageal varices (occur in 58% of Budd-Chiari patients) with risk of variceal bleeding 5
- Splenomegaly from portal hypertension 5
With Positive ANA but Negative Antiphospholipid Antibodies
- The positive ANA suggests possible underlying autoimmune process, but negative antiphospholipid antibodies make antiphospholipid syndrome unlikely as a contributing thrombotic factor 4
- This profile is consistent with PNH as the primary thrombotic driver rather than secondary antiphospholipid syndrome 4
- PNH accounts for approximately 19% of Budd-Chiari syndrome cases 4
Critical Diagnostic Pitfalls
- Do not dismiss thrombosis in unusual sites (hepatic, cerebral, mesenteric veins) as these are hallmark locations for PNH-related thrombosis 4, 1
- Hemoglobinuria may be intermittent or absent in some patients, particularly those with predominantly extravascular hemolysis 2
- Thrombocytopenia and anemia may be masked by hemoconcentration from dehydration or by hypersplenism from portal hypertension in Budd-Chiari patients 4
- Symptoms may worsen with complement triggers including infections, surgery, or pregnancy 1, 2
- Breakthrough hemolysis can occur even on complement inhibitor therapy during strong complement activation events 2