D59.5 Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]

Name of the Condition

• Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli] (ICD-10 Code: D59.5)

Summary

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by the premature destruction of red blood cells, leading to hemolytic anemia, hemoglobinuria, and an increased risk of thrombosis. The condition arises from a somatic mutation in hematopoietic stem cells, resulting in the absence of protective proteins on cell surfaces. This makes red blood cells, white blood cells, and platelets susceptible to complement-mediated destruction, causing clinical manifestations such as fatigue, abdominal pain, and dark urine.

Causes

PNH is caused by a somatic mutation in the PIGA gene, which impairs the synthesis of glycosylphosphatidylinositol (GPI) anchors. These anchors are essential for attaching protective proteins (e.g., CD55 and CD59) to cell surfaces. Without these proteins, cells become vulnerable to complement activation, leading to hemolysis. The mutation occurs spontaneously in hematopoietic stem cells and is not inherited.

Risk Factors

• Underlying bone marrow disorders (e.g., aplastic anemia, myelodysplastic syndromes)
• Prior history of aplastic anemia or myelodysplastic syndromes
• Age (most commonly diagnosed in young to middle-aged adults)
• Ethnicity (higher prevalence in certain populations, though rare overall)

Symptoms

• Dark or red urine (hemoglobinuria), especially in the morning
• Fatigue and weakness due to anemia
• Abdominal pain or discomfort
• Shortness of breath
• Headaches or dizziness
• Unexplained blood clots (thrombosis)
• Pale or yellowish skin (jaundice)
• Increased susceptibility to infections

Diagnosis

Diagnosis involves laboratory tests to detect the absence of GPI-anchored proteins on blood cells. Flow cytometry is the primary method, analyzing red blood cells, white blood cells, or platelets for reduced expression of CD55 or CD59. Additional tests include a complete blood count (CBC) to assess anemia, reticulocyte count, lactate dehydrogenase (LDH) levels, and urine tests for hemoglobin. Bone marrow biopsy may be performed if underlying disorders are suspected.

Treatment Options

• Eculizumab or ravulizumab (complement inhibitors) to reduce hemolysis
• Supportive care, including blood transfusions for severe anemia
• Anticoagulation therapy to prevent thrombosis
• Stem cell transplantation for eligible patients
• Management of underlying bone marrow disorders, if present

Prognosis and Follow-Up

Prognosis has improved with targeted therapies, but PNH remains a chronic condition requiring lifelong monitoring. Regular follow-up includes blood tests to assess hemolysis, anemia, and organ function. Patients are at risk for thrombotic events and may need ongoing anticoagulation. Early detection and treatment of complications are critical to improving outcomes.

Complications

• Thrombosis (blood clots in veins or arteries)
• Kidney failure due to chronic hemolysis
• Pulmonary hypertension
• Increased risk of infections
• Iron deficiency from chronic blood loss
• Progression to bone marrow failure in some cases

Lifestyle & Prevention

• Stay hydrated to reduce hemoglobinuria episodes
• Avoid triggers like infections or certain medications that may exacerbate hemolysis
• Maintain a balanced diet to support overall health
• Engage in regular, moderate exercise to manage fatigue
• Avoid smoking, which may increase thrombosis risk

When to Seek Professional Help

Seek immediate medical attention for:

• Sudden severe abdominal pain or chest pain
• Shortness of breath or dizziness
• Dark urine persisting for more than a day
• Signs of infection (fever, chills)
• Unexplained swelling or pain in limbs (possible thrombosis)

Tips for Medical Coders

Document the presence of hemolysis, hemoglobinuria, thrombosis, or associated bone marrow disorders to support the diagnosis. Include details on complement inhibitor therapy or transfusion history if applicable. Ensure the mutation or flow cytometry results are noted if available, as these confirm the acquired nature of the condition. Avoid coding for inherited hemolytic anemias, as PNH is acquired.