[MIM 300 818]

(Marchiafava-Micheli disease)

Hematopoietic stem cell acquired clonal disorder characterized by corpuscular hemolytic anemia, bone marrow aplasia and frequent thromboses. The disease can occur at all ages but it particularly affects young adults; 15% of cases are younger than 16 years. Prevalence: about 1: 500 000. It is caused by somatic mutations in the PIG-A gene, located on the X chromosome, . The PIG-A gene produces a protein required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. The mutation occurs in one hematopoietic stem cells, which then multiplies and extends (clonal disorder). It causes a deficit (total or partial) in all (especially CD55 and CD59) proteins that normally attach to the cell membrane by binding to the GPI 'anchors'.

Variable clinical manifestations: hemolytic anemia, thrombosis (most frequently venous thrombosis) of the medium and large blood vessels (hepatic vein [Budd-Chiari syndrome, portal vein], abdominal, cerebral, pulmonary, and cutaneous blood vessels. Moderate to severe bone marrow dysfunction may cause pancytopenia. Hemoglobinuria can result in dark urine during the night or in the morning and, in some cases, in kidney failure.

It is a chronic disease, with acute hemolytic episodes. Hemolytic crisis can be triggered by factors such as vaccination, surgery,  antibiotics and infections. Bone marrow dysfunction can initially or secondarily complicate the disease (20% of cases). The prognosis depends on the frequency and severity of hemolytic attacks, thrombosis and associated bone marrow dysfunction. Median survival is 10.3 years. Death may be caused by thrombosis,  bleeding or infections consecutive to bone marrow dysfunction.

Treatment is primarily symptomatic: transfusion, erythropoietin, steroids, and anticoagulants therapy Patients often receive supplemental iron and folic acid. The orphan drug eculizumab (monoclonal antibody that inhibits the complement fraction 5 (C5) and so thus the inflammatory process) has been approved by the U.S. FDA for PNH in 2007. It reduces hemolysis, decreases the need for transfusions, fatigue, the incidence of thrombosis and limits kidney failure. This treatment increases the risk of meningococcal meningitis and thus requires prior vaccination. Bone marrow transplantation is the only curative treatment of PNH.

Anesthetic implications: 

check complete blood count (and the platelets count in case of treatment by eculizumab); increased thromboembolic risk; increased infectious risk. Washing of packed red blood cells units is no more recommended  before transfusion, but a case report of hemolysis of the red blood cells of washed recovered blood during surgery has been published for a patient not treated with eculizumab.

References : 

-        Kathirvel S, Prakash A, Lokesh BN, Sujatha P.
The anesthetic management of a patient with paroxysmal nocturnal hemoglobinuria.
Anesth Analg 2000; 91: 1029-31.

-        Allen TK, George RB, Olufolabi AJ, James AH, Muir HA, Habib AS. 
The management of caesarean delivery in a parturient with paroxysmal nocturnal hemoglobinuria complicated by severe eclampsia. 
Can J Anesth 2007, 54:646-651

-         Vargas M, Lallo C, Marra An Servillo G. 
Anaesthesia and orphan disease : laparoscopic cholecystectomy with paroxysmal nocturnal haemoglobinuria and human mAb therapy. 
Eur J Anaesthesiol 2013 ; 30 :770-2. 

-        Kawamoto Y, Nishihara T, Watanabe A, Nakanishi K et al.
Hemolytic reaction in the washed salvaged blood of a patient with paroxysmal nocturnal hemoglobinuria.
BMC Anesthesiology 2019; 19: 83

Updated: June 2019