Professional Documents
Culture Documents
Hemoglobinuria
March 8, 2005
Case
43 y old Hispanic man who presented to his PCP for
headaches. Labs revealed a pancytopenia. Referred to
hematologist.
Bone marrow revealed hypocellular marrow (5-10%).
Bone marrow repeated 6 months later showed minimally
hypocellular marrow (30%).
Two years later, he developed dark urine and hemolytic
anemia.
Bone marrow showed hypercellularity (80%) with normoblastic
erythroid hyperplasia. A significant population of myeloid cells
(85%) demonstrated atypically diminished expression of CD16,
as well as an aberrant lack of CD55 and CD59 expression. A
significant population of monocytic cells (83%) lacked
expression of CD14, CD55, and CD59.
Findings consistent with PNH.
History
Investigator Year Contribution
Gull 1866 Described nocturnal and paroxysmal nature of
“intermittent haematinuria” in a young man.
Strubing 1882 Distinguished PNH from paroxysmal cold
haemoglobinuria and march haemoglobinuria.
Attributed the problem to the red cells.
van den Burgh 1911 Red cells lysed in acidified serum. Suggested a role
for complement.
Enneking 1928 Coined the name “paroxysmal nocturnal
haemoglobinuria”.
Marchiafava 1928- Described perpetual hemosiderinemia.
and Micheli 1931 Their names became eponymous for PNH
in Europe.
Ham 1937- Identified the role of complement in lysis of PNH red
1939 cells. Developed the acidified serum test, also called
the Ham test, which is still used to diagnose PNH.
Demonstrated that only a portion of PNH red
cells are abnormally sensitive to complement.
Davitz 1986 Suggests defect in membrane protein anchoring
system responsible
Hall & Rosse 1996 Flow cytometry for the diagnosis of PNH
Paroxysmal Nocturnal
Hemoglobinuria
Described as a clinical entity in 1882.
Acquired disorder of hematopoiesis.
Triad: intravascular hemolysis, thrombosis, and
decreased hematopoiesis.
“Nocturnal” refers to belief that hemolysis is triggered by
acidosis during sleep and activation of complement to
hemolyze abnormal RBCs.
However, hemolysis is shown to occur throughout the
day and is not paroxysmal. Urine concentrated overnight
may cause dramatic change in color.
Paroxysmal Nocturnal
Hemoglobinuria
Due to an acquired hematopoietic stem cell mutation defect.
Somatic mutation (from deletions to point mutations identified)
of the PIGA (phosphotidyl-inositol glycan class A) gene on the
X-chromosome. Namely the transfer of N-acetylglucosamine
to phosphatidylinositol.
IBMTR Data
Saso et al, Br J Haematol, 1999
Results
Sustained engraftment: 77%
Graft failure: 17%
Grade 2-4 acute GVHD: 34%
Chronic GVHD: 33%
Causes of death:
graft failure (7), int. pneumonitis (4), GVHD (3),
infection (3), ARDS (2), hemorrhage (1)
IBMTR Data
Saso et al, Br J Haematol, 1999
Stem Cell Transplantation in
PNH
Matched siblings
IBMTR Data
Saso et al, Br J Haematol, 1999
Stem Cell Transplantation in
PNH
Conclusions from reported series:
BMT may cure 50-60% of selected patients with
HLA-identical siblings
Most patients transplanted have been < 30 years
of age
Regimen related toxicity and GVHD remain
significant hurdles
Role of alternative donor transplants unclear,
though initial reports are not encouraging except
in pediatric population
Alternative Treatment
http://www.herbchina2000.com/therapies/
HPH.shtml
Prognosis Based on
Management
http://www.path.sunysb.edu/labs/pnh/PNH_files/frame.
References
.
Luzzatto L, Araten DJ Allogeneic bone marrow transplantation for
paroxysmal nocturnal hemoglobinuria.
Haematologica. 2000 Jan;85(1):1-2
Research