1. Thrombocytopenia due to
Paroxysmal Nocturnal
Hemoglobinuria

2. • Paroxysmal nocturnal hemoglobinuria (Marchiafava-
Micheli syndrome) is a rare, acquired, potentially life-
threatening disease of the blood characterized by
complement-induced intravascular hemolytic
anemia (anemia due to destruction of red blood cells in
the bloodstream), red urine (due to the appearance
of hemoglobin in the urine) and thrombosis.
• It is the only hemolytic anemia caused by an intrinsic
defect in the cell. It may develop on its own ("primary
PNH") or in the context of other bone marrow disorders
such as aplastic anemia ("secondary PNH").

3. • Thrombocytopenia (or thrombopenia) is a relative
decrease of platelets in blood.
• A normal human platelet count ranges from 150,000 to
450,000 platelets per microlitre of blood.
• One common definition of thrombocytopenia is a
platelet count below 50,000 per microlitre.

4. EPIDEMIOLOGY
• PNH is rare, with an annual rate of 1-2 cases per
million. Many cases develop in people who have
previously been diagnosed with aplastic anemia
or myelodysplastic syndrome. The fact that PNH
develops in MDS also explains why there appears to be
a higher rate of leukemia in PNH, as MDS can
sometimes transform into leukemia.
• 25% of female cases of PNH are discovered during
pregnancy. This group has a high rate of thrombosis,
and the risk of death of both mother and child are
significantly increased (20% and 8% respectively).

5. • Forty percent of patients develop thrombocytopenia.
This is the main cause of severe complications and death
in PNH. These may develop in common sites (deep vein
thrombosis of the leg veins and resultant pulmonary
embolism when these clots break off and enter the
lungs), but, in PNH, blood clots may also form in more
unusual sites: the hepatic vein(causing Budd-Chiari
syndrome), the portal vein of the liver (causing portal
vein thrombosis), the superior or inferior mesenteric
vein (causing mesenteric ischemia), and veins of
the skin. Cerebral venous thrombosis, an uncommon
form of stroke, is more common in PNH.

6. Etiology
• PNH is an acquired genetic mutation resulting in a
membrane defect in stem cells and their progeny,
including RBCs, WBCs, and platelets. It results in unusual
sensitivity to normal C3 in the plasma, leading to ongoing
intravascular hemolysis of RBCs and diminished marrow
production of WBCs and platelets.

7. • Persons with this disease have blood cells that are
missing a gene called PIG-A. This gene allows a substance
called glycosyl-phosphatidylinositol (GPI) to help certain
proteins stick to cells.
• Without PIG-A, important proteins cannot connect to the
cell surface and protect the cell from substances in the
blood called complement. As a result, red blood cells
break down too early. The red cells leak hemoglobin into
the blood, which can pass into the urine. This can happen
at any time, but is more likely to occur during the night
or early morning.

10. Thrombocytopenia is often caused by:
• Low production of platelets in the bone marrow
• Increased breakdown of platelets in the bloodstream
(called intravascular)
• Increased breakdown of platelets in the spleen or liver
(called extravascular)

11. Disorders that involve low production in the bone marrow
include:
• Aplastic anemia
• Cancer in the bone marrow
• Cirrhosis (chronic liver disease)
• Folate deficiency
• Infections in the bone marrow (very rare)
• Myelodysplasia
• Vitamin B12 deficiency

13. Signs and symptoms
A person with PNH :
• Abdominal pain
• Back pain
• Blood clots -- may form in some people
• Dark urine -- comes and goes
• Easy bruising or bleeding
• Headache
• Shortness of breath

14. A person with thrombocytopenia:
• Bruising
• Nosebleeds or bleeding in the mouth and gums
• Rash

17. TESTS
• Flow cytometry for CD55 and CD59 on both WBCs and RBCs
• DAT(direct antiglobulin test)
• Sucrose lysis test
• Complete blood count (CBC)
• Coombs' test
• Flow cytometry to measure certain proteins
• Ham's (acid hemolysin) test
• Serum hemoglobin and haptoglobin
• Sucrose hemolysis test
• Urinalysis
• Urine hemosiderin

18. TREATMENT
• Supportive measures
• Possibly monoclonal antibody
• Allogeneic bone marrow transplantation is the only curative
therapy
• Steroids or other drugs that suppress the immune system
may help slow the break down of red blood cells.
• Blood transfusions
• Soliris (eculizumab) is a drug used to treat PNH. It blocks
the breakdown of red blood cells.
• Bone marrow transplantation can cure this disease.
• All patients with PNH should receive vaccinations against
certain types of bacteria to prevent infection.