Red Cell Disorders IV Flashcards
Explain paroxysmal nocturnal hemaglobinuria.
- Complement-mediated intravascular RBC lysis (impaired synthesis of GPI (phosphotidylinositol glycan complementation group A)anchor for decay-accelerating factor that protects RBC membrane from complement).
- Acquired mutation in a hematopoietic stem cell.
- Increased incidence of acute leukemias.
- Triad: Coombs ⊝ hemolytic anemia, pancytopenia, and venous thrombosis.
- Labs: CD55/59 ⊝ RBCs on flow cytometry.
- Treatment: eculizumab (terminal complement inhibitor).
What are CD55 and CD59
CD 55 = decay accelerating factorCD59 = C3 convertase inhibitor
Pathology and clinical features of PNH?
Clinical features
* Anemia
* Hematuria –typical nocturnal hematuria in 25% of cases
* Venous thrombosis
* Transformation to acute myeloid leukemia
Pathology
* Normochromic normocytic anemia
* Positive urinary hemoglobin and hemosiderin I
* Iron deficiency
* Flow cytometric evidence of deficiency of CD55 and CD59 on RBCs and leukocytes
What is the MOA of eculizumab?
It blocks the conversion of C5 to C5a
What is potentially curative treatment of PNH?
Hematopoietic stem cell transplant.
Explain direct and indirect Coombs test.
Direct Coombs test—anti-Ig antibody (Coombs reagent) added to patient’s blood. RBCs agglutinate if RBCs are coated with Ig.Indirect Coombs test—normal RBCs added to patient’s serum. If serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent added.
Explain autoimmune hemolytic anemia.
Warm (IgG)—chronic anemia seen in SLE and CLL and with certain drugs (eg, α-methyldopa) (“warm weather is Great”). Cold (IgM and complement)—acute anemia triggered by cold; seen in CLL, Mycoplasma pneumonia infections, and infectious Mononucleosis (“cold weather is MMMiserable”).
- RBC agglutinates,may cause painful, blue fingers and toes with cold exposure.
- Many warm and cold AIHAs are idiopathic in etiology.
- Autoimmune hemolytic anemias are Coombs test +ve.
Treatment of AHA?
Splenectomy, steroids and rituximab.
How can we differentiate warm AHA from cold AHA on peripheral smear?What is the reason behind this difference in pathology?
We see spherocytes in warm AHA, as opposed to cold AHA where we just see agglutinated RBCs.RBCs agglutinate due to pentavalent nature of IgM in cold AHA.
Explain paroxysmal cold hemaglobinuria.
Paroxysmal Cold Hemoglobinuria
* IgG antibodies against RBC membrane P blood group antigen (Donath-Landsteiner antibody)
* Intravascular, extrinsic, acquired
Pathogenesis
* Antibodies bind below 37C in extremities
* IgG coated RBCs fix complement at 37C in central circulation
* Complement coated RBCs lyse in circulation (massive intravascular hemolysis)
* Clearance of hemoglobin in urine (hemoglobinuria)
Clinical features
* Episodic anemia and hemoglobinuria following cold exposure
* Hemolysis only when incubation at 4 C followed by incubation at 37 C
Explain traumatic hemolytic anemia.
Traumatic Hemolytic Anemia
* RBC destruction by trauma
* Intravascular, extrinsic, acquired Etiology and pathogenesis
* Macroangiopathic –in large vessels Mechanical heart valves Microangiopathic –in small capillaries
* Disseminated intravascular coagulation
* Thrombotic thrombocytopenic purpura
* Hemolytic uremic syndrome
An important lab finding here is the presence of schistocytes.
What are the clinical symptoms of polycythemia?
Leads to hyperviscosity syndrome which can cause visual dysfunction such as blurred vision and neurological deficits such as headache, dizziness, deafness, stupor.It can physiologic such as due to lung disease, heart disease, high altitude or it can pathologic such as due to local kidney hypoxia or EPO secreting tumors.
