Presenter: Dr.

Parshika
Moderator : Dr. P.S singh
Acquired hemolytic anemias

1. Non immune 2. Immune hemolytic anemia

 Mechanical destruction of RBCs  Warm antibody AIHA

 Infection  Paroxysmal cold hemoglobinura

 Drugs  Cold agglutinin disease

 PNH
IMMUNE HEMOLYTIC ANEMIA
 Two distinct mechanisms- innocent bystander mechanism or
true antibodies against RBC surface antigen.

 Onset-abrupt , Hb drop within days to as low as 4 g/dl.

 Triad of HA makes the suspicion of AIHA high.

 Direct antiglobulin test (Direct Coombs test) -broad spectrum”

reagent is used, can detect both immunoglobulins (Ig) as well
as complement (C) components (usually C3 fragments) .
 Warm antibody AIHA
 Most common type of AIHA , can be Idiopathic or secondary.

 Autoantibody reacts best at 37degree celsius.

 Mechanism- RBCs coated with autoantibodies will be recognised by

macrophages triggering erythro-phagocytosis in RES.(extra vascular hemolysis).

 If IgM antibody then antigen-Ab complex will activate complement leading to

formation of large amount of MAC and then destruction of RBCs
directly(intravascular hemolysis).

 Reticulocytosis.

 Can be associated with Autoimmune thrombocytopenia(evan’s syndrome).

 Treatment
• Severe acute AIHA- medical emergency.

 Transfusion of RBCs.

 1mg /kg predisolone

 Rituximab-100mg/week x4

 Splenectomy- relapse cases or refractory to medical treatment.

 Very rare severe refractory cases- myelo immuno-ablative

chemotherapy f/b rescue with either autologous or allogenic
hematopoitic stem cell transplatation.
 Paroxysmal cold hemoglobinuria (PCH)
 Rare AIHA , Mostly in children.

 Triggers- viral infection.

 Involvement of Donath –Landsteiner antibody.

 This Ab has anti –P specificity and binds to red cells only at a low temp (
optimally at 4 degree celsius) and if temp. is shifted to 37, lysis of RBCs
will occur in the presence of compliment.

 Blood transfusion

 Recovery is the rule.

 Cold Agglutinin Disease
 Affects elderly , Chronic condition.

 Auto antibodies react poorly or not at all to RBCs at 37 degree temp.

 Hemolysis is prominent on cold exposure.

 The antibody is usually IgM and has anti –I specificity.

 Ab is produced by an expanded B lymphocyte(low grade mature B cell

lymphoma).

 Plasma protein electrophoresis- spike because of such a high titre of antibody.

 It is monoclonal gammopathy and must be regarded as a form of waldenstrom

macroglobinemia.
 Treatment

 Mild disease-Avoid cold exposure.

 Severe disease- plasma exchange

 Rituximab- Ist line treatment. Can be repeated in relapse.

 Rituximab- fludarabine combination makes remission durable.

 Blood transfusion as a supportive treatment.

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
 PNH
 An acquired chronic HA with persistent intravascular
hemolysis with occasional or frequent recurrent exacerbations.

 M=F

 Never congenital but can be present in small children or in late

seventies. Although most patients are young adults.

 Triad- hemolysis, Pancytopenia ,Thrombosis.

 Clinical Features

 Haematuria - passing blood instead of urine.

 Anemia.

 Associated with neutropenia, thrombocytopenia, or both, thus

signaling an element of bone marrow failure.
.
 PATHOPHYSIOLOGY

 Hyper susceptibility to C due to deficiency in the red cell

membrane of several protective proteins.

 Shortage of a unique glycolipid molecule, GPI which, through

a peptide bond, anchors these proteins to the surface membrane
of cells.

 Shortage of GPI is due to a somatic mutation in an X-linked

gene, called PIGA, required for an early step in GPI
biosynthesis.
 Diagnosis
 Anemia- usually normo-macrocytic.

 Anemia may become microcytic if the patient is allowed to become iron-

deficient as a result of chronic iron loss through hemoglobinuria.

 Unconjugated bilirubin is mildly or moderately elevated.

 LDH is typically markedly elevated (values in the thousands are common).

 Haptoglobin is usually undetectable.

 All of these findings make the diagnosis of HA compelling

 Urine examination

 Hemoglobinuria may be
overt in a random urine
sample.

 Serial urine samples

because hemoglobinuria
can vary dramatically
from day to day and
even from hour to hour.
Bone Marrow Examination

 Usually cellular, with marked to massive erythroid hyperplasia,

often with mild to moderate dyserythropoietic features

 At some stage of the disease, the marrow may become

hypocellular or even frankly aplastic
.  The sucrose hemolysis test –unreliable.

 Acidified serum (Ham) test is highly reliable but is carried out

only in a few labs.

 Gold standard today is flow cytometry, which can be carried

out on granulocytes as well as on red cells, and has a very high
sensitivity.
 TREATMENT
 Continued supportive treatment

 Allogeneic BMT - definitive cure at the cost of non-negligible risks

 Eculizumab - binds to the complement component C5 .

administered intravenously every 14 days.

 Folic acid supplements (at least 3 mg/d) are mandatory.

 Serum iron should be checked periodically and iron supplements

should be administered as appropriate
 Long-term glucocorticoids - not indicated because there is no evidence that they
.
have any effect on chronic hemolysis.

 Venous thrombosis or who has a genetically determined thrombophilic state in

addition to PNH should be on regular anticoagulant prophylaxis , treatment with
tissue plasminogen activator may be indicated.

 BMT for young patient with severe PNH and for patients with PNH-AA
syndrome, since eculizumab has no effect on BMF.

 Immunosuppressive treatment with antithymocyte globulin and cyclosporine A.

 Hemolytic anemia due to drugs
 Chemicals with oxidative potential
Examples- hyperbaric oxygen (or 100% oxygen), nitrates,
chlorates, methylene blue, dapsone, cisplatin, and numerous
aromatic (cyclic) compounds.

 Chemicals may be hemolytic through nonoxidative, with unknown

mechanisms. Examples- arsine, stibine, copper, and lead.

 Severe intravascular hemolysis caused by the venom of certain snakes

(cobras and vipers)
 spider bites.
Mechanism

(1) A drug can behave as a hapten and induce antibody

production. Eg penicilllin.

(2) A drug can trigger, perhaps through mimicry, the production

of an antibody against a red cell antigen. Eg methyldopa.
 Other Causes
Mechanical destruction of RBCs
 Acute and self-inflicted- march hemoglobinuria. Eg. marathon
runner
 Chronic and iatrogenic ( microangiopathic hemolytic anemia). Eg.
patients with prosthetic heart valves, especially when paraprosthetic
regurgitation is present.

Infections –
 Malaria
 HUS – due to Shiga toxin–producing E. coli O157:H7.
 Clostridium perfringens sepsis- due to toxin with lecithinase activity.
Eg. following open wounds, septic abortion, or as a disastrous
accident due to a contaminated blood unit. Rarely, and if at all in
children, HA is seen with sepsis or endocarditis from a variety of
organisms.