Acquired Haemolytic anaemia
http://www.usmlemcq.com/
Acquired Haemolytic Anaemia
Immune
1.Autoimmune
*warm Ab
*cold Ab
Non Immune
1.Mechanical
*March haemoglobinuria
*Prosthetic heart valves
2.Alloimmune
*Transfusion rn
*HDN
3.Infections
*Malaria
*Clostridium welchii
4.Burns
5.Drugs
*Dapsone
6.PNH
2.MAHA
http://www.usmlemcq.com/
18 year old girl
C/O - fever, yellow discolouration
of eyes and abdominal pain – 2 weeks
O/E – Pale ++ , Icteric +, Spleen – 1cm
1. How would you confirm haemolysis?
2. What are the possible causes?
http://www.usmlemcq.com/
Warm autoimmune haemolytic anaemia

Antibodies optimally active at 370. IgG

Causes
*Idiopathic
*secondary
SLE
CLL
Lymphomas
Drugs- Methyl dopa
http://www.usmlemcq.com/
Warm autoimmune haemolytic anaemia cont.
Pathogenesis
 IgG antibodies are present on the red cells, some of
them also bind complement(C3)

Red cells are destroyed mainly in the RE system
(preferentially spleen)
http://www.usmlemcq.com/
Warm autoimmune haemolytic anaemia cont.
Clinical features
 Haemolytic anaemia
 Jaundice
 Splenomegaly
Investigations
 Reticulocytosis
 Spherocytes
 Increased serum bilirubin
 Positive direct coomb test
http://www.usmlemcq.com/
Warm autoimmune haemolytic anaemia cont.
Treatment
 Corticosteroids

Splenectomy

Immunosuppresives- Azathioprine

Folic acid

Treat underlying cause
http://www.usmlemcq.com/
Cold autoimmune haemolytic anaemia

Auto antibodies (IgM) that react best at temp. <370
(0-40)
Causes
*Idiopathic (CHAD)
*secondary
Mycoplasma
Infectious mononucleosis
Lymphoma
SLE
http://www.usmlemcq.com/
Cold autoimmune haemolytic anaemia cont.
Investigations
 Anaemia with
red cell agglutinates
 Macrocytosis
 Reticulocytosis
 Positive direct coomb test
 Features of IV haemolysis



http://www.usmlemcq.com/
RBC – 1.1x1012/l
HB - 6.2g/dl
MCV – 112fl
Cold autoimmune haemolytic anaemia cont.
Clinical features
 Some have acute IV haemolysis & Hburia in cold
weather but maintain a normal Hb in warm weather

Others have a compensated chronic haemolysis with a
mild to moderate reduction of Hb.

Acrocyanosis, Raynauds phenomenon due to
agglutinates.

Spleen may not be enlarged
http://www.usmlemcq.com/
Cold autoimmune haemolytic anaemia cont.
Investigations





Anaemia with red cell agglutinates
Macrocytosis
Reticulocytosis
Positive direct coomb test
Features of IV haemolysis
http://www.usmlemcq.com/
Cold autoimmune haemolytic anaemia cont.
Treatment






Avoid cold
May need blood transfusions
Rituximab (monoclonal anti CD20)
Chlorambucil
Plasmapheresis has been used
Corticosteroids and splenectomy are rarely of any
benefit
http://www.usmlemcq.com/
Allo immune
http://www.usmlemcq.com/
ABO & Rh incompatibilty

Haemolytic transfusion reactions may be immediate or
delayed.

Immediate life threatening reactions associated with
massive IV haemolysis is seen with complement
activating antibodies of IgM & IgG classes(ABO
antibodies)

Severity of the reaction depends on the recipient’s titre of
antibody
http://www.usmlemcq.com/
ABO & Rh incompatibilty cont.

Extra vascular haemolytic transfusion reactions are seen
with the immune antibodies( IgG, unable to bind
complement).

The only feature may be unexplained anaemia with
jaundice
http://www.usmlemcq.com/
Non immune causes of haemolysis
Mechanical causes of haemolysis

Red cells may be injured by excess physical trauma as they
circulate through the vascular system.
http://www.usmlemcq.com/
Mechanical haemolytic anaemia


Cardiac – Occasional complication of open heart surgical
procedures eg. valve prostheses. In severe cases marked
anaemia with intravascular haemolysis.
March haemoglobinuria – Hbnaemia & Hburia following
strenuous exercise in healthy young adult males.
Traumatic effect on the blood within vessels of sole.
soldiers, athletes, karatekas.
http://www.usmlemcq.com/
Microangiopathic haemolytic anaemia

Mechanical haemolytic anaemia in which the red cell
fragmentation is due to contact between red cells &
abnormal intima of partly thrombosed, narrowed, or
necrotic small vessels.
http://www.usmlemcq.com/
Microangiopathic haemolytic anaemia

With associated thrombocytopaenia
1.Disseminated intravascular coagulation
2.Haemolytic uraemic syndrome
3.Thrombotic thrombocytopaenic purpura
4. HELLP syndrome
http://www.usmlemcq.com/
DIC

Widespread intra vascular coagulation induced by pro
coagulants (that overcome the natural anti coagulant
mechanisms), resulting in the formation of thrombin.

These pro coagulants may be produced in the blood or
introduced from out side the circulatory system egsnake venom

This results inFormation of micro thrombi
Ischemia
Consumption of platelets &
clotting factors
Bleeding
http://www.usmlemcq.com/
DIC cont.

Causes
*Trauma
*Cancers
*Bacteraemia
*Severe Haemorrhage
*Obstetric & surgical events
http://www.usmlemcq.com/
DIC cont.
Investigations
 Fragmented red cells

Low platelet count

Prolongation of PT, aPTT, TT, Low fibrinogen

Elevated FDP, D dimers
http://www.usmlemcq.com/
HUS-TTP

Initially described as two distinct entities but thereafter
thought to be two ends of the same spectrum. ? Two
distinct entities

Formation of platelet thrombi (hyaline thrombi) in
terminal arterioles & capillaries.

Microangiopathic haemolytic anaemia with
Thrombocytopaenia
http://www.usmlemcq.com/
HUS-TTP
Clinical features

Fever

Neurological symptoms

Renal failure
+




MAHA
Thrombocytopenia
Coagulation screen – NORMAL
LDH - high
http://www.usmlemcq.com/
Causes of HUS


E.Coli o157 toxin
Shigella dysenteriae
http://www.usmlemcq.com/
TTP
Pathogenesis

Presence of abnormal vwf (platelet adhesion)

Deficiency of vwf cleaving proteases ADAMTS-13

Increase in vwf activity, platelet aggregation

Microthrombi formation
http://www.usmlemcq.com/
Causes of TTP

Inherited deficiency of ADAMTS 13
• Present in neonatal period

Acquired deficiency of ADAMTS 13
• Drugs- clopidogrel, ticlopidine, ciclosporine
• Post transplant
• Pregnancy
• SLE
http://www.usmlemcq.com/
TTP
Treatment
 Plasma exchange

FFP/CPP

Steroids / immunosuppresion

Platelets not given

Rituximab
http://www.usmlemcq.com/
HELLP syndrome

HELLP syndrome occurs in approximately 0.2 to 0.6
% of all pregnancies.

Pre eclampsia occurs in 5 to 7 % percent of
pregnancies.

Superimposed HELLP syndrome develops in 4 to 12
percent of women with pre eclampsia or eclampsia.
http://www.usmlemcq.com/
HELLP








The pathogenesis of HELLP is not well understood.
Findings are attributed to abnormal vascular tone,
vasospasm and coagulation defects.
No common precipitating factor has been found.
Some insult that leads to microvascular endothelial
damage and intravascular platelet activation.
Platelet activation, causing vasospasm, platelet
agglutination and aggregation, and further endothelial
damage.
Fibrin forms networks in the small bld vsl.
Liver appears to be the main site of this process
This cascade is only terminated with delivery.
http://www.usmlemcq.com/
HELLP




MAHA.
Elevated liver enzyme levels are thought to be
secondary to obstruction of hepatic blood flow by
fibrin deposits in the sinusoids.
This obstruction leads to periportal necrosis and, in
severe cases, intrahepatic haemorrhage,
subcapsular hematoma or hepatic rupture.
The thrombocytopenia has been attributed to
increased consumption and/or destruction of
platelets.
http://www.usmlemcq.com/
HELLP



PT, APTT, Fbrinogen usually normal
DIC is also seen in about 20% of all women with HELLP
syndrome
Fibrinogen <3g/l in this setting suspect DIC
http://www.usmlemcq.com/
Infections

Malaria – anaemia is often only mild
*can be severe esp.with falciparum infections
*Blackwater fever rare but serious complication,
seen in endemic areas & in those who have
repeated attacks. Pptd by antimalarial drugs.
*Diagnosis by demonstrating the parasite.
*Antigen tests
http://www.usmlemcq.com/
Infections

Clostridium welchii – due to direct action of toxin
*mostly post abortal or puerperal infections
*Intra vascular spherocytic anaemia, retic count
not very high
http://www.usmlemcq.com/
Drugs

Due to direct toxic effects in normal subjects
*Sulphasalazine

Haemolysis in subjects with metabolic abnormality
G6PD def
*Primaquine, Nitrofurantoin

Due to a immune mechanism
*Quinine, Penicillin, Sulphonamides

Toxins – Snake bite
http://www.usmlemcq.com/
Paroxysmal Nocturnal Haemoglobinuria




Acquired chronic intra vascular haemolysis
May have thrombosis and pancytopenia
Nonmalignant clonal expansion of one or
several hematopoietic stem cells that have acquired
a somatic mutation of PIGA
Affected stem cells are deficient in glycosyl
phosphatidylinositol–anchored proteins (GPI-APs)
http://www.usmlemcq.com/
http://www.usmlemcq.com/




Urine haemosiderin
HAM test
Flow cytometry for GPI –AP
LDH


Transfusion
Iron replacement
http://www.usmlemcq.com/
14 year old boy
C/O - fever, yellow discolouration
of eyes and abdominal pain – 2 weeks
O/E – Pale ++ , Icteric +, Spleen – 1cm
What are the first line investigations?
http://www.usmlemcq.com/