1. Hemolytic anemia and Bacillus cereus septicemia in a patient with thalassemia intermedia
Dr Grace Lam
April 2010

2. Thalassemia intermedia
Splenectomy as a child
Refused iron chelation therapy
Cord compression due to extramedullary hematopoiesis
Clinical admission x Ix of bilateral exudative pleural effusion

3. Developed fever, respiratory failure & shock
Blood cultures Bacillus species, then –ve
ETA Candida species
Urine Legionella Ag –ve
Mycoplasma Ab <10
Bilateral pleural fluid: not suggestive of empyema
CT abd & pelvis: possible early liver abscess
Leptospira IgM –ve
Widal test <1:50

4. Intravascular haemolysis
↑ Plasma Hb mg/L (<50)
↓ Haptoglobin <0.06 ( g/L)
↑ LDH 457
Direct antiglobulin test +ve
Anti-IgG +ve
Anti-C3d –ve
Indirect antiglobulin test –ve
Malaria –ve

5. Waived Treatment Continued to deteriorate despite treatment
Tienam + Anidulafungin + Doxycycline
Drainage of bilateral pleural effusion
CVVH
High dose vasopressor
Continued to deteriorate despite treatment
Δ Septicemia with background thalassemia
Waived

6. Haemolytic anaemia Intravascular haemolysis RBCs lysed in circulation
Released free Hb:
Bound by serum haptoglobin
Excreted by liver
Filtered into urine
Reabsorbed by renal tubules
(Urine haemosiderin)
Haemoglobinuria
Extravascular haemolysis
RBCs phagocytosed by macrophages in liver & spleen
Hb broken down & recycled:
Heme → Unconjugated bilirubin
Conjugated in liver
Excreted into GI tract as stercobilinogen

7. Haemolytic anaemia
or normal

8. Intravascular haemolysis
Mechanisms
Mechanical trauma
Prosthetic heart valves
Microangiopathic HA (TTP, HUS, DIC, HELLP)
March
Complement fixation
Autoimmune hemolytic anaemia - Cold
Drugs (complement-fixing immune complex) e.g. quinine
Paroxysmal nocturnal haemoglobinuria
Transfusion reactions
Toxic damage

9. Intravascular haemolysis
Toxic damage
Infections
Clostridium perfringens
Malaria
Babesiosis
Bacillus cereus
Thermal injury
Snake venom
Severe G6PD deficiency

10. Intravascular haemolysis
Possible cause of intravascular haemolysis in our patient:
+ve Coombs test: Immune-mediated haemolytic anaemia
Toxic damage by infection
Microangiopathic haemolytic anaemia

11. Autoimmune haemolytic anaemia
AIHA
Warm
Ab active at 37oC
Usually IgG
Anti-IgG +ve
Lympho-proliferative disease (CLL, NHL)
Autoimmune diseases (RF, SLE)
Drugs (Methyldopa)
Idiopathic
(60%)
Cold
Ab active <30oC
Complement-fixing IgM
Anti-C3d +ve
Lymphoma
Mycoplasma, Infectious mononucleosis
Paroxysmal cold haemoglobinuria
AIHA causes extravascular hemolysis (in which the Ab-coated RBC membrane is removed bit by bit in the spleen). If the Ab fixed complement, it will result in intravascular hemolysis.
Cold AIHA (also called cold aglutinin disease). Could also occur with influenza, rubella, measles, adenovirus and psittacosis infections.
Donath-Landsteiner test: Biphasic hemolysin pattern in paroxysmal nocturnal hemoglobinuria. Occurs transiently in children as a result of viral infection, associated with syphillus, chronic form in older patients. ?IgG

12. Direct antiglobulin test
Direct Coombs test
Detects abnormal Ab attached to RBCs
Patient’s RBCs incubated with anti-human antiserum:
Antiserum: Anti-IgG or Anti-C3d (detects complement fixation)
-ve = +
+ve

13. Indirect antiglobulin test
Indirect Coombs test
Detects free Ab vs RBCs in serum
Step 1: Incubate patient serum with normal group O RBCs
Step 2: Perform direct antiglobulin test
+ve

14. Coombs test interpretation
Indirect antiglobulin test –ve
Direct antiglobulin test +ve
Anti-IgG +ve
Anti-C3d –ve
Warm AIHA
Unlikely the cause of intravascular haemolysis without evidence of complement fixation

15. Coombs test interpretation
Haematopathologist
Strength of +ve Coombs test
Rated on a 4-point scale in PYNEH:
+ weakest → ++++ strongest
Ag-specificity test on red cell elucidate
Specific red cell Ab: past transfusion
Broad-spectrum Ab: AIHA
Simple bystander as a result of past blood transfusions
Check strength of the positive coombs test + Ag specificity test on red cell elucidate (specific RBC Ab as a result of past transfusion or broad-spectrum Ab in AIHA)

16. Bacillus cereus A gram +ve or gram-variable bacillus
Produces toxins: Enterotoxin, Hemolysin, Phospholipase C & Emetic toxin
Disease spectrum
Food poisoning in Immunocompetent
Opthalmitis: Post-traumatic, IV drug abuse
Fulminant septicemia in Immunocompromised: MOF, massive intravascular hemolysis, rapid death

17. Bacillus cereus septicemia

18. Bacillus cereus septicemia
β-lactamase producing
Resistant to Penicillin & Cephalosporin
Carbapenems or Vancomycin
Progressive clinical course despite appropriate antibiotics
∵ Toxin production
Bacillus circulans – 1 case report on endocarditis
Microbiologist:
Bacillus circulans (commercial kit)
In 1 blood culture only
Likely a contaminant

19. Microangiopathic haemolytic anaemia
Deranged clotting
Platelet
DIC – Contribution to intravascular haemolysis

20. Conclusion Septicemia in thalassemic patient Intravascular haemolysis
Contributed by DIC
Positive Coomb’s test
Bystander as a result of past blood transfusions