L6 Hemolytic anemia Flashcards
How are RBCs destroyed?
- Aged RBC removed extravascularly by macrophages in the spleen, also in BM, liver
- A minority of them are destroyed intravascularly (in blood vessels)
Hemolytic anemia means anemia resulted from an increased RBC destruction > compensated erythropoiesis from BM.
What clinical features may patients present? (3)
- Hyperbilirubinemia > jaundice, pigmented gallstone
- Splenomegaly
- Aplastic crisis (shut down of RBC production in BM transiently due to parvovirus B19 infection)
Is red cell aplasia normal? Explain briefly.
Red cell aplasia is transient in normal indviduals because red cells can outlive the aplasia thus no anemic symptoms.
Problematic if red cell aplasia in the hemolytic anemic patient (RBC with reduced life span) > severe anemia
In blood reports, what can we check for increased breakdown of RBCs?
- increased bilirubin
- increased LDH
(3. decreased haptoglobin)
In blood reports, what can we check for increased production of RBCs?
- Reticulocytes
- BM erythoid hyperplasia (reduced M:E ratio)
- Folate deficiency
- Polychromasia
Osmotic fragility is used to diagnose?
- Thalassemia
2. Hereditary spherocytes
What is the difference in RBC morphology in blood film between intravascular and extravascular hemolysis.
Intravascular: Schistocytes
Extravascular: Spherocytes
In intravascular hemolysis, serum contains free Hb and methaemalbumin.
What is th difference in the content of Urine between intravascular and extravascular hemolysis?
Intravascular hemolysis: Dark urine, due to the presence of haemosiderin, haemoglobinuria
Extravascular hemolysis: no haemosiderin, haemoglobinuria
List the causes of hereditary hemolytic anemia (with intrinsic RBC defect).
(6)
Membrane:
- Hereditary spherocytosis (HS)
- Hereditary elliptocytosis
- South-East Asian ovalocytosis
Enzyme:
- G6PD deficiency
- Pyruvate kinase deficiency
- Hb hemoglobinopathy
List the acquired causes of hemolytic anemia due to extracorpuscular factors. (red cell itself normal, but being attacked)
(7)
Immune
- Autoimmune hemolytic anemia (AIHA)
- Alloimmune: transfusion reaction
Non-immune
- Red cell fragmentation syndrome
- Infections: malaria, clostridium
- Chemicals
- Secondary to liver and renal diseases
- PNH (Paroxysmal nocturnal hemoglobinuria)
Describe the pathogenesis of Hereditary spherocytosis (HS).
- Defects in the proteins involved in vertical interactions between membrane skeleton and lipid bilayer.
- Loss of biconcave shape > spherical RBC (spherocytes)
- Increased fragility, reduced life span
What is the mode of inheritance of HS?
autosomal dominant
with variable expression, can be due to germline de novo mutation too
Which of the following are clinical features of HS?
A. It occurs in young patients only
B. Patient has splenomegaly
C. Patient have pigement gallstones
D. Patient have jaundice if associated with Gilbert’s diease (defect in hepatic conjugation of bilirubin)
E. Patient CBC will show normocytic normochormic anemia with increased MCHC
All except A
Varying at different ages!
How can HS be diagnosed?
Why is the 2nd test done?
- Flow cytometery for eosin-maleimide (EMA) binding to RBCs
- Direct Coomb’s test (DCT)/ Direct antiglobulin test (DAT) -ve
- this is to differentiate from AIHA which also presents with spherocytosis and hemolytic anemia
How can HS be treated? (3)
- Folate replacement
- Monitor growth and development in paediatric patients
- Splenectomy and cholecystectomy: for symptomatic anemia, gallstones, leg ulcers or growth retardation
In _______________, Direct Coomb’s test is positive.
AIHA
Autoimmune hemolytic anemia
Both warm AIHA and cold AIHA can be idiopathic. They can also be secondary to respective causes. List 3 for each type.
Warm AIHA
- Autoimmune disease, e.g. SLE
- Lymphoproliferative: CLL, lymphoma
- Drugs: e.g. methyldopa
Cold AIHA
- Infection: mycoplasma pneumoniae, etc.
- Lymphoproliferative: lymphoma
- Paroxysmal cold haemoglobinuria (rare)
What is the pathogenesis for warm AIHA?
Autoimmune IgG coats RBC, which is recognized by FC gamma region on macrophages, thus part of the coated membrane is lost, RBC becomes spherical > destroyed extravascularly.
What is the pathogenesis for cold AIHA?
Autoimmune IgM against I antigen on RBC surface > fix complement quickly > intravascular hemolysis
How can warm and cold AIHA be distinguished by lab techiques?
Direct Coomb’s Test:
anti-IgG +ve in warm AIHA, spherocytosis can be seen
For cold AIHA: anti-C3d +ve (= presence of IgM), less mared spherocytosis, red cell agglutination in cold
Which of the following will occur in patient with warm type AIHA?
A. Splenomegaly
B. Chornic hemolytic anemia aggrevated by cold conditions
C. Acrocyanosis (purplish skin discoloration) of fingers, nose, ears, toes
D. Evan’s syndrome: when associated with ITP
A and D
The following treatment is given to patient with ________________.
A. Prednisolone
B. Monoclonal antibody: Rituximab (anti-CD20)
C. Splenectomy
D. Supportive: folate and transfusion if seere
warm type AIHA
What treatment is given to cold type AIHA.
- Keep warm
- Treat underlying cause
- Rituximab, chemo
*Splenectomy and steroids are not useful
Schistocytes can be due to altered blood flow in
A. Cardiac hemolysis in prosthetic heart valves
B. Arteriovenous malformation (AVM)
C. Microangiopathic hemolytic anemia (MAHA): TTP, HUS, DIC, HELLP (Hemolysis with elevated LFT, Low Platelets)
All of the above
For Thrombotic thrombocytopenic pupura (TTP),
it is due to the deficiency in ADAMTS13, causing the formation of ultra-large vWF multimers. What will happen next?
Increased platelet adhesion > causing endothelial injury (thrombotic) + thrombocytopenic purpura
Which of the following is associated with TTP? A. Pregnancy B. Malignancies C. Infectoins D. Drugs E. Autoimmune diseases
All of the above
How can we diagnose TTP in lab?
Prothrombin time appears to be?
- reduced ADAMST13
- PT is normal, coagulation time normal
There are 2 types of hemolytic uremic syndrome (HUS). Name them and explain.
- Typical HUS
- GE with E.coli (EHEC) and Shigella > toxin - Atypcial HUS
- non-GE related infections, genetic predisposition (defect in complement pathway)
Compared to TTP, HUS is:
A. not due to ADAMTS13 deficiency
B. More severe renal impairment
C. associated with minimal neurological symptoms
D. suitable for platelet supplement based on platelet count
D is wrong!!
Never give platelets based on platelet count which will add to the clot formation in all 3 diseases: TTP, HUS, DIC
What is Disseminated Intravascular Coagulation (DIC)?
It is a comsumption coagulopathy: widespread inappropriate intravascular deposition of fibrin + consumption of coagulation factors and platelets
What can be the causes of DIC? A. Infections B. Amniotic fluid embolism C. Hypersensitive reaction D. Malignancy E. Severe burns
All of the above
Which of the below are features of DIC? A. Fulminant bleeding (sudden) B. Thrombosis C. Severe organ dysfunction D. Microangiopathic Hemolytic Anemia (depletion if platelets due to consumption)
All of the above
How will the prothrobin time change in DIC?
Increased PT, APTT
- D-dimer can be detected
How will the platelet and fibrinogen change in DIC?
Both decreases (reduced coagulating factors)
Give classical clinical features of TTP . (Classical pentad!!)
- Fever
- MAHA (Microangiopathic Hemolytic Anemia)
- Thrombocytopenia
Microthrombi-formation > ischemia and infarct
- in kidney: 4. renal impairment
- in CNS: 5. fluctuating neurosigns
What is acquired TTP?
Antibodiy inhibits the proteast ADAMTS13 that is responsible for breakdown vWF > platelet aggregration
G6PD deficiency is one of the hereditary hemolytic anemias. What is the function of G6PD?
reduces NADP to NAPDH, required for production of reduced glutathione (GSH) against oxidatice stress.
Mode of inheritance of G6PD deficiency?
X-linked recessive
During crisis of G6PD deficiency, what can be found in PB?
- Heinz bodies (wedding-ring like, denatured Hb) >
2. bite cells (RBCs with removed Heinz bodies)
Why is G6PD checked after the crisis is settled?
G6PD is high in young RBCs, and it can be falsely normal during acute hemolysis
In G6PDD, patients experience acute hemolytic anemia upon oxidative stress due to ? (2)
- Infection, other acute illnesses, e.g. DKA
- Drugs:
- Antimalarials: primaquine, chloroquine
- Sulphonamides: cotrimoxazole, dapsone
- Others: nitrofurantoin, probenecid, mothball
Treatment for G6PDD?
- Stop offending drugs, treat infections
- Maintain urine output to prevent renal toxicity of free Hb
