Approach to hemolysis Flashcards
To find the cause, 4 questions to ask
1) Is there increased RBC breakdown
2) Is there +RBC production
3) Is the hemolysis mainly intravascular or extravascular
4) Why is there hemolysis
Indicators of +RBC breakdown
Anemia w/ N or + MCV
+Bilirubin
-ve haptoglobins
+serum LDH
Indicators of +RBC production
+Reticulocytes causing +MCV
Determining if IV or EV
EV->splenomegaly
IV-> +free Hb, methaemalbuminemia, -ve plasma haptoglobin, hemogobinuria, hemosiderinuria
Clinical features
Key factors presence of risk factors pallor jaundice Other diagnostic factors fatigue shortness of breath dizziness splenomegaly active infections episodic dark urine (haemoglobinuria) triggered by exposure to cold
Important history
Family history Race Jaundice Dark urine Drugs Previous anemia Travel
Risk factors
Strong
autoimmune disorders
lymphoproliferative disorders
prosthetic heart valve
family origin in Mediterranean, Middle East, Sub-Saharan Africa, or Southeast Asia
family history of haemoglobinopathy or RBC membrane defects
paroxysmal nocturnal haemoglobinuria
recent exposure to cephalosporins, penicillins, quinine derivatives, or NSAIDs
recent exposure to naphthalene or fava beans
thermal injury
Weak exceptional exertion recent exposure to nitrites, dapsone, ribavirin, or phenazopyridine recent paraquat ingestion malaria babesiosis bartonellosis leishmaniasis Clostridium perfringens infection Haemophilus influenzae type B infection liver disease
Physicalexamination
anaemia, jaundice, or splenomegaly,
Physical findings of the underlying causes are diverse and include
- > generalised lymphadenopathy in cases of lymphoproliferative disease (chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma);
- > specific cutaneous and joint signs in autoimmune disease (SLE, rheumatoid arthritis);
- > fever in infectious causes;
- > elevated BP in a pregnant patient with pre-eclampsia or HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count);
- > skeletal deformities in sickle cell anaemia or thalassaemia, due to increases in haematopoiesis and bone expansion during childhood.
Initial investigations
- FBC: low Hb
- MCHC: increased
- reticulocyte count: increased reticulocyte percentage (>1.5%), absolute reticulocyte count, and reticulocyte index
- peripheral smear: abnormal forms such as schistocytes (MAHA), spherocytes (HS, AIHA), elliptocytes, spur cells, blister cells (oxidant), bite cells (oxidant), tear drops; RBC inclusions may occur with malaria, babesiosis, and Bartonella infections
- unconjugated (indirect) bilirubin: elevated, but not >70 to 85 micromol/L (5 mg/dL) unless liver function is impaired
- LDH: high
- haptoglobin: low
- urinalysis: dipstick positive for blood, no RBCs
Other investigations to consider
direct antiglobulin test (DAT or Coombs’): positive suggests immune aetiology; negative suggests non-immune aetiology
creatinine, urea: elevated in thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome
LFTs: elevated in liver disease
Donath-Landsteiner antibody: present in cold-immune disease
Hb electrophoresis: HbS present in sickle cell disease; elevated levels of HbA2 and HbF in beta thalassaemia
flow cytometry for CD55/CD59: abnormal
glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test and spectrophotometry: low G6PD activity
ANA: positive if SLE
Acquired causes of hemolytic anemia
1) Immune mediated->coombs test positive
- >Drug induced
- >AIHA
- >Paroxysmal cold hemoglobinuria
2) Direct coombs negative
- >Autoimmune hepatitis
- >hepatitis B and C
- >Post flu
- >Drugs
3) Microangiopathic hemolytic anemia
4) Infection->malaria
5) Paroxysmal nocturnal haemoglobinuria
How does drug induced (CT+ve) cause heolysis
Formation of autoantibodies when bind to RBC membrane (penicillin) or produce immune complexes
Differ warm and cold AIHA
Warm->IgG, forms at core temperature. Management with steroids/immunosuppressants
Cold->IgM, complement binds at cold peripheries (usually associated with raynauds). management is to keep warm.
Causes of AIHA
Mostly idiopathic
May be due to myeloproliferative (CLL, lymphoma), autoimmune disease (SLE), following infections (mycoplasma, EBV)
Cause of Paroxysmal cold hemoglobulinuria
Viruses/syphillis
Donath-landsteiner antibodies sticking to RBCs in the cold, complement mediated self limiting hemolysis on re-warming.
