Tropical haematology Flashcards
What is haemolytic anaemia?
Anemia due to shortened RBC survival
How is haemolytic anemia classified?
Intra vs extravascular
Inherited vs acquired
What is the clinical presentation of haemolytic anemia?
Pallor
Jaundice
Gallstones
Splenomegaly
How can haemolysis be confirmed with laboratory markers?
Elevated
- indirect bili
- LDH
- reticulocyte count
Decreased
- haptoglobin
Urine haemosiderin *intravascular
What are the differences in the mechanism of intravascular vs extravascular haemolysis?
Intravascular = mechanical or complement mediated
Extravascular = immune mediated
What are the differences in the causes of intravascular vs extravascular haemolysis?
Intravascular = microangiopathies (DIC, TTP, HUS) vs macroangiopathies (mechanical heart valve)
Extravascular = autoimmune disorders
What are the differences in the hemolysis of intravascular vs extravascular haemolysis?
Intravascular = hemolysis in plasma
Extravascular = RBCs removed by RES
What are the differences in the haptoglobin level of intravascular vs extravascular haemolysis?
Intravascular = low haptoglobin
Extravascular = normal haptoglobin
What are the differences in the RBC shape of intravascular vs extravascular haemolysis?
Intravascular = non-spherocytic
Extravascular = spherocytes
What are the differences in the iron loss of intravascular vs extravascular haemolysis?
Intravascular = iron loss via haemosiderin excretion via kidneys
Extravascular = no iron loss
Name examples of genetic haematological disorders
Thalassemias
Sickle cell
G6PD
Haemoglobinopathies
Explain what haemoglobin is
Iron-containing oxygen transporting metalloprotein in RBC
Heme - iron at centre with hydrophobic pocket
Globin - 4 chains (2 alpha 2 non-alpha) stabilised by hydrogen bonds
How many alpha genes are on chromosome 16?
4 alpha genes (2 per chromosome)
How many beta globin genes are on chromosome 11?
5 functional genes
2 pseudogenes
What is the globin chain composition of haemoglobin A?
Alpha
Beta
What is the globin chain composition of haemoglobin A2?
Alpha
Delta
What is the globin chain composition of haemoglobin F?
Alpha
Gamma
What is the normal ratio of haemoglobin in an adult?
HbA >95%
HbA2 2-3%
HbF <1%
What is the difference in a thalassemia vs a haemoglobinopathy?
Thalassemia = decreased production of normal globin chain
Haemoglobinopathy = production of abnormal globin chain
Which thalassemia is rare in Africa?
Beta thalassemia (except Liberia and parts of North Africa)
Discuss the clinical features of a thalassemia
Hypochromic microcytic anemia
Tissue hypoxia
Skull deformities (frequent ear and sinus infections)
Pathological fractures
Stunted growth
HSM (causes secondary thrombocytopenia and leucopenia)
What is the difference in point mutations in beta thalassemia?
Beta - = absence of beta chain production from locus
Beta positive = partial deficiency of beta chain production from locus
What will the difference be in homozygous vs heterozygous beta thalassemia?
Homo - severe anemia
Hetero - mild anemia, elevated HbA2 on electrophoresis
Which ratio is highly suggestive of a thalassemia trait?
MCV/RCC <12
Discuss the genetics of alpha thalassemia
Normal genotype = aa/aa
1. 1 gene deletion (aa/-a) silent carrier
2. 2 gene deletion (a-/a- OR –/aa) mild anemia
3. 3 gene deletion (–/a-) Hb H disease
4. 4 gene deletion (–/–) Hb Barts hydrops fetalis = lethal
Why is 3 gene deletion called Hb H disease?
RBCs contain unstable beta 4 chains
Beta 4 = Hb H
What is the difference in time of presentation for beta thalassemia vs alpha thalassemia?
Alpha - neonate
Beta - 3 to 6m
Discuss the management of alpha thalassemia HbH disease
Folic acid supplement
Avoid oxidant drugs
Low iron diet +/- iron chelation therapy
Splenectomy if severe
Monitor closely in pregnancy
What is the mechanism of sickle cell disease?
Change of glutamine to valine (B chain, 6th aa) -> in deoxygenated form, Hb starts to polymerise and precipitate -> becomes rigid -> removed by spleen -> can clump in spleen, fingers, bone
How high is the heterozygote frequency of sickle cell in Africa?
40% (protective from falciparum malaria)
Which sickle cell patients are susceptible to falciparum malaria?
Homozygous
Discuss the clinical presentation of sickle cell disease
Children - pain, infection
Adults - chronic organ damage
3 types of crisis
- vaso-occlusive crisis
- aplastic crisis
- sequestration crisis
Acute chest syndrome
Recurrent strokes
Leg ulcers
Bone infarctions, OM
Haematuria
Priapism
Cholestasis
HSM
Delayed puberty
Retinal neovascularisation
What is vast-occlusive crisis?
Hypoxia
Infection anywhere in body
Painful
What is aplastic crisis?
Dramatic fall in Hb
Parvovirus B19
Folate deficiency (pregnancy)
What is sequestration crisis?
Sudden, massive blood pooling in enlarged spleen -> hypotension
Occurs in children
How is sickle cell disease diagnosed?
Hb 5-11
Normochromic normocytic anemia
Sickle and target cell morphology
Increased WCC
Increased plt
Electrophoresis (HbS present , HbF increased, HbA2 increased)
To which organisms are you predisposed to infection in sickle cell disease?
Encapsulated (s.pneumo, h.influenza, n. meningitidis)
Salmonella (OM)
If iron overloaded -> yersinia
Name precipitating factors for sickle cell disease symptoms
High altitudes
Hypoxia (infarction)
Low temperature (vasoconstriction)
Low pH (acidosis)
Infections (dehydration, acidosis, hypoxia)
What is sickle cell trait?
Less than half the Hb in each RBC is HbS - asymptomatic and only sickle if severe hypoxia or hyperosmolarity
Discuss management of sickle cell disease
Keep extremities warm
Folate
Hydroxyurea in patients with >3 crises per year
Vaccinations
Penicillin prophylaxis <6yo
Stem cell transplant
Which biomarker must be monitored with hydroxyurea use?
White cell count
Discuss the management of acute vase-occlusive crisis
Hydration
Analgesia (avoid pethidine)
Oxygen
Consider transfusion if severe sx anemia
Discuss the management of acute chest syndrome
Antibiotics
Incentive spirometry
Maintenance hydration only
Discuss the management of strokes
Exchange transfusion
What is HbC?
2 normal alpha chains and 2 variant beta chains
Lysine replaces glutamic acid -> unstable Hb -> precipitates in RBCs and forms crystals -> decreased deformability and increased blood viscosity
What is HbE?
Point mutation in beta chain
Change of glutamic acid to lysine
Mild haemolytic with microcytosis and target cells
How is G6PD diagnosed?
Fluorescent spot test
Spectrometry
Discuss classic TTP
Deficiency of von Willebrand factor cleaving protease -> circulating von Willebrand multimers and platelet microthrombi -> red cells fragment on micro thrombi -> microangiopathic hemolytic anemia
What is the pentad of TTP?
Fever
Fragments
Low plt
Renal dysfunction
Neurological symptoms
Discuss management of TTP
Exchange transfusion/plasmaphoresis
Avoid giving plt
Treat until LDH normalises
Which malignancies are associated with EBV?
Burkitt lymphoma
Hodgkin lymphoma
Primary CNS
Primary effusion
Which diseases are associated with HTLV-1?
Adult T cell leukemia/lymphoma
HTLV1 associated myelopathy
Uveitis
Myositis
Dermatitis
What are the features of babesios?
Fever
Mild HSM
Haemolytic anemia
Discuss babesios
Disease of animals
Confused with malaria (no pigment production or RBC changes)
Thrombocytopenia
Normal to low WCC
Discuss trypansosomiasis
African sleeping sickness
Tsetse fly
Discuss the haematological abnormalities seen in trypanosomiasis
Dilutional anemia
Leucocytosis
Thrombocytopenia
Discuss leishmaniasis
Transmitted by phlebotamine sandfly
Discuss the haematological abnormalities seen in leishmaniasis
Normocytic normochromic anemia
Pancytopenia (hypersplenism)
Thrombocytopenia
