Haemolytic Anaemias 2 Flashcards
Hereditary spherocytosis inheritance pattern?
Autosomal dominant
Hereditary spherocytosis pathophysiology?
Spectrin or ankyrin deficiency (membrane proteins)
Diagnosis of Hereditary spherocytosis?
spherocytes, osmotic fagility (lyse in hypotonic solution), flow cytometry
Treatment of Hereditary spherocytosis?
Splenectomy
Folic Acid
Inheritance pattern of Hereditary elliptocytosis?
Autosomal dominant - spectrin mutation
Inheritance pattern of G6PD Deficiency?
X-Linked Commonest RBC enzyme defect
Prevalent in malaria zones
Diagnosis of G6PD Deficiency?
Enzyme assay 2-3 months after crisis
Crisis - rapid anaemia and jaundice, Bite cells and Heinz bodies
Precipitants of G6PD Deficiency?
Oxidants: Drugs, broad beans, acute stressors, moth balls, infection
Treatment of G6PD Deficiency?
Avoid precipitants
Transfuse if severe
Genetic Screening
Inheritance pattern of Pyruvate Kinase Deficiency?
Autosomal recessive
Clinical Features of Pyruvate Kinase Deficiency?
Severe neonatal jaundice
Splenomegaly
Haemoytic Anaemia
Treatment of Pyruvate Kinase Deficiency?
Most untreated
Blood Transfusion
Splenectomy
Inheritance pattern of Sickle Cell Disease?
Autosomal Recessive
Mutation of Sickle Cell Disease
Single base GAG => GTG Glu => Val codon 6 of Beta Chain HbS instead of HbA
4 Types of Sickle Cell and severity
Hb SS - Severe
HbAS - Trait - usually asymptomatic
HbSC - One HbS one HbC (Defective B chain)
HbS/Beta - One HbS one Thalassaemia
What triggers the sickling?
Lowered O2 Tension - HbS polymerisation - sickling
Features of Haemolysis in Sickle Cell Disease?
Anaemia 6-8g/dL Splenomegaly Folate Deficiency Gallstones Aplastic Crisis
Features of Vaso-Occlusion in Sickle Cell Disease?
SICKLED Stroke Infarctions (Hyposlenism, CKD) Crises (Splenic, sequestration, chest and pain) Kidney (Papillary necrosis, nephrotic syndrome) Liver (gallstones) Eyes (Retinopathy) Dactilitis (Impaired growth) Mesenteric Ischaemia Priapism
Diagnosis of Sickle Cell Disease?
Sickle and target cells on blood film
Sickle solubility test
Hb Electrophoresis
Guthrie test - pneumococcal prophylaxis
Treatment of Sickle Cell Disease?
Analgesia Folic Acid Penicillin V Pneumovax HiB vaccine Hydroxycarbamide carotid Doppler monitoring Prophylactic exchange transfusion if turbulent
Pathophysiology of Thalassaemia?
Unbalanced Hb synthesis - unmatched chains precipitate - haemolysis and ineffective erythropoiesis
Signs in Beta THalassaemia?
Skull Bossing
Maxillary Hypertrophy
Hairs on end Skull x-ray
Hepatosplenomegaly
Diagnosis of Beta Thalassaemia
Hb Electrophoresis
Guthrie at birth
Treatment of Beta THalassaemia
Blood transfusions
Desferrioxamine to stop iron overload
Folic acid
How many alpha chains are there and what happens to them in alpha thalassaemia?
4 chains Deleted 2/4 - trait - asymptomatic, mild anaemia 3/4 - Moderate anaemia, splenomegaly 4/4 - Hydrops fetalis - incompatible with life
Immunoglobulin in WAIHA
IgG
Blood film findings in WAIHA
Spherocytes
Causes of WAIHA
Primary Idiopathic
Lymphoma, CLL, SLE, Methyldopa
Management of WAIHA
Steroids
Splenectomy
Immunosupperssion
Immunoglobulin in Cold Agglutinin Disease
IgM
Condition associated in Cold Agglutinin Disease
Raynaud’s Phenomenon
Diagnostic test for Autoimmune Haemolytic Anaemia
Direct Antiglobulin Test (DAT/Coombs Test)
Causes of Cold Agglutinin Disease
Primary idiopathic
Lymphoma
Infections: EBV, mycoplasma
Management in Cold Agglutinin Disease
Treat underlying condition
Avoid the cold
Chlorambucil (chemo)
Cause and symptoms of PCH
Viral Infection
Haemoglobin in Urine: measles, syphilis, VZV
Pathophysiology of PCH
Donath-Landsteiner Antibodies - stick to RBCs in cold, complement-mediated haemolysis on rewarming
Immunoglobulin in PCH
IgG
Self-limiting - dissociate at higher temp than IgM
Name 3 Auto Immune Haemolytic Anaemias
WAIHA
Cold-Agglutinin
PCH
Name 2 Non-immune Haemolytic Anaemias
Paroxysmal Nocturnal Haemoglobinuria
Microangiopathic Haemolytic Anaemia (MAHA)
Pathophysiology of PNH
Acquired loss of surface GPI markers on RBCs - complement mediated lysis - chronic IV haemolysis
Features of PNH
Morning haemoglobinuria
Thrombosis (Budd-Chiari)
Diagnosis of PNH
Immunophenotype - altrered GPI
Ham’s Test - in-vitro acid induced lysis
Treatment of PNH
Iron/Folate supplements
Prophylactic vaccines/ Abx
Monoclonal antibodies (eculizumab) - stops complement from binding to RBCs
Pathophysiology of MAHA
Mechanical RBC destruction - forced through fibrin/plt mesh
Schistocytes
Causes of MAHA
Haemolytic Uraemic Syndrome
Throbotic THrombocytopenic Purpura
DIC
Pre-Eclampsia
Treatment of MAHA
Plasma Exchange
Pentad of TTP
MAHA, Fever, Renal Impairment, Neuro abnormalities, Thrombocytopenia
Cause of TTP
Autoimmune platelet activation
Cause of HUS
E. Coli - Toxin damage to endothelial cells - Fibrin mesh and RBC damage - Impaired renal function - MAHA
Symptoms of HUS
Diarrhea, Renal failure, no neuro problems
Children and Elderly
