Red blood cell disorders Flashcards
What is the pathophysiology of porphyrias?
Defective enzyme activity in heme biosynthesis resulting in an accumulation of intermediates of heme production that deposit into different tissues
How do you classify porphyrias?
Primary - acute hepatic - chronic hepatic Secondary - anemia - alcohol - heavy metal poisoning
What is the most common porphyria?
Porphyria cutanea tarda
What is the peak incidence of porphyria cutanea tarda?
30-50yo
What is the pathophysiology of porphyria cutanea tarda?
Reduced activity of the uroporphyrinogen III decarboxylase enzyme -> uroporphyrin accumulation in the skin
What are the types of porphyria cutanea tarda?
Type I (sporadic) Type II (AD)
Name susceptibility factors for porphyria cutanea tarda
Iron overload Alcohol Smoking Hepatitis C Estrogen therapy Sunlight exposure
Name the clinical features of porphyria cutanea tarda
Blistering photosensitivity Hypertrichosis Hyperpigmentation Scarring Milia Tea coloured urine
How do you confirm the diagnosis of porphyria cutanea tarda?
Urine sample
Serum porphyrins
Discuss the management of porphyria cutanea tarda
General - avoid susceptibility factors - phlebotomy Pharmacological - low dose hydroxychloroquine
What is the peak incidence of acute intermittent porphyria?
20-30yo
Which sex does acute intermittent porphyria predominantly affect?
Females > males
What is the pathophysiology of acute intermittent porphyria
Porphobilinogen deaminase mutation resulting in porphobilinogen and ALA accumulation
What is the inheritance pattern of acute intermittent porphyria?
Autosomal dominant
Name triggers of acute intermittent porphyria attacks
Medications
Alcohol
Smoking
Fasting
Which medications trigger acute intermittent porphyria attacks?
CYP450 inducers Anticonvulsants Sulfonamides Anesthetics Hormone therapy
What are the clinical features of acute intermittent porphyria?
GIT - severe abdominal pain - nausea - vomiting Neurological - non-specific pain - weakness - paresthesia - paresis Autonomic - tachycardia - hypertension Psychiatric - hallucinations - disorientation - anxiety - insomnia Red-purple urine
How do you confirm the diagnosis of acute intermittent porphyria?
Spot urine sample
How do you manage acute intermittent porphyria?
Acute - hemin therapy - glucose loading Long-term - Avoid triggers
Why is glucose loading performed in acute intermittent porphyria?
Glucose decreases heme synthesis and the excretion of heme precursors
What is a differential diagnosis for acute intermittent porphyria?
Lead poisoning
What is the definition of anemia?
A decrease in the absolute number of circulating RBCs
What is the WHO criteria for anemia?
Men: Hb<13.5g/dL
Women: Hb<12g/dL
How can you classify anemia?
Pathophysiological Morphological - microcytic - normocytic - macrocytic
Which MCV values determine the morphological classification of an anemia?
Microcytic <80
Normocytic 80-100
Macrocytic >100
What is the mechanism of microcytic anemia?
Insufficient Hb production
What is the mechanism of normocytic anemia?
Decreased blood volume
Decreased erythropoesis
What is the mechanism of macrocytic anemia?
Defective DNA synthesis
Defective DNA repair
Name causes of a microcytic anemia
Defective heme synthesis - iron deficiency - lead poisoning - chronic disease - sideroblastic Defective globin chain - thalassemia
Name causes of a normocytic anemia
Hemolytic anemias Intrinsic defects 1. Hemoglobinopathies - sickle cell anemia - HbC disease 2. Enzyme deficiencies - G6PD deficiency - pyruvate kinase deficiency 3. Membrane defects - PNH - hereditary spherocytosis - hereditary elliptocytosis Extrinsic defects - autoimmune HA - microangiopathic HA - macroangiopathic HA - infections - mechanical destruction
Non-hemolytic anemias
- blood loss
- aplastic anemia
- chronic kidney disease
Name causes of a macrocytic anemia
Megaloblastic - B12 deficiency - folate deficiency - medications - Fanconi anemia - orotic aciduria Non-megaloblastic - liver disease - alcohol use - myelodysplastic anemia - multiple myeloma - hypothyroidism
Which medications can cause megaloblastic anemia?
Phenytoin Sulfa drugs Trimethoprim Hydroxyurea MTX 6-mercaptopurine
Name the clinical features of anemia
Pallor Exertional dyspnea Fatigue Pica Worsening angina pectoris Hyperdynamic state Extramedullary haematopoesis
What are signs of extramedullary haematopoesis?
Paravertebral mass
Skull diploic space widening
What are laboratory signs of hemolysis?
Decr haptoglobin
Incr LDH
Incr indirect bilirubin
How do you differentiate between folic acid deficiency and vitamin B12 deficiency using bloods?
B12 - incr methylmalonic acid
Folic acid - normal methymalonic acid
How do you treat anemia?
Treat underlying cause
Blood transfusion
Bone marrow transplant
What is aplastic anemia?
A pancytopenia caused by bone marrow insufficiency
Name causes of aplastic anemia
Acute hepatitis Medication Toxins Ionizing radiation Viruses Fanconi's anemia
Which medications can cause aplastic anemia?
Carbamazepine Methimazole NSAIDs Chloramphenicol Sulfa drugs Antimetabolites
Which viruses can cause aplastic anemia?
Parvovirus B19 CMV HBV HIV EBV
What is Fanconi’s anemia?
Bone marrow failure resulting in pancytopenia and normo/macrocytic anemia due to a DNA crosslink repair defect
What is the inheritance pattern of Fanconi’s anemia?
Autosomal recessive
What disease are patient’s with Fanconi’s anemia prone to developing?
Acute myeloid leukemia
Myelodysplastic syndromes
Name the clinical features of aplastic anemia
Pallor Fatigue Malaise Petechiae Purpura Mucosal bleeding Infection
How do you diagnose an aplastic anemia?
Pancytopenia Normo/macrocytic anemia Low reticulocyte count High EPO Dry bone marrow tap
Discuss the treatment of aplastic anemia
Treat the underlying cause Supportive - infection treatment - blood transfusion - platelet transfusion BM stimulants Immunosuppressants Haematopoetic cell transplant
What is the pathophysiology of anemia of chronic disease?
Inflammation
- reduced iron release from macrophages
- reduced iron intestinal absorption
- reduced EPO response
- reduced erythrocyte survival
How do you distinguish between anemia of chronic disease and iron deficiency anemia?
Chronic disease = high ferritin
Iron deficiency = low ferritin
Discuss the treatment of anemia of chronic disease
Treat the underlying cause
Blood transfusion
EPO
Define sideroblastic anemia
Defective heme metabolism -> iron trapped in mitochondria
What is the inheritance pattern of sideroblastic anemia?
X linked
What are the causes of sideroblastic anemia?
Inherited Acquired - B6 deficiency - lead poisoning - alcohol use - drugs - copper deficiency - myelodysplastic syndromes
How can you confirm sideroblastic anemia?
High iron
Prussian blue BM staining
What is pure red cell aplasia?
Normocytic, normochromic anemia characterized by a severe reduction in circulating reticulocytes and marked reduction or absence of erythroid precursors in the bone marrow
What is the pathophysiology of pure red cell aplasia?
Abnormal T-cell function and IgG antibodies that target erythroblasts and erythropoietin
Name causes of pure red cell aplasia
Acquired - idiopathic - thymoma - myelodysplastic syndrome - drugs - parvovirus B19 - AI disorders Congenital - Diamond-Blackfan anemia
How do you confirm the diagnosis of pure red cell aplasia?
Low reticulocyte count
BM - absent erythroid precursors
Discuss your treatment of pure red cell aplasia
Treatment of the underlying cause
RBC transfusions
Immunosuppressants
Cytotoxic agents
What is polycythaemia vera?
A chronic myeloproliferative neoplasm that is characterized by an erythropoietin-independent, irreversible increase in erythrocyte, granulocyte, and platelet counts
Which gene is commonly mutated in polycythaemia vera?
JAK2
What are the clinical features of polycythaemia vera?
Plethora Hyperviscosity syndrome Aquagenic pruritis Hypertension Splenomegaly
What are the laboratory findings in polycythaemia vera?
↑ Hb/Hct, ↑ RBCs ↑ Platelets (> 450,000/μL) ↑ Leukocytes (> 12,000/μL) ↓ Serum iron levels ↓ ESR ↓ EPO Arterial O2 saturation: normal
What is the diagnostic criteria for polycythaemia vera?
3 major/2major + 1 minor
Major
- Increased RBCs
- BM biopsy showing hypercellularity with trilineage growth
- JAK2 gene mutation
Minor
- Decr EPO
Give a differential diagnosis for polycythaemia vera
Severe dehydration Stress erythrocytosis Chronic hypoxia High altitude exposure Paraneoplastic syndrome Polycystic kidney disease
Discuss the management of polycythaemia vera
Phlebotomy
Antiplatelet therapy
Cytoreductive therapy
Name complications of polycythaemia vera
Thrombotic - DVT - stroke - MI Hematological - petechiae - epistaxis - bleeding gums Late stage - acute myeloid leukemia - myelodysplastic syndrome - myelofibrosis
