Haemapoietic Flashcards
What is sickle cell disease? What are the major pathological manifestations of sickle cell disease? In general, how are hemolytic anaemia classified? What are the major precipitants for sickle cell anaemia in a prone individual? Describe the common features of hemolytic anaemia. Apart from anaemia what are the manifestations of intravascular hemolysis?
- Sickle cell disease is a hereditary haemoglobinopathy
- Pathological manifestations of sickle cell disease
- Hemolytic anaemia
- Splenomegaly -> Increases susceptibility to infection
- Microvascular occlusion -> Pain in affected organs
3. Hemolytic anaemia classified as A. Inherited - G6PD - Sickle cell anaemia - Spherocytosis - Thalassemia B. Acquired (Intravascular) - Antibody-mediated destruction: Transfusion reaction - Mechanical trauma: DIC, TTP, heart valves - Infections: Malaria - Toxins: Envenomation
- Precipitant for sickle cell anaemia
- Hypoxia
- Drop in pH
- Dehydration - Common features of hemolytic anaemia
- Reduced RBC lifespan
- Increased accumulation of Hb by-products
- Increased erythropoietin and erythropoiesis
- Reticulocytosis - Manifestations of intravascular hemolysis
- Hemolytic anaemia
- Haemoglobinuria
- Haemoglobinaemia
- Reticulocytosis
- Unconjugated hyperbilirubinaemia
How are the causes of anaemia classified? Describe the pathogenesis of iron deficiency anaemia. Give examples of anaemia in specific ethnic groups.
- Anaemia classified by mechanism
- Blood loss: Acute or chronic
- Increased RBC destruction: Hemolytic anaemia
+ Inherited: G6PD, thalassemia, sickle cell anaemia
+ Acquired:
> Antibody-mediated: Transfusion reaction
> Mechanical trauma: Heart valves, DIC, TTP
> Infection: Malaria
> Toxins: Envenomation
- Reduced RBC production:
> Erythropoietin deficit: Chronic kidney disease
> Poor nutrition: Folate, B12, iron deficiency
> Immune: Aplastic anaemia - Pathogenesis of iron-deficiency anaemia
- Can be caused by acute or chronic blood loss, reduced iron supplements
- Iron stores are depleted first -> Serum ferritin hemosiderin
- Once reserves depleted, serum iron and transferrin reduces
- Results in microcytic, hypochromic anaemia - Anaemia in specific ethnic groups
- Thalassemia: Asians
- Sickle cell anaemia: African descents
- Spherocytosis: Northern Europe
What are the causes of iron-deficiency anaemia? What are the symptoms of iron-deficiency anaemia? Are there any specific features of iron-deficiency anaemia? What are the laboratory findings in iron-deficiency anaemia?
- Causes of iron-deficiency anaemia
- Blood loss: Acute or chronic
- Reduced intake: Elderly, infants, developing countries
- Increased requirement: Pregnancy, children
- Impaired absorption: Gut resection, coeliac disease - Symptoms of iron-deficiency anaemia
- Lethargy
- Pallor
- Dyspnea
- Angina
- Symptoms of blood loss: Menorrhagia, malaena - Specific features of iron-deficiency anaemia
- Koilonychia
- Alopecia
- Pharyngeal web - Laboratory findings in iron-deficiency anaemia
- Microcytic hypochromic anaemia
- Reticulocytosis
- Low iron levels
- Low ferritin levels
- Low transferrin levels
What is the pathogenesis of pernicious anaemia? What are the clinical manifestations of pernicious anaemia?
- Pathogenesis of pernicious anaemia
- Autoimmune disorder causing destruction of gastric mucosa -> Chronic atrophic gastritis
- Reduced gastric parietal cells -> Reduced secretion of intrinsic factor -> Impaired Vit B12 absorption
- Macrocytic or megaloblastic anaemia - Clinical manifestations of pernicious anaemia
- Insidious onset due to large stores of Vit B12 until reserves are depleted
- Macrocytic/megaloblastic anaemia
- General symptoms of anaemia: Lethargy, malaise, pallor, dyspnea, angina
- Symptoms of Vit B12 deficiency: Paraesthesia, peripheral neuropathy, ataxia
What is Haemophillia A? Why do patients with Haemophillia A bleed? What is the association between clinical severity and Factor VIII levels?
- Haemophillia A
- X-linked recessive bleeding disorder
- Affects males > females
- Inherited or due to mutation
- Reduced levels or activity of Factor VIII - Haemophillia A causes bleeding due to
- Factor VIII required in intrinsic clotting pathway as co-factor to activate Factor X
- Factor VIII also affects extrinsic pathway as it is required for thrombin activation - Severity of Haemophillia A dependent on levels of Factor VIII
- 6 - 50% levels = Mild
- 2 - 5% levels = Moderate
- <1% levels = Severe
What are the causes of thrombocytopenia? What is the pathogenesis of immune thrombocytopaenic purpura?
- Causes of thrombocytopenia classified by mechanism
- Reduced platelet production
+ Bone marrow disorders: Aplastic anaemia, leukemia, cancer infiltration
+ Infection: HIV, CMV
+ Drugs: Thiazides
+ ETOH
- Increased platelet consumption
+ Splenomegaly
+ Autoimmune thrombocytopenia: ITP
+ Non-autoimmune cause: DIC, TTP
+ Infection: HIV, CMV, EBV - Pathogenesis of immune thrombocytopenia purpura
- Primary: Idiopathic
- Secondary: Drugs, infection (HIV, EBV, CMV)
- Autoantibodies against platelet -> Platelets to be opsonised -> Destroy by phagocytosis or in spleen
What is von Willebrand disease and describe the types? What are the clinical presentation of von Willebrand disease? What are the effects on clotting?
- von Willebrand disease is a bleeding disorder
- Due to impaired function or reduced levels of vWF
- Bleeding tendencies
- Affects platelet function and coagulation pathway
- 3 types
+ Type 1: Autosomal dominant, most common, reduced vWF levels
+ Type 2: Autosomal dominant, 2nd most common, impaired vWF
+ Type 3: Autosomal recessive, rare - Presentation of von Willebrand’s disease
- Bleeding tendency from skin or mucous membranes
- Increased bleeding from wounds
- Menorrhagia
- Haemarthrosis in severe disease - Effects on clotting/Hematological presentations
- Increased bleeding time
- Increased PT
- Normal platelets but impaired platelet function
- Impaired Factor VIII function
