Haematology Flashcards
How would you define anaemia in adults?
Hb < 125 g/L
List causes of anaemia.
REDUCED RBC PRODUCTION Microcytic (MCV < 80), hypochromic --> - Iron deficiency - Thalassemia Normocytic (MCV 80-100), normochromic --> - Myelofibrosis - Aplastic anaemia - Anaemia of chronic disease Macrocytic (MCV > 100), normochromic --> - B12 deficiency - Folate deficiency
INCREASED RBC LOSS
Bleeding–>
- GI, vaginal, internal (e.g. ruptured AAA), trauma
Haemolysis –>
- Membrane protein defect - hereditary spherocytosis
- Enzyme defect - G6PD
- Haemoglobin defect - thalassemia, sickle cell disease
- Immune - rhesus disease of newborn
- Mechanical trauma - Mechanical heart valve; Microangiopathic: DIC, TTP, HUS, PET
Outline the process of coagulation.
Trauma/ bleeding –>
1. ARTERIOLAR VASOCONSTRICTION
2. PRIMARY HAEMOSTATIS = PLATELET PLUG
- Platelets exposed to subendothelium including von Willebrand factor –>
- Platelets adhere to vessel wall (vWF forms bridge between platetlet GP1b and collagen of vessel wall) –>
- Platelets then:
1. change shape
2. altered GP2b/3a - increases affinity for fibrinogen
3. secretion of granule contents - release of ADP, Ca2+, TXA2 etc.
- Causes cycle of platelet activation and aggregation forming a platelet plug
3. SECONDARY HAEMOSTASIS = COAGULATION CASCADE
Extrinsic pathway = trauma to vessel wall –> exposes tissue factor –> joints with 7 –> to activate factor 10
Intrinsic pathway = trauma to blood –> activation of factor 12 –> activation of 11 –> activation of 9 –> activation of 8 –> activation of 10
Common pathway:
Activated 10 –> joints with factor 5 to form prothrombin activator –> causes prothrombin to become thrombin –> thrombin causes fibrinogen to fibrin + factor 13 cross-links fibrin forming a stable clot.
Explain PT -
- what coagulation pathway/s does it measure?
- what causes a prolonged PT?
Explain APTT -
- what coagulation pathway/s does it measure?
- what causes a prolonged APTT?
PT = EXTRINSIC and COMMON pathways Used to determine INR Prolonged PT is caused by: - Warfarin - NOACs - Liver failure/ vitamin K deficiency - Deficiency of clotting factors in extrinsic or common pathways (extrinsic = 7)
SHOULD NOT be affected by heparin.
APTT = INTRINSIC and COMMON pathways. Prolonged aPTT is caused by: - Heparin - NOACs - Deficiency of clotting factors in intrinsic or common pathways (intrinsic = 12, 11, 9, 8) - haemophilia A and B
To remember: PET APE (AIP)
P(Extrinsic)T
A(Intrinsic)PTT
Outline iron absorption in the GIT.
Heme iron from meat –> heme transporter –> enters enterocyte.
Non-Heme iron in ferric form –> converted to ferrous form –> enters enterocyte via DMT1
Iron inside enterocyte can:
1. Stay in enterocyte if body’s demand is low –> be lost when enterocyte sloughed off.
2. Enter body if body’s demand is high -
Ferroportin 1 transports ferrous iron across basal membrane –> hephaestin converts iron to Fe2+ –> transported by transferrin to liver or bone marrow.
Body’s iron demand is signalled by hepcidin -
Iron in liver high –> hepcidin produced –> inhibition of ferroportin 1
Iron in liver low –> hepcidin reduced –> ferroportin 1 active
How would you treat iron deficiency anaemia?
- Address underlying aetiology –> colonoscopy
- Encourage healthy diet - red meat, leafy green vegetables
- Oral iron supplementation
- Consider need for RBC transfusion
IF THESE INSUFFICIENT - e.g. - Oral iron supplements not tolerated
- GIT problem with absorption of oral iron
- Oral iron supplements unable to meet iron needs - e.g. ongoing iron losses > oral iron supplement intake
Then consider parenteral iron infusion.
Explain the types of alpha thalassemia.
Outline the clinical features of each type.
There are 4 alpha globin genes –> 4 types of alpha thalassemia.
1 gene affected = silent carrier
2 genes affected = trait
3 genes affected = intermedia aka Hb H disease
4 genes affected = major aka Hydrops fetalis aka Hb Bart’s
Silent carrier = normal bloods, asymptomatic
Trait = mild anaemia, asymptomatic
Hb H disease =
Anaemia (microcytic, hypochromic without iron deficiency): SOB, fatigue, jaundice, failure to thrive
Expansion of bone marrow –> facial dysmorphism (frontal bossing, maxillary hypertrophy)
Extramedullary haematopoiesis –> splenomegaly
Hb Barts = death in utero or newborn
Explain the pathophysiology of alpha thalassemia.
Gene defect (usually deletion) –> Insufficient alpha globin –> relative excess of B globin –> excess B globin aggregate into tetramers (known as Hb H) –> problematic because:
- High affinity for O2 –> ineffective at supplying tissues with O2
- Beta globin aggregates damage RBC membrane –> haemolysis
- Ineffective erythropoiesis
Explain the types of beta thalassemia.
Outline the clinical features of each type.
Beta globin coded by 2 genes.
1 gene affected (heterozygous) –> B thalassemia minor
2 genes affected (homozygous) –> B thalassemia major
Minor –> mild anaemia, asymptomatic
Major –>
- Symptoms begin at around 6 months when foetal Hb (2 alpha and 2 gamma) transitions to adult Hb (2 alpha and 2 beta)
- Ineffective erythropoiesis –> bone marrow expansion –> facial dysmorphism (frontal bossing, maxillary enlargement –> ‘chipmunk facies’), fragility fracture; extramedullary haematopoiesis –> splenomegaly, hepatomegaly
- Anaemia (microcytic, hypochromic without iron deficiency) –> failure to thrive, fatigue/lethargic, jaundice, pallor
What tests would you order to diagnose thalassemia?
FBC
Peripheral blood smear
Iron studies
Electrophoresis of Hb (can quantify types of Hb)
Genetic studies for mutations/deletions of Hb beta and alpha globin genes
What is your approach to treating thalassemia?
If symptomatic/anaemic (Alpha thalassemia intermedia/ Beta thalassemia minor)
- Monitor Hb with regular FBC –> Blood transfusions with pRBCs when needed
- Monitor ferritin –> if iron overloaded use iron chelation therapy
- Often splenectomy
List DDX for thrombocytopenia.
BONE MARROW DISORDER
- Myelodysplastic syndromes
- Acute leukaemia
- Aplastic anaemia
THROMBOTIC MICROANGIOPATHY
- TTP - thrombotic thrombocytopenic purpura
- HUS - haemolytic uremic syndrome
IMMUNE-MEDIATED
- ITP - Immune thrombocytopenia
- Secondary to infection: EBV, mumps, varicella, hep C, sepsis (DIC)
MEDICATIONS/ TOXINS
- Iatrogenic: heparin, chemotherapy/radiation (bone marrow suppression)
- Alcohol (direct toxicity to bone marrow)
OTHER MEDICAL CONDITION
Chronic liver disease –> portal htn –> splenomegaly
Preeclampsia - HELLP syndrome
Rheumatic disease - e.g. SLE
Briefly outline the pathophysiology and clinical features of the following platelet conditions:
ITP - immune thrombocytopenia
TTP - thrombotic thrombocytopenic purpura
HUS - haemolytic uremic syndrome
ITP - immune thrombocytopenia
- antibody-mediated destruction of platelets
- normal RBCs and WBCs
- otherwise asymptomatic
TTP and HUS are primary thrombotic microangiopathies. These disorders have a classic pentad: 1. Haemolytic anaemia 2. Thrombocytopenia 3. Fever 4. Renal abnormalities 5. Neurological abnormalities
TTP - thrombotic thrombocytopenic purpura
- caused by deficiency of ADAMTS13 (protease that cleaves vWF –> deficiency causes formation of platelet microthrombi)
- kidney minimally affected
- tx: plasma exchange transfusion (plasmapheresis) with FFP
HUS - haemolytic uremic syndrome
- caused by Shiga toxin (E coli O157:H7) –> toxins cross GI barrier and enter blood stream –> cause microthrombi (activation of platelets, increased fibrin formation)
tx: plasma exchange transfusion + antibiotics
What sites are affected by bleeding with (1) platelet disorders, (2) clotting factor disorders?
Platelet disorder --> - Mucosal bleeding: mouth, nose, urinary, GI etc. - Petechiae - Purpura Clotting factor disorder --> - Muscles - Joints
HAEMOPHILIA A AND B
What causes haemophilia A and B?
What are the clinical features?
What labs would you order & expected findings?
Haemophilia A = inherited deficiency of factor 8; X-linked recessive, 1 in 5000 male births
Haemophilia B = inherited deficiency of factor 9; X-linked recessive, 1 in 20 000 male births.
Features:
- Bleeding at birth - e.g. cephalohematoma, from heel prick testing
- Bleeding in childhood - major bruising, bleeding into joints and muscles
- Family history of haemophilia/ bleeding
Lab findings: FBC, coags
- Prolonged APTT
- Factor 8 or 9 level reduced
- Genetic testing - of patient and family (determine carriers)
