Haematology Physiology PDF

Haematopoeisis Haematopoiesis makes 200 billion cells a day Bone marrow = medullary haematopoiesis Other tissues = extramedullary haematopoiesis  Aplastic Anaemia (AA) Pancytopenia (reduction in all blood cell types) due to bone marrow damage Note: Low reticulocyte count = AA or renal...

Haematopoeisis Haematopoiesis makes 200 billion cells a day Bone marrow = medullary haematopoiesis Other tissues = extramedullary haematopoiesis  Aplastic Anaemia (AA) Pancytopenia (reduction in all blood cell types) due to bone marrow damage Note: Low reticulocyte count = AA or renal impairment (no EPO). But AA will also have neutropenia and thrombocytopenia Aetiology - damage of bone marrow Inherited Diagnosis: bone marrow biopsy ○ Fanconi anaemia Hardly any progenitors ○ Dyskeratosis congenita Mostly Fat ○ Schwachman-Diamond syndrome Acquired ○ Immune mediated ○ Toxins - chloramphenicol, gold, penicillamine, anti-convulsants, anti-thyroid drugs ○ Occupational and environmental - benzene, pesticides ○ Chemotherapy and radiation ○ Infections - EBV  Myelodysplastic Syndrome Group of clonal HSC disorders causing: Dysplastic HSC Peripheral pancytopenia ← how it presents Hypercellular/hypocellular bone marrow Progression to acute myeloid leukaemia  Blood Components 55% plasma Plasma proteins include: albumin, globulins (clotting factors), immunoglobulins, fibrinogen 45% haematocrit (RBC) 4-5) Stored in liver ○ Oval macrocytes Function: Required for B9 function, nerves ○ Pancytopenia (if severe) ○ Poikilocytosis (size/shape) Pathophysiology Autoantibody screen - intrinsic factor Ab Usually due to malabsorption Schilling test - measures absorption of B12 with and ○ Pernicious anaemia - autoantibody produced to without IF IF or parietal cells Confirm with elevated homocysteine (needed as cofactor) ○ Gastrectomy ○ Inflammatory bowel disease Treatment Inadequate intake - vegan Hydroxocobalamin (IM) - 1mg on alternate days for 2 weeks, follow up 1mg every 2 months Presentation Pernicious anaemia requires lifelong therapy Anaemia - lethargy, pallor DO NOT give folic acid alone to any B12 deprived patient Glossitis, Neurological issues - peripheral neuropathy, as it will not correct the neurologic deficit numbness, dementia  Anaemia - Folate deficiency Folate (B9) Treatment Found in - green leafy vegetables, yeast, liver, kidney Oral folic acid supplementation 5mg/day Absorption in jejunum Exclude B12 Function: DNA synthesis Aetiology Dietary deficiency ○ Chronic alcoholics ○ Poor and elderly ○ Overcooking vegetables Malabsorption Increased requirement - pregnancy and infancy, chronic haemolysis Phenytoin (reduces folate absorption) Methotrexate toxicity (folate antagonist) Presentation similar to B12 deficiency but no neurologic features In pregnancy leads to neural tube defects  Anaemia Aetiology MCV (Mean corpuscular volume) normal = 80 Normocytic: ABCD Acute blood loss Microcytic anaemia TAILS: Bone marrow failure Thalassemia Chronic disease Anaemia of chronic disease Destruction (haemolytic anaemia) Iron deficiency Lead poisoning Sideroblastic Macrocytic anaemia: FATRBC Foetus (pregnancy) Alcohol Thyroid (hypothyroidism) Reticulocytosis B12/Folate* Cirrhosis + Drugs (phenytoin, metformin, methotrexate) *Megaloblastic macrocytic  Anaemia - Haemolytic Anaemias Anaemia related to RBC breakdown Diagnosis: Biochemical tests: inc LDH inc bilirubin dec haptoglobin Blood film morphology essential: reticulocytosis Coomb’s test positive - test if red cells are covered with IgG or C3 - agglutination is positive  Anaemia - Haemolytic Anaemias G6PD Deficiency X-linked glucose-6-phosphate dehydrogenase which maintains glutathione (mops up oxidative stress) → RBC more prone to oxidative stress → haemolysis Common where malaria is common Presentation: aSx mostly ○ Dark red/black urine - haemoglobinuria ○ Prolonged or severe neonatal jaundice ○ Triggers: fava beans/broad beans, acute illness/infection, medications (oxidative drugs) Diagnosis: smear review, specific enzyme assay Treatment: avoid precipitants Sideroblastic Anaemia Failure to produce heme  Anaemia - Haemolytic Anaemias Thalassemia Congenital alpha or beta Hb chain deletions Asians and mediterraneans 3 syndromes: Thalassemia trait - aSx, microcytosis Thalassemia intermedia - intermittent haemolysis Thalassemia major - 2 beta chains deleted ○ Nucleated red cells, iron overload, lifelong transfusion dependence Diagnosis: Haemoglobin electrophoresis Blood film - microcytic hypochromic, target cells, anicytosis, poikilocytosis  Anaemia - Haemolytic Anaemias Sickle Cell Anaemia Red blood cell is shaped like a sickle Pathophysiology Diagnosis: Genetics: autosomal recessive, missense mutation in HBB gene Newborn blood spot screen so 6th AA of beta-globin in valine instead of glutamic acid Blood smear Sickle haemoglobin = 2 alpha-globin + 2 mutated beta-globin Protein electrophoresis - HbS Repeated sickling of RBC weakens membrane leading to: ○ Anaemia Management ○ Spillage of haemoglobin → dec in haptoglobin (recycling), Oxygen and fluids unconjugated bilirubin inc (jaundice, gallstones) Pain - opioids Sickle shape also has tendency to cause vaso-occlusion: Infection - antibiotics, prophylaxis ○ Bones → Dactylitis (digit inflammation), Avascular necrosis Blood transfusion ○ Splenic infarct → susceptibility to encapsulated bacteria Bone marrow transplant ○ Brain → Stroke Prevention: ○ Lungs - acute chest syndrome (hypoxic vasoconstriction ○ Children: penicillin and polysaccharide exacerbates deoxygenated cells blocking oxygenated cells. vaccine against strep pneumoniae ○ Kidneys → Haematuria/proteinuria ○ Hydroxyurea - inc gamma-globin, ○ Penic → priapism (painful prolonged erection) increases fetal haemoglobin  Blood Groups - ABO Most common in Australia = O+ Least common = AB- ABO Blood Types Antigen: A and B Antibodies: present in plasma when antigen not on RBC ○ Can test for ABO blood type in serum ○ IgM ABO gene (chromosome 9) - codominant A/B, recessive O Exceptions: Babies don’t make anti-A or anti-B (IgM) until a few months old During pregnancy some of mother’s antibodies (IgG) are transported via placenta into fetal circulation Blood Groups - Rh Rh positive or negative RHD gene on chromosome 1, dominant ○ Foetal blood type inherited from both parents Antigen: D (mainly) - confined to RBC Antibodies: IgG ○ Do not occur naturally in serum ○ Nearly all are formed as immune response to red cells carrying the antigen (usually via transfusion or pregnancy)  Blood Grouping Procedures Cell Typing (Forward grouping) Serum Typing (Reverse Grouping) Determines ABO and Rh antigen on cells Determines antibodies present in serum Donor cells tested with anti-sera with antibodies for Donor serum tested with cells of known blood ABO/Rh antigens group Agglutination suggests positive on cell Agglutination means negative on cell  Haemolytic Disease of Foetus & Newborn (HDFN) Sx: Jaundice and kernicterus ABO incompatibility Almost exclusively in type O mothers with foetuses with type A/B blood 1% of type O mothers have a lot of IgG ab against A and B which cross placenta and cause haemolysis in placenta Rh Blood Group incompatibility - major cause Rh D-negative mother and Rh D-positive child Other forms anti-D which is IgG (able to travel across the placenta)n Not 1st pregnancy - this is when sensitization occurs (requires only small amount of foetal blood to enter the mother’s circulation) Affect subsequent pregnancies of RhD positive babies Prevention: ○ Give all unsensitised mothers anti-D Ig - removes foetal RBC leaked into maternal circulation ○ Use Rh(D) negative blood products in women of child bearing age  Blood Products Whole blood can be centrifuged into: Red cells - Hct, leucocyte depleted, 42D fridge Fresh frozen plasma - all plasma components (including clotting factors), thawed in 30min, 1Y freezer Platelet - buffy coat or aphoresis, 5D room Cryoprecipitate - Cold precipitate of frozen plasma, only factor 8, 13, vWF, and 2 All cellular products in Australia are leukoreduced ○ Prevents: HLA alloimmunization, transfusion transmitted CMV in at risk patients, febrile non-haemolytic transfusion reactions Irradiated blood products (gamma-irradiation) - prevents transfusion associated graft-versus host disease (TA-GVHD) ○ TA-GVHD: presents 2W after transfusion - rash, pancytopenia, abnormal liver function ○ Indication: immunosuppressed patients, HLA type shared ○ Decreases shelf life ○ Effect: RBC - membrane damage, shortened survival Platelets - no clinically significant change (all platelet products are irradiated) Granulocytes - conflicting  Blood Transfusions Pre-Transfusion Testing Transfusing Blood Identify patient specimen ABO RH(D) typing - donor and patient Consider: Ab screen Acute/chronic anaeima ○ Tested against 3 screening cells with known RC Alternatives phenotype ○ If screening cells positive do a panel: How much and how quickly: Indirect antiglobulin test looking for free Give 1 unit (240ml) and reassess ab in patient plasma Raise Hb by 10g/L Gel/column format Transfuse for 2-4H Crossmatch ○ For fresh frozen plasma and packed red cells Emergency release of blood ○ Immediate spin or computer crossmatch if no No specimen (5min) detection/history of clinically significant ○ O Rh(D) neg - women of child bearing age antibodies ○ O Rh(D) pos - all others ○ Faster, less reagent, more efficient Current specimen - ABO/Rh known Release blood for transfusion ○ Release ABO Rh(D) compatible (10-15min) Patient ID at time of blood transfusion ○ Release immediate spin crossmatch compatible (15-30min)  Blood Transfusion Reactions/Complications Complications: Acute Haemolytic Transfusion Reactions 1/50k transfusions Usually due to ABO incompatibility Intravascular haemolysis - IgM antibodies present in blood → activating complement → cytokine Sx: 5 bleeding risks compared with warfarin increases risk of spontaneous or post-traumatic bleeding) Liver clearance Bleeding/Clotting Pathology Too much clotting: DVT PE Too much bleeding: Haemophilia A/B DIC Von Willebrand’s Disease  Deep Vein Thrombosis Thrombus in body’s large veins (usually lower limbs) → complete or Risk Factors to not miss: partial occlusion of circulation in vein Virchow’s triad Incidence = 1/1000 adults Surgery Presentation: Unilateral (can be bilateral) swelling/oedema, Cancer pain, redness/warmth COCP, pregnancy Complications: pulmonary embolism Genetic - factor V leiden (1/25 australian), Protein C/S Diagnosis is 3 step: deficiency, antithrombin 1. Well’s score - assessment deficiency 2. D-dimer - rules out if negative 3. Doppler ultrasound Management: Anticoagulants (apixaban) Surgical - percutaneous aspiration thrombectomy, vena cava filter (PE prevention), venous balloon dilatation and stent Prevention - heparin (surgery), warfarin, weight management, compression stockings  Pulmonary Embolism Thrombus lodged in artery of lung Incidence = 1/2000 Presentation Dyspnoea Sudden, sharp chest pain - aggravated with deep breathing or coughing Cough - blood/pink foamy mucus Tachycardia, tachypnoea Sweating, anxiety Syncope Diagnosis Treatment 1. Modified well’s score - risk assessment Short term: 2. D-dimer - if low rules out ○ Oxygen support 3. Imaging - CTPA (gold standard), V/Q scan (pregnancy) ○ Heparin / LMWH ○ Thrombolysis if massive Long term: warfarin  Haemophilia A and B Deficiency of clotting factor - X-linked Diagnosis: recessive, often new mutation Genetic tests Factor 8 = Haemophilia A APTT - prolonged Factor 9 = Haemophilia B / Christmas Factor 8 - decrease disease vWF - normal Severity: Treatment 5% - mild haemophilia Presentation - nearly identical for A and B Deep haemorrhage - muscles, joints Post-traumatic and post-operative bleeding Mucocutaneous bleeding (gums, nosebleeds) Haematomas, ecchymosis  Disseminated Intravascular Coagulation (DIC) Acquired syndrome characterised by Diagnosis activation of coagulation pathways → more APTT, INR, TT - all prolonged in proportion to severity clotting + more bleeding (due to D-dimer - increase intravascular thrombi and depletion of Platelet count - normal or dec platelets and coagulation factors) Fibrinogen - decreased Presentation: Treat Bleeding - epistaxis, gingival bleeding, Underlying disorder GI bleeding, petechiae, ecchymosis, Replace plasma, platelets and clotting factors haematuria Oliguria Cough, dyspnoea Fever, hypoxia, hypotension Mental disorientation, delirium, coma Complications: Life-threatening haemorrhage Acute renal failure Gangrene, loss of digits  VonWillebrand’s Disease Common genetic disorder - 1% of population Autosomal dominant Causes deficiency in Von Willebrand factor - required for platelet adhesion/activation, and carrier for factor 8 → mimics haemophilia A Presentation: Mild-moderate bleeding disorder Diagnosis: APTT - mildly prolonged vWD assays Factor 8 - decrease Treatment Minimal Heavy periods - tranexamic acid Planned surgery - vasopressin analogue (DDAVP) Severe vWD - infusions of concentrated forms of vWF purified from human plasma Thrombocytopenia Low platelets Aetiology: Mild: 100-150 Increased destruction Moderate: 30-100 ○ Immune - immune thrombocytopenic Severe: