haem w1-6

Left shift

increase in number, associated with bacterial infection/inflammation 

Haematopoiesis

Development of blood cells 

Progenitor cells

immediate progeny of stem cells to cells committed to one differentiation lineage 

 

Thrombopoietin (TPO) 

Megakaryoblasts to proliferate, differentiate and mature 

Erythropoietin (EPO) 

Promotes erythroid differentiation 

RCC

count of number of red blood cells in a sample (x10^12/L)

Hb (haemoglobin)

amount of oxygen-carrying protein, reflects RBC (g/L)

Hct (haematocrit) / PCV

percentage of total blood volume that consists of RBCs (%)

MCV

average size/volume of RBCs (fL)

MCH

average amount of Hb per red cells (pg)

MCHC

average concentration of haemoglobin across RBCs (g/L)

RDW

variation in size of RBCs (%)

MCV equation

(hct / RCC) x 1000

(round to whole number)

MCH equation

Hb / RCC

(round to one decimal place)

MCHC equation

Hb / Hct

(round to whole number)

absolute WCC

(% of cell type) x total WCC

x10^9/L

anaemia

Reduction in concentration in haemoglobin  

hypoxia

body or a part of the body doesn't get enough oxygen at the tissue level

ferritin

primary iron storage

Serum iron

measure of circulating iron 

Total iron-binding capacity (TIBC)

total capacity of transferrin to bind iron 

Transferrin saturation

percentage of transferrin that is saturated with iron 

thalassaemia

Reduced rate of synthesis of one or more globin chains 

haemoglobinopathy

• Inherited disorders that affect structural production of Hb 

• Amina acid deletions or substitutions in globin chain

Alpha thalassaemia 

Reduced production of alpha globin chains

Beta thalassaemia

Chronic haemolysis due to excess alpha chains that precipitate in red cell 

aplastic anaemia

damage to stem cells within BM

haemolysis

Reduced RBC survival or increased RBC destruction 

extravascular haemolysis

• Normal destruction of senescent (old) RBCs 

• Pathological premature removal of RBCs 

 

Intravascular haemolysis 

Not normal (pathological) 

Hereditary Spherocytosis  

• Mutations in membrane proteins 

• Deficiency in vertical proteins  

  • Maintain vertical interactions between membrane + cytoskeleton of RBCs 

Hereditary elliptocytosis  

Defective horizontal interactions of red cell skeletal proteins 

G6PD deficiency 

G6PD enzyme: reduces glutathione in RBCs, protecting from oxidative stress 

Acquired haemolytic anaemia  

Antibody production against own RBCs 

Warm AIHA

RBCs coated with IgG marking them for destruction 

Cold AIHA 

IgM autoantibody attached to RBCs 

Microangiopathic anaemia (red cell fragmentation) 

• Physical destruction of RBCs 

• Caused by RBCs passing through abnormal small vessels 

• Fragmentation of RBCs, sphistocytes  

Disseminated IV coagulation (DIC) 

• Coagulation cascade 

• Damage  

Megaloblastic anaemia

• DNA synthesis 

• Inhibits nuclear division, cytoplasmic maturation – not in synch maturation of erythroblasts 

• Dependent on RNA + protein synthesis 

Non-megaloblastic anaemia 

blood cells are abnormally large (macrocytic) but without impaired DNA synthesis

B12 absorption mouth

B12 bound food proteins 

B12 absorption stomach

protein-bound B12 detaches, R-protein picks up, intrinsic factor secreted

B12 absorption upper small intestine

R-protein releases B12, IF picks up B12

B12 absorption Lower small intestine

IF-B12 attaches to receptor, some unbound B12 absorbed

B12 absorption Intestinal cells

B12 attaches to transcobalamin II

B12 absorption Blood

transcobalamin II carries B12 to cells or to liver for storage (trancobalamin III)

Pernicious anaemia  

Acquired failure to secrete intrinsic factor 

Drug induced macrocytosis 

• Inhibition of folate metabolism 

• Impaired DNA synthesis 

• Direct toxicity to bone marrow 

Myelodysplastic syndrome (MDS) 

Proliferation of a clone of neoplastic haemopoietic cells with abnormal maturation and proliferation: ineffective hematopoiesis 

vascular system

injured blood vessels initiates vasoconstriction

Platelet system

injured vessel exposes collagen that initiates platelet activation and help form plug 

Coagulation

protein factors of intrinsic and extrinsic pathways produce a permanent fibrin plug 

Fibrinolytic

initiated when fibrin is formed and eventually dissolves, endothelium replaces fibrin 

Primary haemostasis 

Mediated by the interaction of platelets and vessel wall following vascular injury 

Secondary haemostasis 

Mediated by the coagulation cascade leading to formation and stabilisation of fibrin clot 

Vessel wall and endothelium 

Produce von Willebrand's factor from WPB, mediating platelets adhesion, Plasminogen activator mediates fibrinolysis 

haemostasis order

1. Vasoconstriction: narrowing blood flow 

2. Primary haemostasis: platelet plug 

3. Secondary haemostasis: fibrinogen to fibrin  

factor I

fibrinogen – fibrin subunit

factor II

prothrombin – serine protease 

factor III

tissue factor – receptor/cofactor 

factor V

labile factor – cofactor

factor VII

proconvertin – serine protease, Circulates bound to vWf 

factor VIII

antihaemophillic factor – cofactor

factor IX

christmas factor – serine protease

factor X

stuart-prower factor – serine protease

factor XI

plasma thromboplastin antecedent – serine protease

factor XII

hageman (contact) factor – serine protease

factor XIII

fibrin-stabilising factor – tranglutaminase, serine protease

instrinsic pathway

• Exposure to negatively charged surfaces (phospholipids, collagen, subendothelial surfaces) 

• Contact initiation > IXa+VIIIa > I, II, V, VIII, X > fibrin clot 

  • Factor 12 exposed to negatively charged surfaces

extrinsic pathway

• Tissue damage and exposure to tissue factor 

• TF complexes with VIIa and initiates pathway 

• TF+VIIa > I, II, V, VIII, X > fibrin clot 

fibrinolytic pathway

• Removes fibrin clots 

• Initiated by activation of the circulating proenzyme plasminogen (proenzyme) 

regulation of haemostasis

• Coagulation: clot formation 

• Fibrinolytic: break down and removal of clot 

• Anticoagulation: proteins that regulate coagulation and fibrinolytic system 

antithrombin

• liver

• Inhibits thrombin, Xa, IXa, XIa 

Tissue factor pathway inhibitor 

• Endothelial cells and platelets 

• Inhibits coagulation in a two step process 

• First binding and inactivating Xa, forming TFPI:Xa complex 

• Complex binds to TF:VIIa and prevent further activation of X and IX 

Protein C regulatory system 

• Vit K dependent, synthesised in the liver 

• Inhibits Va and VIIIa 

Protein S regulatory system 

• Stabilises APC: Argon plasma coagulation 

• Liver 

Alpha2-antitrypsin 

• Major inhibitor of fibrinolysis 

• Inactivates plasmin 

Plasminogen activator inhibitor 1 

• Inhibitor of fibrinolysis 

• Activation of plasminogen by t-PA 

Prothrombin time (PT)

measures extrinsic pathway 

Activated partial thromboplastin time (APTT)

• Measures intrinsic pathway 

• time in seconds for plasma to clot after the addition of phospholipid, calcium and an intrinsic pathway activator 

• Detects deficiencies in factors XII, XI, IX and VIII and in common pathway 

Thrombin clotting time

• Time from addition of thrombin to formation of clot, recorded in seconds  

• fibrinogen to fibrin

• Thrombin added to citrated plasma results in the conversion of fibrinogen to fibrin, formation of stable clot 

Fibrin degradation products/D-dimer

marker of coagulation and thrombosis, fibrin breakdown

Prothrombin time 

Time in seconds for plasma to clot after the addition of calcium and thromboplastin  

fibrinogen

Acute phase reactant 

mixing studies

To distinguish between causes of prolonged PT or APTT 

Haemophilia A and B 

• Mutations – deficiency of factor VIII(A)/IX(B) 

• X linked recessive 

Haemophilia A factor

factor VII

Haemophilia B factor

factor IX

Vessel wall disorders

structural abnormality, inc risk of bleeding, inc fragility of BV walls 

Platelet disorders

affect primary haemostasis, platelet function/number 

Vitamin K

• reduction of production of coagulation factors that rely on vitamin K for synthesis + activation

• Activates: factors II, VII, IX, X, protein X and S 

Liver disease

• TPO + factors production reduced 

• Decreased synthesis of II, VII, IX, X, XI and fibrinogen 

Anticoagulant therapy

interferes with function of coagulation factors, prevents activation, inc risk of bleeding 

DIC

• coagulation cascade activated, platelets + coagulation factors decrease 

• Bleeding tendency due to consumption of clotting factors 

Massive transfusion syndrome

dilution effect, coagulation factors diluted, inc risk of bleeding  

Acquired inhibitors

• antibodies target coagulation factors 

• Autoantibodies 

• Act against complexes in coagulation cascade 

• Most common Anti-factor VIII antibody and lupus anticoagulant