Haematology Flashcards
what are the main functions of blood?
O2 transport
clotting
healing/infection
transport system
homeostasis
what is the function of haemostasis?
limits blood loss (haemorrhage) following vascular damage without compromising blood fluidity
what are the 3 phases of haemostasis?
vasoconstriction
platelet plug
coagulation
what compound is used in blood storage to prevent coagulation?
sodium citrate
what is the extrinsic pathway initiated by and how can it be tested?
tissue factors released by damaged cells
tested using prothrombin time (PT)
what is the intrinsic pathway and how can it be tested?
initiated by active platelets
tested using activated partial thomboplastin time (APTT)
what 3 things are required to carry out the intrinsic and extrinsic pathways?
clotting factors
Ca ions
negatively charged lipid surfaces
how long should each pathway test take?
extrinsic (PT): 10-14 seconds
extrinsic (APTT): 30-45 seconds
explain the final common pathway in coagulation
platelets release prothrombin activator
(turns prothrombin -> thrombin)
thrombin turns soluble fibrinogen into insoluble fibrin
factor 8 cross links fibrin which then strengthens the clot
what is fibrinolysis?
process of clot removal
where is plasminogen synthesised and where does it circulate?
synthesised - liver
circulated - plasma
what is plasminogen activated by?
a serine protease called tissue plasminogen activator (tPA)
what does tPA do?
converts plasminogen into plasmin which breaks down fibrin mesh
what is thrombosis?
occlusion of a blood vessel (venous or arterial) by an intravascular blood clot or platelet lump
what is intravascular blood coagulation inhibited by and how does it inhibit it?
non-thrombogenic surface of endothelium
prostacyclin (PGI2)
NO
inhibits platelet aggregation and adhesion to vascular wall
inhibits natural anticoagulants (antithrombin III)
explain the process of platelet adhesion
adhere to sub-endothelial collagen to activate
platelet surface integrin GPIb permits adhesion to collagen in vessel wall through von willebrand factor bridge
how do platelets promote vasoconstriction?
release agents (thromboxane, ADP) promoting vasoconstriction and aggregation
thromboxane initiates arachnoid acid metabolism (vasoconstriction)
what changes are seen in platelets after activation?
shape change (discoid -> spherical)
pseudopodia development
expose cell surface integrin GPIIb/IIIa cross linking to fibrinogen
what does blood coagulation involve?
coagulation factors (plasma proteins)
phospholipids (platelet surface)
Ca ions
what activated plasma proteins?
proteolic cleavage to become active proteases
name 4 blood clotting disorders and the factor they lack
von willebrand disease (von willebrand)
haemophilia A (8)
haemophilia B (9)
haemophilia C (11)
explain the formation of venous thrombosis
formed by intravascular blood clot in deep veins (often legs)
a fragment may break off (embolus) and block the blood vessel, often the pulmonary artery (DVT)
explain the causation of arterial thrombosis
caused by platelet aggregate at side of ruptured atherosclerotic plaque which is then encapsulated by a clot
common in coronary arteries causing MI, or cerebral artery causing theombotic stroke
what medications are used to treat thrombosis?
anticoagulant - inhibit coagulation cascade
antithrombotics - inhibit platelet activation
thrombolytics - dissolve clots
give an example of anticoagulants and explain their mechanism of action
heparin (sulphated GAG)
binds to antithrombin III (anticoagulant)
complex binds to/inhibits clotting factors (IIa, IXa, Xa, XIa, XIIa)
imediate effect
low molecular weight heparin inhibits Xa mostly
how do the 2 types of heparin differ?
2 forms: UFH (unfractionated) and LMWH
LMWH has more consistent chain length
explain the administration of heparin
intravenously or subcutaneously
cant cross placenta or BBB
used for DVT or pre-eclampsia
what are the side effects of heparin?
allergic reactions
hyperkalaemia
haemorrhage
heparin-induced thrombocytopaenia (HIT)
explain the mechanism of action of oral anticoagulants
warfarin
blocks synthesis of coagulation factors in liver
reduces vitamin K reductase blocking carboxylation resulting in no Ca binding to factors II, VII, IX and X
when is warfarin used?
venous thrombosis
pulmonary embolism prevention (especially in AF patients)
thrombosis prophylaxis after prosthetic insersion (valves)
what are the side effects and disadvantages of warfarin?
active in vivo, not in vitro
effects delayed
can cause haemorrhage
crosses placenta/BBB
explain the INR
measurement of clotting time or ratio of prothrombin to control
target: 2-3
high INR: haemorrhage risk
low INR: thrombosis risk
what are the advantages of new anticoagulants? (+ example)
rivaroxaban (Xa inhibitor)
active imediately
dont involve antithrombin III
what is the function of andexanet?
reverses factor X inhibitors
how does low dose aspirin act as an anti-thrombotic?
irreversibly inhibits cyclooxygenase which causes acetylation of terminal serine which inhibits synthesis of thrombxane A2 and prostacyclin
what are thrombolytic agents used for?
venous thrombosis, MI or thrombotic stroke
never haemorrhagic stroke (side effect is haemorrhage)
what is shock?
life threatening, generalised form of acute circulatory failure with inadequate O2 delivery and utilisation by cells
name 4 markers indicating shock
CV status (BP/HR)
respiratory rate
lactate levels
urine output
what are the 4 types of shock?
distributive
hypervolaemic
cardiogenic
obstructive
what are the causes of distributive shock?
vasoregulation failure (vasodilation)
sepsis (toxic inflammatory response)
anaphylaxis (biochemical mediator release)
neurogenic (spinal injury)
what are the causes of hypervolaemic shock?
loss of intravascular volume
haemorrhage (trauma, GI bleeding)
non haemorrhage (burns)
what are the causes of cardiogenic shock?
pump failure
MI
arrythmias (toxins, medications, valve problems)
mechanical
what are the causes of obstructive shock?
barriers to cardiac flow/filling
pulmonary embolism
cardiac tamponade
pneumothorax
how is distributive shock treated?
fluids
vasosuppressors (targets peripheral vasodilation)
antibiotics
how is hypervolaemic shock treated?
fluid
blood
stop blood loss
how is cardiogenic shock treated?
vasosuppressors
inotropes
fluids
how is obstructive shock treated?
improve obstruction (needle/thrombolysis)
what are the main components of blood?
RBC
WBC
platelets
plasma (water, proteins, coagulation factors etc.)
name the 5 steps of blood loss in order
intravascular volume loss
decreased CO
impaired tissue oxygenation
end organ dysfunction
death
explain the vivious cycle of blood loss
hypothermia = decreased coagulation (clotting problem)
clotting problem = increased lactic acid in blood (blood more acidic)
acidic blood = heart performance decrease resulting in hypothermia
what levels of blood loss are seen with each stage of shock?
S1: 750ml (15%)
S2: 750-1500ml (15-30%)
S3: 1500-2000ml (30-40%)
S4: >2000ml (>40%)
what pulse and BP observations are seen in each stage of shock?
S1: pulse below 100, BP normal
S2: pulse 100-120, BP normal
S3: pulse 120-140, BP lower
S4: pulse 140+, BP low
what respiratory rates and urine outputs are seen in each level of shock?
S1: RR 14-20, UO >30ml/h
S2: RR 20-30, UO 20-30ml/h
S3: RR 30-40, UO 5-15ml/h
S4: RR >40, UO negligible
what is the emergency treatment for a catastrophic haemorrhage?
A - airway (c-spine control)
B - breathing (oxygenation)
C - circulation (haemorrhage control)
D - disability
E - exposure
what is an abrasion wound and how would you treat it?
superficial/deep, dragged against irregular surface
remove debris and dress wound
what is a laceration wound and how would you treat it?
blunt force trauma causing skin to tear/split at tissue bridging
ireegular edges and depth levels
irrigate and clean, close wound with glue, staple/suture wound
what is an incision wound and how would you treat it?
sharp/penetrating trauma (slash/stab), clean edges, uniform shape
investigate for underlying damage
what is a degloving wound?
skin/blood supply torn off by major trauma and severe injuries
could be limbs/digits entirely
what is a bite wound and how would you treat it?
small entry wound prone to infection
possibly deep penetration with foreign body
test for human blood borne viruses (tetanus), antibiotics, ensure vaccinations up to date, delay closure, irrigate
