HAEM - Platelets, Clotting and Coagulation/Anticoagulation Flashcards
What leads to platelet adhesion after endothelium is damaged?
Exposure of collage and vWF
What does platelet adhesion lead to
Degranulation of platelets –> release ADP
Synthesise PG TXA2 –> VC + aggregation
What does ADP do at site of endothelial damage
Stimulates platelet aggregation
What activates the clotting cascade?
Receptors on platelet surface
Mode of action aspirin
Irreversibly inhibits COX1
Preventing conversioon of AA –> endoperoxidases such as PGI2 and TXA2
What can’t anucleate platelets form, PGI2 or TXAs
TXAs
Causes of thrombocytopenia - reduced production (3)
Aplastic anaemia
Marrow infiltration
Marrow suppression
Causes of thrombocytopenia - excess destruction (5)
ITP Autoimmune - SLE, CLL, virus TTP HUS Sequestriation - hypersplenism
PS thrombocytopenia (4)
Mucocutaneous bleeding
Bruising/purpura skin
Epistaxis/menorrhagia
Major haemorrhage (rare)
Cause ITP - children
Virus/imms
Cause ITP - adults
Autoimmune
Ix ITP (3)
FBC - thrombocytopenia ONLY
BM - norm/incr megacaryocyte
Platelet ab +ve 70%
Mx ITP - kids
No Tx necess
Mx ITP - adults
1st line = CCS
IVIG
Splenectomy = 2nd line
What does PT test (prothrombin time)
Extrinsic pathway
VII X, V, II + I
When is PT prolonged (2)
Liver disease
If pt is on Warfarin
What is INR
Ratio of pt’s PT to norm control
Norm INR range
0.9-1.1
Which drug dosing is IR used for
Warfarin
What does APTT test
Intrinsic pathways
Which factors are tested APTT
XII XI IX VIII = extrinsic X V II I = common
Which drug monitoring is APTT used for
Unfractioned heparin
Which conditions are APTT raised in?
Haemophilia
vWD
Liver disease
DICs
What does thrombin time
Adition of thrombin to pt plasma
What pathway is tested in Thrombin time
Common pathway X V II I
What prolongs thrombin time
Fibrinogen deficiency
or abnorm fct
or inhibits
e.g. heparin
What is INR
Ratio of patients PT to normal control
What is APTT
Activated partial thromboplastin time
Addition of surface activator to plasma
Which clotting factors are produced by the liver? (6)
I - fibroinogen II - prothrombin IV V VI VII
What happens if any clotting factors produced by the liver decrease
INR increases
What is required for Vit K absorption and why
Bile salts
As is fat soluble
Vit K dependent factors (6)
II VII IX X Protein C Protein S
Where is Vit K absorbed
Upper ileum
Where is Vit K stored
Liver
What is protamine
antidote to heparin
What are the 4 mechanisms haemostasis occurs by
Behavioural (compression + elevation)
Vascular spasm
Platelet plug (rapid response)
Fibrin clot
What are the 4 control mechanisms in the clotting pathway?
Physical separation
Protein C inhibitory pathway
Antithrombin 3
Fibrinolysis
What is protein C generated by
Vit K
What is protein C activated by?
Thrombin
What does protein C do once activated
Acts w/ co-factor S to induce fibrinolysis
Destroys 5 + 8 meaning no more thrombin made + inhibits stabilization of fibrin clot
Which control mechanism does heparin enhance?
Antithrombin 3
How does fibrinolysis work
Plasminogen –> plasmin (by tPA)
Plasmin breaks down fibrinogen + fibrin –> d-dimer
How is t-PA release stimulated
Thrombin + APC (activated protein C)
What happens to the deficiency of fibrinolysis in severe trauma
Efficiency is enhanced
–> hyperfibrinolysis
What viscosity platelets are ideal
sticky
Signs of VIt K deficiency
Increased PT
Haemorrhage
Causes of Vit K deficiencies (3)
Malabsorptive conditions
Cholestatic jaundice ( no bile salts)
ABx - gut flora disturbance
