Haemostasis 2 Flashcards
What is the balance between coagulation and fibrinolysis when bleeding?
Coagulation factors decrease and platelets decrease
Fibrinolytic factors and anti coagulants increase
Why may coagulation factors be low?
ailure of production: congenital and acquired
defective function of a specific factor:
genetic or acquired from drugs, synthetic defects, inhibition
How do platelets adhere to collagen?
Directly via GLpIa or GLpIb indirectly via VWF
What may be disorders of primary haemostsis?
Platelet disorders
Von Willebrand factor
The vessel wall
What is thombocytopenia?
Low numbers of platelets
What may cause thombocytopenia?
Bone marrow failure due to Leukaemia or B12 defiency
Accelerated clearance e.g. immune, disseminated intravascular coagulation
Pooling and destruction in an enlarged spleen
What may cause an impared function of platelets?
Hereditary absence of glycoproteins or storage granules - this is rare
Acquired due to drugs
What impairment is found with Glenzmann’s thrombasthenia?
Absence of GpIIb/IIIa
What impairment is found with bernal soulier syndrome?
Absence of GpIb receptors
What impairments are found with storage pool disease?
reduction of dense granules in platelet e/g/
ADP
ATP
Which drugs can cause impaired platelet function?
Aspirin
NSAIDs
Clopidogrel (common) - antiplatelet drug
What are the common anti platelet drugs?
Aspirin and clopidogrel
How does aspirin work?
irreversibly blocks COX to stop prostoglandin thromboxane A2 from being produced by the arachidonic acid in platelets
How does clopidogrel work?
irreversibly blocks ADP receptor on platelets
What is von willebrand disease?
Hereditary decrease of quantity which can +/- function
could also be acquired due to an antibody but this is rare
What are the two functions of VWF?
Binding to collagen and capturing platelets
Stabalising Factor VIII
If VWF is low then?
Factor VIII may be low
- because they travel as a complex of glycoproteins and both are involved with hemophilia
What mutations can cause VWF disorder?
Deficiency of VWF - type 1 + 3
VWF with abnormal function - type 2
What can cause vessel wall disorders
inherited haemorrhagic telangiectasia Ehlers-Danlos and other connective tissue disorders - rare
Acquired is more common : steroid therpy, ageing, vasculitis, scurvy
What are the clinical features of disorders of primary haemostasis?
– imemdiate manifestation of bleeding
- prolonged bleeding from cuts
- nose and gum bleeding
- menorrhagia
- Eccyhmosis may be easy
prolonged bleeding after surgery
What is Ecchymosis?
Bruising
What can be seen on the skin due to bleeding under the skin due to thrombocytopenia
petechiae (<3mm) purpura 3-10mm) (these do not blanch when pressure is applied)
What can be seen on the skin due to bleeding under the skin due to vascula disorders?
Purpura
How does severe VWF disorder present?
Haemophilia like bleeding due to low FVIII
How do we test for disorders of primary haemostasis?
- platelet count, morphology
bleeding time- PFA100
assays of VWF
clinical observation
*coagulation screen, PT, APTT are both normal in these patients (except for severe VWF due to low V8)
What platelet count would result in spontaneous bleeding?
less than 40x10^9 / L
if lower than 10x10^9/L then very severe spontaneous bleeding
How to treat failure of production / function that cayses primary haemotasis disorders?
replace : VWF, platelets
- prophylactic
- therapuetic
stop aspirin/NSAIDS
How to stop immune destruction based primary haemostasis disorder?
immunosuppression - prednisolone
splenectomy for ITP - Immune thrombocytopenic purpura
How to treat increased consumption causing primary disorders
treat cause
replace as necessary
What is Desmospressin used for?
Vasopressin analogue and can increase VWF from endogenous stores * only useful in mild disorders
What is tranexamic acid used for?
Antifibrinolytic
- used in heavy periods
What other (non conventional) haemostatic treatments are there for primary disorders?
fibrin glues and sprays in theatre
OCP - for menorrhagia
What is secondary haemostasis?
coagulation
Platelet plug being stabilised by fibrin to stop blood loss
What is the role of coagulation?
generate thrombin = 2a
converts fibrinogen to fibrin
Deficiency of any coagulation factor can cause failure of thrombin generation an hence the fibrin plug
What can cause disorders of coagulation?
Coagulation factor production deficiency
dilution
increased consumption
What can cause dificiency of coagulation factor production?
Hereditary: factor V8 / 9
haemophilia a/b
acquired: liver disease anticoagulation drugs (warfarin and DOACs)
What is dilution?
From blood transfusion
what causes increased consumption disorders of coagulation?
Disseminated intravascular coagulation - common
immune antibodies - rare
What is Haemophilia A and B?
a = factor 8 deficiency
b = factor 9
sex linked
What is Haemarthrosis and what is this the hallmark of?
Spontaneous joint bleeding when factors 8/9 is low
- can be avoided with propholaxis replacement therapy
if is it chronic haemarthrosis it can cause muscle wasting and joint deformity
can you give a px with haemophilia intramuscular injection?
No
What are some examples of lethal coagulation factor deficiencies?
Prothrombin
What are the clinical bleeding signs of factor 11 deficiency?
bleed after trauma not spontaneously
What are the bleeding signs of factor XII deficiency?
no bleeding
Why does liver failure result in coagulation disorder?
Most factors are made in the liver
How to avoid a dilutional effect after haemorrhage?
When giving blood transfusion do not just give red blood cells
require plasma and platelets to otherwise will lose coagulation factors
What occurs in dissemniated intravascular coagulation?
general activation of coagulation - tissue factor
associated with SEPSIS or cancer, major tissue damage and inflammation
depletes factors
thrombocytopenia too
activation of fibrinolysis depletes fibrinogen == raised D dimer
What is the D-dimer?
A breakdown product of fibrin
What does the deposition of fibrin in vessels following increased consumption cause?
Organ failure
and sheering of red blood cells = fragmentation
What are the clinical features of coagulation disorders?
Superficial cuts do not bleed as platelets are fine
bruising common
spontaneous bleeding is deep into muscles of joints
bleeding after trauma may be delayed and is prolonged
bleeding frequently restarts after stopping
What tests are done for coagulation disorders?
Screening tests :
PT
APTT
full blood count
Coagulation factor assays for factor VIII
tests for inhibitors
What could cause these results:
PT = 10.6s (normal)
APTT = 85s (high)
- haemophilia A/B
- factor XI, XII deficiency
intrinsic pathway
What could cause these results:
PT = 26s (high)
APTT = 29s (normal)
Factor VII deficiency in extrinsic pathway
What could cause these results:
both PT and APTT are high?
- liver disease
- anti coagulation drug
- DIC
- dilution
How can we replace factors?
Factor replacement therapy
–> plasma FPP with all coagulation Factors
–> cryoprecipitate with fibrinogen, 8, 13, VWF
–> factor concentrates, available for all except factor 5
Prothrombin complex concentrates include factor 2, 7, 9, 10
Recombinant forms of Factor 8 and 9 are available on demand for bleed and on prophylaxis
How was haemophilia first treated?
plasma derived clotting factors, however this was an issue to due to widespread viral contamination
then changes to recombinant clotting factors
recent developments to modify the half lives of the factors to less frequent injections
What novel agents are being looked into for haemophilia treatment?
Bispecific antibody- Emicizumab binds to F8a and 10 to mimic function of F8 for Haem 8
Anti TFPI antibody
Antithrombin RNAi
What novel treatments are being looked into for haemophilia?
Gene therapy
RNA silencing : targets natural anticoagulant antithrombin
How do disorders of thrombosis present?
pulmonary embolism
Deep vein thrombosis
How does pulmonary embolism present?
heart racing
palpitations
hypoxia
chest pain
haemoptysis
sudden death
How may deep vein thrombosis - DVT present?
painful leg
swelling
red
warm
may embolise to lungs
post thrombotic syndrome
- px may just say feels like pulled calf muscle
- can cause post thrombotic syndrome
what is thrombosis?
intravacular, inappropriate coagulation
venous or arterial
obstructs flow
may embolise to lung
what is virchows triad?
3 factors contributing to thrombosis
- blood
- vessel wall
- blood flow
What is changes in blood a risk factor for?
venous thrombosis
What is changes in vessel wall a risk factor for?
arterial thrombosis
What is changes in blood flow a risk factor for?
both arterial and venous thrombosis
What is thrombophilia?
increased risk of venous thrombosis
How may thrombophilia present?
thrombosis at young
spontaneous thrombosis
multiple times
thrombosis whilst anticoagulated
What happens to fibrinolytic factors and anticoagulant proteins during thrombosis?
decrease
antithrombin
protein C
protein S
What happens to coagulation factors during thrombosis?
Increase
F 8, 2, 5 (due to activated protein C resistance)
myeloproliferative disorders can increase platelets
what are the risk factors for venous thrombosis?
- increasing age
- inherited thrombophilic traits:
anticoagulant deficiency (antithrombin, protein C/S)
procoagulant excess (factor 5 Leiden Factor 8, 2)
How does the vessel wall changes cause arterial thrombosis?
Inflammatory endothelial cell changes can express coagulation proteins
How does blood flow changes affect thrombosis?
travel e.g. flight
surgery
pregnancy
How is venous thrombosis prevented?
assess and prevent
prophylactic anticoagulant therpay
How to reduce risk of recurrence of venous thrombosis?
lower procoagulant factors e.g. warfarin, DOACs
increase anticoagulant activity e.g. heparin
