Bleeding Disorders Flashcards
In what layer are endothelia cells found?
Tunica intima
What things does formation of the platelet plug involve?
Involves endothelial cells, collagen, subendothelial fibrils, VWF and platelets
Why are women much more likely to present with vWF factor deficiency?
Women are much more likely to present with VWF than men as they have regular periods and menorrhagia whereas men don’t usually present until they have surgery
What can the causes of failure of the platelet plug to form be differentiated into?
- Vascular
- Platelets - reduced number/reduced function
- Von Willebrand Factor
Vascular abnormalities can be either _________ or _________
Hereditary or acquired
Hereditary vascular abnormalties are common
FALSE - they are rare
Give an example of a hereditary vascular abnormality.
Marfan’s
Give examples of acquired vascular abnormalities which can result in failure of formation of the platelet plug.
Henoch-Schonlein Purpura
Children, affecting mucous membranes, purpuric rash on lower limbs, GI bleeding (PR blood), but self-limiting.
Why is age an acquired vascular abnormality that results in failure of the platelet plug to form.
As we age we use collagen
_______ is a vitamin D deficiency seen in alcoholics who eat little fruit
Scurvy
What does scurvy cause?
Acquired vascular abnormality resulting in failure of the platelet plug to form
Outline the main clinical features seen in someone with an acquired vascular abnormality resulting in failure of the platelet plug to form.
Most likely to get a non-blanching purpuric rash on the lower limbs.
May also get bleeding from small vessels in mucous membranes - epistaxis, blood blisters in mouth
Retinal haemorrhages.
What is thrombocytopenia?
LOW platelets
What can thrombocytopenia be classified as?
Can be hereditary or acquired, although acquired is significantly more common
How can acquired thrombocytopenia be classified?
- Reduced production (marrow failure)
or - Increased destruction
What are 3 causes of peripheral platelet destruction?
- Coagulopathy e.g DIC
- Autoimmune
- Hypersplenism
Give example of a coagulopathy which causes peripheral platelet destruction.
Disseminated intravascular coagulation (DIC)
What happens in DIC?
Haemostasis is activated and clotting factors and platelets are used up
What is the most common autoimmune cause of peripheral platelet destruction?
Immune thrombocytopenic purpura (ITP)
What happens in ITP?
Everyone has white blood cells which make things called antibodies which recognise foreign material (things that aren’t meant to be there) in our body
In autoimmune conditions, the antibodies get a bit confused and attack the body’s own cells. Antibodies stick to platelets and cause them to be removed.
What is alcoholics liver disease a common cause of?
Hypersplenism
Why does hypersplenism result in peripheral platelet destruction?
Anything that makes the spleen enlarged will lead to thrombocytopenia as the spleen is responsible for the breakdown of platelets
How does alcoholics liver disease a common cause of hypersplenism?
Alcoholics liver disease causes cirrhosis and scarring of the liver, this leads to varices, back pressure of fluid, portal hypertension and eventually an enlarged spleen - hypersplenism
Platelet functional defects can be _________ or _________
Hereditary or acquired
Suggest acquired causes of platelet functional defects.
Drugs – aspirin, NSAID’s (stop platelets sticking together).
Renal failure – uraemia can lead to problems with platelet function.
How is inherited vWF factor deficiency inherited?
Autosomal dominant
vWF factor deficiency can be _________ or ________
Hereditary or acquired
Is hereditary vWF factor deficiency common or rare?
COMMON, but variable severity (generally mild)
Who is vWF factor deficiency seen more in?
Women – because it affects their periods
(although it is equally as common in males and females).
What does vWF factor deficiency lead to problems with?
Problems with primary haemostasis where vWF is important for helping platelets stick together.
What does a vWF factor deficiency present with?
PRIMARY HAEMOSTASIS PROBLEMS . . .
- Mucosal bleeding - epistaxis, blood blisters in mouth
- Purpura
- Bleeding after dental extraction etc
Explain why the symptoms of vWF factor deficiency occur.
vWF carries factor VIII around, but don’t usually get secondary haemostatic bleeding problems unless have a very specific type of vWF deficiency.
Factor VIII levels fall, affecting screening tests for secondary haemostasis.
Prolonged APTT.
What is secondary haemostasis initiated by?
Tissue factor being released from damaged endothelial cells, and activating factor VII.
What are the 2 main causes of failure of the fibrin clot to form? Are each of these generally hereditary or acquired? Give an e.g. for each.
- Multiple clotting factor deficiencies
- generally acquired
- e.g. disseminated intravascular coagulation
- Single clotting factor deficiency
- generally hereditary
- e.g. haemophilia
If you check someones LFT’s and their albumin is low, what does this tell us?
They are unlikely to be making clotting factors
Give 3 examples of causes of multiple factor deficiencies.
- Liver failure
- Vitamin K deficiency/warfarin therapy
- Complex coagulopathy – DIC
What happens to PT and APTT in liver failure? Why?
Both are prolonged – not making clotting factors.
What clotting factors are affected by vitamin K deficiency/warfarin therapy?
II, VII, IX and X
What happens to prothrombin time (PT) and activated partial thromboplastin time (APTT) in vitamin K deficiency/warfarin therapy?
They are prolonged
PT – because factor VII is most affected
Where are all coagulation factors synthesised?
In liver hepatocytes
What is the clinical significance of all coagulation factors being synthesised in liver hepatocytes?
Their production is reduced in liver failure
What is the relationship between clotting factors and vitamin K? (EXAMS)
Factors II, VII, IX and X are carboxylated by vitamin K – which is essential for function
What are the sources of vitamin K?
- Diet - green, leafy veg
* Intestinal synthesis
Where is vitamin K absorbed?
In the upper intestine
What is needed for absorption of vitamin K in the upper intestine?
Bile salts
Suggest causes of vitamin K deficiency (EXAMS!!!).
- Poor dietary intake (from leafy green veg).
- Malabsorption.
- Obstructive jaundice e.g. gall stones, carcinoma of head of pancreas stops release of bile salts into intestine.
- Vitamin K antagonists (warfarin) – used to reduce clotting factors to reduce thrombus formation.
- Haemorrhagic disease of the newborn – give all babies vit K at birth to prevent bleeding.
What is DIC?
Excessive and inappropriate activation of the haemostatic system.
Primary, secondary and fibrinolysis
What does DIC lead to?
- Microvascular thrombus formation – end organ failure.
* Clotting factor consumption – bruising, purpura and generalised bleeding.
What happens in sepsis that leads to haemolysis?
No clotting factors left so bleeding within all their tissues
What are the 2 screening tests for fibrin clot formation?
- Prothrombin time – PT.
* Activated partial thromboplastin time – APTT.
How does the PT test work?
Add TF and phospholipid, and push through TF/VII side
Why is PT initially more prolonged than APTT?
All of the clotting factors have different half-lives.
Factor VII has the shortest half-life, at 6hours, so tends to fall first meaning PT is more prolonged.
What converts fibrin to fibrin degradation products? Where does this come from?
Plasmin, from plasminogen
Describe d-dimers in DIC.
DIC involves excessive fibrinolysis and use of clotting factors.
Therefore, d-dimer will be hugely elevated in DIC.
D-dimer is slightly elevated in liver failure.
Suggest 4 causes of DIC.
- Sepsis.
- Obstetric emergencies.
- Malignancy.
- Hypovolaemic shock.
Basically caused by anything that can lead to lots of tissue damage.
Outline how sepsis can cause DIC.
Sepsis can cause DIC either because of direct action of bacteria, or due to hypotension resulting in lack of perfusion
What is the placenta rich in? Why is this important?
Tissue factor.
If the placenta infarcts, it can activate haemostasis quite dramatically.
Malignancy is associated with lower grade DIC, and high incidence of venous thrombosis as well.
T
What are the 2 main parts of the treatment of DIC?
- Treat the underlying cause
- Replacement therapy. (buys time for you to treat the cause)
- Platelet transfusions.
- Plasma transfusions (FFP).
- Cryoprecipitate (full of fibrinogen and factor VIII).
What is haemophilia? (mention inheritance and the syndrome caused)
An x-linked hereditary disorder in which abnormally prolonged bleeding recurs episodically at one or a few sites on each occasion.
What are the 2 types of thrombophilia?
- Haemophilia A – factor VIII deficiency (5x as common)
- Haemophilia B – factor IX deficiency
(remember A before B, VIII before IX)
What is different in thrombophilia between men and women?
Males = affected. Females = carriers. (will have low factor levels, but still enough to stop bleeding)
This is an X linked condition
What is there NO defect of in thrombophilia?
Primary haemostasis - no problem with paper cuts or nose bleeds
Where does bleeding occur in thrombophilia?
Medium to large blood vessels
Is thrombophilia always inherited?
No – 1/3rd of cases are new mutations
Describe the results of screening tests for fibrin clot formation in haemophilia.
PT – normal
Because there’s no issue with TF, VII, V, X, prothrombin or fibrinogen.
What are the clinical features of severe haemophilia?
- Recurrent haemarthroses
Especially in joints which take most of the pressure in the body (ankles, knees, elbows)
Irritates synovial lining of joints, neovascularisation occurs, new vessels are fragile and more likely to bleed again . . . leads to the formation of ‘target joints.’
- Recurrent soft tissue bleeds.
Bruising in toddlers.
- Prolonged bleeding after dental extractions, surgery and invasive procedures.
(not from minor cuts though)
What should you give to stop bleeding in severe haemophilia?
GIVE FACTOR REPLACEMENT TO STOP BLEED!
How is haemophilia arthropathy prevented?
By giving factor VIII replacement.
