Bleeding Disorders Flashcards
Basic components of Haemostasis
primary - platelet plug
secondary - fibrin clot
fibrinolysis
anticoagulant defences
when is secondary Haemostasis used
if the platelet plug is not enough and need a more stable clot
how do platelets bind directly to the damaged endothelium/collagen
glycoproteins (A4B1 and glycoprotein VI)
how do platelets stick to VWF
via glycoprotein Ib
what can go wrong with the formation of a platelet plug
Vascular problem
Platelet problems (reduced number - thrombocytopenia, or reduced function)
Von Willebrand Factor
what is the most common cause of thrombocytopenia
autoimmune thrombocytopenia
causes of reduced function of platelets
often drug adverse effects
Causes of vascular abnormalities
Hereditary disorders (rare) -marfans (collagen problems)
Acquired
- vasculitis eg. HSP IgA mediated vasculitis in children
- scurvy (vit c needed for collagen production)
- senile purpura (less collagen in walls in old age)
what causes thrombocytopenia
hereditary (rare)
Acquired
- reduced production (bone marrow problems eg. leukaemia/lymphoma)
- increased destruction (most common cause, immune related)
what comes along with reduced production thrombocytopenia
pancytopenia
what are the causes of peripheral platelet destruction
Coagulopathy
-anything causing a lot of tissue damage activates both primary and secondary Haemostasis and uses up the platelets
Autoimmune
-anti-bodies against platelets
Hypersplenism
-liver disease = most common cause as blood cant get into liver so it backs up through the portal vein and damages/enlarges the spleen
what does platelet destruction look like on blood film
platelets start off big and then get smaller
increased big platelets due to increased destruction?????
what causes platelet function defects
Hereditary
-rare
Acquired
- drugs (aspirin, NSAIDs)
- renal failure
causes of VWF deficiency
Acquired
-autoimmune
Hereditary
- AD
- common
- variable severity (generally mild)
- present with primary Haemostasis problems (mucosal bleeding, epistaxis, menorrhagia etc)
what is the most common cause of primary haemostatis dysfunction
Thrombocytopenia usually acquired
caused by marrow failure or peripheral destruction
treatment for peripheral destruction thrombocytopenia
treat cause - cant give platelet transfusion because they’ll just get broken down
causes of failure of secondary Haemostasis (fibrin clot formation)
Multiple clotting factor deficiencies
(acquired eg. disseminated intravascular coagulation)
single clotting factor deficiency
- hereditary
- haemophilia
what is disseminated intravascular coagulation
clotting factors used up faster than can be made
multiple thrombi in the capillaries
often caused by underlying sepsis
Causes of multiple clotting factor deficiency
Liver failure (if low albumin check clotting factors, prolongation of prothrombin time and activated partial prothrombin time)
Vitamin K deficiency/warfarin therapy
Complex coagulopathy
-disseminated intravascular coagulation
which 4 blood clotting factors require vitamin K to work
II, VII, IX, X
2,7,9,10 are carboxylated by vit K
causes for low vitamin K
warfarin poor dietary intake malabsorption obstructive jaundice (bile salts cant get out) haemorrhage disease of the newborn
where is vitamin K from
Diet
Intestinal synthesis
baby’s have vit K deficiency at birth, all given IM vit K at birth to prevent haemorrhage disease of the newborn
how is vit K absorbed
absorbed in upper intestine
required bile salts for absorption
common dietary source of vit K
leafy green veg
what is warfarin used to treat most commonly
Atrial fibrillation
to prevent blood clot breaking off and causing a stroke (bc in AF blood isn’t pumped out the heart properly so pools and forms a clot in LV)
what is disseminated intravascular coagulation
Excessive inappropriate activation of haemostats system
(primary, secondary and fibrinolysis)
microvascular thrombus formation
-end organ failure
clotting factor consumption and break down
- bruising
- purpura
- generalised bleeding
what happens if you use up all your clotting factors
prothrombin time and Activated partial thromboplastin time
what is increased in vit K deficiency
prolonged prothrombin time and activated partial thromboplastin time
what is the most sensitive test for liver disease
prothrombin time
-because factor VII has the shortest half life so is the first one to go
what fibrin degradation products can be measured
D-dimers
to show increased breakdown of fibrin clots
used to identify of PE/DVT
causes of disseminated intravascular coagulation
Sepsis
Obstetric emergency (placental abruption)
Malignancy (adenocarcinoma)
Hypovolaemic shock
treatment of DIC
treat underlying cause (eg. antibiotics)
Replacement therapy
- platelet transfusions
- plasma transfusions (FFP)
- fibrinogen replacement (cryoprecipitate)
what causes an individual clotting factor deficiency
Heretidary conditions
What is haemophilia
X-linked disorder
abnormality prolonged bleeding recurs episodically at one or a few sites on each occasion
no primary Haemostasis problems
what is haemophilia A
Factor VIII deficiency
what is haemophilia B
factor IX deficiency
presentation of haemophilia
bleeding from medium to large blood vessels
milk moderate and severely effected families depending on factor VII/IC level
what is prolonged in haemophilia
v prolonged activated partial thromboplastin time (VIII/IXa not working at all)
prothrombin time is fine (TF-VIIa is working normally)
clinical features of severe haemophilia
recurrent haemarthroses
recurrent soft tissue bleeds (bruising in toddlers)
prolonged bleeding after dental extractions, surgery and invasive procedures
how are haemophilias managed
IV clotting factor given exert second day
