Bleeding disorders Flashcards
What are the 3 causes of bleeding (and any subtypes)?
Vascular disorders
Platelet disorders:
- Thrombocytopenia
- Defective function
Defective coagulation:
- Inherited
- Acquired
What are the 2 different patterns of bleeding?
Vascular and platelet causes - Bleeding into mucous membranes and skin
Coagulation disorders - Bleeding into joints and soft tissues
What causes vascular bleeding?
Problems with vessel wall
What are the 2 types of vascular bleeding and name some examples
Inherited:
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
Acquired:
- Scurvy, steroids, senile
What condition is this and what type of bleeding is it?
Hereditary haemorrhagic telangiectasia
Also known as Osler-Weber-Rendu
Vascular bleeding - inherited
What is thrombocytopaenia and what is the reference range?
Low platelets
Thrombocytopenia – plts < 150
Symptoms when plts < 10
What are disorders of coagulation and are they more often inherited or acquired?
Due to a defect in the coagulation cascade
Inherited causes (rare)
Acquired causes (common)
What are the symptoms of thrombocytopaenia?
Epistaxis, GI bleeds, menorrhagia, bruising
What are the inherited and acquired causes of thrombocytopaenia?
Inherited causes (rare)
Acquired csuses (common)
eg: immune thrombocytopaenia (ITP), drug-related, DIC
What condition is this?
ITP = immune thrombocytopenia
For immune thrombocytopaenia, when do you treat and what the 4 treatment options?
Treatment options if bleeding or platelets < 20:
1) steroids and/or intravenous immunoglobulins
2) thromboietin agonists e.g., romiplostim
3) immunosuppression e.g., rituximab
4) splenectomy
In disorders of platelet function, is the platelet count low, normal or high?
Normal
What are the causes of disorders of platelet function?
Inherited:
Many rare diagnoses e.g., Glanzmann’s thrombasthenia
Acquired:
Drugs – much more common e.g., Aspirin, NSAIDs
Draw the coagulation cascade
What are the 3 main coagulation tests and which pathway do they test?
APTT = activated partial thromboplastin time
Assesses the intrinsic pathway
PT = prothrombin time
Assesses the extrinsic pathway
TT = thrombin time
Assesses terminal common pathway
Name 3 other coagulation tests which don’t test specific pathways in the coagulation cascade
Fibrinogen level
Clotting factor assays (normal level 100%)
D-dimers = breakdown products of fibrin clot
What are the 2 types of haemophilia and what is the deficiency?
Haemophilia A – deficiency of factor VIII
Haemophilia B – deficiency of factor IX (also known as Christmas disease)
What type of genetic inheritance is haemophilia A and B?
Both X-linked conditions affecting males only
What are the clinical features of haemophilia?
◦Spontaneous bleeding into joints and muscle
◦Unexpected post-operative bleeding
◦Chronic debilitating joint disease
◦Family history in majority of cases
What clinical features is this and what dieases does it occur in?
Major haematoma
Haemophilia
What clinical feature is this and which disease does it occur in?
Haemarthrosis
What clinical feature does this show and what disease does it occur in?
Chronic joint deformity
Haemophilia
Which family member passes haemophilia to which family member?
Carrier mums have haemophiliac sons
Draw a genetic diagram for a carrier mum and normal father (haemophilia)
What happens when a father with haemophilia has children?
Draw a genetic diagram for this
Dads pass gene to carrier daughters
What 3 tests are done to diagnose haemophilia and what do they test?
Prolonged APTT
tests factors VIII, IX, XI, XII in the intrinsic pathway
Normal PT
tests factors II, V, VII, X in the extrinsic pathway
Low factor VIII or IX levels
◦<1% = severe; 1-5% = moderate; >5% = mild haemophilia
What is the treatment for haemophilia?
What is the genetic inheritence pattern for von Villebrand disease?
Autosomal dominant
What is von Villebrand disease?
vWD = deficiency of vWF and FVIII in plasma
von Willebrand factor = large multimeric protein that carries factor VIII in the blood
vWF also binds platelets to endothelial collagen
What are the symptoms of von Villebrand disease?
Mucocutaneous bleeds, nosebleeds, menorrhagia
What 6 test results would be abnormal in von Villebrand disease?
Prolonged APTT
Normal PT
Low vWF antigen level and/or vWF function
Low factor VIII level
Prolonged bleeding time
Defective platelet function
What is the treatment for von Villebrand disease and how does it work?
Treatment with desmopressin (DDAVP), anti-fibrinolytics and plasma products
DDAVP stimulates release of vWF from Weibel-Palade storage bodies from endothelial cells
What are the 3 acquired disorders of coagulation?
Liver disease
◦Deficient synthesis of clotting proteins
◦Impaired platelet function and fibrinolysis
Vitamin K deficiency
◦Infants who do not receive vitamin K at birth
◦Malabsorption due to jaundice
Disseminated intravascular coagulation (DIC)
◦Release of pro-coagulant material into circulation
◦Results in consumption of clotting factors
Causes both bleeding and thrombosis to occur
What does this picture show?
Meningococcal DIC
Disseminated intravascular coagulation (DIC)
What tests would be abnormal in disseminated intravascular coagulation (DIC)?
- Prolonged PT, APTT, TT
- Low fibrinogen, low platelets
- Raised D-dimers or FDPs
What disease is this?
Disseminated intravascular coagulation (DIC)
Name 3 causes of DIC
cancer, sepsis, obstetric disasters
What does iatrogenic mean?
Overdose of anti-coagulant drugs
Name the 3 types of anti-coagulants
Heparin – used to treat MIs, PEs, DVTs
Warfarin – used to treat PEs, DVTs, AF, prosthetic valves
DOACs = direct oral anti-coagulants
- Direct thombin inhibitors (dabigatran, argatroban)
- Factor Xa inhibitors (rivaroxaban, apixaban)
What medication caused this?
What is the role of vitamin K in clotting?
Vitamin K is required for gamma-carboxylation of factors II, VII, IX, X
What drug inhibits vitamin K?
Inhibited by warfarin (monitored using the INR)
What are the 3 causes of deficiency of vitamin K?
◦Malabsorption of vitamin K
◦Biliary obstruction (jaundice)
◦Haemorrhagic disease of the newborn (give 1mg at birth)
What is the extrinsic pathway?
factors II,V,VII,X,
monitored by PT (basis of the INR)
What is the intrinsic pathway?
factors VIII, IX, (also XI and XII)
monitored by APTT (APTR = APTT ratio)
What do both intrinsic and extrinsic pathways activate?
Both pathways activate prothrombinase
(factors V, X, Ca and phospholipid)
What happens when prothrombin is activated?
}Prothrombin is activated leading to a “thrombin burst”
What does the cleavage of fibrinogen form?
Fibrin and clot formation
