Theme 2: Lecture 6 - Bleeding disorders Flashcards
What causes bleeding disorders
- Vascular disorders
- Platelet disorders
- Defective coagulation
What pattern of bleeding is seen in vascular and platelet disorders
bleeding into mucous membranes and skin
What pattern of bleeding is seen in coagulation disorders
Bleeding into joints and soft tissues
haemarthrosis
Bleeding into the joints
What causes vascular bleeding
problems with the vessel wall
Name 2 inherited vascular bleeding disorders
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
Name 3 acquired vascular bleeding disorders
- Scurvy
- Steroids
- Senile
What is hereditary haemorrhagic telangiectasia also known as
Osler-Weber-Rendu
What are 2 platelet disorders
- Thrombocytopenia
- Defective function
Normal platelet range
150-400 x 10^9/L
Thrombocytopenia platelet range
<150 /L
When are there symptoms of thrombocytopenia
Platelets < 10/L
Symptoms of thrombocytopenia
- Epistaxis
- GI bleeds
- Menorrhagia
- bruising
Epistaxis
Nose bleeds
acquired causes of thrombocytopenia
- Immune thrombocytopenia purapura (ITP)
- Drug related
- Disseminated intravascular coagulation (DIC)
DIC
- Disseminated intravascular coagulation
- abnormal blood clotting throughout the body’s blood vessels
- caused by another disease or condition that makes the body’s normal blood clotting process become overactive.
ITP
- Immune thrombocytopenia purapura
- Autoimmune condition where body generates antibodies against own platelets
Treatment options for ITP if bleeding or platelets are below 20/L
- steroids and/or intravenous immunoglobulins
- thromboietin agonists
- immunosuppression
- splenectomy
Romiplostim
a thromboietin agonist
Rituximab
an immunosuppression drug
thromboietin
Hormone that stimulates production of platelets
Name an inherited platelet disorder
Glanzmann’s thrombasthenia
What causes acquired platelet disorders
Drugs e.g.
- Aspirin
- NSAIDs
NSAIDs
Nonsteroidal anti-inflammatory drugs
What are disorders of coagulation due to
defect in the coagulation cascade
APTT
Activated partial thromboplastin time
What does the APTT assess
- The intrinsic pathway
- Factors VIII, IX, XI, XII
PT
Prothrombin time
What does the PT assess
- The extrinsic pathway
- Factors II, V, VII, X
TT
Thrombin time
What does the TT assess
The common terminal pathway
What are the tests for coagulation
- APTT = activated partial thromboplastin time
- PT = prothrombin time
- TT = thrombin time
- Fibrinogen level
- Clotting factor assays (normal level 100%)
- Bleeding time (time to stop bleeding) - no longer done
- D-dimers = breakdown products of fibrin clot
What are the inherited coagulation disorders
- Haemophilia A and B
- von Willebrand disease
What causes Haemophilia A
Factor VIII deficiency
What causes Haemophilia B
Factor IX deficiency
Clinical features of Haemophilia
- Spontaneous bleeding into joints and muscle
- Unexpected post-operative bleeding
- Chronic debilitating joint disease
- Family history in majority of cases
- X-linked recessive
Haematoma
An accumulation of blood in the tissues
Diagnosis for haemophilia
-Prolonged APTT
-Normal PT
-Low factor VIII or IX levels
<1% = severe; 1-5% = moderate; >5% = mild haemophilia
Treatment for haemophilia
- infusions of recombinant factor VIII or factor IX to 50-100% of normal
- Prophylactic treatment has revolutionised management of haemophilia patients
Tests for diagnosing von Willebrand disease
- Prolonged APTT
- Normal PT
- Low vWF antigen level and/or vWF function
- Low factor VIII level
- Prolonged bleeding time
- Defective platelet function
Treatment of von Willebrand disease
- Desmopressin AKA DDAVP
- anti-fibrinolytics
- Plasma products
What does desmopressin (DDAVP) do
stimulates release of von Willebrand factor from Weibel-Palade storage bodies from endothelial cells
Weibel-Palade bodies
small storage granules in the endothelial cells of the blood vessels and heart
von Willebrand disease
- Autosomal dominant disease
- Deficiency of von Willebrand factor and factor VIII in the plasma
Symptoms of von Willebrand disease
- Mucocutaneous bleeds
- nosebleeds
- menorrhagia
What is von Willebrand factor
- large multimeric protein that carries factor VIII in the blood
- vWF also binds platelets to endothelial collagen
What are some acquired causes of coagulation disorders
- Liver disease
- Vitamin K deficiency
- Disseminated Intravascular Coagulation (DIC)
How does liver disease cause coagulation disorders
- Deficient synthesis of clotting proteins
- Impaired platelet function and fibrinolysis
How does DIC cause coagulation disorders
- Release of pro-coagulant material into circulation
- Results in consumption of clotting factors
- Causes both bleeding and thrombosis to occur
What is seen in meningococcal DIC
- Prolonged PT, APTT, TT
- Low fibrinogen, low platelets
- Raised D-dimers or FDPs (fibrin degradation products)
Anti-coagulation drugs
- Heparin
- Warfarin
- DOACs = direct oral anti-coagulants
- Direct thombin inhibitors
- Factor Xa inhibitors
What is heparin used to treat
MIs, PEs, DVTs
What is warfarin used to treat
PEs, DVTs, AF, prosthetic valves
DOACs
direct oral anti coagulants
name 2 direct thrombin inhibitors
- dabigatran
- argatroban
Name 2 factor Xa inhibitors
- rivaroxaban
- apixaban
What is vitamin K required for
for gamma-carboxylation of factors II, VII, IX, X
What is vitamin K inhibited by
Warfarin
INR
- International normalized ratio
- Standard measurement that works out how long it takes blood to clot
What causes vitamin K deficiency
- Malabsorption of vitamin K
- Biliary obstruction (jaundice)
- Haemorrhagic disease of the newborn (give 1mg at birth)
