Acquired bleeding disorders Flashcards
What are the main acquired bleeding disorders?
- Vitamin K deficiency
- DIC
- Liver disease
What is the function of vitamin K?
Vitamin K is necessary for the γ-carboxylation of glutamic acid residues on coagulation factors II, VII, IX and X and on proteins C and S. Without it, these factors cannot bind calcium that makes them active
What are causes of vitamin K deficiency?
- Inadequate stores
- Malabsorption of vitamin K
- Oral anticoagulant drugs
What would you find on investigation of clotting screen in someone with Vitamin K deficiency?
- Increased APTT and PT
- Normal Bleeding time
- Normal Factor levels
What are features of vitamin K deficiency?
- Bruising
- Haematuria
- Gastrointestinal bleeding
- Cerebral bleeding
What causes vitamin K deficiency in newborn babies?
Classical haemorrhagic disease of the newborn
How does liver disease cause defects in haemostasis?
- Vitamin K deficiency
- Reduced synthesis of coagulation factors - result of severe hepatocellular damage.
- Thrombocytopenia - results from hypersplenism due to splenomegaly associated with portal hypertension or from folic acid deficiency.
- Functional abnormalities of platelets and fibrinogen
- Disseminated intravascular coagulation - occurs in acute liver failure.
Why does thrombocytopenia occur in liver failure?
Results from hypersplenism due to splenomegaly associated with portal hypertension or from folic acid deficiency.
What causes vitamin K deficiency in liver failure?
Occurs owing to intrahepatic or extrahepatic cholestasis.
What is Disseminated Intravascular Coagulopathy?
A common state in which a combination of haemorrhage and thrombosis complicates another disorder. Activation of coagulation leads to the formation of microthrombi in numerous organs and to the consumption of clotting factors and platelets in the process of clot formation, in turn leading to a haemorrhagic diathesis.
What are causes of DIC?
- Malignant disease
- Septicaemia
- Haemolytic transfusion reactions
- Obstetric causes
- Trauma, burns, surgery
- Other infections (e.g. falciparum malaria)
- Liver disease
- Snake bite
What are obstetric causes of DIC?
- Abruptio placentae
- Retained dead fetus
- Amniotic fluid embolism
- Toxaemia
What are traumatic causes of DIC?
- Burns
- Major accidental trauma
- Major surgery
- Shock
- Intravascular haemolysis
- Dissecting aortic aneurysm
What is the pathogenesis of DIC?
Centres on the enhanced generation of thrombin. Factors contributing to the process include increased TF expression, suboptimal function of natural anticoagulants and dysregulation of fibrinolysis. This dysregulated activity results in the production of plasmin, which causes digestion of fibrin and fibrinogen-generating split products (fibrinogen and fibrin degradation products; FDP), which themselves have an anticoagulant and anti-platelet effect and contribute to the haemorrhagic diathesis.
Thrombi, composed of platelets and fibrin, may be found in the microvasculature of brain, lungs, kidneys, heart, spleen and liver.
What are features of DIC?
Patient is often acutely ill and shocked
Presentation varies
- No bleeding at all
- Profound haemostatic failure with widespread haemorrhage
- Thrombotic events - Any organ
- Renal Failure
Where does bleeding most commonly occur in DIC?
- Mouth
- Nose
- Venepuncture sites
- Widespread ecchymoses
What are the most commonly involved organs in DIC?
- Skin
- Brain
- Kidneys
What investigations would you do if you suspected DIC?
- Bloods - FBC, PT, APTT, Thrombin Time, D-dimer, Fibrinogen
- Blood film
What might you find on investigation of PT in DIC?
Increased PT
What might you find on investigation of APTT in DIC?
Increased APTT
What might you find when investigating FBC in DIC?
Decreased platelets
What might you find on investigation of D-Dimer in DIC?
Greatly increased D-Dimer
What might you find on investigation of fibrinogen levels in someone with DIC?
Decreased fibrinogen - correlates with severity
What might you find on blood film in someone with DIC?
Schistocytes - Microangiopathic haemolysis
How would you manage someone with DIC?
- Treat the cause
- Replace platelets - if <50x109/L
- Cryoprecipitate to replace fibrinogen
- FFP to replace coagulation factors
What should not be used in DIC?
Tranexamic acid
When would you consider using activated protein C in the treatment of DIC?
- Severe Sepsis
- Multi-organ failure
