Haemostasis: Physiology and inherited coagulation disorders Flashcards
Normal haemostasis
Localized vasoconstriction at site of injury
Adhesion of platelets to damaged vessel wall and formation of platelet aggregate or plug
Activation of coagulation cascade leading to fibrin formation, reinforcing platelet plug
Activation of fibrinolytic system which digests haemostatic plug, re-establishing vascular patency
Vessel injury –>
–>local vasoconstriction –> platelet adhesion and activation of coagulation cascade
Platelet adhesion –> platelet aggregation –> haemostatic plug –> fibrinolytic activity –> repair of vessel damage
Activation of coagulation cascade –> fibrin formation –> haemostatic plug –> fibrinolytic activity –> repair of vessel damage
Platelets
Small non-nucleated cells Fragments of megakaryocyte cytoplasm Essential for primary haemostatic plug Normal platelet count is 140-350x109/l Platelets <20 Spontaneous bleeding >80 Haemostatic Thrombocytopenia = reduced platelet count Thrombocytosis = increased platelet count
Coagulation problems: primary haemostasis
Involves vessel wall, platelets, and von Willebrand factor
Present with purpura, bruising, bleeding from cuts, heavy periods and surgical bleeding
Coagulation problems: secondary haemostasis
Involves the coagulation cascade
Presents with joint and muscle haematomas and surgical bleeding. Bruising is not prominent
Management of patient with bleeding disorder
History
Examination
Investigations
Treatment
Management of patient with bleeding disorder: history
Easy bruising ?spontaneous Bleeding after cuts/minor injury Epistaxis Menorrhagia Bleeding after dental extractions Bleeding after surgery Family history of a bleeding disorder Drugs eg aspirin, warfarin, cytotoxics Alcohol
Menorrhagia
Heavy menstrual periods
Epistaxis
Nosebleed
Haemoptysis
Coughing blood
Haematemesis
Vomiting blood
Haematuria
Blood in the urine
Malaena
Black stool due to bleeding from upper GI tract
Management of patient with bleeding disorder: examination
Ecchymoses (Bruises) Purpura Haemarthrosis Damaged joints Anaemia (due to bleeding) Signs of liver disease Splenomegaly
Management of patient with bleeding disorder: investigations
Full Blood Count - Platelet count Clotting screen -Prothrombin time (PT) -APTT -Thrombin time -Fibrinogen Bleeding time or PFA (automated Platelet Function Analysis) Depending on the above results, more specialised investigations can be performed
Management of patient with bleeding disorder: treatment
Depends on diagnosis eg
- haemophilia A - FVIII concentrate
- haemophilia B – FIX concentrate
- thrombocytopenia – Platelet transfusion
- warfarin overdose – Vitamin K
Vascular Bleeding Disorders
Inherited -hereditary haemorrhagic telangiectasia -Ehlers-Danlos syndrome Acquired -senile Purpura scurvy (Vitamin C deficiency) steroid Purpura
Coagulation factor disorders
Haemophilia A -X-linked Haemophilia B -X-linked Von Willebrand disease -autosomal dominant Others -autosomal recessive -deficiency of fibrinogen, FII, FV, FVII, FX, FXI, FXIII
Frequency of Haemophilia A
Sheffield: 250
UK: 5000
Prevalence: 1:5000
Frequency of Haemophilia B
Sheffield: 50
UK: 1000
Prevalence: 1:25000
Frequency of VWD
Sheffield: 300
UK: 6000
Prevalence: 1:100-1:1000
Haemophilia
Haemophilia A – FVIII deficiency Haemophilia B – FIX deficiency Identical clinical features Sex linked inheritance Sites of bleeding -joints, muscles, post trauma, post operative Severity -<1% severe -1-5% moderate ->5% mild (Normal FVIII level 50-150%)
Haemophilia treatment
If mild haemophilia A: Desmopressin (DDAVP)
-releases FVIII from endothelium
For all severities: FVIII/IX concentrate
-in UK recombinant products, elsewhere could be plasma derived
-main side effect of plasma derived products is risk of infection as each batch is made from up to 30,000 blood/plasma donations
-all products virally inactivated since 1985
BEWARE: Haemophiliacs treated prior to 1985
-HIV 30%, Hepatitis B 5%, Hepatitis C 98%
Von Willebrand Disease
Commonest inherited bleeding disorder
Affects up to 1% of the population
Autosomal dominant
3 main types with many subtypes
In general, a milder bleeding disorder than haemophilia
Clotting factor PLUS platelet abnormality
Sites of bleeding: Bruising, cuts, gums, epistaxis, menorrhagia, post operative, post trauma
Treatment:
-DDAVP
-intermediate purity (plasma derived) FVIII
