Haemostasis - Bleeding: Disorders of Coagulation Flashcards
what is occurring in secondary haemostasis?
stabilisation of the platelet plug with fibrin
what is the role of the coagulation?
to generate thrombin IIa which will convert fibrinogen to fibrin
deficiency of any coagulation factor results in?
failure of thrombin generation and hence fibrin formation
list 3 causes of coagulation factor deficiencies
deficiency of coagulation factor production
dilution
increased consumption
list a hereditary cause for deficiency of coagulation factor
haemophilia A/B > factor VIII/IX
list an acquired cause for deficiency of coagulation factor
liver disease (decreased production) anticoagulant drugs (warfarin, DOACs)
list an acquired cause for dilution of coagulation factors
blood transfusion
list an acquired cause of increased consumption
disseminated intravascular coagulation (DIC)
immune - autoantibodies
haemophilia A causes a deficiency in what coagulation factor?
factor VIII
haemophilia B causes a deficiency in what coagulation factor?
factor IX
what is haemarthrosis?
bleeding into the joints (hallmark of haemophilia)
chronic haemarthrosis can lead to?
permanent damage > limit movement > muscle wasting
what medical procedure should be avoided in patients with haemophilia?
intramuscular injections
how does deficiency if factors VIII and IX present?
haemophilia: severe but compatible with life, spontaneous joint and muscle bleeding
how does deficiency if factor II (prothrombin) present?
lethal
how does deficiency of factor XI present?
bleed after trauma but not spontaneously
how does deficiency of factor XII present?
no bleeding at all
how does transfusion lead to dilution?
red cell transfusions no longer contain plasma
what is disseminated intravascular coagulation?
condition where blood clots are excessively formed in the body’s blood vessels
disseminated intravascular coagulation is associated with?
sepsis
major tissue damage
inflammation
clinical features of coagulation disorders
superficial cuts do not bleed, bruising is common, nosebleeds are rare, spontaneous bleeding is deep, into muscles and joints, bleeding after trauma may be delayed and is prolonged, bleeding frequently restarts after stopping
clinical distinction between bleeding due to platelet and coagulation defects
platelet/vascular: superficial bleeding into skin, mucosal membranes, bleeding immediate after injury
coagulation: bleeding into deep tissues, muscles, joints, delayed, but severe bleeding after injury, often prolonged
tests for coagulation disorders
screening (clotting screen): prothrombin time, activated partial thromboplastin time, FBC
coagulation factor assays
tests for inhibitors
the activated partial prothrombin time measures what pathway?
intrinsic
the prothrombin time measures what pathway?
extrinsic
what could cause normal PT but high APPT?
haemophilia A + B
factor XI, XII deficiencies
what could cause high PT but normal APPT?
factor VII deficiency
what could cause high PT and high APPT?
Liver disease
Anticoagulant drugs e.g. warfarin
DIC (platelets and D dimer)
Dilution following red cell transfusion
principles of treatment of abnormal haemostasis (failure of production/function)
replace missing factors/platelets (prophylactic, therapeutic), stop drugs e.g. aspirin, NSAIDs
principles of treatment of abnormal haemostasis (immune destruction)
Immunosuppression (e.g. prednisolone)
Splenectomy for ITP
principles of treatment of abnormal haemostasis (increased consumption)
Treat cause
Replace as necessary
factor replacement therapy
plasma (fresh frozen plasma)
cryoprecipitate
factor concentrates
recombinant forms of FVII and FIX
fresh frozen plasma contains?
Contains all coagulation factors
cryoprecipitate contains?
Rich in Fibrinogen, FVIII, VWF, Factor XIII
factor concentrates contain?
Concentrates available for all factors except factor V.
Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X
novel treatments for haemophilia
gene therapy
bispecific antibodies
RNA silencing
how do bispecific antibodies work as a treatment for haemophilia?
Binds to FIXa and FX
Mimics procoagulant function of FVIII
how does RNA silencing work as a treatment for haemophilia?
target natural anticoagulant - antithrombin
list additional haemostatic treatments
desmopressin (increase VWF, vasopressin analogue)
tranexamic acid (antifibrinolytic)
fibrin spray/glue
hormonal (OCP for menorrhagia)
