disorders of haemostasis Flashcards
what are bleeding disorders?
Deficiency in coagulation factors that cause a tendency to bleed excessively
what are the 2 types of bleeding disorders?
Hereditary
Acquired
what are 2 possible reasons for bleeding disorders?
Low levels of coagulation factors
Disfunctional coagulation factors
what are the hereditary bleeding disorders?
Haemophilia A
Haemophilia B
Haemophilia C
Von Willebrands disease
what is haemophilia A?
Deficiency of factor VIII
when does haemophilia A occur?
Absence or low levels of F VIII
what are the symptoms of haemophilia A?
Onset of symptoms in infancy Profuse bleeding following circumcision Excessive bruising when start to become active Muscle haematomas Haemarthroses Bleeds into joints Bleeds into internal organs Post-op and post-trauma haemorrhage can be life-threatening
is haemophilia A more common in males or females?
males - X linked disorder
what causes Haemophilia B?
Absence or low levels of F IX
how is the difference between haemophilia A and haemophilia B distinguished?
Distinguished only by factor IX assay
– Measure of factor IX levels
what causes haemophilia C?
Deficiency of FXI
what does treatment of haemophilia include?
- In specialised haemophilia centres
- Treated with prophylactic factor replacement therapy
- Reduced crippling haemarthroses
- Additional treatment to cover surgery, trauma and spontaneous bleeds
what is included in the laboratory diagnosis of haemophilia A, B and C?
- Activated Partial Thromboplastin Time test (APTT)
- Measures the intrinsic coagulation pathway
- – Extended (XII,XI, IX and VIII deficiency)
- Prothrombin time (PT)
- Measures extrinsic coagulation pathway
- – Normal
- Assay to measure level of coagulation factor
- Reduced
- Platelet function
- Normal
- Bleeding time
- Normal
which is the most common hereditary bleeding disease?
Von Willebrand’s disease?
why is Von Willebrand’s disease termed pseudo-haemophilia?
no joint bleeds.
what are the 3 subtypes of von Willebrand’s disease?
Type I - Mild reduction in VWF
Type II - Functionally abnormal VWF
Type III - No VWF, most severe form
what is the role of von Willebrand factor in the coagulation cascade?
- promotes platelet adhesion
- carrier molecular for factor VIII
what is the laboratory diagnosis of vWD?
- Abnormal platelet function tests
- Defective platelet aggregation
- Low FVIII levels
- APPT prolonged (Intrinsic pathway)
- vWF levels low
- Low platelet count in type 2
what is the treatment for type I von Willebrand disease?
DDAVP (vasopressin)
– Releases vWF from endothelial cells
what is the treatment for type II and III von Willebrand’s disease?
- Plasma derived FVIII/vWF concentrates
- Recombinant vWF in phase II clinical trials
what are other clotting factor deficiencies?
- fibrinogen, FV, FVII
- Prothrombin, FXIII
what causes acquired bleeding disorders?
- production problems
- consumption problems
what are examples of production problems that lead to acquired bleeding disorders?
- Vitamin K deficiency
- Liver disease
what are examples of consumption problems that lead to acquired bleeding disorders?
- disseminated intravascular coagulation (DIC)
which factors are impacted by vitamin K deficiency?
decreased synthesis of factors II VII IX X
what are the diagnostic test results of vitamin K deficient acquired bleeding disorder?
Abnormal PT and APTT
how does liver disease lead to an acquired bleeding disorder?
impaired absorption of vitamin K
as well as APPT and PT being abnormal what else is affected due to liver disease?
intrinsic and extrinsic pathway
what is DIC secondary to?
Sepsis
Malignancy
Acute myeloid leukaemia
Snake venom
what does DIC lead to?
- Deposition of fibrin in the microcirculation
- amputation
- Haemorrhage due to consumption of coagulation factors and platelets
what causes DIC?
Increase of TF expression
what are acquired inhibitors of coagulation?
Inhibitors of factor VIII
what are the hereditary disorders of platelet function?
- Glanzmann’s thrombasthenia
- Bernard Soulier syndrome
- von Willebrand disease
what occurs during Glanzmanns disease?
failure of primary platelet aggregation
what causes Glanzmanns disease?
Deficiency in membrane protein GPIIbIIIa
what is seen in Glanzmann’s disease?
Clinically severe platelet function defect
what does Clinically severe platelet function defect lead to?
Epistaxis Purpura Bruising Gum bleeding Menorrhagia Bleeding after surgery
what causes Bernard Soulier syndrome?
Absent or decreased expression of GPIb-V-IX complex on platelet surface
what occurs in Bernard Soulier syndrome?
- Defective binding to vWF
- Defective adherence to exposed subendothelial connective tissue
- Variable degree of thrombocytopenia
what is seen in Bernard Soulier syndrome?
large/giant platelets
what are the acquired disorders of platelets that are due to production?
Leukaemia
Post viral
Immunosuppression
what can shorten the lifespan of platelets and lead to acquired disorders?
malaria
bleeding
what impacts the function of platelets and lead to acquired disorders?
drugs
what are the drugs that affect platelet function?
Aspirin/NSAIDs Caffeine Antimicrobials Cardiovascular agents Anticoagulants Chemotherapy drugs
what is thrombosis?
Formation of a solid mass, a thrombus, in the lumen of a blood vessel during life.
what is a thrombus formed from?
Formed from blood constituents
- Platelets
- Fibrin
what are the 2 types of thrombosis?
Venous thrombosis-occurs in veins
Arterial thrombosis-occurs in arteries
what are thrombi associated with?
- Myocardial infarction
- Cerebral vascular disease
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
what is the pathogenesis of arterial thrombosis?
- Atherosclerosis of vessel wall
- Injury to vessel wall
- Expose blood to subendothelial collagen and tissue factor
- Formation of platelet nidus
- Platelets adhere and aggregate
- Block artery
what are the risk factors of arterial thrombosis?
- Family history
- Male
- Raised lipids
- Raised blood pressure
- Diabetes
- Smoking
what is the pathogenesis of venous thrombosis?
- Coagulability of blood
- Slowing down of blood flow
- Coagulation of blood at site of initiation of thrombus
what are the risk factors for venous thrombosis?
- Factor V leiden gene mutation
- Prothrombin gene mutation
- Protein S and C deficiency
- ABO blood group
- Raised levels of factor VIII, fibrinogen and homocysteine
- Lupus anticoagulant
- Oral contraception
- Pregnancy
- Trauma
- Malignancy
- Obesity
- Age
- Varicose veins
- Immobility
when is hereditary thrombophilia suspected?
- Young people with spontaneous thrombosis
- Recurrent DVT
- Unusual site of thrombosis
what is the most common inherited cause of venous thrombosis?
Factor V leiden mutation
what happens in Factor V leiden mutation?
Arginine replaced with glutamine position 560 on factor V gene
what does antithrombin deficiency lead to?
Recurrent venous thrombosis in early adult life
how is protein C activated?
by thrombin
what is the function of protein C?
Cleaves activated factor V and VIII
– Inactivates them
what is protein S?
Cofactor for protein C
what does prothrombin gene mutation lead to?
Causes increased levels of prothrombin in circulation
what happens in the prothrombin gene mutation?
guanine to adenine at position 20210
which blood groups have a higher risk of thrombosis?
Group A, AB and B
what is the treatment of thrombosis?
- Heparin
- Oral anticoagulants
- Warfarin
what are some new drug types used to treat thrombosis?
- FXa inhibitors
- Direct thrombin inhibitors
- Antiplatelet drugs
what are example of FXa inhibitor drugs?
Fondaparinux
Rivaroxaban
what are examples of direct thrombin inhibitor drugs?
bivalirudin
dabigatran
what are examples of antiplatelet drugs?
Clopidogrel
Aspirin
