8: Disorders of haemostasis Flashcards
2 main general reasons why abnormal haemostasis occurs
Lack of a specific factor (increased consumption, failure of production)
Defective function of a factor (genetic or acquired defect)
What is primary haemostasis?
Formation of an unstable plug
Platelet adhesion + aggregation
What are the 3 types of disorders of primary haemostasis?
Disorders of PLATELETS: Thrombocytopenia (low platelet) or impaired function
Disorders of VWF
Disorders of VESSEL WALL
What is the autoimmune cause of thrombocytopenia?
Auto-immune (auto-ITP)
Anti-platelet autoantibodies sensitizes platelets, meaning they are cleared faster by macrophages
What are mechanisms of thrombocytopenia?
Bone marrow failure (leukemia, B12 deficiency) Accelerated clearance (ITP) Pooling/destruction of platelets in enlarged spleen (hypersplenism)
What are mechanisms of impaired function of platelets?
Hereditary absence of glycoproteins or storage granules
ACQUIRED due to drugs (aspirin, NSAIDs, clopidogrel)
Example of a hereditary platelet defect?
Lack of glycoproteins Gp2b/3a = Glanzmann’s thrombasthenia (autosomal recessive)
What is a disorder of VWF known as?
Von Willebrand Disease
Hereditary (COMMON) - less VWF or impaired function
Acquired (RARE) - due to anitbodies
Oral contraceptives can be used for menhorragia
What are the 2 functions of VWF in haemostasis?
- Binds to collagen and captures platelets
2. Stabilises F8
What are the disorders of the vessel wall?
Acquired: scurvy, steroid therapy, age
Hereditary vascular disorders
Bleeding in primary haemostasis disorders?
Immediate, prolonged bleeding from cuts Epistaxis Gum bleeding Easy bruising Menorrhagia
In thrombocytopenia: PETECHIAE
In severe VWD: Haemophilia-like bleeding
How do you test for primary haemostasis
Clinical observation
Platelet count/morphology
Assays of VWF
Platelet function analyser in lab
What is secondary haemostasis?
Stabilisation of plug with fibrin
- Blood COAGULATION stage
What is the role of the coagulation cascade?
To generate a BURST OF THROMBIN which will convert fibrinogen to fibrin
What is haemophilia?
Failure to generate fibrin to stabilise platelet plug
What are the disorders of coagulation?
Deficiency of coagulation factor
(Hereditary/acquired)
Increased consumption of coagulation factor
What are examples of hereditary coag. factor deficiency?
Haemophilia A (F8 deficiency) Haemophilia B (F9 deficiency)
What are the differences between haemophilia and other coag. factor deficiency diseases?
Haemophilia A/B = severe but compatible with life, spontaneous joint/muscle bleeding
Pro-thrombin deficiency = LETHAL
Factor 11 deficiency = bleed after trauma but NOT spontaneously
Factor 12 def. = No bleeding at all
What are examples of acquired coag. factor deficiency?
Liver disease (most coag factors produced here) Dilution of blood (red cell transfusions dont have plasma) Anticoags (warfarin)
What are examples of increased consumption of coag factor?
Disseminated Intravascular coagulation (DIC)
Autoimmune disease
Explain DIC
Generalised activation of coagulation around the body
Depletes coag factors, platelets, fibrinogen, etc..
Associated with sepsis, inflammation, major tissue damage
Bleeding in coagulation disorders?
Superficial cuts do not bleed since platelets are fine
More bruising, but nosebleeds rare
HAEMOARTHROSIS = SPONTANEOUS deep bleeding into JOINTS/muscles
Major differences between haemostasis due to platelet and coagulation disorders
Platelet: SUPERFICIAL bleeding into skin + mucosal membranes
IMMEDIATE bleeding after injury
Coagulation: SPONTANEOUS bleeding DEEP into joints, muscles and tissue
DELAYED but SEVERE bleeding after injury
How do you test for coag. disorders?
Screening test (APTT) Factor assays (F8) Test for inhibitors
What happens to APTT in haemophilia?
PROLONGED
Most of the common bleeding disorders not usually detected by routine clotting tests. What else can you do?
Look at bleeding history
What are the disorders of fibrinolysis?
Hereditary: Antiplasmin deficiency
Acquired: drugs, DIC
Rare disorder
Genetics of haemophilia?
X linked recessive
XY (males) with haemophilia gene will have haemophilia
XX (females) with one gene will be carriers
Genetics of VWD?
Autosomal dominant
Treatment of abnormal haemostasis?
Failure of production/function: Factor replacement therapy, gene therapy for haemophilia, stop drugs
Immune destruction: immunosuppressants, splenectomy for ITP
Increased consumption: Treat cause, replace if necessary
What are the types of factor replacement?
Plasma (contains all factors)
Cryoprecipitate
Factor concentrates
Additional treatments?
DDAVP (Vasopressin analogue) - increases release of VWF from endothelial cells. Endogenous VWF hence only for mild disorders
Tranexamic acid - inhibits fibrinolysis
Fibrin glue/spray
Prolonged PT may result from..
Factor 7 deficiency
Prolonged of APTT may result from..
Haemophilia A/B
What can you used for management of patients of VWD?
Oral contraceptive pill - for menhorragia
VWF/F8 concentrates
DDAVP - increases VWF
Tranexamic acid
