Bleeding Disorders Flashcards
Primary homeostasis actions
-Vasoconstriction (immediate)
-Platelet adhesion (within seconds)
-Platelet aggregation and contraction (within minutes)
Secondary homeostasis actions
-Activation of coagulation factors (within seconds)
-Formation of fibrin (within minutes)
Fibrinolysis actions
-Activation of fibrinolysis (within minutes)
-Lysis of the plug (within hours)
Approach to a patient with suspected bleeding disorder
-Personal history
=Site of bleed
=Duration of bleeding
=Precipitating cause
=Surgery
-Systemic illness
-Family history
-Drugs
-Clinical examination
-FBC, BF, U&E’s, LFTS’s, coag screen, TFT’s, PP
-Coagulation factor assays
-Platelet function assays
Disorders of primary haemostasis
-Collagen – Ehlers-Danlos syndrome
-Platelet function - Bernard Soulier disease
-Platelet number – inherited thrombocytopenia
-VWF - Von Willebrand disease
Pattern of bleeding in disorders of primary homeostasis
-Easy bruising
-Prolonged bleeding from cuts
-Menorrhagia
-Epistaxis
-Bleeding after trauma
Disorders of secondary haemostasis
-Haemophilia A and B
-Other factor deficiencies
Pattern of bleeding in secondary haemostasis
-Bleeding is prolonged and can be delayed
-Deep sites
=muscles
=joints
Examples of acquired coagulation disorders
-Reduced synthesis - liver disease, bone marrow failure, vitamin K deficiency
-Immune - acquired haemophilia, ITP
-Drugs – Warfarin, Aspirin
-Consumptive - DIC
-Metabolic - uraemia
Role of liver in coagulation
-Synthesis of most coagulation factors II, VII, IX, X XI
-Carboxylation of vitamin K dependent factors
-Synthesis of anticoagulant proteins
=protein C and S, Antithrombin
-Clearance of activated coagulation factors and fibrinolytic factors
Primary haemostasis bleeding disorders
-Thrombocytopenia
=TPO production
=Splenic sequestration
=Direct ETOH toxicity on megakaryocytopoiesis
=Folate deficiency
-Reduced platelet aggregation
=Defective aggregation
=Defective thromboxane synthesis
=Storage pool deficiency
=Abnormalities gpIb
Primary haemostasis thrombosis disorders
-High VWF
=Endothelial damage
=Enhanced VWF expression in the diseased liver
=In severe cirrhosis up to x10 normal range
-Low ADAMTS-13
Secondary haemostasis bleeding disorders
-Low pro-coagulant factors
Secondary haemostasis thrombosis disorders
-High factor VIII
-Low anticoagulants
Fibrinolysis bleeding disorders
-Decreased clearance of tPA
-Low α2-antiplasmin
Fibrinolysis thrombosis disorders
-Low plasminogen
-High PAI-1
Describe the liver dysfunction involved in secondary haemostasis
-Site of synthesis of all plasma proteins (factor VIII produced by endothelial cells and liver sinusoidal cells, not hepatocytes)
-Reduced levels of coagulation factors II, V, VII, IX, X, XI are commonly observed in both acute and chronic liver failure
-Vitamin K dependent factors defective in function as a result of decreased γ-carboxylation
-Elevated VIII-endothelial activation
-Reduced protein C production
-Reduced fibrinogen
Overall liver dysfunction takeaway
-Abnormal coagulation tests are a common feature in patients with liver dysfunction
-INR does not always correlate with bleeding risk in these patients
Management of liver disease in acquired coagulation disorders
-Avoid non-essential surgery/procedures
-Monitor coagulation closely
-FFP, cryoprecipitate and platelets if active bleeding
-Likely poor response to vitamin K
Definition of DIC
DIC is characterized by loss of localization or compensated control of intravascular activation of coagulation
In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding.
Role of tissue factor in DIC
TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon activation, TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.
Epidemiology of DIC
-Always secondary to an underlying disorder
-Complicates 1% of all hospital admissions
-25%-50% of patient with sepsis develop overt DIC
-Associated with a high mortality
Common clinical conditions associated with DIC
-Sepsis
-Malignancy
-Trauma
=Head injury
=Fat embolism
-Obstetric complications
=Placental abruption
=Amniotic fluid embolism
=HELLP syndrome
-Vascular abnormalities
-Reaction to toxin (e.g. snake venom, recreational drugs)
-Immunological reactions
=Severe transfusion reactions
=Transplant rejection
Clinical manifestations of DIC
-Underlying cause
-Bleeding
-Microvascular thrombosis
-Organ failure
