Haem: Coagulation Pt.3 Flashcards
What can cause immune-mediated thrombocytopaenia?
- Idiopathic
- Drug-induced (e.g. quinine, rifampicin)
- Connective tissue disorder (e.g. SLE)
- Lymphoproliferative disease
- Sarcoidosis
List two non-immune mediated conditions that cause thrombocytopaenia.
DIC
MAHA
Describe the pathophysiology of ITP.
- Autoantibodies are generated against platelets
- Platelets are tagged by autoantibodies and then destroyed by the reticuloendothelial system (liver, spleen, bone marrow)
What are the main differences between acute and chronic ITP?
Acute:
- Mainly children
- Usually there is a preceding infection
- Abrupt onset of symptoms
- Lasts 2-6 weeks
- Spontaneously resolves
Chronic:
- Mainly occurs in adults
- More common in females
- Can be abrupt or indolent
- Does not resolve spontaneously
How is ITP treated?
Mainly with steroids and IVIG based on the platelet count
Give some examples of causes of thrombocytopaenia that can be diagnosed by blood film.
- Vitamin B12 deficiency
- Acute leukamia
What clotting study abnormality would be seen in Haemophilia?
Prolonged APTT
Outline the clinical features of haemophilia.
- Haemarthroses (MOST COMMON)
- Soft tissue haematomas (e.g. shortened tendons, muscle atrophy)
- Prolonged bleeding after surgery/dental extractions
NOTE: haemophilia A and B are clinically indistinguishable
What is a typical lesion seen in coagulation factor disorders?
Ecchymoses
What is the most common coagulation disorder? What is its inheritance pattern?
- Von Willebrand disease
- Autosomal dominant - type 1 and 2
- Autosomal recessive - type 3
What is the main clinical feature in von Willebrand disease?
Mucocutaneous bleeding
Outline the classification of von Willebrand disease.
- Type 1 - partial quantitative deficiency
- Type 2 - qualitative deficiency
- Type 3 - complete quantitative deficiency
Describe the relationship between vWF and factor 8.
- Binding of factor 8 to vWF protects factor 8 from being destroyed
NOTE: type 3 vWD has a very similar phenotype to haemophilia A (because absent vWF leads to low factor 8)
Describe the expected laboratory test results for the three types of von Willebrand disease.
- Type 1 - low antigen, low activity, normal multimer (decreased size)
- Type 2 - normal antigen, low activity, normal multimer (structurally abnormal)
- Type 3 - very low antigen, very low activity, absent multimer
Name a source of vitamin K.
- Green vegetables
- Vitamin K is synthesised by intestinal flora
What is vitamin K required for?
- Synthesis of factors 2, 7, 9 and 10
- Synthesis of protein C, S and Z
List some causes of vitamin K deficiency.
- Malnutrition
- Biliary obstruction
- Malabsorption
- Antibiotic therapy
Outline the pathophysiology of DIC.
- Release of thromboplastic material into the circulation causes widespread activation of coagulation and fibrinolysis
- This results in increased vascular deposition of fibrin, which leads to thrombosis of small and mid-size vessels with organ failure
- Depletion of platelets and coagulation factors leads to bleeding
List some causes of DIC.
- Sepsis (MOST COMMON)
- Trauma (e.g. fat embolism)
- Obstetric complications (e.g. amniotic fluid embolism)
- Malignancy
- Vascular disorders
- Reaction to toxin
- Immunological (e.g. transplant rejection)
Describe the typical clotting study results in DIC.
- Prolonged APTT, PT, TT
- Decreased fibrinogen
- Increased FDP
- Decreased platelets
- Schistocytes (due to shearing of red blood cells as it passes through a fibrin mesh)
Outline the treatment of DIC.
- Treat underlying disorder
- Anticoagulation with heparin
- Platelet transfusion
- FFP
- Coagulation inhibitor concentrate
Describe how liver disease leads to bleeding disorders.
- Decreased synthesis of clotting factors 2, 7, 9, 10, 11 and fibrinogen
- Dietary vitamin K deficiency
- Dysfibrogenaemia
- Enhanced haemolysis (decreased alpha-2 antiplasmin)
- DIC
- Thrombocytopaenia due to hypersplenism
Outline the treatment of:
- Prolonged PT/APTT
- Low fibrinogen
- DIC
-
Prolonged PT/APTT
- Oral vitamin K
- FFP infusion
-
Low fibrinogen
- Cryoprecipitate
-
DIC
- Replacement therapy
What is the management of vitamin K deficiency due to warfarin overdose based on?
INR
NOTE: warfarin is reversed by giving vitamin K (oral or IV). If severe, FFP or PCC could be given.
What is PCC?
Prothrombin complex concentrate (contains vitamin K-dependent clotting factors)
