Lecture 13: Coagulation disorders Flashcards
What are the laboratory tests for clotting?
APTT
PR (Prothrombin ratio)
TCT
What pathways do the various lab tests assess?
APTT = Intrinsic pathway
Prothrombin ratio = Extrinsic pathway
Thrombin clotting time = Thrombin / platelet function
What factors does the APTT assess?
All factors except factor 7.
Therefore prolonged APTT could be any factor deficiency except 7.
Xii, Xi, IX, Viii are APTT only.
What is APTT and how is it done?
Activated partial thromboplastin time
- Venous blood sample collected into citrate (removes Ca and prevents clotting, chelate)
- Spin down, plasma collected
- Phospholipid + Activator + Ca added
- Length of time to form clot is informative.
What are the contact factors for APTT?
Contact factor
- Kaolin
- Silica
- Ellagic acid
Contact factor + Phospholipid + Ca
What is prothrombin time measuring and how is it done?
It is measuring the time for prothrombin to form, it reflects factors 5, 7, 10
How is prothrombin time expressed?
- Converted to prothrombin ratio
- Prothrombin time (patient) / prothrombin time (normal plasma)
- Normally is around 1
What does prolonged PR and APTT indicate?
Common factor deficiency
What is thrombin clotting time? what can it be used to measure?
Measures fibrinogen
- Can be used to measure impact of inhibitors such as heparin and dibigotran
Whats normal APTT?
25-37 seconds
What can be done to follow up on a prolonged APTT and how does it work?
Mixing studies: i.e is a factor deficiency or inhibitor present
1:1 mixing with normal plasma + incubation
= Sample corrects to normal and remains normal indicating a factor deficiency in patient.
Sample does not fully correct then an inhibitor is present
Describe the physiological inhibitors impact on APTT:
Antithrombin, protein C+S are natural inhibitors and DO NOT affect APTT
Inhibitors that affect APTT are different
What inhibitors prolong the APTT 1+1?
Lupus anticoagulant
Factor inhibitors i.e autoimmune antibodies
Heparin
Debigatran
How does lupus anticoagulant prolong APTT 1+1? whats its impact on bleeding?
- Might be part of antiphospholipid syndrome
- Can present transiently in patients whom are unwell
- Antibodies in plasma interfere with APTT assay
DOES NOT CAUSE BLEEDING
Write some notes on factor autoantibodies and they impact on bleeding?
- Usually anti-factor 8
- Can be life threatening
- Associated with bleeding including bruising
RARE but should be considered in bleeding patient
How does heparin interfere with ATPP 1+1 and its impacts on clotting:
- Heparin causes prolonged 1+1
- Confirmed by the addition of protamine (Corrects it)
- Heparin upregulates antithrombin (GAG chains)
- Biological GAGs dont affect APTT B/c heparin infusion is much larger amount
- Thrombin clotting time also very prolonged. (but again corrected with protamine)
What is heparin commonly used for and how can it contaminate samples?
- Commonly used to lock central lines…
- Contamination common if tube collected this way
How does dabigatran affect APTT?
- Prolongs APTT 1+1 and DOES NOT correct with protamine
- Direct inhibitor of thrombin
- Thrombin clotting time also very prolonged. (DOES NOT correct with protamine)
Interpret: APTT prolonged, PT normal:
Deficiencies of factor(s): 8,9,11,12
Interpret: PT prolonged, APTT normal:
Deficiency of factor 7 (extrinsic)
Occasionally mild deficiencies of 2,5,10 or 1
Interpret: Both PT and APTT prolonged:
- Deficiency of factors 2,5,10 or 1 (common)
- Multiple factor deficiency
What does prolonged TCT indicate?
- Deficiency of fibrinogen
- Thrombin inhibitor (i.e dabigatran or heparin)
What are some other ways of assessing clotting?
- Single factor assays
- Whole blood clotting tests
- Primary heamostasis: platelet function testing
- D-dimers
What commonly leads to multiple factor deficiencies?
- Warfarin or Vit K deficient (Factors 2, 7, 9, 10)
- Massive blood loss i.e loss of coag factors + fluids dilution
- DIC (factors, platelets and fibrinogen used up)
- Liver disease: Lack of factors and inhib production (except factor 8)
What can cause a prolonged PT?
Extrinsic pathway (APTT normally prolonged also)
- Warfarin or Vit K deficient (2,7,9,10)
- Liver disease
- Low factor 7 (APTT normal)
How is a prolonged PT monitored?
Monitor with International Normalized Ratio
How does warfarin function?
Inhibits recycling of Vit K
- Doses are adjusted based on the INR
- Used in atrial fibrilation, venous thromboembolism etc
How is warfarin reversed?
Vit K (or plasma products replacing clotting factors)
Describe the symptoms of severe heamophilia:
Spontaneous joint bleeds
- Chronic arthropathy
- Joint destruction
- Arthritis
Soft tissue bleeds
- Tissue damage
- Nerve damage
- Deformity
Whats happening in heamophilia A?
- Factor 8 deficiency
- X linked
- Mild to severe bleeding
Whats happening in heamophilia B?
- Deficient in factor 9
- X linked recessive
- Clinical features identical to A
Whats the most common COD for heamophilia?
Intracranial bleed was the commenest cOD
Whats the treatment for heamophilia?
Replace the missing factor, normal outcomes except when inhibitors develop
How is heamophilia tested and diagnosed?`
- Prolonged APTT, normal PR
- Single factor assays; low factor 8 or 9
- Genetic analysis
What else can cause low factor 8?
Von willibrand disease
What does VWF do?
- Tethers platelets to vessel walls
- Serves as carrier for factor 8, stabilizing it and preventing degredation
What is the most common inherited bleeding disorder?
Von willibrand disease
- Autosomal dominant
How is von willibrands disease tested?
- Abnormal platelet screen
- Marginally prolonged APTT (not all)
- Low factor 8
- Low level and function of VWF
What are the symptoms of VWF?
Mucosal bleeding
- Epistaxis
- Gum bleeds
- GI loss
Bruising
Menorrhagia
Post-partum or perioperative bleeding
Autosomal family history
What can cause DIC?
Sepsis-many bacteria
Malignancy
Organ damage i.e pancreatitis
Trauma
