Bleeding Disorders Flashcards
List 3 causes of vascular abnormalities associated with primary Haemostasis failure
Vit C deficiency (scurvy) (reduced collagen synthesis),
Vasculitis (henoch-schonlein purpura),
Steroids (reduces vessel wall collagen)
What is a purpura rash
Red or purple spots/patches/bruises
On skin or mucosal membrane
Are non-blanching
Are caused by broken blood vessels/ bleeding
List 4 causes of acquired thrombocytopenia (leading to primary haemostatic failure)
- Malignancy in the bone marrow (reduced production)
- Coagulopathy e.g. DIC (increased destruction)
- Autoimmune e.g. ITP (increased destruction)
- hypersplenism (increased destruction)
List 2 drugs that can cause defects in platelet function
- Aspirin
- NSAIDs e.g. ibuprofen
Failure of what organ can lead to defect in platelet function
Renal failure
Is vWF deficiency usually acquired or hereditary? If hereditary, what inheritance does it display?
Hereditary, autosomal dominant
What is the most common cause of primary haemostatic failure and how would this direct your investigations & treatment
Thrombocytopenia
- If pancytopenia - biopsy to check for marrow malignancy
- If only thrombocytopenia - assume ITP (unless specific signs of other cause) and start immunosuppression
Name 3 causes of multiple factor deficiency associated with secondary haemostatic failure
- Liver failure (reduced synthesis)
- Vitamin K deficiency/ warfarin therapy (reduced ‘activation’)
- Complex coagulopathy (DIC) (increased use)
What are the two screening tests for secondary haemostasis and what factors/pathways do they assess
Prothrombin Time (PT)
- Extrinsic (TF/VII) & common pathway
Activated partial thromboplastin time (APTT)
- Intrinsic (VIII/IX) & common pathway
What is a screening test for primary haemostatic failure
Platelet count
Where are coagulation factors synthesised
Hepatocytes
Which 4 factors are carboxylated by vitamin K in order to function
II (prothrombin), VII, IX, X
What are the two sources of vitamin K
Intestinal absorption from diet (jejunum & ileum)
Intestinal synthesis (large intestine)
What is required for vitamin K absorption
Bile salts
List 4 causes of vitamin K deficiency
- Poor dietary intake
- Malabsorption conditions
- Obstructive jaundice (bile duct obstructed)
- Vitamin K antagonists e.g. warfarin
(+ haemorrhagic disease of newborn)
Why are all baby’s given vitamin K at birth
Newborns have very low vitamin K as it can’t easily cross teh placenta and is not in breastmilk
Vitamin K deficiency in newborns can cause haemorrhagic disease of the newborn
Therefore, newborns must be injected with vitamin K at birth
What is disseminated intravascular coagulation, describe its pathophysiology
1) Cytokine signalling as part of inflammatory response OR
Release of procoagulant material e.g. TF
2) Excessive activation of haemostatic system
(Primary, secondary & thrombolysis)
3) Microvascular thrombus formation => end organ damage
4) Clotting factor consumption & hence depletion => brusing, purpura, generalised bleeding
What test can be used to differentiate between DIC and other causes of multiple factor deficiencies
D-dimer test (d-dimer is a fibrin degradation product)
DIC causes excessive fibrinolysis, unlike in other causes of multiple factor deficiency
DIC aetiology
- Sepsis
- Obstetric emergencies
- Malignancy
- Hypovolaemic shock
- ABO incompatible blood transfusion
DIC clinical presentation
- Petechiae/purpura/bruising
- Excessive bleeding
- Acutely ill - fevers, confusion, hypotension, potential coma
DIC investigations & findings summary
- Severe thrombocytopenia (low platelet count)
- Prolonged PT, APTT & TT (low clotting factors)
- High FDPs e.g. d-dimer (excess fibrinolysis)
- Fragmented RBCs on blood film
DIC treatment
Treat cause!
Replacement therapy!
- Platelet transfusions
- Plasma transfusions
- Fibrinogen replacement
What is haemophilia and what is its inheritance pattern
X-linked, hereditary disorder (more likely in men)
Abnormal, prolonged, episodic bleeding at one or a few sites
Haemophilia A vs B, what factor does it affect?
Haemophilia A - Factor VIII deficiency (most common)
Haemophilia B - Factor IX deficiency
How is primary haemostasis affected with haemophilia
Primary haemostasis is normal
Severe haemophilia clinical presentation
Recurrent haemarthroses (knee, ankle, elbow)
Recurrent soft tissue bleed (extensive bruising in kids)
Prolonged bleeding after medical/ dental procedures
Thinking about the factors affected in haemophilia, what screening tests would likely be abnormal?
Haemophilia A & B affects the intrinsic pathway
& so APTT would be prolonged
& PT would be normal
Haemophilia investigations summary
Bloods - APTT (prolonged), PT (normal)
Bloods - coagulation factor assays (VII - A, IX - B)
Genetic testing
Haemophilia long term management & risk
Prophylactic clotting factor replacement
- in severe disease only
- risk of individual developing antibodies against the factor
Summarise primary haemostatic failure aetiology
Vascular (collagen) defect (usually acquired)
- Severe vitamin C/ scurvy
- Steroids
- Vasculitis e.g. henoch-schonlein purpura
Thrombocytopenia (low platelets) (usually acquired)
- Reduced production - marrow malignancy
- Increased destruction - DIC, ITP, splenomegaly
vWF deficiency (usually herediatry)
Summarise secondary haemostatic failure aetiology
Multiple factor deficiency (usually acquired)
- Liver disease (reduced production)
- DIC (increased use)
- Vitamin K deficiency (reduced ‘activation’)
- malnutrition/absorption/obstructive jaundice/warfarin
Single factor deficiency (usually hereditary)
- Haemophilia A or B
If a patient with haemophilia (mild or severe disease) was acutely bleeding or was about to undergo surgery, would treatment would you provide
- Minor bleed - Desmopressin (stimulates vWF which stimulates clotting factor)
- Major bleed - Clotting factor (VIII or IX) infusion
- Bleeding wounds (not muscle haematoma/haemarthrosis/haematuria) - Option of anti-fibrinolytics
What screening tests would be affected in a multiple factor deficiency such as liver disease/DIC/vitamin K deficiency
All! - PTT, APTT & TT
What does an isolated prolonged APTT mean?
Haemophilia A or B
What is Von willebrand’s disease, what effect does it have on primary haemostasis & factor VIII
- Inherited bleeding disorder
- Reduced quantity or function of vWF, varying severity
- low vWF => impaired platelet adhesion to subendothelium
- low vWF => factor VIII deficiency (as vWF ‘protects’ VIII)
vWF investigations & findings
FBC
- normal
- or low platelet count
- or microcytic anaemia (iron deficiency)
Coagulation tests
- PT normal
- APTT normal or prolonged if factor VIII deficiency
Specialised vWF tests
What is the relationship between vWF and factor VIII
VWF protects factor VIII from proteolysis
VWF treatment
Desmopressin OR
Plasma-derived factor VIII concentrates with intact vWF
What reaction is involved in immune thrombocytopenia purpura (ITP)
Type II hypersensitivity - Antibody production against platelets
Immune thrombocytopenia purpura (ITP) an isolated (primary) conditions or can be secondary to another disorder. Name 5 disorders associated with ITP
- Autoimmune - SLE, APS
- Infections - viral, helicobacter pylori
- Medications - antibiotics, anticonvulsants, NSAIDs…
- Lymphoproliferative disorders
**Viral infection in children most common!!
Immune thrombocytopenia purpura (ITP) clinical presentation
- History of recent viral illness
- Usually children <10yrs
- 1 or 2 day history of bleeding/ bruising
- bleeding gums, epistaxis, menorrhagia
- petechia or purpura rash
Immune thrombocytopenia purpura (ITP) investigations & findings
FBC & blood film - isolated thrombocytopenia
Immune thrombocytopenia purpura (ITP) management
Usually self-limiting, monitoring till normal platelets
If severe or actively bleeding
- prednisolone => IV immunoglobulins => blood transfusion
