Haematology Flashcards
What is haemolytic uraemic syndrome?
Triad of:
1. Microangiopathic haenolytic anaemia (MAHA)
2. Thrombocytopenia
3. Renal failure (really severe / anuric)
What are the causes of HUS?
- Infection associated
- Atypical (inherited complement dysregulation)
What infections is HUS associated with?
- Verotoxin-producing enterococci (E.coli 0157) or shigella. Prodrome of bloody diarrhoea
- Pneumococcus
What is the pathophysiology of infection associated HUS?
The toxin causes direct injury to the renal vascular endothelium, which leads to excessive platelet aggregation, plt microvascular thrombi and ultimately AKI. Subsequent hypertension and fluid overload is common.
What investigations would you perform in someone with suspected HUS?
- Blood tests
- FBC
- Blood film (reticulocytes, evidence of haemolysis and thrombocytopenia)
- LDH (raised in haemolysis)
- U+Es (AKI)
- LFTS incl split bilirubin
- Clotting including fibrinogen and D-dimers
- HIV and hepatitis serology
- Full renal screen - Stool for MC+S
- Urinalysis
- Consider renal imaging to look for other cause of AKI
How would you manage a pt with HUS?
- Careful fluid and electrolyte balance
- CVS support/ BP control
- Renal and haematology input
- Treat cause e.g. cipro for e.coli / shigella
- Plasma exchange
What is thrombotic thrombocytopenic purpura?
Autoimmune disorder characterised by a pentad of:
1. Thrombocytopenia
2. MAHA
3. Neurology
4. Renal impairment
5. Fever
Often fever might not be present
What’s thr pathophysiology of TTP?
Autoantibody against ADAMTS13, which is a von-Willebrand factor-cleaving protease.The absence of ADAMTS13 is large multimers of vWF resulting in uncontrolled platelet activation and shredding of RBCs
What are the diagnostic features of TTP?
- Low plts (often 10-30)
- Anaemia due to intravascular haemolysis
- Rasied LDH
- Raised reticulocytes
- Rasied bilirubin
- Low haptoglobin - Haemoglobinuria
- Mild-to-mod renal impairment
- Low ADAMTS13 activity
How is TTP managed?
1.Plasma exchange (reduces mortality from 90% to 10%)
2. Methylpred
3. Rituximab
4. Caplacizumab
5. Recombinant ADAMTS13
What are the causes of psueodthrombocytopenia?
- Clotted blood sample
- EDTA-dependent antibodies
- Medications - heparin / HIT, clopidogrel, tirofiban
- Acute alcohol toxicity
What haemotinic deficiency can cause low plts?
Acute B12 deficiency which is a/w nitrous oxide abuse
What are the causes of low plts?
- Sepsis
- Major haemorrhage
- Mechanical fragmentation - RRT/CPB etc
- Immune-mediated - immune thrombocytopenic purpura, APLS, post transfusion purpura
- MAHA - DIC, TTP, HUS
- Hypersplenism
- Other - myelodysplastic syndrome, malignancy, hereditary thrombocytopenia
How much does cryo raise fibrinogen levels?
4-5 pools will raise fibrinogen by 1g/l
In major haemorrhage if Apttr > 1.5 how might you manage that?
15-20mls/kg FFP
What is DIC?
Charachterised by widespread coagulation system activation resulting in intravascular thrombosis in small vessels and critical organ dysfunction. Haemorrhage occurs due to loss of haemostatic factors
How is DIC diagnosed?
- Clinical suspiscion
- Lab findings
- Exclusion of other causes?
ISTH criteria is based on plt count, raised d dimer/FDPs, raised PT, fibrinogen level. A score of 5 of more is consistent with overt DIC
What causes DIC?
A/w many medical conditions including:
Sepsis
Trauma
Malignancy
Obstetrics
How is DIC managed?
- Early and aggressive treatment of underlying condition
- Algorithm-led transfusion of blood products for those that are bleeding or at high risk e.g. invasive procedures
- Use of blood products in those not bleeding is controversial
- Prophylactic doses of heparin may be appropriate in some patients
Should TXA be used in DIC?
The recovery of DIC is dependent on breakdown of widespread microvascular thrombosis by endogenous fibrinolysis therefore antifibrinolytic drugs are not recommended
How does renal failure affect clotting?
- Impaired plt adhesion, activation and aggregation
- Decreased clearance of vWF, F VIII and fibrinogen plus simultaneous reduciton in synthesis of physiological anticoagulants protein C,S and antithrombin
- Renal failure increases bleeding, thrombosis and mortality
What is cardiolipin?
An important component of the inner mitochondrial membrane
What is the pathophysiology of APLS?
- Antiphospholipid antibodies (aPLs) are produced by B cells
- These aPLs are directed against particular phospholipid-binding proteins e.g. B2 glycoprotein I and prothrombin
- These aPLs interact with proteins in a way that can activate the endothelial cells, up-regulate procoagulants and stimulate inflammatory processes
What does binding of aPLs to B2GPI result in?
Occurs in APLS
Results in:
- upregulaiton of tissue factor
-suppression of TF pathway inhibitor
-down reg of endothelial NO synthase
- complement activation
- inhibition of fibrinolysis
