Haematology Flashcards
What is the mechanism of action of Dabigatran?
Direct thrombin inhibitor
What is the reversal agent for Dabigatran?
Idarucizumab
What is the mechanism of action of apixaban and rivaroxaban?
Direct factor Xa inhibitor
What is the reversal agent for apixaban and rivaroxaban?
Andexanet alfa (recombinant form of factor Xa)
What is the mechanism of action of fondaparinux?
Activates antithrombin III
What is an example of a direct thrombin inhibitor other than dabigatran?
Bivalirudin usually IV
What does unfractionated heparin inhibit?
Thrombin, factors Xa, IXa, XIa, XIIa
What is the mechanism of action of LMWH?
Activates the action of antithrombin III on factor Xa
What are the benefits of LMWH vs standard heparin?
Less risk of heparin induced thrombocytopenia and osteoporosis
How do you monitor standard heparin?
Activated partial thromboplastin time
How do you monitor LMWH?
Anti-factor Xa
How do you reverse heparin overdose?
Protamine sulphate (only partially reverses LMWH)
What is the mechanism of action of warfarin?
Inhibits epoxide reductase preventing the reduction of vitamin K to its active form
This usually works on clotting factors II, VII, IX, X and protein C
What is target INR for mitral valve?
3.5
What things potentiate warfarin?
Liver disease
P450 enzyme inhibitors e.g. amiodarone, ciprofloxacin
Cranberry juice
Drugs which displace warfarin from plasma albumin e.g. NSAIDs
Drugs that inhibit platelet function e.g. NSAIDs
What are inducers of the P450 system?
Antiepileptics e.g. phenytoin, carbamazepine
Barbiturates e.g. phenobarbitone
Rifampicin
St John’s Wort
Chronic alcohol intake
Griseofulvin
Smoking
What are inhibitors of the P450 system?
Antibiotics e.g. cirpofloxacin, clarithromycin
Isoniazid
Cimetidine, omeprazole
Amiodarone
Allopurinol
Imidazoles e.g. ketoconazole, fluconazole
SSRIs e.g. fluoxetine, sertraline
Ritonavir
Sodium valproate
Acute alcohol intake
Quinupristin
Do inhibitors or inducers of the P450 system increase INR?
Inhibitors
How do you reverse warfarin in major bleeding?
Give IV Vitamin K 5mg
Prothrombin complex concentrate (FFP if not available)
How do you manage INR > 8?
Minor bleeding: Stop warfarin, IV Vitamin K 1-3mg, repeat if necessary, restart warfarin when INR <5
No bleeding: Stop warfarin, give oral Vitamin K 1-5mg using IV preparation, repeat if necessary, restart warfarin when INR <5
How do you manage INR 5-8?
Minor bleeding: Stop warfarin, give IV Vitamin K 1-3mg, restart when INR <5
No bleeding: withhold 1 or 2 doses of warfarin and reduce subsequent maintenance dose
What antiplatelets are first line for ACS?
Aspirin and ticagrelor (12 months)
What antiplatelet is second line in ACS if aspirin CI?
Clopidogrel
What antiplatelets are first line for PCI?
Aspirin and prasugrel or ticagrelor (12 months)
Which antiplatelet is first line for TIA, stroke, PAD?
Clopidogrel lifelong
Which antiplatelets are second line for TIA and stroke if clopidogrel CI?
Aspirin (lifelong) and dipyridamole (lifelong)
Which antiplatelet is second line for PAD if clopidogrel CI?
Aspirin lifelong
Which blood product is used for chronic anaemia?
Packed red cells
What does fresh frozen plasma contain?
Clotting factors, albumin and immunoglobulin
What does cryoprecipitate contain?
Factor VIII and fibrinogen
What is the transfusion threshold?
Patient without ACS: 70g/L
Patient with ACS: 80g/L
What is the target for after transfusions?
Patient without ACS: 70-90g/L
Patient with ACS: 80-100g/L
What causes acute haemolytic transfusion reaction?
Mismatch of blood group ABO e.g. secondary to human error
Which transfusion reaction is due to a mismatch of blood group ABO e.g. secondary to human error?
Acute haemolytic transfusion reaction
How quickly does acute haemolytic transfusion reaction happen?
Minutes after
Fever
Abdominal and chest pain
Agitation
Hypotension
How is acute haemolytic transfusion reaction manages?
Stop transfusion
Generous fluid resuscitation with saline solution
Check patient identity
Send blood for direct Coombs test
Repeat typing and cross matching
What causes non-haemolytic febrile reaction?
HLA antibodies reacting with WCC fragments in the blood profit and cytokines that have leaked from the blood cell during storage
Often the result of sensitisation by previous pregnancies or transfusions
How is a non-haemolytic febrile reaction managed?
Slow or stop transfusion
Paracetamol
Monitor
What are the symptoms of a non-haemolytic febrile reaction?
Fever
Chills
How is a minor allergic reaction to blood transfusion managed?
Temporarily stop
Give antihistamine
May restart when symptoms have resolved
How is anaphylaxis to blood transfusion managed?
Stop transfusion
Give IM adrenaline
ABC support
Antihistamine
Corticosteroid
Bronchodilator
What causes anaphylaxis to blood transfusion?
Patients with IgA deficiency who have anti-IgA antibodies (hypersensitivity reaction)
What is a transfusion related acute lung injury (TRALI)?
Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
How quickly does transfusion related acute lung injury (TRALI) present?
ARDS within 6 hours
What are the symptoms of transfusion related acute lung injury (TRALI)?
Fever
Hypotension
Infiltrates on CXR
How is transfusion related acute lung injury (TRALI) managed?
Stop the transfusion
Oxygen
Supportive care
What causes transfusion associated circulatory overload?
Excessive rate of transfusion or pre-existing HF
What are the signs of transfusion associated circulatory overload?
Pulmonary oedema
Hypertension
How is transfusion associated circulatory overload managed?
Slow or stop the transfusion
Consider IV loop diuretic
Oxygen
How do you differentiate between TRALI and TACO?
TRALI = hypotension
TACO = hypertension
What infection can be passed in blood transfusions?
variant Creutzfeldt-Jakob disease
What is the role of the spleen?
Remove immature or abnormal RBC from the circulation
What is seen on histology of hyposplenism?
Howell-Jolly bodies (cytoplasmic inclusions)
Siderocytes
What should patients with hyposplenism be vaccinated for?
Hib, meningitis A&C
Annual influenza
Pneumococcal vaccine every 5 years
What antibiotic prophylaxis is given for at least 2 years in hyposplenism?
Penicillin V or amoxicillin
What causes hyposplenism?
Splenectomy
Sickle-cell (atrophied spleen due to repeated infection)
Coeliac
Graves
SLE
Amyloid
What are indications for splenectomy?
Trauma
Spontaneous rupture (EBV)
Hypersplenism: hereditary spherocytosis or elliptocytosis
Malignancy: lymphoma or leukaemia
Splenic cysts, heated cysts, abscess
How is neutropenic sepsis defined?
Neutrophil count <0.5 in a patient having active anticancer treatment and:
Temperature >38 OR
Other signs consistent with sepsis
What is a common pathogen in neutropenic sepsis?
Staph epidermis due to indwelling lines
What is prophylaxis for neutropenic sepsis?
Fluoroquinolone
How does DIC present on blood test?
Low platelets
Low fibrinogen
Increased PT and APTT
Increased fibrinogen degradation products
Schistocytes due to microangiopathic haemolytic anaemia
What is the role of thrombin?
Converts fibrinogen to fibrin
What is the role of plasmin?
Breaks down fibrin
What is a key mediator of DIC?
Release of a transmembrane glycoprotein (tissue factor)
What is DIC?
Widespread clotting with resultant bleeding due to dysregulated coagulation and fibrinolysis
What is Budd-Chiari syndrome?
Obstruction to the outflow from the liver caused by thrombosis in the hepatic veins or IVC
What is the classic triad of Budd-Chiari syndrome?
Abdominal pain
Hepatomegaly
Ascites
How is a diagnosis of Budd-Chiari syndrome made?
Doppler US
What is the management of Budd-Chiari syndrome?
Anticoagulation e.g. LMWH, warfarin
Endovascular procedures e.g. thrombolysis or angioplasty
Transjugular intrahepatic protosystemic shunt (TIPS)
Liver transplant
