Haematology & Oncology Flashcards
Unfractionated heparin (UFH) MOA
UFH enhances the activity of antithrombin, leading to the inhibition of coagulation factors IIa (thrombin) and Xa.
Low molecular weight heparins (LMWHs) MOA
LMWHs exert their anticoagulant effect by targeting factor Xa
Dabigatran MOA
Dabigatran is an inactive prodrug. It acts by reversibly inhibiting free thrombin, fibrin-bound thrombin, and thrombin-induced platelet aggregation.
Apixaban, edoxaban and rivaroxaban MOA
These DOACs competitively inhibit both free and clot-bound factor Xa,
DIC blood results
Platelet count
Fibrinogen
PT
D d-dimer
TT
Coag factors
Platelet count - low
Fibrinogen - low
PT - prolonged
D d-dimer - elevated
TT - prolonged
Coag factors - low
INR 5-8 no bleeding
Withhold 1-2 doses of warfarin and reduced maintenance dose
INR 5-8 w/ bleeding
IV Vit K (phytomenadione)
Stop warfarin and restart when INR <5
INR >8 but no bleeding
Give oral Vit K (rpt if still high after 24hrs)
Stop warfarin and restart when INR <5
INR >8 minor bleeding
Give IV Vit K (rpt if still high after 24hrs)
Stop warfarin and restart when INR <5
Major bleeding on wafarin
IV Vit K & dried PT complex (or FFP if not available)
Stop warfarin
Reversal agent for dabigatran?
Idaruccizumab
What is andexanet alfa used for?
To reverse apixaban & rivaroxaban in pts with life threatening or uncontrolled bleeding, IF THE BLEED IS IN THE GI TRACT
Heparin reversal agent
Protamine sulfate
Which virus causes sickle cell aplastic crisis?
Parovirus B19
Most common cause of osteomyelitis in children with sickle cell
Salmonella enterica
Most common leukaemia in adults
CLL
MSCC signs / symptoms
Severe or progressive lumbar back pain
Nocturnal pain interfering with sleep
Localised spinal tenderness
Radicular pain
Neurological symptoms
MASCC Risk Index Score cut off for OP tx of neutropenic sepsis
21 or greater
Most common causes of MSCC
prostate (1st), lung, breast and myeloma
peripheral blood smear in iron deficiency anaemia
poikilocytosis (variation in shape) and anisocytosis (variation in size). Pencil cells are typical of iron deficiency anaemia.
The most common virus transmitted by blood transfusion
parvovirus B19
The most common bacterial organism associated with transfusion-transmitted bacterial infection
Yersinia enterocolitica
Treatment for Transfusion-associated graft-vs-host disease
Supportive only
Microcytic anaemia
(MCV < 80 fl)
(6)
Iron deficiency anaemia
Thalassaemia
Anaemia of chronic disease (can also be normocytic)
Sideroblastic anaemia (can also be normocytic)
Lead poisoning
Aluminium toxicity (affects some haemodialysis patients but now rare)
Normocytic anaemia
(MCV 80-100 fl)
(8)
Haemolysis
Acute haemorrhage
Bone marrow failure
Anaemia of chronic disease (can also be microcytic)
Mixed iron and folate deficiency
Pregnancy
Chronic renal failure
Sickle-cell disease
Macrocytic anaemia
(MCV > 100 fl)
(9)
B12 deficiency
Folate deficiency
Hypothyroidism
Reticulocytosis
Liver disease
Alcohol abuse
Myeloproliferative disease
Myelodysplastic disease
Drugs e.g. methotrexate, hydroxyurea, azathioprine
Bacterial infection is more common with what blood products
Platelet transfusion (as platelets are stored at room temperature)
Previously frozen components thawed by immersion in a water bath
Red cell components stored for several weeks
Most common type of transfusion reaction
Febrile transfusion reactions are the commonest type of transfusion reaction, occurring in approximately 1 in 8 transfusions.
Glanzmann’s thrombasthenia
is a rare congenital platelet disorder in which platelets contain defective or low levels of glycoprotein IIb/IIIa.
Distinguish iron-deficiency anaemia from anaemia of chronic disease
TIBC is typically increased, and serum ferritin is typically low
Auer rods most commonly seen on blood films in which disease states?
They are most commonly seen in acute myeloid leukaemia but can also be seen in high-grade myelodysplastic syndromes and myeloproliferative disorders.
Sickle-cell disease is caused by a point mutation in what?
The beta-globin chain of haemoglobin
Febrile transfusion reaction is caused by?
Usually caused by cytokines from leukocytes in transfused red cell or platelet components.
Acute haemolytic reaction is caused by?
Often ABO incompatibility due to administration error.
Allergic reaction in the context of a blood transfusion is caused by?
Usually caused by foreign plasma proteins but may be due to anti-IgA.
Transfusion Related Acute Lung Injury is caused by?
Step 1: underlying illness -> complement activation -> pulmonary sequestration of neutrophils
Step 2: transfusion -> neutrophil activation -> endothelial cell damage and capillary leak syndrome
Graft vs host disease in the context of blood transfusions
Viable T lymphocytes in blood components are transfused, engraft and react against the recipient’s tissues and the recipient is unable to reject the donor lymphocytes because of immunodeficiency, severe immunosuppression, or shared HLA antigens.
Multiple myeloma is a malignant neoplasm of
Plasma cells
Monitoring blood test for Unfractionated heparin
APTT/APTTr
Monitoring blood test for LWMH / Fondaparinux?
Anti-factor Xa assay
Fondaparinux reversal agent?
Recombinant factor VIIa (minimal evidence)
LMWH reversal
LMWH has no specific antidote for its reversal but protamine will neutralise approximately 60% of its anticoagulant effect.
Asymptomatic / minor bleeding
Monitoring time for:
UFH
LMWH & fondiparinux
6 hrs
24hrs
Dabigatran reversal agent
Idarucizumab
What is used for immediate reversal of warfarin?
Octaplex and Beriplex
What is seen on a blood smear in DIC?
Schistocytes (fragmented blood cells)
Thrombotic Thrombocytopenic Purpura pathogenesis
Characterised by a decrease in proteolytic activity of enzyme ADAMTS 13 (cleaves VWF), usually as a result of abnormal antibody production
Causes of secondary ITP?
Infectious diseases such as HIV, Hepatitis C, Helicobacter pylori, and immunodeficiencies
Autoimmune disorders, for instance, systemic lupus erythematosus, antiphospholipid syndrome, and autoimmune thyroid disease
Lymphoproliferative disorders
ITP triggered by specific medications
Cases related to vaccine exposure
Coagulation profile in ITP
Normal
Fibrogen level in ITP
Normal
D-dimer level in ITP
Normal
First line treatment in ITP where treatment warrented (Platlets <30 or <50 and bleeding)
prednisolone: 1-2 mg/kg/day orally or methylprednisolone: 30 mg/kg/day orally or dexamethasone: 40 mg/day orally.
Indications for Hospital Admission in ITP
Unclear Diagnosis
Challenges in Arranging Timely Follow-Up
Significant Bleeding
Severely Low Platelet Count (<10,000/uL)
Sickling can produce two mechanisms that lead to pathology:
a shortened red cell survival and impaired passage through the microcirculation leading to obstruction and infarction.
Hydroxycarbamide (hydroxyurea) MOA in sickle cell patients
It works by increasing the HbF concentration, which does not polymerise, therefore interfering with HbS polymerisation. This leads to less sickling complications.
Important side effect of Hydroxycarbamide (hydroxyurea) in sickle cell patients
Importantly, it can cause neutropenia and thrombocytopenia, so check FBC if the patient is presenting with a fever or bleeding symptoms.
Crizanlizumab MOA in sickle cell patients
Approved to reduce frequency of vaso-occlusive crises in patients aged 16 or over. It is a monoclonal antibody that targets an adhesion molecule on endothelium and platelets.
Most common cause for sickle cell chest crisis (organism) ?
Chlamydia pneumoniae
Acute transfusion reaction
Reactions occurring within 24 hours of the administration of blood or blood components
Delayed transfusion reaction
Occur more than 24 hours after transfusion
Define mild febrile transfusion reaction
and the recommended management
Mild – temperature ≥38°C or 1-2°C above pre-transfusion baseline
BSH guidelines recommend that patients with mild febrile reactions only are treated with oral paracetamol and the transfusion continued with close observation.
Management of mild to moderate allergic reactions to transfusion
Antihistamines and slow down the transfusion
TRALI is defined as:
Non-cardiogenic pulmonary oedema and acute hypoxia occurring within six hours of a transfusion in the absence of other causes of acute lung injury or circulatory overload.
If bacterial contamination is suspected, the implicated unit should be…?
Sent to the lab for further testing
Transfusion-Associated Graft-Versus-Host Disease pathophysiology
It is primarily observed in immunodeficient patients, where lymphocytes in a blood donation mount an immune response against the recipient’s cells.
Which biomarker can differentiate between TACO and TRALI
BNP
Treatment for Post-Transfusion Purpura
Treatment is with high dose intravenous immunoglobulin
Management for patients with recurrent febrile reactions to transfusions
BSH guidelines recommend premedication with oral paracetamol one hour before the reaction is anticipated
Management for patients with recurrent mild allergic transfusion reactions
There is no evidence to support routine prophylaxis with antihistamines or corticosteroids
Management for patients with recurrent moderate to severe allergic reactions
Antihistamine prophylaxis and transfusion of washed products can be considered
Cells in the Myeloid lineage
Neutrophils, eosinophils, basophils, monocytes and platelets
Cells in the Lymphoid lineage
B-lymphocytes, T-lymphocytes and NK-cells
Leukaemia =
Refers to the presence of malignant cells in the peripheral blood
Lymphoma =
malignant proliferation of lymphocytes; which can present with lymphadenopathy or with diseased cells within the blood (i.e. a leukaemia
Threshold for diagnosis of leukaemia on a blood film / bone marrow
A diagnosis of acute leukaemia is made if blasts account for over 20% of the total white cell count in either peripheral blood or bone marrow
Predominant cell in CLL?
B cells
Causes of ‘target cells’ on blood films include:
Sickle cell
Thalassaemia
Liver disease
Iron-deficiency anaemia
Post splenectomy
Haemoglobin C disease
The most common virus transmitted by blood transfusion:
Parovirus, B19
Abx prophylaxis in those at risk of neutropenic sepsis?
Fluroquinolone e.g. Ciprofloxacin
Which paraneoplastic syndrome is most commonly associated with Small cell lung Ca?
Ectopic ACTH
