haem onc Flashcards
Describe the PD and PK of Heparin
Binds and activates ATIII, causing inactivation of thrombin and factor Xa<div>Vd 5L</div><div>Protein binding complex and variable</div><div>Elimination is dose independent renal clearance and dose dependent depolymerisation</div><div>t1/2 1 - 2 hours</div><div>Reversible, give protamine 1mg for every 100units heparin given in past 4hrs</div>
Describe the PD and PK of Dabigatran
Direct thrombin inhibitor<div>Active metabolite accounts for 20% activity</div><div>Peak effect 2hrs</div><div>t1/2 12 - 14hrs</div><div>Vd 60L</div><div>35% protein bound</div><div>Not reversible, takes >12hrs to wear off</div><div>Consider RRT</div>
The major biochemical abnormalities associated with tumour lysis syndrome include
Hyperphosphatemia<div>Hyperkalemia</div><div>Hypocalcemia</div><div>Hyperuricemia</div><div>Metabolic acidosis</div>
Hemostatic resuscitation involves
Correcting hypothermia<div>Correcting acidosis</div><div>Treating coagulopathy early and aggressively</div><div>The use of blood products instead of isotonic crystalloid fluid aiming for limited volume replacement</div>
Methylprednislone is a …….
Glucocorticoid
Prednisolone dose equivelent vs methylprednisone, hyrdocortisone and dexamethasone
Pred: 1<div>Methylpred: 0.8</div><div>Hyrdrocortisone: 4</div><div>Dexamethasone: 0.2</div>
Parotiditis is cause by what? And via what mechanism?
ETOH liver disease<div>Due to fatty infiltration</div><div>In 70% of patients</div>
Sarcoidosis is syndrome causing what disease process?
Deposition of chronic inflammatory cells (granulomas) that form nodules in multiple organs.
Are sarcoid nodules caseating or not?
“No they aren’t”
What organs are effected by sarcoidosis?
Lung<div>Liver</div><div>Skin</div><div>Heart</div><div>Eyes</div><div>Blood</div><div>Lymph nodes</div><div>CNS</div><div>Exocrine glands</div>
What is the common treatment for sarcoid?
Prednisolone
MAG3 Scan: is also called?
Radioisotope renography
How does MAG3 work?
Tc99m-MAG3 are radiolabelled isotopes that are injected.
What is a MAG3 scan?
MAG3 clearance is well correlated to renal plasma flow.
How much of MAG3 injected is excreted into the tubules?
30-40%
What does PET stand for?
Positron emission topography
How does PET work?
It produces a 3D image by detecting pairs of gamma rays that are emitted by a tracer. This tracer is administered into the body and is attracted to highly metobolically active tissues.
Why is PET tracer attracted to biologically active tissues?
The tracer is called FDG, which is an analogue of glucose, and is this taken up by active cells
Suggested criteria for activation of Massive Transfusion Protocol
<p>Actual or anticipated 4 units RBC in <4hrs, +haemodynamics unstable, +/-anticipated ongoing bleeding</p>
<p>Severe thoracic, abdominal, pelvic, multiple long bone trauma</p>
<p>Major obstetric, gastrointestinal or surgical bleeding</p>
Blood product dosage in trauma
<p>Plt < 50 = 1 therapeutic dose</p>
<p>INR > 1.5 = FFP 15mL/kg</p>
<p>Fibrinogen < 1g/L = Cryoprecipitate 3 - 4g</p>
<p>Tranexamic acid = loading dose 1g over 10m then 1g over 8hrs</p>
Ticagrelor
<p>180mg load then 90mg BD</p>
<p>Reversible and non-competitive binding of ADP P2Y12 receptor</p>
<p>Prevents ADP-mediated GP IIb/IIIa activation therefore inhibiting aggregation</p>
<p>Absorption rapid, 36% bioavailability</p>
<p>Vd 88L, protein binding 99%</p>
<p>T1/2 parent drug ~ 7hrs, active metabolite 9hrs</p>
<p>Hepatic metabolism, excreted 58% faeces and urine 26%</p>
Prasugrel
<p>60mg load, 10mg OD</p>
<p>Prodrug converted to active metabolite</p>
<p>Irreversibly blocks the ADP P2Y12 receptor</p>
<p>Absorption rapid, 80% bioavailabilty</p>
<p>Vd 60L, protein binding 98%</p>
<p>Metabolism to active metabolite by serum esterases and CYP450</p>
<p>T1/2 7hrs</p>
<p>Excreted 68% urine and 27% faeces</p>
What blood products have high plasma volume components?
FFP<div>Plasma frozen within 24 hours (FP-24)</div><div>plasma</div><div>Cryo-reduced plasma</div><div>Apharesis platelets</div><div>Whole blood</div><div><br></br></div>
Definition of Cachexia is
Weight loss and skeletal muscle wasting due to illness where the body does not reduce catabolism (unlike starvation)
List lab Ix to diagnose lymphoma?
Biopsy<div>Raised ALP, Ca and ACE levels.</div><div><br></br></div>
Where does primary B cell lymphoma arise from?
Thymus.
When thoracic lymphoma is being considered what other imaging is required?
- PET scan<div>2. CT Chest/Abdo/Pelvis</div>
When considering a patient for chemotherapy what needs to be assessed?
Cardiac function (Echo) pre chemo.
What is Dabigatran?
It is a direct thrombin inhibitor.
What is the trade name for Dabigatran?
Pradaxa
Pharmacokinetics of Dabigatran?
Absorption - 3 -7% bioavailability<div>Distribtion - Pb 30%</div><div>Metabolism - Cleared unchanged</div><div>Excretion - Renally excreted (CI in those with CKI/AKI)</div><div>t1/2 12 hours</div>
Describe the clinical use of Dabigatran? Advantages and disadvantages?
It is an oral anticoagulant (direct thrombin inhibitor) which has been studied for use in chronic intermittent AF.<div>Advantages: no INR requirment.</div><div>Disadvantages:</div><div>GI bleeds and extra-cranial bleeds in those . 75yo</div><div>inc risk of MI</div><div>inc risk of bleeding when transitioning from warfarin.</div>
RELY/RECOVER
<div>Comparing Dabigatran with Warfarin in chronic AF.</div>
<div>18000 patients and 2500 patients respectively</div>
<div>RELY - AF.</div>
<div>RECOVER - Recurrence of venous thromboembolism.</div>
HITTS - Pretest probability
<p><strong>Thrombocytopaenia<br></br></strong>PLT fall 50% and nadir >20 = 2 pts<br></br>PLT fall 30-50% and nadir 10 - 19,000micrmol/L = 1 pt <br></br>PLT fall <30% or nadir <10 = 0 pt</p>
<p><strong>Timing of PLT count fall</strong><br></br>Onset b/w d5 - 10, or <=d1 if prior heparin in last 30d = 2 pts<br></br>Onset prob bw d5-10, after d10 or fall <=d1 with prev heparin in last 30-100d = 1 pts<br></br>Onset at <4d without recent exposure = 0 pts</p>
<p><strong>Thrombosis<br></br></strong>New thrombosis / skin necrosis / acute systemic reaction after IV heparin bolus = 2 pts<br></br>Recurrent / progressvie / suspectedthrombosis, non-necrskin lesion = 1pt<br></br>None = 0 pts</p>
<p><strong>Other causes for thrombocytopaenia<br></br></strong>None apparent = 2 pts<br></br>Possible = 1 pt<br></br>Definite = 0</p>
<p><u>Test interpretation<br></br></u>0 - 3: Low<br></br>4 - 5: Intermediate<br></br>6 - 8: Likely</p>
What is is Vincristine? What class of drug is it?
It is a chemotherapeutic agent. It is an alkaloid.
What is vincristine commonly used to treat?
Non hodgkins lymphoma as part of CHOP<div>Hodkins are part of MOPP/COPP</div><div>ALL with dexemathosone</div><div>Rarely as an immunosuppressant in TTP</div>
“What is vincristine’s main SE?”
Peripheral neuropathy and hyponatremia
At what level platelets is TTP thought to be in remission?
150
What is found in TTP urinalysis?
Blood +<div>Protein +</div>
What is deficient in TTP?
Deficiency of ADAMTS13<div>This is a protease</div><div>Which prevents aggregation</div>
Risk factors for lumour lysis?
Large tumour burden<div>LDH > 1500</div><div>Extensive marrow involvement</div><div>ALL</div><div>Burkitt lymphoma</div><div>Chemo.</div>
“<img></img><div>The following data refer to a 67-year-old male 8 days following initiation of treatment for acute leukaemia:</div><div><div>a) Give the underlying cause of the above abnormalities and give your reasoning to explain these findings. (20% marks)</div><div><br></br></div><div>b) List the treatment options for this condition. (30% marks)</div><div><br></br></div></div><div><br></br></div>”
<div>a)Tumour lysis syndrome - Renal impairment with hyperkalaemia, hyperphosphataemia, hyperuraecamia and increased LDH</div>
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<div>b)Resuscitation – Adequate IV hydration</div>
<div>Treatment of hyperkalaemia – Calcium chloride, bicarbonate if ECG changes, dextrose- insulin, dialysis, resonium??Renal replacement therapy – metabolic acidosis, hyperkalaemia and hyperphosphataemia Allopurinol??Rasburicase</div>
Risks of 0 negative uncrossmatched blood administration.
<div>Risks associated with 0-ve uncrossmatched:</div>
<div>Non ABO, Non Rh antigen/antibodies leading to allo-immunisation and delayed heamolytic reactions</div>
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List blood products and wether they require cross matching.
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How to predict likelihood of HITTS?
“<div>4 T’s is a scoring system for HITTS.</div><div><br></br></div><div>1. Thrombocytopenia - severity</div><div>2. Timing of platelet fall</div><div>3. Thrombosis or other sequalea</div><div>4. Other causes of thrombocytopenia</div><div><br></br></div><div>If there is a high degree of suspicion then don’t wait for labratory confirmation.</div><div><br></br></div><br></br>”
4T scoring system?
Thrombocytopenia:<div>2 points > 50% fall OR</div><div>Lowest is 20 -100.</div><div>1 point 30 - 50% fall</div><div>0 points < 30% fall</div><div><br></br></div><div>Timing:</div><div>2 points if 5 - 10 days post</div><div>OR within 2 days of reexposured within 30 days initial exposure</div><div>1 point > 10 days</div><div><br></br></div><div>Thrombosis:</div><div>2 points new proven thrombosis</div><div>1 point progressive/recurrent thrombosis</div><div><br></br></div><div>Alternative cause:</div><div>2 points no other cause</div><div>1 point if there is a possible</div><div>0 points if definite other cause</div><div><br></br></div><div>0-3 unlikely</div><div>4-5 intermediate probability</div><div>6-8 highly likely</div><div><br></br></div>
List DDx for pancytopaenia.
<b>Decreased marrow function:</b><div>Aplasia</div><div>Acute leukemia</div><div>Myelodysplasia</div><div>Myeloma</div><div>Infiltration:</div><div>- lymphoma</div><div>- solid tumours</div><div>- TB</div><div>Megaloblastic anaemia</div><div>Myelofibrosis</div><div>Haemophagocytic syndrome</div><div>(AAMI HMMM)</div><div><br></br></div><div><b>Destruction:</b></div><div>Trauma</div><div>Sepsis</div><div>Massive Haemolysis</div><div>Spenomegally</div>
Compare and contrast:<div>Enoxaparin, Abciximab, Danaparoid, Aspirin.</div>
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ABC score in trauma.
Predicts need for massive transfusion.<div>No = 0</div><div>Yes = 1</div><div><br></br></div><div>ED SBP < 90</div><div>ED HR > 120 bpm</div><div>Penetrating mechanism</div><div>Positive fluid on FAST scan</div><div><br></br></div><div>Score of 3 predicts 45% need for massive transfusion.</div><div><br></br></div><div>Score of 4 predicts 100% need for massive transfusion.</div>
How to subclassify MACROCYTIC anaemia?
Megaloblastic - B12/Folate def.<div>Non megaloblastic - ETOH, low thyroid, drugs.</div><div><br></br></div>
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Anaemic of chronic disease:<div>Describe findings.</div>
Microcytosis (mild)<div>Normochromia</div><div>No reticulocytes.</div><div><br></br></div>
How can anaeamia of chronic disease be distinguished from Fe def anaemia?
- By a lack of increase in Hb when administered IV or PO iron.<div><br></br></div><div>2. Lack of increase in Serum Transferrin Receptor Concentration with IV or PO iron.</div>
When is a bone marrow biopsy required in Fe def anaemia?
Occasionally required to assess total body iron stores
Micro/normo/macrocytic classification of anaemia.
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What is the mechanism by which chronic inflammation causes iron deficiency anaemia?
Release of cytokines (specifically IL) causes:<div>1. Reduced release of iron from marrow and macrophages</div><div>2. Reduced absorption of iron from gut</div><div>3. Supressed erythropoeisis</div>
Define Leukoerythroblastosis:
<div>1. A leukoerythroblastic (or leucoerythroblastic) anemia is any anemic condition resulting from space-occupying lesions in the bone marrow;</div>
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<div>2. the circulating blood contains immature cells of the granulocytic series and nucleated red blood cells, frequently in numbers that are disproportionately large in relation to the degree of anemia.</div>
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<div>3. picture on blood film can be the bone marrow response to any irritation including marrow infiltration [causing immature red cells].</div>
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<div>4. Marrow infiltrative disorders include myelomas, malignancy, myelofibrosis,</div>
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<div>5. It can also occur as a response to severe critical illness, such as trauma, septicemia, massive hemolysis, or severe megaloblastic anemia.</div>
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<div>7. Leukoerthyroblastic change refers to the presence of nucleated red blood cells and primitive white blood cells.</div>
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<div>8. Seen in bone marrow failure, myelofibrosis and extramedullary hematopoiesis.</div>
Howell-Jolly Bodies.
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Classify anaemia.
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Management of sickle cell crisis:
ABC<div>Keep sats > 96%</div><div>IVH</div><div>Adequate analgesia</div><div>Seek and treat precipitants</div>
List diseases associated with target cells.
Hb-opathies<div>Fe deficiency</div><div>Spleen removal</div><div>Thalassaemia</div><div>Enzyme def - lecithin cholesterol acyl transferase</div>
What is the standard therapy for venous sinus thrombosis?
Warfarin
When is endovascular thrombectomy used?
“Large vessel thrombus in ischaemic stroke.<div>Especially if recanalisation hasn’t occured with thrombolysis, or if the patient is outside time window.</div><div>Can cause direct vascular damage or dissection.</div><div><br></br></div><div>CI:</div><div>Tortuous vessels</div><div>Coagulopathy</div><div>Established infarct</div><div>Contrast allergy</div>”
What causes raised APTT and normal PT/INR in the setting of DVT in a young male?
Heparin<div>Artefactual</div><div>Haemophilia A and B</div><div>Factor VII and XI deficiency</div><div>vWD</div><div>Lupus inhibitor</div>
“<img></img><div>What?</div><div>When?</div>”
Target cells.<div>Found in defective Hb chain synthesis.</div><div><br></br></div>
