IC3- Blood Dyscrasias Flashcards
What are the 3 types of anaemias we will talk about here?
- Nutritional deficiency anaemia
- Aplastic anaemia
- Haemolytic anaemia
Describe anaemia caused by nutritional deficit.
Which nutritional deficit leads to micro/macrocytic RBCs?
Vit B12, folate and iron deficiency.
- Vit B12 and folate deficiency → macrocytic RBCs
- Iron deficiency → microcytic RBCs
What Tx can we give for iron-deficient anaemia?
Oral Fe3+ salts [ferrous sulphate], parenteral (IV) [iron sucrose]
How is iron supplements eliminated? What must we be careful of?
Elimination: minimal elimination in faeces, bile, urine and sweat
Careful dosing to avoid toxicity
ADEs of iron supplements? (Acute: 1, Chronic: 1)
Acute:
- Necrotizing gastroenteritis (necrosis of GI tract) with vomiting, abdominal pain, bloody diarrhoea followed by shock, lethargy, dyspnea, metabolic acidosis, coma and death
Chronic:
- Haemochromatosis → iron deposited in heart, liver, pancreas, other organs → organ failure, death
What are the Tx of overdose of iron? (2)
Parenteral deferoxamine or oral deferasirox iron chelators
What Tx can we give for Vit B12-deficient anaemia?
Cyanocobalamin, parenteral [hydroxocobalamin]
Hydroxocobalamin preferred as more protein binding → retains longer in circulation
Why is Cyanocobalamin/ Hydroxocobalamin not given as oral agent?
Oral not usually effective → deficiencies usually caused by GI malabsorption
What is the elimination and elimination t1/2 of Cyanocobalamin/ Hydroxocobalamin?
E: bile and urine (excess stored in liver, normally 3 years supply stored)
E t1/2: 26 - 31h (IV)
ADEs of Cyanocobalamin/ Hydroxocobalamin?
- Photosensitivity → avoid direct exposure to sunlight
- Injection site pain
- HTN, hot flushing, arrhythmias secondary to hypokalemia
- GI disturbances
- Dizziness, tremor, headache,
- Paresthesia (tingling/ numbing)
- Chromaturia (abnormal urine colour)
- Acneiform, bullous eruptions, rash, itching
DDIs of Cyanocobalamin/ Hydroxocobalamin?
PPIs → reduce oral absorption
Absorption (F, time to peak plasma conc), metabolism (name the active metabolite) and excretion of folic acid?
A; rapidly absorbed, F ~100%, peak plasma conc: 1h
M; liver and plasma, converted to active metabolite 5-methyltetrahydrofolate (5MTHF) → enterohepatic circulation
E; urine
Contraindications of folic acid? (2)
- Untreated cobalamin deficiency (including untreated pernicious anaemia or other causes eg lifelong vegetarians)
- Malignant disease
Special precautions of folic acid use? (5)
- Folate-dependent tumours, haemolytic anaemia, alcoholism
- Women with pre-existing diabetes, obesity, family Hx of neural tube defects, previous pregnancy affected by neural tube defect
- Not appropriate for monoTx in pernicious, aplastic, or normocytic anaemia when anaemia is present with vit B12 deficiency
- Children
- Pregnancy & lactation
ADEs of folic acid? (3)
- GI disturbances: bitter/ bad taste, nausea, abdominal distension (swelling), flatulence
- Immune system disorders (rare): allergic reactions (rash, pruritus, erythema, urticaria (hives), dyspnoea, shock), allergic sensitization
- Metabolism and nutrition disorders: anorexia (rare)
DDIs of folic acid? (6)
- ↓ plasma conc of anticonvulsants (phenytoin, phenobarbital, carbamazepine, valproic acid)
- ↑ efficacy of lithium
- ↓ therapeutic effect of methotrexate chemotherapy
- ↑ elimination with aspirin
- ↓ absorption with sulfasalazine and triamterene
- Chloramphenicol and sulfamethoxazole + trimethoprim may interfere with folate metabolism
Name the 2 Erythropoiesis -Stimulating Agents (ESAs)
Darbepoetin alfa, epoetin alfa
Contraindications of ESAs? (2)
- *Uncontrolled HTN
- Hypersensitivity (rare)
Special precautions of ESAs? (6)
- *HTN
- *Hx of seizure
- Ischaemic vascular disease
- Hepatic impairment, renal impairment
- Sickle cell anaemia
- Pregnancy, lactation, children
ADEs of ESAs? What are the ADEs specific to Epoetin alfa and Darbepoetin alfa?
- *HTN, edema, ↑ platelet count, *thrombosis, stroke, hyperK, seizures, myalgia (muscle aches), arthralgia, limb pain, GI effects (n/v)
- *Epoetin alfa: pruritus
- *Darbepoetin alfa: dyspnoea, cough, bronchitis
What are the 2 types of aplastic anaemia and drugs that cause them (ALL impt!)?
- Dose-dependent direct drug toxicity → cancer chemotherapies, chloramphenicol
- Idiosyncratic (toxic metabolites) → carbamazepine, phenytoin
What is the management for aplastic anaemia? (6)
- Withdraw causative drug if possible
*2. Immunosuppressants: glucocorticoids, ciclosporin, cyclophosphamide, azathioprine, antithymocyte immunoglobulin - Transfusion of erythrocytes and platelets
- Symptomatic Tx for infections
*5. GM-CSF (granulocyte-macrophage colony-stimulating factor), G-CSF (granulocyte colony-stimulating factor) [filgrastim, sargramostim], interleukin-14 may be given - HSCT (haematopoietic stem cell transplantation) may be necessary
What are the 2 types of haemolytic anaemia?
- Immune haemolytic anaemia
- Non-immune haemolytic anaemia
What are the 3 types of immune haemolytic anaemia and drugs that cause it?
- Drug-induced true autoAb production → *methyldopa
- Innocent bystander (immune complex) autoAb production → quinine, *quinidine
- Hapten-induced haemolysis → *penicillins, *cephalosporins, *streptomycin
What are the types of non-immune haemolytic anaemia and drugs that cause it (ALL impt!)?
Protein adsorption → cisplatin, oxaliplatin, β-lactamase inhibitors
What is the management for haemolytic anaemia?
- Withdraw drug if possible
- RBC transfusion if VERY LOW Hb
- HD may be required for pts with acute renal failure
*4. Steroids and immunoglobulins in serious cases (eg glucocorticoids, antithymocyte immunoglobulin)
*5. For auto-immune haemolytic anaemia, rituximab (human anti-CD20 monoclonal Ab) can be used
What are the type of drugs used for Tx of thrombocytopenias?
Name specifically the drug name also
Megakaryocyte growth factors/ Platelet-Stimulating Agents (PSAs)
- Recombinant IL-11 (oprelvekin)
- Fc-fusion protein thrombopoietin receptor agonist (romiplostim)
- Oral non-peptide thrombopoietin receptor agonists (eltrombopag) → higher dose for non-east asian pts (NOT chinese, koreans, japanese, taiwanese, thai)
General ADEs of Megakaryocyte growth factors/ Platelet-Stimulating Agents (PSAs)? (esp for oprelvekin?)
- *Thromboembolic events
- *Oprelvekin: fluid rtn, peripheral edema, dyspnoea on exertion
Special precautions of Megakaryocyte growth factors/ Platelet-Stimulating Agents (PSAs)?
- *Pt with or Hx of cerebrovascular disease
- *Risk factors for thromboembolism (eg. advanced age, prolonged immobilisation, malignancies, surgery/ trauma, bleeding, obesity, smoking, contraceptives and HRT)
- *Oprelvekin: chronic HF/ at risk of developing HF/ susceptibility to develop fluid rtn
What are the drugs that cause immune thrombocytopenia? (ALL impt!)
Heparin, sulfonamides, carbamazepine, phenytoin, GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)
Management of immune thrombocytopenia?
- Withdraw causative drug if possible
*2. Immunosuppressants: glucocorticoids, ciclosporin, cyclophosphamide, azathioprine, antithymocyte immunoglobulin - Platelet transfusion
What are the drugs used for treatment of neutropenia?
Name the specific drug names too
What is their MOA?
Myeloid growth factors (MGF):
- Recombinant G-CSF (filgrastim, pegfilgrastim (+ plerixafor))
- Recombinant GM-CSF (sargramostim)
MOA: stimulate myeloid progenitor cells
General ADEs of MGF?
- Potentially fatal (severe sickle cell crisis, capillary leak syndrome, respiratory failure or acute respiratory distress syndrome ARDS, (rare) splenic rupture)
What are the special precautions for use of MGF in neutropenia?
- Pts with premalignant or malignant myeloid condition, acute myeloid leukaemia, sickle cell trait or disease, recent Hx of pneumonia/ lung infiltrates, osteoporotic bone disease
Contraindications of use of MGF in neutropenia?
AVOID IN chronic myeloid leukaemia or myelodysplastic syndrome
In clinical practice, is G-CSF (-grastims) or GM-CSF (-gramostims) used more commonly?
G-CSF used first (better tolerated), if no response then GM-CSF
Difference between MOA of G-CSF (-grastims) and GM-CSF (-gramostims)?
G-CSF (-grastims):
- Stimulates proliferation and differentiation of progenitors committed to neutrophil lineage
- Additionally activates phagocytic activity of mature neutrophils and prolongs survival in circulation
GM-CSF (-gramostims):
- Broader effects than G-CSF → stimulates proliferation and differentiation of early and late granulocytic, erythroid and megakaryocyte progenitors
What is the difference between G-CSF filgrastim and pegfilgrastim?
Pegfilgrastim is filgrastim covalently conjugated with PEG to extend t1/2
ADEs of G-CSF?
Bone pain (reversible if drug discontinued)
ADEs of CM-CSF?
- Fever, malaise, arthralgias, myalgias
What are the types of neutropenia and what drugs cause them? (3)
- Direct drug toxicity → *thiamazole, chlorpromazine, ticlopidine, busulfan, zidovudine
- Toxic metabolite → *clozapine, *carbimazole
- Immune (hapten/ complement mediated) → *β-lactam antibiotics, propylthiouracil
Management of neutropenia?
- Withdraw causative drug if possible
- *Prophylactic administration of haematopoietic growth factors such as G-CSF (filgrastim/ pegfilgrastim) or GM-CSF (sargramostim)
- Routine (weekly) monitoring of WBC, esp for pts treated with clozapine
