IC7- Haematologic disorders Flashcards
Define anaemia. What are the specific numerical values for men and women?
It is characterised by a decrease in either Hb or volume of RBCs, resulting in decreased O2-carrying capacity of blood.
Defined as Hb < 13 g/dL in men and < 12 g/dL in women.
What are the types of microcytic anaemia? (2)
- Iron deficiency anaemia
- Anaemia of chronic disease
What are the types of macrocytic anaemia? (2)
- Vit B12
- Folate deficiency anaemia
How is reticulocyte count useful in checking bone marrow function?
If bone marrow responding appropriately: when there is anaemia there is ↑ numbers of immature RBC (reticulocytes) released into the bloodstream
If MCV is normal and reticulocyte count is higher, what could it be? (3)
- Acute blood loss
- Hemolysis
- Splenic sequestration
Describe iron deficiency anaemia in terms of MCV, serum ferritin and TIBC.
What do you evaluate for?
MCV low, low serum ferritin, high TIBC
Prompt evaluation for blood loss/ causes of ↓ iron absorption
Describe anaemia of chronic disease in terms of MCV, serum ferritin and TIBC.
MCV low, normal/ high serum ferritin, low TIBC
What should we consider if MCV is high but normal vit B12/ folate levels?
- Hepatic disease
- Drug-induced anaemia
- Hypothyroidism
- Reticulocytosis
What are the possible causes of iron-deficiency anaemia? (2 main causes, each 7 & 3)
- Decreased iron absorption due to:
- Atrophic gastritis
- Celiac disease
- Gastric bypass
- H. pylori infection
- Calcium-rich foods
- PPIs
- Medications that ↓ gastric acidity - Blood/ iron loss due to:
- Pulmonary hemosiderosis
- Intravascular hemolysis
- Hematuria or hemoglobinuria
What are the formulations iron is available in?
What is the dosing and duration of iron for Iron-deficiency anaemia?
PO, IV
100-200mg/day
- Requires ~1000-1500mg (cumulative) elemental Fe for complete supplementation, treat for at least 3-6 months
What may happen if vit B12. deficiency is not treated properly?
Neurologic SSx may be irreversible
What is pernicious anaemia?
What are its common causes?
Lack of intrinsic factor produced by stomach to absorb vit B12 in small intestine
- Gastric disruption
- PPIs, H2RAs, H. Pylori infection
Which drug commonly causes vit B12 and folate deficiency?
Co-trimoxazole
What is the treatment for pernicious anaemia? (include route and dosing)
Parenteral (IM/ SQ) vit B12
1000 μg OD x 1w f/b
1000 μg weekly x 4w f/b
1000 μg monthly LIFELONG
What is the treatment for vit B12 deficiency due to other causes apart from pernicious anaemia? (include dosing and route)
Parenteral, oral Vit B12
1000 μg/ 2000 μg OD
What are the common drug causes of folic acid deficiency? (3)
- Co-trimoxazole
- Phenytoin
- Phenobarbital
What is the treatment for folic acid deficiency? (include route, dosing and duration)
PO folic acid (including pts w absorption problems)
1mg OD x 1-4 months or until haematologic recovery achieved
Define aplastic anaemia
Presence of 2 of the following:
1. WBC count ≤ 3,500 cells/mm3 (3.5 x 109/L)
2. Platelet count ≤ 55,000 cells/mm3 (55 x 109/L)
3. Hb value ≤ 10 g/dL (100 g/L; 6.21 mmol/L) PLUS reticulocyte count ≤ 30,000 cells/mm3 (30 x 109/L)
What are the common drugs that cause aplastic anaemia? (6)
Other than drug-induced aplastic anaemia, what else can cause it?
- Furosemide
- NSAIDs
- Carbamazepine
- Cytotoxic chemotherapy
- Radiation therapy
- ***Chloramphenicol
Infection
Goals of tx of aplastic anaemia? (3)
- Improve peripheral blood counts
- Limit the requirement for transfusions
- Minimise risk for infections
If aplastic anaemia is very severe, what is the treatment?
May require allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (cyclosporine)
What is the tx for aplastic anaemia caused by infection?
Prophylactic abx and antifungal agents when neutrophil counts < 500 cells/mm3 (0.5 x 109/L)
Febrile neutropenia: broad spectrum abx
What is the tx for aplastic anaemia caused by bleeding?
What can we do if pt is heavily transfused?
Transfusion support with erythrocytes and platelets
If heavily transfused → iron chelation therapy with deferoxamine or deferasirox (avoid iron overload)
Define neutropenia/ agranulocytosis
- Neutropenia: absolute neutrophil count (ANC) < 1500/ μL
- Agranulocytosis: absence of granulocytes (ANC = 0); although term often used loosely to indicate severe degrees of neutropenia (ie, ANC < 100, < 200 or even < 500/μL)
What are the 3 classes of drugs that cause neutropenia/ agranulocytosis?
Name the specific drugs under each class too
- Antipsychotics: carbamazepine, clozapine
- Abx: β-lactam abx, trimethoprim-sulfamethoxazole
- Antithyroid: carbimazole, methimazole, propylthiouracil
What is the onset of neutropenia/ agranulocytosis caused by clozapine and other phenothiazines?
2-15w after Tx initiation, peak onset between 3-4w
What is the onset of neutropenia/ agranulocytosis caused by abx?
Rapid onset of SSx, dose-related
What is the onset of neutropenia/ agranulocytosis caused by antithyroid drugs?
What alleles could be implicated also?
- More frequent in pts > 40 y/o and within 2m of Tx initiation (longer term also possible)
- HLAB38:02 and HLADRB108:03 in ethnic Chinese
- HLAB*27:05 white European adults
Goals of tx of neutropenia/ agranulocytosis? (1)
Improving mortality rate
Tx of neutropenia/ agranulocytosis?
How long does it take for blood cell counts to return to normal?
What should we do if neutrophil < 100 cells/mm3 (0.1 x 109/L)?
WITHHOLD offending drug FIRST
Blood cell counts usually return to normal within 2-4w, frequently within 4-24 days.
If neutrophil < 100 cells/mm3 (0.1 x 109/L): filgrastim (G-CSF) SQ 300mcg/day recommended
If really needed: penicillin can be restarted at LOWER dosage, AFTER neutropenia has resolved, without any recurrence of drug-induced agranulocytosis
How is haemolytic anaemia diagnosed (what tests)?
Direct and indirect Coombs’ test
What is a metabolic cause of haemolytic anaemia?
G6PD deficiency
What are some unsafe medications to avoid for G6PD deficiency in haemolytic anaemia? (4)
- Fluoroquinolones (-floxacin)
- Primaquine, tafenoquine (antimalarials)
- Sulfonylureas
What are some chemicals and foods to avoid for G6PD deficiency in haemolytic anaemia? (3)
- Fava beans
- Henna compounds
- Naphthalene (mothballs, lavatory deodorant)
What are some drugs to try not to use/ use with caution for G6PD deficiency regarding haemolytic anaemia? (3)
- Chloroquine, hydroxychloroquine (antimalarials)
- Sulfamethoxazole-trimethoprim
Define thrombocytopenia
Any of the following:
1. Platelet count ≤ 100,000 cells/mm3 (100 x 109/L) or greater than 50% reduction from baseline
2. Typically presents 1-2w after new drug initiated, may also present IMMEDIATELY after a dose when agent has been used intermittently in the past (hypersensitivity induction)
3. Rapid onset may occur with GPIIb/IIIa inhibitor class (eptifibatide) of drugs
Which type of heparin causes Heparin-induced thrombocytopenia (HIT)?
UFH
(not LMWH!)
Upon withholding the drug causing thrombocytopenia, how long does recovery take?
Recovery starts ~1-2 days of discontinuation of offending agent, and is complete at one week
For drug-induced thrombocytopenia, should we continue the drug?
Advise pt to avoid the drug indefinitely as Ab may persist for years
Regarding the “4-T’s” clinical probability score for HIT, what does each score represent?
Clinical probability of HIT:
6-8: High
4-5: Intermediate
0-3: Low
