Module 9 Haematology Flashcards
What are the features of iron deficiency anaemia?
Early: Normocytic, normochromic
•Late: Blood smear shows microcytic, hypochromic cells with central pallor
•MCV 55-74 fL, MCHC 25-30 gm/dL
•Serum iron
What are the features of clinical presentation of iron deficiency anaemia?
- Weakness
- Irritability
- Fatigue
- Headache
- Exercise intolerance
- Tachycardia
- Shortness of breath
- Restless Leg Syndrome
- Pica - craving for non nutritive items
Decreased Iron Absorption - these medications can decrease iron absorption.
To avoid decreased absorption - separate the administration of iron and acid-reducing medications by as much time as possible (e.g., for antacids).
Antacids (containing Al3+, Mg2+ & Ca2+)
H2 receptor antagonists
Proton pump inhibitors
Cholestyramine
Iron Decreases Absorption or Serum Concentration of these medications.
Thus, administration should be at least 2 hours before or 4 hours after the administration of the iron therapy.
Levodopa Levothyroxine Penicillamine Quinolone antibiotics Tetracycline derivatives Bisphosphonates For bisphosphonates, iron should be administered at least 30 minutes after alendronate and risedronate and at least 60 minutes after ibandronate.
Replacement for Iron Deficiency Anaemia
•Oral Iron Preparations:
–Ferrous sulfate 325mg 1 to 3 times daily
–Side effects include constipation, cramping, diarrhea, nausea
–Manage side effects by giving with meals or substituting ferrous gluconate, or ferrous fumarate, polysaccharide-iron complex
–Bioavailability can be increased by administering with Vitamin C or orange juice
–Different forms contain different amounts of elemental iron (see next slide)
•Parenteral Iron
•Blood Transfusion (Hg
Enteric coated preparations of iron
Enteric coated preparations should not be used in achlorhydric patients. Achlorhydria is when there is low or no gastric acid in the stomach.
What should happen to patients with very high iron requirements
Poor absorption (gastrectomy patients), or intolerance of oral preparations should receive parenteral iron.
IV iron dextran precautions and warnings
IV iron dextran has a black box warning. A 0.5 mL test drug dose should be administered before therapy is started. Patients should be observed for one hour after therapy for reactions. Epinephrine and emergency resuscitation equipment should always be readily available when using IV iron dextran. Patients have experienced delayed arthralgias, myalgias for one to two weeks after the infusion. Patients with a history of allergies, asthma or inflammatory diseases are at higher risk of reactions.
Sodium ferric gluconate and iron sucrose
Alternate parenteral iron products without the black box warning. Iron sucrose has a low incidence of hypersensitivity reaction and patients receiving it should be closely monitored for at least 30 minutes.
Monitoring of oral iron
A reticulocytosis should occur in 5-7 days with an increase in Hb of 2-4 g/dL every 3 weeks until normalized. Iron therapy needs to continue until iron stores are restored. Usually 3-6 months of therapy is needed. Serum ferritin should be normal before iron is discontinued.
Anemia of Chronic Disease (ACD)
–Laboratory findings: •No definitive test confirms the diagnosis •Early: Normocytic, normochromic •Long-standing disease: microcytic, hypochromic •Peripheral smear normal, with possible microcytes •Serum Fe, TIBC - both decreased •Transferrin saturation decreased •Serum ferritin normal to increased –Clinical Presentation: •Pallor •Tachycardia •Asymptomatic
Treatment of Anemia of Chronic Disease (ACD)
–Treatment of underlying disease
–Elimination of nutritional deficiencies, marrow-suppressive drugs
–Not responsive to common deficiency therapies (iron, B12, folic acid)
–Erythropoietic agents (EPAs) or erythropoietic stimulating agents (ESAs) – not FDA-approved for ACD, but may be for underlying causes when low erythropoietin levels are observed
Erythropoietic Stimulating Agents (ESAs) Epoetin Alfa (Epogen®)
Anemia in CKD, HIV, cancer, and some surgeries
Three times weekly; weight and indication based dosing
Adverse reactions:
Hypertension, fever, headache, pruritus, rash, nausea, vomiting, injection site reaction, arthralgia, cough
Monitoring:
Transferrin saturation and serum ferritin, Hb (weekly until goal and after dose changes), blood pressure, seizures
Erythropoietic Stimulating Agents (ESAs) Darbepoetin Alfa (Aranesp®)
Anemia in CKD and cancer
Once weekly to every 2-3 weeks; weight and indication based dosing
Adverse reactions:
Hypertension, peripheral edema, edema, abdominal pain, dyspnea, cough
Monitoring:
Hb (weekly until goal and after dose changes), transferrin saturation and serum ferritin, serum chemistry, blood pressure, fluid balance, seizures
Macrocytic anemias types
Classified by larger than normal red blood cells (RBCs), typically reticulocytes, or immature red blood cells. They are divided into megaloblastic (abnormal DNA metabolism as a result of B12 or folic acid deficiency that result in abnormal cell growth) and nonmegaloblastic (resulting from other causes).
Vitamin B12 Deficiency
Neurologic complications •Bilateral paraesthesia •Ataxia •Dementia-like symptoms •Psychotic symptoms •Unexplained neuropathies
Folic acid anaemia
- Loss of appetite
- Weight loss
- Weakness
- Irritability
- Heart palpitations
B12 Deficiency Causes
- Inadequate intake
- Malabsorption
- Inadequate utilization
Folic Acid Deficiency Causes
- Inadequate intake
- Malabsorption
- Increased folate requirements
Laboratory Diagnosis – Vitamin B12
Serum B12 deficiency
•Serum B12 levels: normal 170-820 pg/mL
•Mild leukopenia and thrombocytopenia
•Methylmalonic acid (MMA) and homocysteine may be elevated
–MMA is more specific to Vitamin B12 deficiency
–Homocysteine can be elevated in both Vitamin B12 deficiency and folic acid deficiency
•Rule in/out Pernicious Anemia
Laboratory Diagnosis – Folic Acid
Folic Acid deficiency
•B12 level normal (170-820 pg/mL)
•RBC folate levels decreased (normal =165-760 ng/mL)
•Serum homocysteine levels usually increased
•MCV, serum lactate dehydrogenase (LDH), indirect bilirubin all may be elevated
•Peripheral smear may show anisocytosis, poikilocytosis, macrocytes, hypersegmented polymorphonuclear leukocytes
•Low reticulocyte count (normal = 33-137 x103/mcL)
Causes of folic acid and Vitamin B12 deficiency
•Hydroxyurea (folic acid) •Zidovudine (folic acid) •Methotrexate (folic acid) •5-fluorouracil (folic acid) •Phenytoin (folic acid) •Trimethoprim (folic acid) •Pentamidine (folic acid) •Pyrimethamine (folic acid) •Metformin (folic acid and B12) •Cytarabine, Cladrabine •Azathioprine •6-mercaptopurine •Alcohol •Barbiturates •Triamterene •Nitrofurantoin •Primidone •Thiopental •Sulfasalazine Many have less well understood mechanisms and are therefore not classified by the deficiency they cause
Vitamin B12 Deficiency Anemia Treatment
Various dosing regimens based on disease severity and other patient factors
Cyanocobalamin (Vitamin B12) 1000 mcg IM or SQ once a week for 4-6 weeks until stores are replenished and hemoglobin and hematocrit are normalized. For an oral therapy option, Vitamin B12 1000 mcg by mouth daily for one month can be used.
•Monitor vitamin B12 and CBC at 1-2 months and then continue every 3-6 months.
Pernicious Anemia treatment
Lifelong IM Vitamin B12 supplementation
A dose of 100-1000 mcg a day for one week, then on alternating days for 2 weeks, then every 3-4 days for 2-3 weeks. Parenteral therapy is typically needed in order to by pass the lack of intrinsic factor. Maintenance therapy is typically 100-1000 mcg once a month. Oral therapy (1000 mcg by mouth once daily) may be used for maintenance in patients who are unwilling to receive injections
Folate Deficiency Anemia treatment
Folic Acid 1 mg PO daily until corrected (4 months)
Sideroblastic Anemia - Causes
- Toxins: lead, copper, and zinc poisoning
- Drug-induced: ethanol, isoniazid, chloramphenicol, cycloserine, linezolid, and oral contraceptives
- Nutritional: pyridoxine (vitamin B6) or copper deficiency
- Diseases: rheumatoid arthritis or multiple myeloma
Sideroblastic Anemia
Diagnosis:
- Reticulocyte count is low
- MCV may be low, normal or high
- Serum iron, transferrin, saturation, ferritin levels high
- Peripheral smear shows marked anisocytosis, poikilocytosis
Sideroblastic Anemia Treatment
- If drug induced, the offending agent should be stopped.
- Pyridoxine 200mg daily
- If unresponsive, treat symptomatically
Hemolytic Anemia - Intrinsic (intracorpuscular, usually membrane defect inherited)
•Spherocytosis and elliptocytosis •Hb defect –Sickle cell anemia –Thalassemia •Metabolic defect –Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemolytic Anemia -
Extrinsic (extracorpuscular, acquired)
•Membrane defect
–Autoimmune hemolytic anemia
•Oxidants
Hemolytic Anemia: Laboratory
- Normocytic normochromic
- Increased reticulocyte count
- Elevated LDH
- Elevated indirect bilirubin
- Positive Coombs test (autoimmune) - conclusive for autoimmune hemolytic anemia, the most common type among the elderly
microangiopathic hemolytic anemia - causes
penicillin, quinidine, alpha-methyldopa, and cephalosporins - Rx remove offending agent
Glucocorticoids also sometimes used.
Anemia - Summary
WHO definition: Hb
Petechiae and Ecchymoses
Possible Etiology:
Possible Etiology: •Thrombocytopenia •Platelet dysfunction •Autoimmune disorder •Myelodysplastic syndrome •Acute leukemia •Chronic lymphocytic leukemia •Infection •HIV •Medications
Thrombocytopenia - diagnosis
•Decreased platelet count (
Drug-induced Thrombocytopenia - causes
Direct Marrow Suppression: chemotherapy
Hapten-mediated immune: quinine, quinidine, gold salts, sulfonamide antibiotics, rifampin, glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists, and heparin
Drug-dependent antibodies: quinine, anticonvulsants, and NSAIDs
Treatment: Stop the offending agent!
Abnormal Bruising and Bleeding
High Risk Medications: •Aspirin •Clopidogrel •Heparin •Non-steroidal anti-inflammatory drugs (NSAIDs) •Warfarin •Dabigatran •Rivaroxaban •Apixaban
Abnormal Bruising and Bleeding
Low Risk Medications: •Ginkgo biloba •Gold •Interferon •Penicillins •Selective serotonin reuptake inhibitors (SSRIs) •Propylthiouracil •Testosterone •Tricyclic antidepressants
Abnormal Bruising and Bleeding
Important Diagnostic Tests:
- PT
- aPTT
- CBC with platelet count
Immune (or idiopathic) Thrombocytopenic Purpura (ITP) lab testing and symptoms
- Thrombopoietin (TPO)
- Complete blood count
- Peripheral blood smear
- Petechiae
- Purpura
- Ecchymoses
ITP Treatment
- 1st line: Glucocorticoids
- Severe ITP & high risk for bleeding: Rituximab
- For relapse: Splenectomy
- For relapse after splenectomy: Thrombopoietin receptor agonists
- Life threatening bleeding/surgery: Immune globulin, intravenous immunoglobulin (IVIG), Rho(D) Immune globulin (IGIV) (WinRho®) (anti-Rho(D) antibody to red cell antigen Rho(D)
- Refractory: Immunosuppressants
ITP Treatment - Glucocorticoids
For profound thrombocytopenia with signs of bleeding, very high dose steroids, in the form of methylprednisolone 1 g/d for 3 days is used. High dose dexamethasone 40mg (po or IV) for 4-8 days in cycles has also been used. For less acute cases, prednisone 1 mg/kg daily will be started.
