Hematologic & Immunologic Disorders: Anemias, Anticoagulation & Immunizations
Key Takeaways
- Iron deficiency anemia presents with microcytic hypochromic red cells, serum ferritin < 30 ng/mL, elevated TIBC, and increased RDW; new iron deficiency in an adult mandates evaluation for occult GI bleeding.
- Megaloblastic macrocytic anemia due to Vitamin B12 deficiency features elevated serum Methylmalonic Acid (MMA) and Homocysteine along with potential irreversible neurologic deficits, whereas Folate deficiency presents with elevated Homocysteine but normal MMA.
- Apixaban dosage must be reduced from 5 mg BID to 2.5 mg BID if a patient meets at least 2 of 3 clinical criteria: Age >= 80 years, Body Weight <= 60 kg, or Serum Creatinine >= 1.5 mg/dL.
- CDC ACIP guidelines recommend pneumococcal vaccination for all adults aged >= 65 years using either a single dose of PCV20/PCV21 alone OR a single dose of PCV15 followed by PPSV23 at least 1 year later.
- Recombinant zoster vaccine (Shingrix) is a 2-dose series recommended for all immunocompetent adults aged >= 50 years to prevent herpes zoster and postherpetic neuralgia.
Hematologic & Immunologic Disorders: Anemias, Anticoagulation & Immunizations
Diagnostic Approach to Anemias
Anemia is defined as hemoglobin (Hb) <13 g/dL in adult males or <12 g/dL in non-pregnant adult females. Initial clinical classification is dictated by the Mean Corpuscular Volume (MCV) on the CBC:
- Microcytic Anemia: MCV < 80 fL.
- Normocytic Anemia: MCV 80 to 100 fL.
- Macrocytic Anemia: MCV > 100 fL.
Microcytic Anemias (MCV < 80 fL)
Iron Deficiency Anemia (IDA)
- Etiology: Chronic occult gastrointestinal blood loss (colon cancer, peptic ulcer, diverticula, angiodysplasia) is the predominant cause in adult males and postmenopausal females. Mandatory Rule: Unexplained iron deficiency anemia in an adult or older adult requires thorough gastrointestinal evaluation via colonoscopy and EGD to rule out occult GI malignancy.
- Laboratory Profile: Low serum iron, low transferrin saturation (<20%), elevated Total Iron Binding Capacity (TIBC), elevated Red Cell Distribution Width (RDW > 15%, reflecting anisocytosis), and Serum Ferritin < 30 ng/mL (ferritin is the most sensitive and specific single test; levels <30 ng/mL are diagnostic of depleted iron stores).
- Physical Signs: Pica (craving non-nutritive substances like ice [pagophagia] or dirt), koilonychia (spoon-shaped nails), angular cheilitis, atrophic glossitis, and fatigue.
- Oral Iron Treatment: Oral Ferrous Sulfate (325 mg tablet containing 65 mg elemental iron) administered once daily or every other day (alternate-day dosing minimizes hepcidin upregulation and improves fractional intestinal absorption while reducing GI side effects). Co-administration with Vitamin C (ascorbic acid) enhances absorption; antacids, calcium, and PPIs must be avoided.
- Response Monitoring: Reticulocytosis occurs within 7 to 10 days; hemoglobin normalizes in 6 to 8 weeks; iron therapy must be continued for 3 to 6 months post-correction to fully replenish tissue ferritin stores.
Thalassemia Trait (Alpha or Beta)
- Microcytic, hypochromic anemia characterized by normal RDW, normal or elevated total RBC count, normal serum ferritin, and normal TIBC.
- Mentzer Index: Calculated as $\text{MCV} / \text{RBC count}$. A Mentzer index < 13 strongly suggests Thalassemia Trait, whereas an index > 13 suggests Iron Deficiency Anemia.
- Diagnostic Confirmation: Hemoglobin Electrophoresis (elevated HbA2 >3.5% and elevated HbF confirms Beta-Thalassemia Trait).
Normocytic Anemias (MCV 80 - 100 fL)
Anemia of Chronic Disease (ACD) / Inflammation
- Driven by inflammatory cytokines (IL-6, TNF-alpha) stimulating hepatic synthesis of hepcidin. Hepcidin degrades ferroportin, trapping iron inside macrophages and enterocytes, causing iron-restricted erythropoiesis.
- Lab Profile: Low serum iron, low or normal TIBC, normal or elevated Ferritin (acute phase reactant), and low transferrin saturation.
Anemia of Chronic Kidney Disease (CKD)
- Decreased erythropoietin (EPO) production by peritubular capillary endothelial cells in the kidney when eGFR falls <30-45 mL/min.
- Managed with Erythropoiesis-Stimulating Agents (ESAs) such as epoetin alfa or darbepoetin alfa initiated when Hb < 10 g/dL, targeting Hb 10 to 11 g/dL. (Targeting Hb > 11 g/dL increases serious cardiovascular events and stroke).
Macrocytic Anemias (MCV > 100 fL)
Divided into Megaloblastic (impaired DNA synthesis causing nuclear-cytoplasmic asynchronous maturation and hypersegmented neutrophils on peripheral smear) and Non-Megaloblastic (alcohol abuse, liver disease, hypothyroidism, MDS).
Vitamin B12 (Cobalamin) vs. Folate Deficiency
| Clinical / Lab Parameter | Vitamin B12 Deficiency | Folate Deficiency |
|---|---|---|
| Etiologies | Pernicious anemia (anti-intrinsic factor antibodies), vegan diet, post-bariatric surgery, terminal ileum resection, chronic PPI or Metformin use | Alcohol use disorder, poor dietary intake, malabsorption, medications (methotrexate, TMP-SMX, phenytoin) |
| Neurologic Deficits | PRESENT: Peripheral paresthesias, sensory ataxia, loss of vibratory/position sense, subacute combined degeneration of spinal cord, dementia | ABSENT |
| Serum Methylmalonic Acid (MMA) | ELEVATED | NORMAL |
| Serum Homocysteine | ELEVATED | ELEVATED |
| Peripheral Smear | Macrocytes, Hypersegmented Neutrophils (>5 lobes) | Macrocytes, Hypersegmented Neutrophils |
CRITICAL PHARMACOLOGIC WARNING: Giving high-dose folic acid alone to a patient with unrecognized B12 deficiency will correct the megaloblastic anemia but will allow severe, irreversible neurological damage to progress. Always check serum B12 and MMA levels prior to or concurrently with folate replacement.
Treatment of severe B12 deficiency: IM Cyanocobalamin (1000 mcg daily for 1 week, then weekly for 4 weeks, then monthly for life) or high-dose oral cyanocobalamin (1000-2000 mcg daily).
Primary Care Anticoagulation Management
Anticoagulation is indicated for stroke prevention in non-valvular Atrial Fibrillation (AFib) based on the CHA2DS2-VASc score and for treatment of Venous Thromboembolism (DVT/PE).
Warfarin (Vitamin K Antagonist)
- Inhibits Vitamin K epoxide reductase, blocking functional synthesis of Factors II, VII, IX, X, and Proteins C/S.
- Target INR: 2.0 to 3.0 for AFib, DVT, PE, and bioprosthetic valves; 2.5 to 3.5 for mechanical prosthetic mitral valves.
- Significant drug-food interactions (consistent Vitamin K diet intake required) and CYP2C9 interactions (metronidazole, TMP-SMX, amiodarone dramatically elevate INR).
- Reversal: Oral/IV Vitamin K (phytonadione) and 4-Factor Prothrombin Complex Concentrate (4F-PCC).
Direct Oral Anticoagulants (DOACs)
First-line preferred over warfarin for non-valvular AFib and VTE treatment due to lower intracranial hemorrhage risk and fixed dosing without routine INR monitoring.
- Direct Factor Xa Inhibitors: Apixaban, Rivaroxaban, Edoxaban.
- Direct Thrombin Inhibitor: Dabigatran.
- Apixaban Dosing Rule: Standard dose is 5 mg BID. The dose MUST be reduced to 2.5 mg BID if the patient meets at least 2 of the following 3 criteria: Age >= 80 years, Body Weight <= 60 kg, or Serum Creatinine >= 1.5 mg/dL.
- Rivaroxaban: 15-20 mg daily doses MUST be taken with the evening meal to ensure bioavailability. Renal clearance monitoring (Cockcroft-Gault CrCl) is required annually.
- Reversal Agents: Idarucizumab (Praxbind) for Dabigatran; Andexanet alfa (Andexxa) for Apixaban and Rivaroxaban.
Adult & Geriatric Immunization Protocols (CDC ACIP Guidelines)
Pneumococcal Vaccination (Adults >=65 years or Adults 19-64 with Chronic Risk Conditions)
CDC ACIP recommends one of two pathways for vaccine-naive adults:
- Pathway 1 (Single Dose): Administer 1 dose of PCV20 (Prevnar 20) OR 1 dose of PCV21 (Capvaxive) alone. No subsequent pneumococcal vaccines are required.
- Pathway 2 (Two-Dose Series): Administer 1 dose of PCV15 (Vaxneuvance) followed by 1 dose of PPSV23 (Pneumovax 23) at least 1 year later (or 8 weeks later in immunocompromised patients).
Influenza, RSV & Herpes Zoster Vaccines
- Influenza: For adults aged >= 65 years, high-dose (HD-IIV4), recombinant (RIV4), or adjuvanted (aIIV4) influenza vaccines are preferentially recommended.
- RSV: Single dose of RSV vaccine (Arexvy, Abrysvo, mRESVIA) for all adults aged >= 75 years and for adults aged 60 to 74 years at increased risk of severe disease.
- Herpes Zoster (Shingrix / RZV): 2-dose series (2 to 6 months apart) recommended for all immunocompetent adults aged >= 50 years regardless of past zoster episodes.
A 72-year-old female presents with progressive fatigue, balance instability, and numbness in her feet over the past 4 months. Complete blood count shows Hemoglobin 9.4 g/dL, MCV 112 fL, and peripheral smear displaying hypersegmented neutrophils. Which laboratory assay will definitively differentiate Vitamin B12 deficiency from Folate deficiency in this patient?
A 78-year-old postmenopausal male presents with fatigue and dyspnea on exertion. Laboratory studies show Hemoglobin 8.8 g/dL, MCV 72 fL, Serum Ferritin 14 ng/mL, and Total Iron Binding Capacity (TIBC) 460 mcg/dL. What is the mandatory next step in the clinical management of this patient?
An 82-year-old male weighing 58 kg presents for initiation of stroke prophylaxis for newly diagnosed non-valvular atrial fibrillation. His serum creatinine is 1.1 mg/dL. According to FDA labeling and clinical practice guidelines, what is the correct dosage of apixaban for this patient?
A 67-year-old female with no prior history of pneumococcal vaccination presents for her annual Medicare wellness visit. She has no chronic immunocompromising conditions. According to CDC ACIP guidelines, which of the following pneumococcal vaccination strategies is recommended?