39.1 Hematology, Immunology and Systemic Infections: Anemias (Iron Deficiency, Thalassemia, G6PD Deficiency, Megaloblastic, Hemolytic), Acute and Chronic Leukemias and Their Emergencies, Allergic Disorders, Dengue in Adults, COVID-19, Malaria and HIV/AIDS Opportunistic Infections

Why this area matters

Dengue causes tens of thousands of adult admissions every rainy season, and HIV in the Philippines has been one of the fastest-growing epidemics in the Asia-Pacific region. Iron deficiency, thalassemia trait and G6PD deficiency are common causes of anemia in Filipinos. The PLE tests the first steps: which test to order, which patient to admit, and which drug to start or avoid.

Anemia

• Approach: classify by MCV and reticulocyte count (low means underproduction, high means blood loss or hemolysis).
• Iron deficiency anemia:
  • the most common anemia; low ferritin (the best single test), low iron, high TIBC, high RDW;
  • causes: menstrual loss, pregnancy, poor intake, hookworm, and in men and postmenopausal women GI blood loss (ulcer or colorectal cancer) until proven otherwise;
  • treated with oral ferrous sulfate (daily or alternate-day dosing), with a reticulocyte rise in about a week and hemoglobin rising over 2 to 4 weeks; continue for about 3 months to refill stores. IV iron for intolerance, malabsorption or ongoing loss.
• Thalassemia:
  • alpha and beta thalassemia traits are common in Filipinos;
  • trait: mild microcytic anemia with a normal or high RBC count, target cells and normal ferritin; a Mentzer index (MCV divided by RBC count) below 13 favors thalassemia;
  • hemoglobin electrophoresis shows high HbA2 in beta thalassemia trait (alpha trait needs DNA testing);
  • do not give iron unless iron deficiency is proven; offer genetic counseling;
  • thalassemia major needs regular transfusion with iron chelation (deferasirox, deferoxamine).
• G6PD deficiency:
  • X-linked, common in the Philippines and detected by newborn screening;
  • acute hemolysis after oxidant drugs (primaquine, sulfonamides, nitrofurantoin, dapsone), fava beans, mothballs (naphthalene) and infections;
  • Heinz bodies and bite cells; the enzyme level may be falsely normal during hemolysis;
  • managed by avoiding triggers, with supportive care and transfusion.
• Megaloblastic anemia:
  • B12 deficiency (pernicious anemia, vegetarian diet, gastrectomy, metformin) causes neurologic signs (subacute combined degeneration);
  • folate deficiency (poor diet, alcohol, pregnancy, methotrexate, phenytoin) does not;
  • give B12 before folate if B12 deficiency is possible, because folate alone can worsen neurologic damage.
• Hemolytic anemia: high LDH and indirect bilirubin, low haptoglobin and high reticulocytes. A positive direct Coombs test means autoimmune hemolysis (warm IgG: SLE, CLL, drugs; treated with steroids).
• Anemia of chronic disease: normocytic or microcytic, high ferritin, low TIBC.
• Aplastic anemia: pancytopenia with a hypocellular marrow, from drugs (chloramphenicol), viruses and radiation.
• Transfusion: a restrictive threshold of hemoglobin 7 g/dL for most stable inpatients (8 g/dL with cardiovascular disease). Acute hemolytic transfusion reactions (ABO mismatch) cause fever, back pain, hypotension and red urine: stop the transfusion at once.

Leukemias

• Acute leukemia:
  • presents with the effects of marrow failure: anemia (fatigue), thrombocytopenia (bleeding, petechiae) and neutropenia (infections), plus bone pain, hepatosplenomegaly, lymphadenopathy and gum hypertrophy (monocytic AML);
  • blasts on the peripheral smear, confirmed by bone marrow with flow cytometry and cytogenetics;
  • AML in adults and ALL in children.
• Acute promyelocytic leukemia (APL, t(15;17)): presents with DIC and bleeding. Start ATRA immediately on suspicion (with arsenic trioxide), and watch for differentiation syndrome.
• Emergencies:
  • tumor lysis syndrome: high potassium, phosphate and uric acid with low calcium and acute kidney injury after starting chemotherapy; prevent with hydration and allopurinol (rasburicase for high risk);
  • febrile neutropenia (neutrophils below 500/µL and fever 38.3 °C once or 38.0 °C sustained): blood cultures and an antipseudomonal beta-lactam within 1 hour;
  • leukostasis (very high blast counts) causing dyspnea and confusion.
• Chronic myeloid leukemia: very high WBC with all stages of maturation, basophilia and massive splenomegaly; BCR-ABL is targeted with imatinib and other tyrosine kinase inhibitors.
• Chronic lymphocytic leukemia: elderly patients with lymphocytosis, smudge cells and lymphadenopathy; often observed until symptoms develop.

Allergic disorders

• Urticaria: wheals that come and go within 24 hours. Acute urticaria follows foods, drugs, infections or insect stings; chronic urticaria (more than 6 weeks) is usually spontaneous. Treated with non-sedating H1 antihistamines (up to 4 times the standard dose), then omalizumab.
• Angioedema:
  • with urticaria: allergic (histamine), responds to antihistamines, steroids and epinephrine;
  • without urticaria: bradykinin-mediated, from ACE inhibitors or hereditary angioedema (low C4, C1 inhibitor deficiency), which does not respond to epinephrine or antihistamines and needs C1 inhibitor, icatibant or fresh frozen plasma, and airway protection.
• Anaphylaxis: IM epinephrine first (see shock in cardiovascular medicine).
• Drug allergy:
  • beta-lactam allergy labels are often wrong, and many patients can be tested and safely re-exposed;
  • severe cutaneous reactions (SJS/TEN, DRESS) are covered in dermatology.
• Allergic rhinitis: intranasal corticosteroids are the most effective treatment, with antihistamines and allergen avoidance. Allergic rhinitis is linked to asthma.

Dengue in adults

• WHO 2009 classification: dengue without warning signs, dengue with warning signs, and severe dengue (plasma leakage with shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ involvement).
• Phases: febrile (2 to 7 days), critical (around defervescence, about 24 to 48 hours of plasma leakage), and recovery (reabsorption of fluid, a risk of overload).
• Warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement more than 2 cm, and a rising hematocrit with a rapid fall in platelets.
• Management by group:
  • Group A (no warning signs, able to drink, passing urine): home care with oral fluids, paracetamol and daily review;
  • Group B (warning signs or risk factors such as pregnancy, old age, diabetes, kidney disease): admit, and give isotonic crystalloid starting at about 5 to 7 mL/kg/hour for 1 to 2 hours, then taper according to hematocrit, vital signs and urine output (target about 0.5 mL/kg/hour);
  • Group C (severe dengue, shock): crystalloid 5 to 10 mL/kg over 1 hour for compensated shock, or 20 mL/kg over 15 to 30 minutes for hypotensive shock, then colloids if shock persists; consider occult bleeding and transfuse if hematocrit falls with unstable vital signs.
• Avoid NSAIDs, aspirin, IM injections and unnecessary platelet transfusion (prophylactic platelet transfusion does not prevent bleeding).
• Stop IV fluids after 24 to 48 hours of the critical phase to prevent fluid overload during reabsorption.

COVID-19

• Severity:
  • mild: symptoms without pneumonia or hypoxia;
  • moderate: pneumonia without hypoxia;
  • severe: SpO2 below 94% on room air (WHO uses below 90%), RR above 30;
  • critical: ARDS, sepsis or shock.
• Treatment:
  • mild disease: symptom care; nirmatrelvir-ritonavir within 5 days of symptoms for high-risk patients (watch drug interactions), or remdesivir;
  • patients needing oxygen: dexamethasone 6 mg daily for up to 10 days (no benefit and possible harm in mild disease), remdesivir for those on low-flow oxygen, prophylactic anticoagulation, and tocilizumab or baricitinib for rapidly worsening disease;
  • awake proning and high-flow nasal oxygen for hypoxemia;
  • lung-protective ventilation for ARDS.
• Prevention: vaccination, especially for the elderly and those with comorbidities, plus isolation and masks for symptomatic patients.

Malaria

• Philippine epidemiology: most remaining cases come from Palawan, with most provinces now malaria-free. Ask about travel and residence.
• Diagnosis: thick and thin blood smears (the gold standard) or rapid diagnostic tests.
• Treatment (DOH program):
  • uncomplicated P. falciparum: artemether-lumefantrine for 3 days, with a single low dose of primaquine to block transmission;
  • P. vivax: chloroquine (or artemether-lumefantrine) plus primaquine for 14 days to clear liver hypnozoites, after G6PD testing; primaquine is avoided in pregnancy;
  • severe malaria (impaired consciousness, seizures, severe anemia, kidney injury, jaundice, hypoglycemia, acidosis, high parasitemia): IV artesunate (2.4 mg/kg at 0, 12 and 24 hours, then daily), followed by a full oral course;
  • watch for hypoglycemia and fluid overload.

HIV/AIDS: clinical care

• The Philippine HIV and AIDS Policy Act (RA 11166, 2018) allows voluntary testing from age 15 without parental consent, requires informed consent and confidentiality, and prohibits discrimination.
• ART for everyone with HIV, ideally on the same day or within 7 days (TLD first-line; see HIV/AIDS in microbiology).
• Opportunistic infections by CD4 count:
  • TB (any CD4): the leading cause of death in people with HIV. Start ART within 2 weeks of TB treatment, but delay ART for 4 to 8 weeks in TB meningitis;
  • Pneumocystis pneumonia (CD4 below 200): subacute dyspnea, dry cough, hypoxia on exertion, bilateral interstitial infiltrates and high LDH. Treated with high-dose TMP-SMX for 21 days, plus prednisone if PaO2 is below 70 mmHg;
  • cerebral toxoplasmosis (CD4 below 100): multiple ring-enhancing lesions, treated with pyrimethamine-sulfadiazine or high-dose TMP-SMX;
  • cryptococcal meningitis (CD4 below 100): headache and fever with very high opening pressure, positive cryptococcal antigen or India ink. Treated with amphotericin B (single high-dose liposomal) plus flucytosine and fluconazole, with therapeutic lumbar punctures; delay ART for 4 to 6 weeks;
  • CMV retinitis, MAC and esophageal candidiasis at low CD4 counts;
  • Talaromyces marneffei in Southeast Asia: fever, anemia and umbilicated skin papules.
• Prophylaxis: cotrimoxazole at low CD4 counts (below 200, or below 350 in WHO guidance for resource-limited settings) prevents PCP and toxoplasmosis.
• Immune reconstitution inflammatory syndrome (IRIS): paradoxical worsening of an infection after starting ART. Continue ART and treat the infection, adding steroids for severe TB IRIS.