PBL 5 Notes: Triggers and Laboratory Interpretation

Trigger 1: Weakness, paresthesia, chronic gastritis, Hb 9.2 g/dL

• Anemia causing weakness and fatigue
• Tingling in hands and feet suggests peripheral neuropathy
• Chronic gastritis may cause loss of parietal cells and reduced intrinsic factor, which is required for vitamin B12 absorption
• Hb 9.2 g/dL indicates moderate anemia

• Vitamin B12 is needed for DNA synthesis in rapidly dividing cells.
• Deficiency causes defective nuclear maturation in erythroid precursors, resulting in megaloblastic anemia.
• It also causes accumulation of methylmalonic acid, contributing to demyelination and neurologic manifestations.
• Neurologic deficits distinguish B12 deficiency from isolated folate deficiency.

• CBC: increased MCV, macrocytosis, possible leukopenia and thrombocytopenia
• Peripheral smear: macro-ovalocytes and hypersegmented neutrophils
• Serum B12: low
• Serum methylmalonic acid and homocysteine: elevated
• Anti-intrinsic factor antibody and anti-parietal cell antibody if pernicious anemia is suspected
• Consider upper GI evaluation if clinically indicated for chronic gastritis/atrophic gastritis

• Start vitamin B12 replacement, often initially by intramuscular route if absorption is impaired or neurologic symptoms are present.
• Identify and treat the underlying cause.
• Neurologic recovery may be incomplete if treatment is delayed.
• Do not give folate alone until B12 deficiency has been excluded or treated, because anemia can improve while neurologic injury progresses. The Merck Manual guidance similarly emphasizes checking B12 and folate together.

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Trigger 2: Young man with fatigue, intermittent abdominal pain, affected sibling, no transfusion history

• Onset in young adulthood
• Family history in a sibling supports an inherited hemoglobin disorder
• No transfusion history makes severe beta-thalassemia major less likely
• Intermittent abdominal pain may result from splenomegaly, hemolysis, gallstones, or extramedullary hematopoiesis

• Thalassemias result from reduced synthesis of alpha or beta globin chains.
• Reduced globin production causes microcytic hypochromic anemia.
• Imbalanced globin chains cause ineffective erythropoiesis and hemolysis.
• Chronic hemolysis may cause jaundice, pigment gallstones, splenomegaly, and increased iron absorption.

• CBC: low Hb and low MCV, often with a relatively high RBC count for the degree of anemia
• Peripheral smear: microcytosis, hypochromia, target cells, anisopoikilocytosis, possibly basophilic stippling
• Reticulocyte count: may be raised due to hemolysis
• Iron studies: usually normal or raised, unlike iron-deficiency anemia
• Hemoglobin electrophoresis/HPLC:
  • Beta-thalassemia trait: raised HbA2, sometimes mildly raised HbF
  • Beta-thalassemia intermedia: raised HbF with variable HbA reduction
• Molecular testing may be used for confirmation and genetic counseling
• Ultrasound abdomen: assess spleen, liver, and gallstones

• Confirm the type of thalassemia before treating.
• Do not prescribe iron unless iron deficiency is demonstrated.
• Folic acid supplementation is often used in chronic hemolysis.
• Monitor for splenomegaly, gallstones, pulmonary hypertension, bone disease, and iron overload.
• Genetic counseling and screening of family members/partner are important.

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Trigger 3: Fatigue, early satiety, weight loss, occasional night sweats

• Early satiety commonly occurs because of splenomegaly.
• Constitutional symptoms, including fatigue, weight loss, sweating, and fever, can occur in CML.
• The case is suggestive of chronic-phase disease, although blood counts and examination are needed.

1. CML with splenomegaly
2. Lymphoma with splenic or abdominal nodal involvement
3. Primary myelofibrosis
4. Other myeloproliferative neoplasms
5. Chronic infection or another malignancy

• CBC with differential count
• Peripheral smear:
  • CML: marked leukocytosis with cells at different stages of granulocytic maturation, often basophilia and eosinophilia
• Physical examination and ultrasound/CT to assess splenomegaly and lymphadenopathy
• Bone marrow aspiration and trephine biopsy
• Cytogenetic or molecular testing for BCR::ABL1 fusion gene and Philadelphia chromosome, which confirms CML
• LDH and uric acid, which may be elevated due to high cell turnover

• Refer to hematology.
• First-line therapy is generally a BCR::ABL1 tyrosine kinase inhibitor, such as imatinib, dasatinib, nilotinib, or bosutinib, selected according to patient factors.
• Regular quantitative BCR::ABL1 monitoring is required.
• Monitor for progression to accelerated phase or blast crisis.

• Diagnosis requires adequate tissue, preferably an excisional lymph-node biopsy when accessible. Lymphoma should not be diagnosed from symptoms alone. The textbook-indexed diagnostic principle is that biopsy and histopathology establish the diagnosis.

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Trigger 4: Long-term alcohol use, abdominal distension, leg edema, bruising, confusion

• Chronic alcohol exposure
• Abdominal distension suggests ascites
• Leg swelling suggests hypoalbuminemia, sodium and water retention, and portal hypertension
• Easy bruising suggests thrombocytopenia, impaired liver synthesis of clotting factors, or vitamin K deficiency
• Confusion suggests hepatic encephalopathy
• Fatigue is common in advanced chronic liver disease

• Chronic alcohol-related hepatocyte injury causes inflammation, fibrosis, and nodular regeneration.
• Cirrhosis raises portal venous pressure, producing ascites, splenomegaly, varices, and thrombocytopenia.
• Reduced hepatic synthesis leads to low albumin and reduced clotting-factor production.
• Impaired detoxification and portosystemic shunting increase ammonia and other neurotoxins, leading to encephalopathy.

• CBC, liver function tests, bilirubin, albumin, PT/INR, renal function, electrolytes
• Abdominal ultrasound with portal-vein assessment
• Diagnostic ascitic tap:
  • Cell count and differential
  • Culture
  • Albumin and total protein
  • Calculate SAAG
• Screen for varices by upper GI endoscopy
• Assess severity using Child-Pugh and MELD-Na scores
• Screen for hepatocellular carcinoma with ultrasound, with or without AFP according to local protocol

• Absolute alcohol cessation and nutritional support, including thiamine.
• Salt restriction and diuretics, typically spironolactone with or without furosemide, for ascites.
• Therapeutic paracentesis with albumin support for tense ascites.
• Lactulose is used to treat hepatic encephalopathy; rifaximin may be added for recurrent episodes.
• Search for encephalopathy precipitants: infection, GI bleeding, constipation, dehydration, electrolyte disturbance, sedatives, renal failure.
• Consider nonselective beta-blocker/endoscopic management for variceal bleeding prevention when appropriate.
• Refer for transplant assessment if decompensated disease persists despite abstinence and optimal care.

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Laboratory Data 1

• Isolated severe thrombocytopenia
• Normal WBC and near-normal RBC morphology
• Increased megakaryocytes indicate active marrow compensation
• Normal coagulation profile supports a platelet disorder rather than a coagulation-factor disorder

• Repeat CBC and peripheral smear to rule out pseudothrombocytopenia
• Review medications, infections, alcohol use, autoimmune symptoms
• Test for secondary causes where relevant: HIV, hepatitis C, autoimmune disease
• Bone marrow examination is not routinely needed in a typical ITP presentation, but this report already supports peripheral platelet destruction.

• Platelet count of 18,000/mm³ carries significant bleeding risk.
• Assess urgently for mucosal bleeding, melena, hematuria, headache, or neurologic symptoms.
• First-line treatment in significant thrombocytopenia or bleeding: corticosteroids, with IV immunoglobulin when a rapid rise is needed.
• Platelet transfusion is generally reserved for severe or life-threatening bleeding alongside definitive therapy.

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Laboratory Data 2A: Macrocytic pancytopenia

• Replace vitamin B12 first or concurrently with folate.
• Then replace folate.
• Investigate causes: dietary deficiency, malabsorption, pernicious anemia, chronic gastritis, celiac disease, medication use, alcohol use, and increased requirements.
• Monitor reticulocyte response, CBC, potassium, and neurologic symptoms.

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Laboratory Data 2B: Acute hepatitis A

• Markedly elevated ALT and AST with positive IgM anti-HAV indicate acute hepatitis A.
• Normal INR and albumin are reassuring because they suggest no acute liver failure currently.

• Supportive treatment: hydration, nutrition, rest, and antiemetics if required.
• Avoid alcohol and potentially hepatotoxic medications, especially unnecessary acetaminophen.
• Monitor bilirubin, INR/PT, glucose, mental status, and liver enzymes.
• Urgent referral/admission is needed if encephalopathy, rising INR, hypoglycemia, persistent vomiting, severe dehydration, or rapidly worsening jaundice develops.
• Advise hygiene measures and identify contacts who may need post-exposure prophylaxis as per local public-health guidance.

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Laboratory Data 3

• Systemic activation of coagulation produces widespread microthrombi.
• Platelets and clotting factors are consumed, causing bleeding.
• Fibrinogen falls and PT/aPTT become prolonged.
• Common triggers include sepsis, obstetric emergencies, major trauma, malignancy, acute promyelocytic leukemia, pancreatitis, and severe transfusion reactions.

• D-dimer/fibrin degradation products: expected to be raised
• Peripheral smear: schistocytes may be present
• Serial platelet count, PT/INR, aPTT, fibrinogen, renal function, liver function, and lactate
• Search urgently for the underlying trigger

• This is a medical emergency.
• Treat the underlying cause immediately.
• Give blood components if bleeding, before an invasive procedure, or with severe laboratory derangement:
  • Platelets for significant thrombocytopenia with bleeding/high-risk procedure
  • Fresh frozen plasma for factor replacement
  • Cryoprecipitate or fibrinogen concentrate for severe hypofibrinogenemia
• Balance bleeding risk against thrombosis risk and involve senior hematology/critical-care support.