Medicine Marrow Pg 161-170 (Hematology)
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Questions and Answers

Which of the following is NOT a manifestation of anemia?

  • Nocturnal diarrhoea (correct)
  • Gustatory sweating
  • Postural hypotension
  • Progressive fatigue

    • Gustatory sweating is a common symptom associated with hematology disorders.

    True

    What is the main treatment mentioned for managing hematological disorders?

    High dose IV melphalan + Dexamethasone

    In males, __________ is associated with carpal tunnel syndrome.

    <p>carpal tunnel syndrome</p> Signup and view all the answers

    Match the following hematological manifestations with their respective descriptions:

    <p>Macroglossia = Enlarged tongue Waxy eyelid = Skin changes around the eyes Postural hypotension = Drop in blood pressure upon standing Reflex tachycardia = Rapid heart rate response</p> Signup and view all the answers

    Which mutation is commonly associated with Waldenstrom's Macroglobulinemia?

    <p>MYD88 mutation</p> Signup and view all the answers

    Waldenstrom's Macroglobulinemia primarily secretes IgA.

    <p>False</p> Signup and view all the answers

    What is one clinical feature associated with hyperviscosity in Waldenstrom's Macroglobulinemia?

    <p>Headache</p> Signup and view all the answers

    The presence of _______ is a key diagnostic criterion for Waldenstrom's Macroglobulinemia.

    <p>IgM monoclonal gammopathy</p> Signup and view all the answers

    Match the following clinical features to their description:

    <p>Cold agglutination autoimmune hemolytic anemia = Destruction of red blood cells due to cold antibodies Epistaxis = Nosebleeds caused by hyperviscosity Raynaud-like symptoms = Reduced blood flow causing color changes in fingers Neuropathy = Nerve damage leading to weakness or pain</p> Signup and view all the answers

    Which of the following is a poor prognostic factor in plasma cell disorders?

    <p>↑ β2-microglobulin</p> Signup and view all the answers

    Daratumumab is used only for patients who are eligible for transplant.

    <p>False</p> Signup and view all the answers

    What is the induction treatment for standard-risk plasma cell disorders?

    <p>Bortezomib + Lenalidomide for 3 cycles</p> Signup and view all the answers

    Carpal tunnel syndrome in males is a result of __________.

    <p>amyloidosis</p> Signup and view all the answers

    Match the following treatments with their risk categories:

    <p>Bortezomib + Lenalidomide = Standard risk Carfilzomib + Lenalidomide + Dexamethasone = High risk Autologous transplant = If eligible Daratumumab = Consolidation phase</p> Signup and view all the answers

    What characteristic distinguishes monoclonal gammopathy from polyclonal gammopathy in a serum protein electrophoresis graph?

    <p>A tall, sharp peak in the middle</p> Signup and view all the answers

    Increased levels of β2 microglobulin are a common serum marker observed in plasma cell disorders.

    <p>True</p> Signup and view all the answers

    What is a common finding in the microscopic view of bone marrow in patients with plasma cell disorders?

    <p>Numerous cells with dark nuclei, typical of plasma cells.</p> Signup and view all the answers

    The deletion of chromosome 17p is classified as a ______ risk factor in Multiple Myeloma.

    <p>high</p> Signup and view all the answers

    Match the classification of Multiple Myeloma with their risk factors:

    <p>High Risk = t(4; 14) Standard Risk = t(6; 14)</p> Signup and view all the answers

    What is the most common hematological malignancy?

    <p>Leukemia</p> Signup and view all the answers

    Acute kidney injury in the context of multiple myeloma can be caused by light chain cast nephropathy.

    <p>True</p> Signup and view all the answers

    What is a common symptom associated with multiple myeloma related to bone issues?

    <p>Back pain</p> Signup and view all the answers

    The primary cytogenetic abnormalities leading to multiple myeloma include mutations in Ras and abnormalities in ______.

    <p>c-myc</p> Signup and view all the answers

    Match the following conditions with their renal effects:

    <p>Light chain cast nephropathy = Interstitial nephritis Light chain deposition disease = Nodular glomerulosclerosis Proximal renal tubular acidosis = Type 2 renal tubular acidosis Overflow proteinuria = Presence of light chains in urine</p> Signup and view all the answers

    What is the lifespan of platelets?

    <p>10 days</p> Signup and view all the answers

    Thrombocytopenia is defined as a platelet count below 100,000/μL.

    <p>True</p> Signup and view all the answers

    What is the increase in platelet count expected from 1 unit of single donor platelets (SDP)?

    <p>30,000-50,000/μL</p> Signup and view all the answers

    A platelet count below __________ can result in significant bleeding.

    <p>10,000/μL</p> Signup and view all the answers

    Match each type of platelet transfusion with its characteristic:

    <p>Single donor = Apheresis, Costly Random donor = Pooling &amp; centrifugation, Cheap</p> Signup and view all the answers

    Which of the following is a major criterion for the diagnosis of POEMS syndrome?

    <p>Organomegaly</p> Signup and view all the answers

    Vascular Endothelial Growth Factor (VEGF) is decreased in the pathogenesis of POEMS syndrome.

    <p>False</p> Signup and view all the answers

    What is the commonest type of heavy chain disease?

    <p>α chain disease (Seligman's disease)</p> Signup and view all the answers

    The condition characterized by chronic inflammatory demyelinating polyneuropathy is known as __________.

    <p>POEMS syndrome</p> Signup and view all the answers

    Match the following heavy chain disease types with their associated features:

    <p>α chain disease = Familial Mediterranean lymphoma, Campylobacter jejuni γ chain disease = Autoimmune diseases, fever, hepatosplenomegaly µ chain disease = Chronic Lymphocytic Leukemia, vacuoles in lymphocytes None = Sclerosis of bone lesions</p> Signup and view all the answers

    What is the most common cause of sudden cardiac death in patients with amyloidosis?

    <p>Restrictive cardiomyopathy</p> Signup and view all the answers

    Normal serum protein electrophoresis is typically observed in patients with amyloidosis.

    <p>True</p> Signup and view all the answers

    What type of biopsy is preferred when investigating amyloidosis?

    <p>Abdominal pad of fat</p> Signup and view all the answers

    In 2° amyloidosis, patients may present with __________ range proteinuria.

    <p>nephrotic</p> Signup and view all the answers

    Match the following clinical features with their associated manifestations:

    <p>Low voltage ECG = Restrictive cardiomyopathy Hepatomegaly with increased ALP = Liver involvement Nephrotic range proteinuria = Kidney involvement Sensory motor axonal neuropathy = Neuropathy</p> Signup and view all the answers

    What are non-branching fibrils associated with Primary AL Amyloidosis?

    <p>Thread-like structures</p> Signup and view all the answers

    Insoluble amyloid fibrils have a uniform width range of 10-15 nm.

    <p>False</p> Signup and view all the answers

    What is the primary role of thrombopoietin in thrombopoiesis?

    <p>To stimulate platelet development</p> Signup and view all the answers

    What type of amyloidosis is associated with light chain proteins?

    <p>Primary AL Amyloidosis</p> Signup and view all the answers

    Endomitosis is the process of differentiation of megakaryocytes.

    <p>False</p> Signup and view all the answers

    The positive reaction of amyloid when stained with congo red is referred to as _______.

    <p>bright congo red positive</p> Signup and view all the answers

    Name the type of megakaryocyte associated with immune thrombocytopenic purpura.

    <p>Giant megakaryocyte</p> Signup and view all the answers

    Match the soluble precursor with its corresponding type of amyloidosis:

    <p>Light chain = AL Serum amyloid A = AA AB₂ microglobulin = AB₂M Transthyretin = ATTR</p> Signup and view all the answers

    The process that requires IL-3 for platelet development is known as __________.

    <p>Early Thrombopoiesis</p> Signup and view all the answers

    Match the type of megakaryocyte with its associated condition:

    <p>Giant megakaryocyte = Immune thrombocytopenic purpura Dwarf megakaryocyte = Chronic myeloid leukemia Cloud megakaryocyte = Primary myelofibrosis Staghorn megakaryocyte = Essential thrombocytosis</p> Signup and view all the answers

    Study Notes

    Hematology

    • Active space manifestations:
      • Nocturnal diarrhea
      • Gustatory sweating
      • Postural hypotension
      • Reflex tachycardia
    • Carpal tunnel syndrome is common in men.
    • Anemia presents as progressive fatigue.
    • Hemorrhagic manifestations:
      • Macroglossia
      • Waxy eyelids and papules
    • Poor prognosis factors:
      • Elevated NT-Pro BNP
      • Elevated serum Trop T
      • Decreased free light chains
    • Management includes:
      • High-dose intravenous melphalan and dexamethasone
      • Autologous transplant

    Waldenstrom's Macroglobulinemia

    • AKA Lymphoplasmacytic Lymphoma
    • Pathogenesis:
      • Originates from memory B-cells
      • Associated with MYD88 and CXCR4 mutations
      • Lymphoplasmacytic cells express CD19, CD20, CD38, CD135, and surface IgM
    • Clinical Features:
      • Peripheral circulation:
        • Cold agglutination autoimmune hemolytic anemia
        • Hyperviscosity causing headache, tinnitus, and dizziness
        • Epistaxis
        • Neuropathy
        • Raynaud-like symptoms
    • Diagnosis:
      • Criteria:
        • IgM monoclonal gammopathy of any concentration
        • Small lymphocytic infiltration of bone marrow
        • Plasmacytoid/plasma differentiation
        • Markers: Surface IgM+, CD5+, CD10+, CD19+, CD20+, CD22, CD23, CD25-, CD27+, FMC 7+, CD103, CD138+
      • Investigations:
        • Serum protein electrophoresis showing an IgM m-band
      • Bone marrow:
        • Anemia
        • Pancytopenia (rare)
        • Weight loss

    Plasma Cell Disorders

    • Cord compression symptoms:

      • Compressive neuropathy
      • Radiculopathy
      • Neuromyeloma (due to vertebral fracture)

    • Causes of neuro-manifestations:

      • Hypercalcemia
      • Hyperviscosity (due to increased plasma cells)
      • Headache, Tinnitus
      • Psychiatric overtones
      • Carpal tunnel syndrome in males (due to amyloidosis)
      • Cord compression symptoms
      • Plasma cells
      • Plasmacytosis
      • Rouleaux formation

    • Poor Prognostic Factors:

      • Lambda or free light chains
      • IgA, D, E myeloma
      • Elevated β2-microglobulin
      • Elevated circulating plasma cells
      • Decreased serum albumin
      • Elevated LDH

    • Management:

      • Standard risk:
        • Induction: 3 cycles of bortezomib + lenalidomide
      • High risk:
        • Carfilzomib + lenalidomide + dexamethasone
      • If eligible for consolidation:
        • Autologous transplant (extract stem cells → ablation → reinfusion → engraftment in 2 weeks)
      • Daratumumab (Anti-CD38): Used in the consolidation phase, unfit for transplant, and relapse cases

    Plasma Cell Disorders (continued)

    • Normal serum protein electrophoresis: Shows a smooth, bell-shaped curve.
    • Monoclonal m-band: Shows a tall, sharp peak in the middle.

    Bone Marrow Biopsy

    • Microscopic views: Microscopic image of bone marrow cells present.
    • Description (Likely): The image shows numerous cells with dark nuclei, typical of plasma cells.

    Serum Markers

    • Increased levels of Ca+, BUN, creatinine, uric acid, and β2 microglobulin are observed.

    Multiple Myeloma Classifications (MSMART 3.0)

    • High Risk Multiple Myeloma:

      • 17p deletion
      • t(14; 16)
      • t(14; 20)
      • t(4; 14)

    • Standard Risk Multiple Myeloma:

      • Trisomies
      • t(1; 14)
      • t(6; 14)

    • Additional Risk Factors:

      • Double hit mm: 2+ risk factors
      • Triple hit mm: 3+ risk factors
      • p53 mutation
      • Gain 1q
      • β2 microglobulin

    Hematology

    • Pathogenesis of Multiple Myeloma:
      • B-lymphocyte → Primary cytogenetic abnormalities → MGUS → Random second-hit → Multiple myeloma:
        • Ras mutation
        • c-myc abnormalities
        • ↑ IL-6
      • Detection of plasma cells > 100 cells/mic.
      • Isolated light chain Ig → Nephrotoxic.
      • Most common hematological malignancy: Leukemia.
    • Clinical Presentation:
      • Age > 70 years (practical > 40 years)
      • Gender: Male > female
      • Bone pain and lytic lesions:
        • Most common: Back pain
        • Increased pain on movement
        • Fracture due to trivial trauma
        • Cause: Osteoclast activation
        • Hypercalcemia
        • Nephrogenic DI → Prerenal AKI
        • Normal ALP (No bone formation)
      • Recurrent Infections: Hypogammaglobulinemia → Pneumonia, UTI.
      • Acute Kidney Injury:
        • Overflow proteinuria: 24 hours urine protein to identify light chain
        • Light chain cast nephropathy (LCCN): Light chains cause interstitial nephritis. λ > κ
        • Fractured cast (Not visualized in urine)
        • Light chain deposition disease (LCDD): Nodular glomerulosclerosis (κ > λ)
        • Proximal renal tubular acidosis (Type 2)

    Platelets

    • Lifespan of platelets is 10 days.
    • Normal count: 1.5 - 4 lakh/μL
    • Thrombocytopenia: < 1,00,000/μL
    • Bleeding risk: < 20,000/μL
    • Significant bleeding risk: < 10,000/μL
    • Lifespan in stored blood: 72 hours
    • Investigations:
      • Coagulation studies: Platelet-poor plasma
      • Platelet studies: Platelet-rich plasma
      • Conducted at room temperature (exception: Lupus anticoagulant at 4°C)
    • Other information:
      • AKA satellitism: Caused by EDTA
      • Clumping of platelets: Identified by 3.2% trisodium citrate

    Platelet Transfusion

    • Completion time: Within 20 minutes

    Types of Platelet Transfusion

    Type Process Cost
    Single donor Apheresis Costly
    Random donor Pooling & centrifugation Cheap

    Post-Transfusion Increase in Platelet Count

    • SDP: ↑ by 30,000-50,000/μL
    • RDP: ↑ by 6,000/μL (4-6 units)

    Management

    • Plasmapheresis (PLEX)
    • BR regimen (4-6 cycles):
      • Bendamustine
      • Rituximab

    POEMS Syndrome

    • Pathogenesis: ↑ VEGF (vascular endothelial growth factor)
    • Associated with Castleman's Disease
    • Major criteria: P & M
      • P: Polyneuropathy (CIDP → Chronic inflammatory demyelinating polyneuropathy)
      • O: Organomegaly
      • E: Edema (extravascular overload)
      • M: m-protein
    • Minor criteria:
      • Endocrinopathy (eg: Hypogonadism)
      • S: Sclerotic bone lesions
      • Skin changes

    Heavy Chain Disease

    • Different types based on heavy chains: | Types | Associations and features | |---|---| | a chain disease (m/c) AKA Seligman's disease, immuno-proliferative small intestinal disorder (IPSID) | * Familial Mediterranean lymphoma.* Campylobacter jejuni infection.| | γ chain disease AKA Franklin's disease | * Autoimmune diseases.* Fever + anemia + hepatosplenomegaly.* Palatal edema.| | µ chain disease | * Chronic Lymphocytic Leukemia (CLL).* Vacuoles in lymphocytes.|

    Investigations (Amyloidosis)

    • Biopsy:
      • Abdominal pad of fat (preferred)
      • Renal
      • Congo red +ve
    • Immunohistochemistry:
      • +ve for Amyloid A / transthyretin, etc.
    • Serum protein electrophoresis: Normal.
    • Serum immunoelectrophoresis: ↑λ proliferation (m/c)

    Clinical Presentation (Amyloidosis)

    • 1. Heart:
      • Restrictive cardiomyopathy (RCMP):
        • Most common type of cardiomyopathy
        • Non ischemic cardiomyopathy
        • ECG: Low voltage
        • ECHO: Hypertrophy
      • Sudden cardiac death (SCD): Most common cause of death
    • 2. Kidney:
      • In secondary amyloidosis
      • Nephrotic range proteinuria with/without nephrotic syndrome (in elderly)
    • 3. Liver:
      • Hepatomegaly with increased ALP
      • Biopsy is contraindicated due to increased risk of bleeding (Anti-xa antibodies)
    • 4. Sensory motor axonal neuropathy
    • 5. Chronic inflammatory demyelinating polyneuropathy (CIDP)

    Platelets - Basics

    • Formation of Platelets:
      • Common myeloid progenitor → RBC → Granulocyte → Monocyte → Megakaryocyte → Platelet
    • Early Thrombopoiesis:
      • Requires:
        • Thrombopoietin (from liver)
        • IL-3 (platelet development)
        • IL-II
        • Recombinant IL-II (Oprelvekin): Rx of induced thrombocytopenia in chemotherapy
    • Late Thrombopoiesis:
      • Requires SDF-1
    • Stages of Megakaryocyte Development:
      • Stage II: Basophilic
      • Stage III: maximal granules, multilobed nuclei
      • Stage IV: mature, lesser granules, pyknotic nuclei
    • Endomitosis: Process of multiplication of megakaryocytes

    Morphological Variation of Megakaryocytes

    • Giant megakaryocyte: Immune thrombocytopenic purpura
    • Dwarf megakaryocyte: Chronic myeloid leukemia
    • Cloud megakaryocyte: Primary myelofibrosis
    • Staghorn megakaryocyte: Essential thrombocytosis

    Primary AL Amyloidosis

    • AKA Light chain disease
    • Pathogenesis:
      • **Soluble Precursors: ** (examples: Serum Amyloid A, light chain, transthyretin, etc.)
        • Possibly due to: Misfolding or protein conformation disorder (α → β).
      • Insoluble Amyloid:
        • Extracellular: Located outside of cells
        • Non-branching fibrils: Thread-like structures without branches
        • Indefinite length: Variable length
        • 7.5-10 nm width: Specific size range
        • Congor red (stain) +ve: A positive reaction when stained with congo red.

    Classification of Amyloidosis

    Soluble precursor Type Clinical Syndrome
    Light chain AL Primary amyloidosis
    Serum amyloid A AA Secondary amyloidosis: in kidney (associated with chronic inflammatory condition: TB, rheumatoid arthritis, bronchiectasis etc)
    AB₂ microglobulin AB₂M Dialysis associated
    Transthyretin ATTR Senile systemic: wild type, FAP (Familial amyloid polyneuropathy): mutant type
    Amyloid β protein AB Alzheimer's disease, Cerebral amyloid angiopathy
    Cystatin C ACYS
    Calcitonin ACal medullary carcinoma of thyroid
    Atrial natriuretic factor AANF Atrial fibrillation

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    Description

    Test your knowledge on the key concepts of hematology, specifically focusing on Waldenstrom's macroglobulinemia. This quiz covers clinical features, management strategies, and important diagnostic indicators related to the condition. Understand the manifestations and prognosis factors associated with hematological disorders.

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