Hematology Flashcards
1
Q
What are the characteristics of lymphocytes on a peripheral smear?
A
• Smallest WBC.
• Round nucleus.
• No granules.
2
Q
What are the features of monocytes in a peripheral smear?
A
• Largest WBC.
• Reniform (kidney-shaped) nucleus.
3
Q
Describe the appearance of granulocytes on a peripheral smear.
A
• Eosinophils: Bilobed nucleus, brick-red granules.
• Neutrophils: 3–5 lobes in nucleus, bluish granules.
• Basophils: Dense purple granules that obscure the cytoplasm.
4
Q
What is the preferred position for bone marrow examination?
A
• Left lateral position, with the back facing the doctor.
5
Q
What are the common sites for bone marrow aspiration?
A
• Adults: Posterior superior iliac spine (PSIS) > Anterior superior iliac spine (ASIS) > Sternum.
• Children: Tibia (shin).
6
Q
Name the types of needles used for bone marrow procedures.
A
- Salah’s needle.
- Klima needle.
- Jamshidi needle (used for both biopsy and aspiration).
7
Q
What causes a “dry tap” during bone marrow aspiration?
A
- Aplastic anemia: Fat > Cells.
- Myelofibrosis.
- Hairy cell leukemia.
- Space-occupying lesions in bone marrow (e.g., granulomas, metastasis).
- AML M7
8
Q
What is observed in a bone marrow aspirate (BMA)?
A
• Presence of both mature and immature cells and fat.
9
Q
What is observed in a bone marrow biopsy (BM bx)?
A
• Cellularity: % cellularity = 100 - age.
• Fat, RBCs, and bony trabeculae.
10
Q
In which condition is AML-M7 associated with bone marrow changes?
A
• Associated with increased platelet-derived growth factor leading to myelofibrosis.
11
Q
What are the causes of neutrophilia (> 40–70%)?
A
• Acute /bacterial infections.
• Tissue necrosis: Burns, myocardial infarction (MI).
12
Q
What are the causes of eosinophilia (> 2–6%)?
A
- Allergic reactions: Asthma, hay fever, Type I hypersensitivity.
- Parasitic infections.
- Malignancy: Hodgkin’s lymphoma.
- Tropical pulmonary eosinophilia.
13
Q
What are the causes of monocytosis (> 1–8%)?
A
• Chronic infections : TB.
• Rickettsia.
• IBD.
• Malaria.
14
Q
What condition is associated with basophilia (≥ 1%)?
A
• Myeloproliferative disorders (e.g., chronic myeloid leukemia - CML).
15
Q
What are the causes of lymphocytosis (> 15–40%)?
A
• Chronic infections.
• Viral infections.
16
Q
What triad suggests a myeloproliferative disorder (e.g., CML)?
A
- Splenomegaly.
- ↓ Neutrophil alkaline phosphatase (NAP) score.
- Basophilia.
17
Q
What are toxic granules and Döhle bodies?
A
• Toxic granules: Coarse azurophilic granules seen in infections.
• Döhle bodies: Patches of dilated endoplasmic reticulum, seen in infections.
18
Q
Compare hypersegmented and hyposegmented neutrophils (Pseudo-Pelger-Huet cells).
A
• Hypersegmented neutrophils:
• Definition: Neutrophils with > 5 lobes.
• Cause: Megaloblastic anemia (e.g., vitamin B12 deficiency).
• Hyposegmented neutrophils (Pseudo-Pelger-Huet cells):
• Definition: Neutrophils with < 3 lobes.
• Cause: Myelodysplastic syndrome.
19
Q
What are the diagnostic criteria for acute leukemias?
A
WHO :
• > 20% blasts (Immature precursors) in BM/PS OR
• < 20% blasts + t(15:17)/t(8:21)/Inversion-16 translocation.
FAB : > 30% blasts in BM/PS
20
Q
What are the features of lymphoblasts?
A
• Size: Small.
• Cytoplasm: Scanty.
• Granules: Absent.
• Auer rods: Absent.
• Chromatin: Coarse, dark blue, and clumped.
• Nucleoli: Inconspicuous.
• Special stain: Positive for PAS (Periodic Acid-Schiff).
21
Q
What are the features of myeloblasts?
A
• Size: Large.
• Cytoplasm: Moderate amount.
• Granules: Present.
• Auer rods: Present (sometimes in clusters, called faggot cells).
• Chromatin: Homogeneous, opened up, and pink.
• Nucleoli: 2–5, prominent.
• Special stains: Positive for MPO (Myeloperoxidase), SBB (Sudan Black B), and NSE (Non-specific Esterase).
22
Q
What is the most common age group for ALL?
A
• 2–9 years (Most common leukemia in children).
23
Q
Clinical features of ALL?
A
- Anemia:
• ↓ RBCs → Pallor, fatigue.- Leukopenia:
• ↑ Blasts, ↓ Mature WBCs → Increased infections. - Thrombocytopenia:
• ↓ Platelets → Bleeding manifestations. - Organ involvement:
• Hepatosplenomegaly.
• CNS, testes, and lymph nodes (involvement absent in AML).
- Leukopenia:
24
Q
What are the subtypes of ALL based on FAB classification?
A
- L1:
• Blast: Small, round.
• Cytoplasm: Scant.
• Nucleus: Round.
• Chromatin: Homogeneous.
• Nucleoli: Indistinct.
• Occurrence: 75% (Most common).
• Prognosis: Best. - L2:
• Blast: Pleomorphic, larger.
• Cytoplasm: Moderate.
• Nucleus: Irregular.
• Chromatin: Fine.
• Nucleoli: ≥ 1, large, distinct.
• Occurrence: 20%. - L3:
• Blast: Large.
• Cytoplasm: Moderate, basophilic, vacuolated.
• Nucleus: Round/oval.
• Chromatin: Stippled.
• Nucleoli: Large, distinct.
• Occurrence: 5%.
• Prognosis: Worst.
25
What is the WHO classification of ALL based on flow cytometric markers?
1. B-ALL:
• Occurrence: 85% (Most common).
• Age group: Usually children.
• Mediastinal involvement: Absent.
• Associated mutation: Loss-of-function (LOF) in PAX5, E2A, RUNX1, EBF genes.
• Prognosis: Better.
2. T-ALL:
• Occurrence: 10–15% (Less common).
• Age group: Usually adults and adolescents.
• Mediastinal involvement: Present.
• Associated mutation: Gain-of-function (GOF) in NOTCH-1 gene.
• Prognosis: Poor.
26
What are the key diagnostic investigations for ALL?
1. Complete Blood Count (CBC):
• ↓ Hemoglobin (Hb), ↓ Platelets.
• WBC count may be ↑ or ↓.
2. Peripheral Smear (PS):
• >20% lymphoblasts.
• Special stain: PAS (Block/Dot pattern) positive.
Diffuse + in AML:M6
3. Flow Cytometry:
• B-ALL markers: CD19, CD20, CD22, PAX5, TdT, CALLA.
• T-ALL markers: CD1, CD2, CD3, CD5, CD7, TdT, CALLA.
27
What factors indicate good prognosis in ALL?
1. Age: 2–9 years.
2. Sex: Female.
3. Race: Whites.
4. FAB type: L1.
5. WHO type: B-ALL.
6. Organ involvement: Absent in CNS, testes, or lymph nodes.
7. Cytogenetics: Hyperdiploidy, trisomy 4/7/10, t(12;21).
8. Leukocyte count: < 100,000/mL.
28
What factors indicate poor prognosis in ALL?
1. Age: < 1 year or > 10 years.
2. Sex: Male.
3. Race: Blacks.
4. FAB type: L2 or L3.
5. WHO type: T-ALL.
6. Organ involvement: CNS, testes, or lymph nodes.
7. Cytogenetics: Hypodiploidy, t(9;22) (Philadelphia chromosome).
If t(9;22) present in CML=Good prognosis.
8. Leukocyte count: > 100,000/mL.
29
What is the typical age group affected by AML?
• 15–39 years (Same as Chronic Myeloid Leukemia - CML).
30
What are the clinical features of AML?
• Similar to ALL (anemia, infections, bleeding).
• Specific features:
1. Gum hypertrophy/bleeding.
2. Disseminated intravascular coagulation (DIC).
3. Chloroma (Granulocytic sarcoma):
• Soft tissue involvement.
• Most common site: Orbit.
• MPO positive.
• Presence of Arbiskov cells (Monocytes in chloroma).
31
What are the subtypes of AML based on cell type and differentiation?
1. M0:
• Undifferentiated AML.
2. M1:
• AML with minimal maturation.
3. M2 (Most common):
• AML with maturation.
• Associated with t(8;21) and chloroma.
4. M3:
• Acute promyelocytic leukemia.
• Best prognosis.
• Maximum Auer rods and Faggot cells.
• Associated with t(15;17), RunX1/RunX1T1, and DIC.
• Treatment: All-trans retinoic acid (ATRA) and Arsenic trioxide.
5. M4:
• Acute myelomonocytic leukemia.
• Associated with inversion 16.
6. M4 eos:
• Acute myelomonocytic leukemia with eosinophilia.
7. M5:
• Monocytic leukemia (variants a and b).
• Most commonly associated with gum bleeding (M5 > M4).
• Leukemia cutis and NSE positive (due to monoblasts).
8. M6:
• Acute erythroid leukemia (Di Guglielmo disease).
• Diffusely PAS positive.
9. M7 (Least common):
• Acute megakaryocytic leukemia.
• Associated with Down’s syndrome and myelofibrosis.
• Causes dry tap on bone marrow aspiration.
• Markers: CD41, CD61.
32
What is the significance of Auer rods in AML?
• Present in myeloblasts and indicative of AML.
• Seen maximally in M3 subtype (Acute promyelocytic leukemia).
33
What is MPO positivity in AML?
• Myeloperoxidase positive in myeloblasts, confirming the diagnosis of AML.
34
What conditions cause a decreased or increased NAP score?
• Decreased NAP score:
• Paroxysmal nocturnal hemoglobinuria (PNH).
• CML.
• Increased NAP score:
• Leukemoid reaction.
• Pregnancy.
• Stress.
• Other myeloproliferative disorders.
35
What are the differential diagnoses for massive splenomegaly?
1. Malaria.
2. Polycythemia vera.
3. Myelofibrosis.
4. Kala-azar.
5. Myelodysplastic syndrome (MDS).
6. Gaucher’s disease.
36
What is the first-line treatment for CML?
• Imatinib mesylate: A tyrosine kinase inhibitor (TKI).
37
What are the WHO criteria for the accelerated phase of CML?
1. Blasts: 10–19% in peripheral blood or bone marrow.
2. Peripheral blood basophils: > 20%.
3. Persistent thrombocytopenia (<100 × 10⁹/L) unrelated to therapy, or thrombocytosis (>1000 × 10⁹/L) unresponsive to therapy.
4. Increasing spleen size and WBC count unresponsive to therapy.
5. Cytogenetic evidence of clonal evolution.
38
What are the diagnostic investigations for CML?
1. Complete Blood Count (CBC):
• Normal hemoglobin (Hb).
• Markedly increased WBC and platelet count.
2. Peripheral Smear (PS):
• Mimics bone marrow.
• All stages of myeloid maturation are present.
3. Bone Marrow Aspiration (BMA):
• Sea blue histiocytes.
• Pseudo Gaucher cells.
4. NAP Score (Neutrophil Alkaline Phosphatase):
• Decreased (Normal range: 40–100).
5. Fluorescent In Situ Hybridization (FISH):
• Detects t(9;22).
39
What are the hallmark clinical features of CML?
1. Massive splenomegaly: Often causing a dragging sensation in the abdomen.
2. Basophilia.
3. Symptoms related to myeloproliferation: Fatigue, weight loss, and early satiety.
40
What is the genetic abnormality associated with CML?
• t(9;22) Philadelphia chromosome in 95% of cases.
• Leads to constant activation of tyrosine kinase (TK), causing uncontrolled myeloproliferation.
41
What is the typical age group for CLL presentation?
• 60–70 years (Elderly).
42
What are the genetic abnormalities associated with CLL?
• Deletion of chromosomes:
• 13q, 11q, 17p.
• Trisomy 12.
43
What are the key clinical features of CLL?
1. Painless lymphadenopathy: Enlargement of lymph nodes without pain.
2. History of Autoimmune Hemolytic Anemia (AIHA).
44
What are the diagnostic investigations for CLL?
1. Complete Blood Count (CBC):
• Absolute lymphocytosis: > 5000/mm³.
2. Peripheral Smear (PS):
• Mature lymphocytes.
• Smudge cells (also called parachute or basket cells).
3. Lymph Node Biopsy:
• Proliferation centers (Pathognomonic feature for CLL).
4. Markers:
• CD5, CD23, CD200.
45
What is the appearance of cells in CLL and CML on peripheral smear?
• CLL: “Convent girl” appearance (Uniform appearance of cells).
• CML: “College girl” appearance (No cell uniformity).
46
What are the key disorders of myeloproliferative neoplasms and their associated pathways?
1. Chronic Myeloid Leukemia (CML): Tyrosine kinase pathway.
2. Polycythemia Vera: JAK-STAT pathway.
3. Essential Thrombocytosis: JAK-STAT pathway.
4. Myelofibrosis: JAK-STAT pathway.
47
What are the main diagnostic criteria for polycythemia vera (2014)?
• Diagnosis requires:
• All 3 major criteria or
• First 2 major criteria + 1 minor criterion.
Major Criteria:
1. Hemoglobin (Hb):
• >16.5 g/dL in men.
• >16 g/dL in women.
2. Bone marrow (BM) biopsy showing trilineage myeloproliferation with pleomorphic megakaryocytes.
3. Presence of JAK2 mutation.
Minor Criterion:
• Subnormal serum erythropoietin (S. EPO) level.
48
What differentiates relative polycythemia from polycythemia vera?
• Relative Polycythemia:
• Seen in high altitude, smokers, or COPD.
• Associated with increased serum erythropoietin levels.
49
Clinical features of polycythemia vera?
Headache, dizziness d/t↑Hb
Intense itching after bath d/t↑basophils & mast cells (↑TLC)
Erythromelalgia (Throbbing/burning sensation) d/t↑platelets leads to Vaso-occlusion
50
Myeloproliferative Neoplasms Features?
• Panmyelosis : ↑Hb, ↑TLC, ↑platelet count.
• Mutation of growth signaling pathways.
• Hepatosplenomegaly.
• Development of myelofibrosis.
51
ESSENTIAL THROMBOCYTOSIS Diagnostic Criteria?
All 4 criteria must be present :
1. Platelet count ≥ 450,000/mm3 .
2. JAK2V617F (+) or no evidence of reactive thrombocytosis.
3. Not meeting WHO criteria for other MPNs.
4. Megakaryocyte proliferation with large and mature morphology.
52
What are the major diagnostic criteria for primary myelofibrosis (PMF)?
1. Atypical megakaryocytic hyperplasia with reticulin or collagen fibrosis (caused by PDGF).
2. Exclusion of WHO criteria for other myeloproliferative neoplasms (MPNs).
3. Presence of JAK2V617F mutation or other clonal markers. If absent, rule out secondary causes of fibrosis.
53
What are the minor diagnostic criteria for PMF, and how many are required?
• Minor criteria: (At least 2 out of 4 required)
1. Leukoerythroblastosis (presence of immature myeloid and erythroid cells in peripheral blood).
2. Elevated serum LDH levels.
3. Anemia (myelophthisic anemia).
4. Palpable splenomegaly.
54
What are the characteristic findings in a complete blood count (CBC) and peripheral smear in PMF?
• CBC findings:
• ↓ Hemoglobin (anemia).
• ↓ Total Leukocyte Count (TLC).
• ↓ Platelet count.
• Peripheral smear findings:
• Dacrocytes (tear-drop cells).
• Leukoerythroblasts (immature myeloid and erythroid cells).
55
Why is a bone marrow aspirate challenging in primary myelofibrosis?
• Bone marrow aspirate: Often results in a dry tap due to extensive fibrosis.
Conditions with a dry tap:
1. Aplastic anemia.
2. Myelophthisic anemia.
3. Myelofibrosis.
4. Hairy cell leukemia.
5. AML-M7.
56
What are the key findings on a bone marrow biopsy in PMF?
1. Reticulin fibers (identified with reticulin staining).
2. Bony trabeculae.
Investigation of choice (IOC): Bone marrow biopsy.
57
What is the difference in age distribution between Hodgkin’s and Non-Hodgkin’s Lymphoma?
• Hodgkin’s Lymphoma (HL): Bimodal distribution (peaks in young adults and elderly).
• Non-Hodgkin’s Lymphoma (NHL): Common in the elderly.
58
How do Hodgkin’s and Non-Hodgkin’s Lymphoma differ in lymph node involvement?
• Hodgkin’s Lymphoma:
• Involves a single axial group of lymph nodes.
• Common sites: Cervical (most common), mediastinal, para-aortic lymph nodes.
• Non-Hodgkin’s Lymphoma:
• Involves multiple peripheral lymph nodes.
• Common sites: Axillary, mediastinal, inguinal lymph nodes.
59
What is the difference in the pattern of spread between HL and NHL?
• Hodgkin’s Lymphoma: Contiguous spread (to adjacent lymph nodes).
• Non-Hodgkin’s Lymphoma: Non-contiguous spread.
60
How do Hodgkin’s and Non-Hodgkin’s Lymphoma differ in mesenteric node and Waldeyer’s ring involvement?
• Hodgkin’s Lymphoma: Rarely involves mesenteric nodes and Waldeyer’s ring.
• Non-Hodgkin’s Lymphoma: Commonly involves mesenteric nodes and Waldeyer’s ring.
61
How do Hodgkin’s and Non-Hodgkin’s Lymphoma differ in extranodal involvement?
• Hodgkin’s Lymphoma: Extranodal involvement is uncommon.
• Non-Hodgkin’s Lymphoma: Extranodal involvement is common.
62
What is Hodgkin’s Lymphoma?
• Hodgkin’s Lymphoma is a B-cell lymphoma characterized by the presence of Reed-Sternberg (RS) cells.
63
What are the clinical features of Hodgkin’s Lymphoma?
1. Systemic symptoms (B symptoms):
• Fever.
• Night sweats.
• Unexplained weight loss.
2. Lymphadenopathy:
• Commonly cervical lymphadenopathy with rubbery, painless lymph nodes.
3. Pel-Ebstein fever:
• Fever with a waxing and waning pattern.
64
What are the WHO classifications of Hodgkin’s Lymphoma?
• Classical HL:
1. Nodular sclerosis (most common subtype).
2. Mixed cellularity.
3. Lymphocyte-rich.
4. Lymphocyte-depleted.
• Non-classical HL (Nodular Lymphocyte Predominant HL - NLPHL):
• Distinct from classical HL.
65
What are the Reed-Sternberg cell markers in classical vs non classical Hodgkin’s Lymphoma?
• Classical HL (RS cells):
• CD15+ and CD30+.
• Non-classical HL (NLPHL):
• CD20+, CD45+, and Epithelial Membrane Antigen (EMA)+.
• Negative for CD15 and CD30.
66
What are the key features of a Reed-Sternberg (RS) cell?
1. Binucleate or multinucleate.
2. Eosinophilic macronucleoli.
3. Characteristic owl’s eye appearance (due to prominent nucleoli).
67
What are the variants of Reed-Sternberg (RS) cells, and in which conditions are they seen?
1. Lacunar variant: Seen in Nodular Sclerosis HL.
2. Popcorn cell/L-H cell: Seen in Nodular Lymphocyte Predominant HL (NLPHL).
68
Where else can the owl’s eye appearance be observed, apart from RS cells?
• Owl’s eye appearance is also seen in Cytomegalovirus (CMV) infection.
69
What is the most common subtype of Hodgkin’s Lymphoma globally?
Nodular Sclerosis HL is the most common subtype globally.
70
What is the most common subtype of Hodgkin’s Lymphoma in India?
Mixed Cellularity HL is the most common subtype in India.
71
What are the key features of Nodular Sclerosis HL?
1. Most common subtype globally.
2. Equal prevalence in males and females (M=F).
3. Affects adolescents and young adults.
4. Characterized by Lacunar variant RS cells (clear space surrounding the cell).
5. Markers: CD15+ and CD30+.
6. Rarely associated with Epstein-Barr Virus (EBV).
7. Prognosis: Excellent.
72
What are the key features of Mixed Cellularity HL?
1. Most common subtype in India.
2. More common in males (M > F).
3. Biphasic age distribution (young adults and >55 years).
4. Contains eosinophils and plasma cells with maximum RS cells.
5. Markers: CD15+ and CD30+.
6. Frequently associated with EBV.
7. Prognosis: Very good.
73
What are the key features of Lymphocyte-Rich HL?
1. More common in males (M > F).
2. Affects older adults.
3. Contains mononuclear RS cell variants.
4. Markers: CD15+ and CD30+.
5. Frequently associated with EBV.
6. Prognosis: Good to excellent.
74
What are the key features of Lymphocyte-Depleted HL?
1. Associated with HIV infection.
2. More common in males (M > F).
3. Affects older adults.
4. Contains pleomorphic, necrobiotic, or mummified RS cell variants.
5. Markers: CD15+ and CD30+.
6. Frequently associated with EBV.
7. Prognosis: Poor.
75
What are the key features of Lymphocyte-Predominant HL (NLPHL)?
1. More common in males (M > F), particularly young males.
2. Contains L&H cells (Popcorn cells) with scanty background cells.
3. B cells are absent.
4. Markers:
• CD15- and CD30-.
• Positive for CD20+, BCL6+, and EMA+.
5. Not associated with EBV.
6. Prognosis: Best among all types.
76
What staging system is used for Hodgkin’s Lymphoma?
Ann Arbor Staging System is used.
77
What is the first-line treatment regimen for Hodgkin’s Lymphoma?
ABVD regimen:
1. A: Adriamycin.
2. B: Bleomycin.
3. V: Vinblastine.
4. D: Dacarbazine.
78
Follicular lymphoma?
M/c indolent NHL in world
• t (14; 18)
• MLL gene
• Follicular arrangement
• Centrocytes
• Centroblasts
BCL-2+
Paratrabecular lymphoid aggregates
79
Mantle cell lymphoma?
t (11; 14)
Small to medium irregular lymphocytes
Cyclin D1 + CD 5 + ,
CD 23 - , SOX 11
Lymphomatoid polyposis
80
Burkitt’s lymphoma?
• t (8; 14): C-myc amplification.
• t (2; 8)
• t (8; 22)
• Ki67 high ↑Proliferation.
• Chemosensitive.
Starry sky appearance
CD 19+, CD 20 + , BCL-6 +
• EBV association
• Jaw/GIT involvement
81
3 myc gene (Proto-oncogene)?
• C-myc : Burkitt lymphoma.
• L-myc : Lung cancer.
• N-myc : Neuroblastoma.
82
Types of Burkitt’s Lymphoma?
African : • A/w : EBV (Epstein Barr virus)
• M/c site : Jaw/mandible
Sporadic : Site : GIT (Peritoneal/ Ileal involvement)
HIV associated
83
Diffuse Large B Cell lymphoma?
M/c NHL in India/ world
Dysregulation BCL 6
Large pleomorphic cells in diffuse pattern
CD 19+ CD 20 + , BCL-6 +
84
Marginal zone lymphoma?
t (11; 18)
Lymphoepithelial lesion (Lymphocytes entering epithelium)
CD 43+
Site of chronic inflammation
85
Massive splenomegaly causes?
• CML.
• Polycythemia vera.
• Myelofibrosis.
• Gaucher’s disease.
• Hairy cell leukemia.
• Malaria. India.
• Kala-azar
86
What are the diagnostic findings in Hairy Cell Leukemia?
1. CBC: Pancytopenia (due to myelofibrosis).
2. Peripheral smear (P/S): Presence of hairy cells.
3. Bone marrow aspiration: Often dry tap.
4. Bone marrow biopsy: Fried egg or honeycomb appearance.
5. Special stain: TRAP+ (Tartrate-resistant acid phosphatase).
6. Annexin A1, CD 25, CD 11c, CD 103 +
87
Hairy Cell Leukemia Features?
• B cell disorder.
• Hair-like projections (Best seen : Phase contrast microscope).
• Massive splenomegaly.
• Pathology : BRAF V 600 E mutation.
88
What are the key types of T-cell NHL?
1. Adult T-cell leukemia/lymphoma (ATLL)
2. Mycosis fungoides/Sezary syndrome
3. Anaplastic large cell lymphoma (ALCL)
89
Adult T-cell leukemia?
Human T-lymphotropic virus (HTLV) 1
Flower cell/Clover leaf cells
90
Mycosis fungoides/ Sezary syndrome?
Cutaneous T-cell lymphoma
Sezary cells (Cerebriform nuclei)
91
Anaplastic large cell lymphoma?
ALK gene on chromosome 2p
Hallmark (Doughnut) cell
92
ALK gene mutation is a/w :?
• ALL.
• Adenocarcinoma lung.
• Inflammatory myofibroblastic tumor.
93
What are the diagnostic criteria for Multiple Myeloma?
• Clonal bone marrow plasma cells ≥10% or biopsy-proven bony/extramedullary plasmacytoma + Myeloma defining event.
• SLIM criteria (One or more biomarkers of malignancy):
1. Clonal bone marrow plasma cells ≥60%.
2. Involved: Uninvolved free light chain ratio >100.
3. >1 focal lesion on MRI.
CRAB criteria indicating end organ damage
1. C: Hypercalcemia
2. R: Renal insufficiency
3. A: Anemia
4. B: Bone lesions (axial skeleton involvement, particularly lumbar vertebrae)
94
What are the characteristic findings in bone marrow aspirate in multiple myeloma?
1. Flame cells
2. Mott cells (grape-like cytoplasm)
3. Russell bodies (intracytoplasmic immunoglobulin)
4. Dutcher bodies (intranuclear immunoglobulin)
95
What are the common clinical features of multiple myeloma?
• Fatigue, pallor, bone pain, pathological fractures.
• Most common set of bones affected: Axial skeleton
• Most common vertebrae affected: Lumbar vertebra
• Most common cause of death: Renal failure
96
What are the common findings in biochemical tests for multiple myeloma?
1. ↑ Serum calcium (metastatic calcifications)
2. ↓ Hb (anemia of chronic disease)
3. ↑ ESR
4. ↑ Serum beta-2 microglobulin (best prognostic factor)
5. Abnormal renal function tests
6. S. Albumin/Globulin reversed
7. Bence Jones proteinuria: Precipitates at 40-60°C, disappears at 100°C, reappears on cooling
97
What are the common pathology markers in multiple myeloma?
1. CD 138 (Syndecan-1)
2. CD 56
98
What are the radiological findings in multiple myeloma?
• X-ray: Lytic/punched-out lesions
• Electrophoresis:
• ↑ Immunoglobulin (Ig): IgG > IgA > IgM > IgD > IgE
99
Plasma cell leukemia?
>20% plasma cell
100
Smoldering/ Asymptomatic myeloma
• BM plasma cell >10%
• No CRAB lesions
• S. monoclonal M protein > 3g/dL
101
Monoclonal gammopathy of undetermined significance?
• BM plasma cell <10%
• No myeloma defining events
• S. IgG <3 g/dL
102
Waldenstrom macroglobulinemia?
• ↑IgM (Hyper viscosity syndrome) leads to Lymphoplasmacytic lymphoma
• A/w MYD 88 mutations
103
What is the characteristic feature of Langerhans Cell Histiocytosis (LCH)?
• Abnormal proliferation of immature dendritic cells (antigen-presenting cells).
104
What genetic mutation is associated with Langerhans Cell Histiocytosis (LCH)?
• BRAF V600E mutation.
• Associated with LCH, papillary carcinoma of thyroid, hairy cell leukemia, and pilocytic astrocytoma.
105
What are the features of Hand-Schuller-Christian Disease, a form of LCH?
1. Diabetes insipidus.
2. Exophthalmos.
3. Bone defects (e.g., skull lesions).
106
What are the histological features of Langerhans Cell Histiocytosis (LCH)?
• Coffee bean nuclei (longitudinal groove appearance).
• Also seen in papillary carcinoma of thyroid, Chondroblastoma, Granulosa cell tumor ovary and Brenner’s tumor.
107
What is observed under electron microscopy in Langerhans Cell Histiocytosis (LCH)?
• Birbeck granules (Tennis racquet-shaped granules).
108
Outline the stages of RBC development.
1. Hematopoietic stem cell → Common myeloid progenitor (CMP)
2. Proerythroblast
• Hb production starts (visible only on electron microscopy).
3. Early/Basophilic normoblast (blue cytoplasm).
4. Intermediate/Polychromatic normoblast (pink + blue cytoplasm).
• Hb first appears at this stage.
5. Late/Orthochromatic normoblast (pale pink cytoplasm).
6. Reticulocyte
• First stage without a nucleus.
• Matures into an RBC in 1-2 days.
109
What are reticulocytes, and how do they differ from mature RBCs?
• Reticulocytes are the immediate precursors of RBCs.
• They contain a bluish meshwork due to residual RNA and histones.
• Mature RBCs lack this meshwork.
110
Which stains are used to identify reticulocytes, and how do they work?
• Supravital stains are used to stain living cells in vitro.
• Examples: Brilliant cresyl blue and New methylene blue.
• Prussian blue is not a supravital stain but stains iron deposits.
111
What is the normal reticulocyte count?
• Normal: 0.5% - 1.5%.
112
In which conditions is the reticulocyte count increased?
• Hemolytic anemia
• Acute blood loss
• Response to iron or B12 therapy
113
In which conditions is the reticulocyte count decreased?
• Aplastic anemia
• Bone marrow suppression
114
How is the corrected reticulocyte count calculated?
Retic count xPatient Hb/HCT / normal Hb/HCT for that age
Normal Hb: 15 g/dL, HCT: 45%
115
Microcytic hypochromic anemia seen in ?
Mnemonic : SITA
• Sideroblastic anemia, lead poisoning
• Iron deficiency anemia
• Thalassemia
• Anemia of chronic disease
116
Macrocytic anemia seen in ?
Mnemonic : Lady Hardinge Medical College
• Liver disease
• Hypothyroidism
• Megaloblastic anemia (Vit B12/Folate)
• Cytotoxic drugs
117
Pencil cells seen in?
Iron deficiency anemia
118
Bite cells
G6PD deficiency
119
Spherocytes?
• Smaller.
• No central pallor
Seen in :
• Hereditary spherocytosis • Autoimmune hemolytic anemia (M/c)
• Blood transfusion reaction
• Burns
120
Burr cell/Echinocytes seen in ?
• Chronic renal failure
• Uremia
• Liver disease
121
Spur cell/Acanthocytes
Abetalipoproteinemia
122
Target cell aka?
Seen in ?
Codocytes
• Thalassemia
• Liver disease
• Iron deficiency anemia
123
Schistocytes/Helmet/ Fragmented RBC
• Microangiopathic Hemolytic Anemia (MAHA), HUS, TTP, DIC.
• Cardiac prosthetic valves
124
Tear drop cells/ Dacrocytes
• Myelofibrosis
• Myelo dysplastic syndrome
• Myelophthisic anemia
125
Heinz bodies stain & seen in ?
Supravital stain
G6PD deficiency
126
Howell Jolly bodies?
Nucleus remnant
• Asplenia
• Megaloblastic anemia
127
Pappenheimer bodies
Sideroblastic anemia
128
What is Cabot ring and in which condition it is seen?
Figure of 8 configuration composed of microtubules
• Megaloblastic anemia
• Thalassemia
129
Rouleaux
Multiple myeloma
130
Polychromasia
Hemolytic anemia
131
Basophilic stippling
• Sideroblastic anemia
• Lead poisoning
• Thalassemia
• Megaloblastic anemia
132
Stomatocyte
Hereditary stomatocytosis
133
What is the Mean Corpuscular Volume (MCV), and what does it indicate?
• Definition: Average volume of red cells.
• Normal range: 82-96 fL.
• Significance:
• Microcytic: <82 fL (e.g., iron deficiency anemia, thalassemia).
• Normocytic: 82-96 fL (e.g., anemia of chronic disease, acute blood loss, aplastic anemia).
• Macrocytic: >96 fL (e.g., Vitamin B12/Folate deficiency, liver disease, hypothyroidism).
134
What is the Mean Corpuscular Hemoglobin (MCH), and what does it indicate?
• Definition: Average mass of hemoglobin per RBC.
• Normal range: 27-32 pg.
• Significance:
• Hypochromic RBCs: MCH <27 pg (e.g., iron deficiency anemia, thalassemia).
• Normochromic RBCs: MCH within normal limits.
135
What is the Mean Corpuscular Hemoglobin Concentration (MCHC), and what does it indicate?
• Definition: Average hemoglobin concentration in a volume of packed RBCs.
• Normal range: 33-37 g/dL.
• Significance:
• Increased: Hereditary spherocytosis.
136
What is the Red Cell Distribution Width (RDW), and what does it measure?
• Definition: Coefficient of variation of red cell size (anisocytosis).
• Normal range: 11-14%.
To differentiate b/w thalassemia and IDA
137
What is the Mentzer index, and how is it used?
• Definition: MCV divided by RBC count.
• Significance: Differentiates iron deficiency anemia (IDA) from thalassemia.
• <13: Suggests thalassemia.
• >13: Suggests IDA.
138
What conditions are associated with normocytic anemia?
• Normocytic (82-96 fL):
1. Aplastic anemia.
2. Acute blood loss.
3. Anemia of chronic disease.
4. Paroxysmal nocturnal hemoglobinuria (PNH).
5. Hemolytic anemia.
139
What are the major categories of anemia based on the underlying mechanism?
1. Hypoproliferative anemia: Decreased production of RBCs.
• Examples: Aplastic anemia, pure red cell aplasia, myelophthisic anemia.
2. Hemolytic anemia: Increased destruction of RBCs.
3. Deficiency anemia: Due to lack of essential nutrients (e.g., iron, B12, folate).
140
What is myelophthisic anemia?
• Anemia caused by space-occupying lesions in the bone marrow.
141
What is pure red cell aplasia, and which infection is commonly associated with it?
• Definition: Selective reduction of RBC precursors in bone marrow.
• Associated infection: Parvovirus B19.
142
What are the clinical features of aplastic anemia?
1. Anemia:
• Symptoms: Pallor, fatigue, breathlessness.
• Findings: ↓Hemoglobin (Hb), ↓Reticulocyte count.
2. Thrombocytopenia:
• Symptoms: Petechiae, purpura, bleeding tendency.
3. Leukopenia:
• Finding: Increased risk of infections.
143
What are the key diagnostic tests for aplastic anemia?
1. Bone marrow aspiration: Dry tap.
2. Bone marrow biopsy (Gold standard):
• Hypocellular marrow with increased fat.
144
What is the main characteristic of hemolytic anemia?
• Increased destruction of RBCs leading to anemia
• Increased risk of gallstones (pigment stones) due to excessive hemoglobin breakdown.
145
What are the classic clinical features of hemolytic anemia (the triad)?
1. Pallor
2. Jaundice
3. Splenomegaly
146
What is the difference between intravascular and extravascular hemolysis?
1. Intravascular Hemolysis:
• Signs: Hemoglobinuria, hemosiderinuria, ↓ haptoglobin.
• Location: Blood vessels.
• Example conditions: Paroxysmal nocturnal hemoglobinuria (PNH), paroxysmal cold hemoglobinuria.
2. Extravascular Hemolysis:
• Signs: Hepatosplenomegaly, ↑ bilirubin.
• Location: Liver and spleen.
• Example conditions: Hereditary spherocytosis, sickle cell anemia, thalassemia, autoimmune hemolytic anemia (AIHA).
147
What are some common examples of intravascular hemolytic anemia?
1. Paroxysmal Nocturnal Hemoglobinuria (PNH)
2. Paroxysmal cold hemoglobinuria
3. Microangiopathic Hemolytic Anemia (MAHA)
4. G6PD deficiency
5. Infections (e.g., malaria)
6. Prosthetic cardiac valves
148
What is the inheritance pattern and common genetic defects in hereditary spherocytosis?
• Inheritance: Autosomal dominant (M = F).
• Genetic defects:
• Most common: Ankyrin.
• Most severe: Spectrin.
149
What are the clinical features of hereditary spherocytosis?
• Symptoms:
1. Pallor.
2. Jaundice.
3. Splenomegaly.
• Hemolysis: Extravascular.
• Key finding: Presence of spherocytes on peripheral smear.
150
How is hereditary spherocytosis diagnosed and treated?
• Tests:
1. Osmotic fragility test (increased fragility of RBCs).
2. Flow cytometric analysis of membrane proteins is BEST TEST
• Treatment:
• Splenectomy (often curative).
151
What is the inheritance pattern and basic defect in G6PD deficiency?
• Inheritance: X-linked recessive (M > F).
• Genetic defect: Deficiency of G6PD enzyme.
152
What are the clinical features and triggers of G6PD deficiency?
• Symptoms:
1. Episodic hemolysis.
2. Hemoglobinuria.
3. No splenomegaly or gallstones.
• Triggers:
• Infections, drugs (e.g., sulfa drugs, quinine), and fava beans.
153
How is G6PD deficiency diagnosed and treated?
• Tests:
1. Bite cells and Heinz bodies on peripheral smear.
2. Methaemoglobin reduction test.
• Management:
• Avoidance of oxidative stress (e.g., certain medications and foods).
154
What is the inheritance pattern and genetic defect in sickle cell anemia?
• Inheritance: Autosomal recessive (M = F).
• Genetic defect: Missense point mutation: Glutamic acid (Glu) replaced by valine (Val) at position 6 of the β-globin chain of hemoglobin.
155
What are the clinical features of sickle cell anemia?
• Symptoms:
1. Pallor, jaundice.
2. Autosplenectomy (due to recurrent splenic infarctions).
3. Crisis-like episodes: Bone pain, fractures, chest pain.
• Hemolysis: Extravascular.
• Peripheral smear: Presence of sickle cells.
156
How is sickle cell anemia diagnosed?
• Tests:
1. Sickling test (screening test).
2. Hemoglobin electrophoresis.
BEST TESTS:
3. High-performance liquid chromatography (HPLC).
4. Globin chain sequencing.
157
What is the treatment for sickle cell anemia?
• Treatment:
1. Hydroxyurea (increases HbF, reduces sickling).
2. Stem cell transplant (curative).
158
What is the epidemiology and protective aspect of HS, thalassemia, G6PD deficiency, sickle cell anemia?
• Common in: African and Mediterranean populations.
• Protection from: Plasmodium falciparum (malaria).
159
What does the osmotic fragility test help diagnose?
• Hereditary spherocytosis (HS): Right shift (increased fragility).
• Thalassemia: Left shift (decreased fragility).
160
“Crew cut” or “hair on end” skull seen in ?
thalassemia
sickle cell anemia
161
Best investigation for hemoglobinopathies?
High Performance Liquid Chromatography (HPLC)
Gives % of different Hbs
162
Hb electrophoresis anode to cathode?
Mnemonic : HAFSA2
163
Normal adult Hb?
• HbA : α2 β2 (95-97%)
• HbF : α2 γ2 (< 1%)
• HbA2 : α2 δ2 (2-3.5%)
164
What are the two main types of thalassemia, and what are their genetic causes?
• Beta Thalassemia:
• Cause: Mutation on Chromosome 11 (decreased beta chain synthesis).
• Most common type.
• Alpha Thalassemia:
• Cause: Gene deletion on Chromosome 16 (decreased alpha chain synthesis).
165
What are the clinical features of Beta Thalassemia Major?
• Symptoms:
1. Severe pallor and jaundice.
2. Hepatosplenomegaly.
3. Chipmunk facies (due to bone marrow expansion).
4. History of repeated blood transfusions.
• Hemoglobin (Hb): 3-5 gm%.
• Peripheral Smear (P/S):
1. Many target cells.
2. Basophilic stippling.
3. Cabot rings.
• RBC Indices:
• MCV, MCH, MCHC: Decreased.
• RDW: Normal.
• Iron Profile: Increased iron.
• HPLC & Hb Electrophoresis:
• Increased HbF.
166
What are the clinical features of Beta Thalassemia Intermedia?
• Symptoms:
1. Mild pallor and jaundice.
2. Hepatosplenomegaly.
• Hemoglobin (Hb): 5-8 gm%.
• Peripheral Smear (P/S): Few target cells.
• RBC Indices:
• MCV, MCH, MCHC: Decreased (moderately).
• RDW: Normal.
• Iron Profile: Normal.
• HPLC & Hb Electrophoresis:
• Increased HbF.
• Increased HbA2.
167
What are the clinical features of Beta Thalassemia Minor (Trait)?
• Symptoms:
• Usually asymptomatic or mild symptoms.
• Hemoglobin (Hb): >8 gm%.
• Peripheral Smear (P/S): No target cells.
• RBC Indices:
• MCV, MCH, MCHC: Slightly decreased.
• RDW: Normal.
• Iron Profile: Normal.
• Hb Electrophoresis: HbA2 : 3.5-9%
HPLC: ↑HbA2
168
What are the different types of Alpha Thalassemia, and their corresponding genotypes and features?
• Silent Carrier:
• Genotype: αα/α(1 gene deleted).
• MCV: Normal.
• Anemia: None.
• Hb Electrophoresis: Normal (<3% Hb Barts at birth).
• Alpha Thalassemia Minor:
• Genotype: αα/– or α-/α(2 genes deleted).
• MCV: Low.
• Anemia: Mild.
• Hb Electrophoresis: Normal, 3-8% Hb Barts at birth.
• Hb H Disease (Deletional):
• Genotype: α-/-(3 genes deleted).
• MCV: Low.
• Anemia: Moderate.
• Hb Electrophoresis: 5-30% HbH in adults, 20-40% Hb Barts at birth.
• Alpha Thalassemia Major (Fetal Hydrops / Hb Barts):
• Genotype: –/-(4 genes deleted).
• MCV: Low.
• Anemia: Fatal (incompatible with life).
• Hb Electrophoresis: Hb Barts and HbH present, HbA, HbF, and HbA2 absent.
169
What are the clinical features of Hb H disease (3 α gene deletion)?
• Peripheral Smear (P/S): Golf ball inclusions in RBCs (due to inclusion bodies formed by excess β chains).
• Supravital stain: Used to visualize inclusion bodies in Hb H disease.
170
What is the most common cause of death in Beta Thalassemia Major?
• Cause of death: Cardiotoxicity due to iron overload from repeated blood transfusions.
171
INVESTIGATION FOR HAEMOGLOBINOPATHIES
• Screening : Hb electrophoresis.
• IOC : HPLC.
• Definitive diagnosis : Globin gene sequencing.
• Mass screening : Nestrof test.
172
What are the key investigations for Paroxysmal Nocturnal Hemoglobinuria (PNH)?
• Ham’s Test (Acidified Serum Lysis Test): Detects increased hemolysis in acidified serum.
• Flow Cytometry (CD55 and CD59): Best test to detect PNH by assessing deficiency of CD55 and CD59 on RBCs.
173
What are the clinical features of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
• Pancytopenia with hypercellular bone marrow.
• Nocturnal intravascular hemoglobinuria (hemoglobinuria during the night).
• Thrombosis (Most common cause of death, often leads to Budd-Chiari syndrome).
Increased risk of leukemia
174
What is the pathogenesis of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
• ONLY Acquired intra-corpuscular defect due to PIGA gene mutation.
• Decreased synthesis of:
• CD55 (DAF)
• CD59 (MiRL) - More important for inhibiting complement activation.
175
What mutations are associated with Microangiopathic Hemolytic Anemia (MAHA)?
• ADAMTS-13 mutation: Associated with Thrombotic Thrombocytopenic Purpura (TTP).
• ADAM33 mutation: Associated with Bronchial asthma.
176
What is the clinical pentad of Microangiopathic Hemolytic Anemia (MAHA)?
mnemonic: RAT
• Fever
• MAHA (Microangiopathic Hemolytic Anemia)
• Thrombocytopenia
• Renal abnormality (most common in HUS).
• Neurological abnormality (most common in TTP).
177
What are the types of Microangiopathic Hemolytic Anemia (MAHA)?
• Hemolytic Uremic Syndrome (HUS):
• Cause: History of E. coli O157/H7 infection.
• Thrombotic Thrombocytopenic Purpura (TTP):
• Cause: Mutation in ADAMTS-13 enzyme.
• Disseminated Intravascular Coagulation (DIC).
178
What is the most common worm causing Iron Deficiency Anemia (IDA)?
Hookworm (Ancylostoma duodenale)
179
Where is iron primarily absorbed in the body?
Duodenum
180
What factors increase iron absorption?
• Ascorbic acid (Vitamin C)
• Citric acid
181
What factors decrease iron absorption?
• Alkalis like phytates and tannates.
182
What is the storage form of iron in the body?
• Hemosiderin and ferritin.
183
What is the transport form of iron?
Transferrin
184
What is the master regulator of iron metabolism?
Hepcidin
185
What are common clinical features of Iron Deficiency Anemia (IDA)?
• Cheilosis (cracks at the corners of the mouth).
• Koilonychia (spoon-shaped nails).
• Palpitations, pallor, fatigue, breathlessness, headache, dizziness.
186
What is Plummer-Vinson syndrome and its classic triad?
• Triad:
• Atrophic glossitis
• Esophageal webs
• Iron Deficiency Anemia (IDA).
187
In which group of patients is Iron Deficiency Anemia (IDA) commonly found?
• Elderly patients with gastrointestinal malignancy.
• PICA (particularly common in women).
188
What is the stain used for detecting iron in tissues?
• Prussian blue or Perl’s stain.
189
What are the causes of Sideroblastic Anemia?
1. Genetic:
• X-linked inheritance
2. Acquired:
• Alcohol consumption
• Anti-tuberculosis (TB) drugs
• Vitamin B12 deficiency
• Lead poisoning
190
What are the findings on Peripheral Smear (P/S) in Sideroblastic Anemia?
1. Pappenheimer bodies:
• Iron-laden inclusions, visible with Prussian blue stain.
2. Ringed sideroblasts:
• Erythroblasts with iron deposits in mitochondria.
3. Coarse basophilic stippling:
• Small dark spots in RBCs due to defective hemoglobin synthesis.
191
What are the laboratory findings in Sideroblastic Anemia?
1. Increased:
• Serum iron
• Ferritin
2. Decreased:
• Total iron-binding capacity (TIBC)
192
What are the causes of Anemia of Chronic Disease?
1. Chronic infections
2. Neoplasms
3. Autoimmune disorders
4. Idiopathic causes
193
What role does Hepcidin play in Anemia of Chronic Disease?
1. Hepcidin:
• Most important molecule affected in this condition.
2. Function:
• Acts as the master regulator of iron metabolism.
• Increased Hepcidin levels lead to decreased iron absorption and sequestration in macrophages.
194
What are the key lab findings in Iron Deficiency Anemia?
• Iron: Decreased
• Ferritin: Decreased
• TIBC: Increased
• Peripheral Smear: Pencil cells, microcytic hypochromic RBCs
• Extra Findings: ↑ RDW, Mentzer index > 13
195
What are the key lab findings in Sideroblastic Anemia?
• Iron: Increased
• Ferritin: Increased
• TIBC: Decreased
• Peripheral Smear: Ringed sideroblasts (in bone marrow), coarse basophilic stippling
196
What are the key lab findings in Anemia of Chronic Disease?
• Iron: Decreased
• Ferritin: Increased or normal
• TIBC: decreased
• Peripheral Smear: Microcytic hypochromic RBCs
• Extra Findings: ↑ ESR
197
What are the key lab findings in Beta Thalassemia Trait?
• Iron: Normal
• Ferritin: Normal
• TIBC: Normal
• Peripheral Smear: Normal
• Extra Findings: ↑ HbA2 (> 3.5%), Mentzer index < 13
198
What are the common causes of Megaloblastic Anemia?
• Vegetarian diet
• Gastrectomized individuals/Ileal resection
• Tapeworm infection (most common worm)
199
What are the clinical features of Megaloblastic Anemia?
• Anemia
• Beefy tongue (glossitis)
• Pigmented knuckles
• Neurological complications:
• Subacute combined degeneration of the spinal cord
• Pancytopenia (due to nuclear-cytoplasmic asynchrony)
• Increased risk of thrombosis
200
What are the characteristic lab findings in Megaloblastic Anemia?
• Peripheral Smear:
• Megaloblasts (↑MCV, MCH)
• Hypersegmented neutrophils (>5 lobes)
• Howell-Jolly bodies
• Bone Marrow Aspiration:
• Megaloblasts with sieve-like chromatin
201
How does Vitamin B12 deficiency differ from Folate deficiency in terms of neurological manifestations?
• Vitamin B12 deficiency: Neurological manifestations (e.g., subacute combined degeneration of the spinal cord)
• Folate deficiency: No neurological manifestations
202
Pernicious Anemia?
• Autoimmunity against parietal cell/Intrinsic factor.
• Type 2 hypersensitivity.
• Anti-parietal cell Ab + .
203
What mediates the process of Hemostasis?
• Platelets
• Vascular endothelium
• Coagulation cascade
204
What is the process of Primary Hemostasis?
• Formation of platelet plug
• Platelet adhesion and aggregation
205
What is the mechanism of platelet adhesion in Primary Hemostasis?
• Platelet Adhesion:
• gp 1b IX (Platelets) binds to vWF (von Willebrand Factor) on the endothelium.
206
What is the mechanism of platelet aggregation in Primary Hemostasis?
• Platelet Aggregation:
• gp IIb-IIIa (Platelets) binds to fibrinogen, enabling platelet aggregation.
207
What is the process of Secondary Hemostasis?
• Coagulation Cascade (Clotting Factors):
• Activation of fibrin to stabilize the platelet plug.
208
What are the two main pathways in Secondary Hemostasis?
• Intrinsic Pathway: Measured by aPTT (Activated Partial Thromboplastin Time)
• Extrinsic Pathway: Measured by PT (Prothrombin Time)
209
What is the difference between bleeding disorders and coagulation disorders in terms of inheritance?
• Bleeding Disorders:
• Mostly autosomal (Male = Female)
• Coagulation Disorders:
• X-linked (Male > Female)
210
What are the clinical features of Bleeding Disorders?
• Minor Bleeding:
• Petechiae
• Purpura
• Mucosal bleeds
• Prolonged bleeding after injury
211
What are the lab findings in Bleeding Disorders?
• Platelet Count: Can be affected
• BT (Bleeding Time): Can be affected
• PT (Prothrombin Time): Normal
• aPTT (Activated Partial Thromboplastin Time): Normal
212
What are the clinical features of Coagulation Disorders?
• Major Bleeding:
• Hemarthrosis (joint bleeding)
• Ecchymosis
213
What are the lab findings in Coagulation Disorders?
• Platelet Count: Normal
• BT (Bleeding Time): Normal
• PT (Prothrombin Time): Can be affected
• aPTT: Can be affected
214
Give examples of Bleeding and Coagulation Disorders.
• Bleeding Disorders:
• ITP (Immune Thrombocytopenic Purpura)
• Coagulation Disorders:
• Hemophilia
BOTH:
• vWD (von Willebrand Disease)
• DIC (Disseminated Intravascular Coagulation)
215
What is the pathogenesis of Bernard-Soulier Syndrome?
• Pathogenesis: Deficiency of gp Ib-IX, leading to defective platelet adhesion.
216
What are the key clinical and lab features of Bernard-Soulier Syndrome?
• Platelet Count: Normal
• Bleeding Time (BT): Increased
• PT: Normal
• aPTT: Normal
• Key Features:
• Abnormal Ristocetin Induced Platelet Aggregation (RIPA)
• Giant platelets
217
What is the pathogenesis of Glanzmann’s Thrombasthenia?
• Pathogenesis: Defect in gp IIb-IIIa, leading to defective platelet aggregation.
218
What are the key clinical and lab features of Glanzmann’s Thrombasthenia?
• Platelet Count: Normal
• Bleeding Time (BT): Increased
• PT: Normal
• aPTT: Normal
• Key Features:
• Abnormal platelet aggregation with ADP
219
What is the pathogenesis of Immune Thrombocytopenic Purpura (ITP)?
• Pathogenesis:
• Antiplatelet antibodies (autoimmune)
• Type 2 hypersensitivity reaction
220
What are the key clinical and lab features of ITP?
• Platelet Count: Decreased
• Bleeding Time (BT): Increased
• PT: Normal
• aPTT: Normal
• Key Features:
• Bone marrow aspiration :↑Megakaryocytes.
• Acute form: Typically <6 months with history of viral infection
• Chronic form: >6 months
221
What is the pathogenesis of Hemolytic Uremic Syndrome (HUS)?
• Pathogenesis: Infection by E. coli O157:H7 or Shigella, leading to endothelial damage and thrombotic microangiopathy.
222
What are the key clinical and lab features of HUS?
• Platelet Count: Decreased
• Bleeding Time (BT): Increased
• PT: Normal
• aPTT: Normal
• Key Features:
• Schistocytes • ↑Reticulocyte count
• Renal defects (acute kidney injury)
223
What is the pathogenesis of Thrombotic Thrombocytopenic Purpura (TTP)?
• Pathogenesis: Mutation of ADAMTS 13, leading to impaired degradation of von Willebrand factor (vWF), resulting in platelet aggregation and microthrombi formation.
224
What are the key clinical and lab features of TTP?
• Platelet Count: Decreased
• Bleeding Time (BT): Increased
• PT: Normal
• aPTT: Normal
• Key Features:
• Neurological defects
• Schistocytes (due to microangiopathic hemolysis)
225
What is the pathogenesis of Hemophilia A?
• Pathogenesis: Factor VIII deficiency (Hemophilia A)
226
What are the key clinical and lab features of Hemophilia A?
• Platelet Count: Normal
• Bleeding Time (BT): Normal
• PT: Normal
• aPTT: Prolonged
• Key Features:
• Hemarthrosis (joint bleeding)
• Males > Females (X-linked inheritance)
227
What is the pathogenesis of Hemophilia B (Christmas disease)?
• Pathogenesis: Factor IX deficiency (Hemophilia B)
228
What are the key clinical and lab features of Hemophilia B?
• Platelet Count: Normal
• Bleeding Time (BT): Normal
• PT: Normal
• aPTT: Prolonged
• Key Features:
• Hemarthrosis
• Males > Females (X-linked inheritance)
229
What is the pathogenesis of Von Willebrand Disease (vWD)?
• Pathogenesis: vWF deficiency and secondary deficiency of Factor VIII.
230
What are the key clinical and lab features of Von Willebrand Disease (vWD)?
• Platelet Count: Normal
• Bleeding Time (BT): Increased
• PT: Normal
• aPTT: Prolonged
• Key Features:
• Factor VIII deficiency
• Ristocetin Induced Platelet Aggregation (RIPA): Abnormal
• Inheritance: Autosomal dominant and Autosomal recessive
231
What is the pathogenesis of Disseminated Intravascular Coagulation (DIC)?
• Pathogenesis:
• Endothelial injury leads to widespread coagulation and fibrinolysis.
• Secondary activation of the coagulation and fibrinolytic systems.
232
What are the key clinical and lab features of Disseminated Intravascular Coagulation (DIC)?
• Platelet Count: Decreased
• Bleeding Time (BT): Increased
• PT: Prolonged
• aPTT: Prolonged
• Key Features:
• Fibrin degradation products (FDP): Increased
• D-dimer: Increased
• Common causes: Obstetric complications (most common), AML-M3 (Acute Myelogenous Leukemia, M3)
233
What is the pathogenesis of Vitamin K deficiency?
• Pathogenesis: Deficiency of Factor II, VII, IX, and X due to insufficient Vitamin K.
234
What are the key clinical and lab features of Vitamin K deficiency?
• Platelet Count: Normal
• Bleeding Time (BT): Normal
• PT: Prolonged
• aPTT: Prolonged
235
What are the key clinical features of Vascular Disorders?
• Pathogenesis: Due to various causes like endothelial injury or connective tissue defects (e.g., Telangiectasia, scurvy).
• Platelet Count: Normal
• Bleeding Time (BT): Normal
• PT: Normal
• aPTT: Normal
• Key Features:
• Examples include Telangiectasia (small blood vessel malformations) and Scurvy (due to vitamin C deficiency).
236
Treatment of Haemophilia A & B?
• Haemophilia A : Factor VIII concentrate (Cryoprecipitate).
• Haemophilia B : Factor IX concentrate (Absent in cryoprecipitate).
237
What is the normal volume of a blood bag?
• Normal volume: 350 mL
238
What is the volume of a blood bag used for component separation?
Volume for component separation: 450 mL
239
What is the shelf life of blood stored with CPD (Citrate Phosphate Dextrose) as an anticoagulant?
Shelf life with CPD: 21 days.
240
Which anticoagulants are commonly used in blood bags?
• CPD (Citrate Phosphate Dextrose).
• CPDA (CPD + Adenine).
• SAG-M (Sodium, Adenine, Glucose, Mannitol).
241
How does CPDA (Citrate Phosphate Dextrose + Adenine) affect the expiry of stored blood?
• Shelf life with CPDA: 35 days.
242
What is the storage duration for blood preserved with SAG-M?
• Shelf life with SAG-M: 42 days.
243
What is the volume, storage temperature, shelf life, and primary use of whole blood?
• Volume: 350 mL.
• Storage temperature: 2–6°C.
• Shelf life:
• CPD: 21 days.
• CPDA: 35 days.
• SAG-M: 42 days.
• Use:
• Acute blood loss.
• Severe anemia.
• 1 unit increases hemoglobin by approximately 1 g/dL.
244
What is the volume, storage temperature, shelf life, and primary use of Fresh Frozen Plasma (FFP)?
• Volume: 200 mL.
• Storage temperature: -30°C or lower.
• Shelf life: 1 year.
• Use:
• Multiple coagulation factor deficiencies.
• Disseminated Intravascular Coagulation (DIC).
• Liver disease.
245
What is the volume, storage temperature, shelf life, and primary use of cryoprecipitate?
• Volume: 10–20 mL.
• Storage temperature: -30°C or lower.
• Shelf life: 1 year.
• Use:
• Hemophilia A.
• Hypofibrinogenemia.
• von Willebrand disease (vWD).
• Factor XIII deficiency.
246
What is the volume, storage temperature, shelf life, and primary use of random donor platelets?
• Volume: 50–70 mL.
• Storage temperature: 20–24°C with agitation.
• Shelf life: 5 days.
• Use:
• Thrombocytopenia.
• 1 unit increases platelets by approximately 10,000/mm³.
247
What is the volume, storage temperature, shelf life, and primary use of single donor platelets?
• Volume: 200–300 mL.
• Storage temperature: 20–24°C with agitation.
• Shelf life: 5 days.
• Use:
• Thrombocytopenia.
• 1 unit increases platelets by approximately 30,000–50,000/mm³.
248
Which infection can be transmitted by all blood products?
Malaria
249
Which blood component is most prone to bacterial contamination?
Platelets
250
What is the lifespan of transfused red blood cells (RBCs)?
• Lifespan of transfused RBCs: 50–60 days.
251
What are the key points in the transfusion protocol for blood products?
• Start transfusion: Within 30 minutes of taking the product out of the fridge.
• End transfusion: Within 4 hours.
• Needle size: 18–19 gauge (G).
• Micropore filter size: 170 microns.
252
What is the definition of massive blood transfusion?
• Replacement of the patient’s whole blood volume within 24 hours.
253
What are the complications of massive blood transfusion?
Mnemonic: CATCH
1. Coagulation abnormalities (e.g., DIC, most common cause of death).
2. Acidosis, alkalosis.
3. Tingling and numbness due to citrate toxicity.
4. Cold-induced hypothermia.
5. Hyperkalemia (can cause arrhythmias) and hypocalcemia.
254
What is Transfusion-Related Acute Lung Injury (TRALI)?
• Acute respiratory symptoms occurring <6 hours of transfusion.
• Chest X-ray findings: Bilateral pulmonary infiltrates, “white-out” appearance.
• Cause: Anti-leukocyte antibodies.
• Most common with: Plasma products.
255
What is the etiology of Transfusion-Related Acute Lung Injury (TRALI)?
• Antibodies against HLA class II or anti-neutrophilic antibodies.
256
What is the etiology of Transfusion-Associated Circulatory Overload (TACO)?
• Volume overload due to excessive or rapid transfusion.
257
What are the clinical features & Rx of TRALI?
• Hypoxemia.
• Respiratory failure.
• Hypotension.
• Fever.
Rx: Supportive care
258
What are the clinical features of TACO?
• Dyspnea.
• Cough.
• Hypertension.
• Tachycardia.
Rx: • Oxygen support.
• IV diuretics.
• Phlebotomy (if severe).
259
What is the use and principle of Sahli’s Hemoglobinometer?
• Use: Estimation of hemoglobin.
• Principle: Hemoglobin reacts with HCl to form acid hematin, which is matched with a comparator box for color.
260
What is the use of an Improved Neubauer Chamber?
• Use: For cell counts (e.g., RBCs, WBCs, platelets).
261
What are the diluting fluids used for WBC, RBC, and platelet counts in the Improved Neubauer Chamber?
• WBC count: Turk’s fluid.
• RBC count: Dacie’s or Hayem’s fluid.
• Platelet count: Rees & Ecker diluting fluid.
262
What is the function of Wintrobe’s tube?
• Use: ESR (Erythrocyte Sedimentation Rate) determination.
• Anticoagulant used: EDTA.
• Identification: Closed at one end.
263
What is the function of Westergren’s tube?
• Use: ESR determination.
• Anticoagulant used: Citrate.
• Identification: Longer tube, open at both ends.
264
What are the features of the RBC and WBC pipettes?
• RBC pipette: Contains a red bead, with markings 0.5, 1, 101.
• WBC pipette: Contains a white bead, with markings up to 11.
265
What is the anticoagulant in the purple-top vacutainer, and what are its uses?
• Contains: EDTA (1.5–2 mg/mL).
• Uses:
• Routine blood tests.
• ESR determination by Wintrobe’s method.
266
What is the anticoagulant in the blue-top vacutainer, and what are its uses?
• Contains: Trisodium citrate.
• Uses:
• ESR determination by Westergren’s method.
• Platelet function assay.
• Coagulation tests.
267
What is the anticoagulant in the grey-top vacutainer, and what is it used for?
• Contains: Sodium fluoride (inhibits enolase).
• Uses: Blood sugar estimation.
268
What is present in the red-top vacutainer, and what are its uses?
• Contains: Clot activator (no gel).
• Uses:
• Chemistry tests.
• Serology.
• Immunohematology.
269
What is the anticoagulant in the yellow-top vacutainer, and what are its uses?
• Contains: Acid citrate dextrose.
• Uses:
• RBC preservation for blood banking.
• HLA typing.
270
What is the anticoagulant in the green-top vacutainer, and what are its uses?
• Contains: Sodium heparin.
• Uses:
• Osmotic fragility test.
• Blood gas analysis.
• Immunophenotyping.
271
What is the correct order of blood draw based on the mnemonic?
1. Blood culture (Be).
2. Light blue (Loving).
3. Red (Respectful).
4. Green (Gracious).
5. Lavender (Light-hearted).
6. Grey (Gentle).
