Hematology 1 Flashcards
(150 cards)
1
Q
G6PD
What is the genetic inheritance of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency⁉️
A
➡️ X-linked recessive disorder affecting RBCs
2
Q
G6PD
What are the possible clinical manifestations of G6PD deficiency⁉️
A
🔹 Asymptomatic
or
🔹 acute hemolytic anemia
3
Q
G6PD
What triggers acute hemolytic anemia in G6PD deficiency⁉️
A
🚩Fava beans
🚩Infections
🚩Drugs (anti-malarials, sulfonamides, nitrofurantoin, cotrimoxazole)
4
Q
G6PD
What are the symptoms of an acute hemolytic episode in G6PD deficiency⁉️
A
▪️ Malaise
▪️ Weakness
▪️ Abdominal pain
▪️** Jaundice**
▪️Dark urine (appears ~3 days after onset)
5
Q
G6PD
What lab findings suggest hemolysis in G6PD deficiency⁉️
A
▪️ High LDH
▪️Low haptoglobin
▪️Hemoglobinemia
▪️Hemoglobinuria
6
Q
G6PD
What characteristic findings appear on blood smear in G6PD deficiency⁉️
A
➡️ “Bite cells”
and
➡️ “Heinz bodies”
7
Q
G6PD
When should G6PD enzyme levels be screened for diagnosis⁉️
A
➡️ After the acute hemolytic attack has ended
8
Q
G6PD
What is the treatment approach for G6PD deficiency⁉️
A
➡️ Avoid exposure to triggers (fava beans, infections, drugs).
9
Q
What is amyloid❓
A
➡️ Insoluble protein that deposits extracellularly
10
Q
What are the different types of amyloidosis❓
A
▪️ AL
▪️ AF
▪️ AA
▪️ Aβ
🚩 all associated with different diseases
11
Q
What is AL amyloidosis composed of, and what is it associated with❓
A
➡️ Immunoglobulin light chains
➡️ linked to myeloma/lymphoma.
12
Q
What causes AF (familial) amyloidosis❓
A
➡️ Mutation in the transthyretin gene.
13
Q
What is AA amyloidosis composed of, and what diseases is it associated with❓
A
➡️ Serum amyloid A
➡️ seen in chronic inflammatory/infectious diseases (⚠️ RA, FMF, IBD).
14
Q
Where is Aβ amyloidosis most commonly seen❓
A
➡️ Alzheimer’s disease
15
Q
How is amyloidosis diagnosed❓
A
➡️ Fat tissue biopsy followed by Congo red staining (shows amyloid deposits)
16
Q
What are the clinical manifestations of AA amyloidosis❓
A
🚩Hepatosplenomegaly
🚩 Autonomic neuropathy
🚩 Cardiomyopathy
17
Q
How is AA amyloidosis treated❓
A
➡️ Treating the underlying cause lowers serum amyloid A levels
18
Q
What type of amyloid is associated with diabetes mellitus❓
A
➡️ Islet amyloid polypeptide
19
Q
What is multiple myeloma (MM)❓
A
➡️ Plasma cell neoplasm that produces monoclonal immunoglobulin
20
Q
Multiple myeloma
What are the diagnostic tests for MM❓
A
🔹 Serum & urine electrophoresis → M spike (IgG) or Bence-Jones protein
🔹 Bone marrow biopsy → >10% plasma cells
🔹 Blood smear → Rouleaux formation
🔹 X-ray → Lytic bone lesions
21
Q
Multiple myeloma
What is the most common symptom of MM❓
A
➡️ Bone pain
22
Q
Multiple myeloma
What are the features used to diagnose multiple myeloma❓
A
🧠 CRAB
🚩 C - Hypercalcemia (Ca ≥11.5 mg/dL)
🚩 R - Renal impairment (Cr ≥2 mg/dL or eGFR <40 ml/min)
🚩 A - Anemia (Hb <10 g/dL)
🚩 B - Bone lesions (lytic lesions ≥5mm on imaging)
23
Q
Multiple myeloma
What are the biomarkers used to define multiple myeloma❓
A
🧠 SLiM
🚩 S - ≥ 60% clonal plasma cells in bone marrow
🚩 Li - FLC ratio ≥100
🚩 M - MRI with >1 focal bone lesion
24
Q
Multiple myeloma
What are the complications of MM❓
A
🚩 Pathological fractures & lytic bone lesions
🚩 Infections (hypogammaglobulinemia → pneumonia & pyelonephritis)
🚩 Hyperviscosity syndrome
25
# Multiple myeloma
What can **vertebral fractures** in MM lead to❓
🚨 **Spinal cord compression** and related symptoms
26
# Multiple myeloma
What are the **high-risk features** in MM❓
⚠️ **β2-microglobulin**
⚠️ **High-risk gene profile**
⚠️ **Extramedullary disease**
⚠️ **Elevated LDH**
⚠️ **Low albumin**
27
# Multiple myeloma
What is the treatment for MM patients who **cannot undergo transplantation**❓
➡️**Thalidomide, lenalidomide, or bortezomib** combined with **dexamethasone**.
28
# Multiple myeloma
What is the treatment for **transplant-eligible MM patients**❓
➡️ **Melphalan + hematopoietic stem cell transplantation** after **induction chemotherapy**
29
# Multiple myeloma
What is the **most appropriate MM treatment** for an **elderly patient with functional limitations❓**
➡️ **Steroids + lenalidomide** (without bone marrow transplantation).
30
# Multiple myeloma
What are the **key drug classes** used in **MM induction therapy**❓
🔸 **Proteasome inhibitors** (bortezomib)
🔸 **Immunomodulatory drugs** (lenalidomide)
🔸 **Alkylating agents** (cyclophosphamide)
🔸 **Monoclonal antibodies** (daratumumab)
🔸 **Steroids**
31
# Multiple myeloma
What is the **next step** after **MM induction therapy**❓
➡️ **Autologous bone marrow transplantation** as consolidation treatment
32
# Multiple myeloma
What supportive therapy is used for **MM-related hypercalcemia and lytic bone lesions**❓
✅ **Bisphosphonates**
33
# Multiple myeloma
When is **surgical or radiation therapy** required **in MM❓**
➡️ **Spinal stenosis**
34
# Multiple myeloma
Why are some MM patients **not eligible** for transplant❓
⚠️ Age **>70** or **significant comorbidities**
35
# Multiple myeloma
What are **common causes of acute kidney injury (AKI) in MM**❓
🔸 **Light chain cast nephropathy** (drug-related)
🔸 **Hypercalcemia**
🔸 **Plasma cell infiltration**
🔸 **Recurrent infections**
36
What is **acute promyelocytic leukemia (APL)**❓
🚩 A **subtype of acute myeloid leukemia (AML)**
▪️ caused by **t(15;17) translocation**,
▪️ creating the **PML-RARA fusion protein**, which **prevents cell differentiation**.
37
What is the **underlying mechanism** of APL❓
➡️ **Failed differentiation** of hematopoietic progenitor cells into mature cells.
38
What are the **risk factors** for AML/APL development❓
➡️ **Hereditary causes**
➡️ **radiation**
➡️ **chemicals**
➡️ **drugs**
➡️ **occupational exposures**
39
What are the **diagnostic tests** used in APL❓
➡️ **Blood smear** → **Blasts ± Auer rods**
➡️ **Bone marrow biopsy** → **>20% blast cells**
➡️ **Cytogenetic tests**
40
What are the **bone marrow and peripheral blood findings** in APL❓
🔹 **Increased blasts**
🔹 **low RBC**
🔹 **neutrophils**
🔹 **platelets**
41
What are the **clinical manifestations** of APL❓
🔸 **Fatigue (anemia)**
🔸 **Fever (neutropenia-related infection)**
🔸 **Bleeding (thrombocytopenia)**
🔸 **Leukostasis & DIC (especially in APL)**
42
What **physical findings** are seen in APL❓
🔸**Fever**
🔸 **lymphadenopathy**
🔸 **splenomegaly**
🔸 **hepatomegaly**
🔸 **sternal tenderness**.
43
Which drugs can **induce DIC and lead to fatal complications** in APL❓
⚠️ **Cytarabine + Daunorubicin**
44
What is the first-line **treatment** for **low-risk APL patients**❓
✅ **Tretinoin (ATRA)**
▪️usually combined with **arsenic trioxide** (ATO).
45
What is **APL syndrome**, a complication of ATRA therapy❓
⚠️ Adhesion of **neoplastic cells** to pulmonary endothelium → causes ▪️**fever**
▪️**fluid retention**
▪️**dyspnea**
▪️**chest pain**
▪️**pulmonary infiltrates**
▪️**pleural/pericardial effusions**
▪️**hypoxemia**
46
How is **APL syndrome** managed❓
▪️**Glucocorticoids**
▪️**chemotherapy**
▪️**supportive care**
47
When is **allogeneic bone marrow transplantation** used in APL❓
🚨 In **relapsed cases**
or
🚨 **failure to achieve remission** (negative RT-PCR for PML-RARA)
48
What is the **long-term survival rate** for APL patients❓
➡️ **~85% long-term survival**
49
What is the **immediate treatment for a patient on warfarin who develops bleeding**❓
➡️ **Prothrombin complex concentrate (PCC)**
➕
➡️ **IV vitamin K (5–10 mg)**
50
When are **Four factors of prothrombin complex concentrates** (which contain the clotting factor that is vitamin K dependent) used❓
➡️ **In life-threatening bleeds**
➡️ **Urgent surgery**
➡️ **Patients who can't tolerate the volume load of fresh frozen plasma** (FFP)
51
What is the **antidote for heparin toxicity**❓
➡️ **Protamine sulfate**
52
Is **platelet transfusion** indicated for warfarin-related bleeding❓
🙅**NO,** not recommended
53
What does **cryoprecipitate** contain❓
🔹 **vWF**
🔹 **fibrinogen**
🔹 **factors VIII & XIII**
54
What is **Immune Thrombocytopenic Purpura (ITP)**❓
➡️ An **acquired disorder** of **immune-mediated platelet destruction**, possibly inhibiting **platelet release from megakaryocytes**.
55
How does ITP **differ in children vs. adults**❓
➡️ **Acute in children**, usually post-infection, **self-limited**.
➡️ **chronic in adults**, with **spontaneous remission in months**
56
What conditions can cause **secondary ITP**❓
⚠️ **Autoimmune diseases or infections**
57
What are the **clinical manifestations** of ITP❓
🚩**Mucocutaneous bleeding**
(petechiae, ecchymoses, oral/GI bleeding, heavy menstrual bleeding, rare CNS bleeding).
🚩 **low platelet count**
58
**What lab findings suggest ITP❓**
🔸**Low platelet count**
🔸 large platelets on **peripheral smear**
🔸 possible **iron deficiency anemia**.
59
When should **bone marrow examination** be considered in ITP❓
🚩 If there are **other unexplained lab abnormalities**
🚩 If **ITP is refractory to initial treatment**
60
What tests should be considered to **evaluate secondary causes** of ITP❓
61
When is **ITP treatment NOT necessary**❓
➡️ If **platelet count >30,000/μL** with **no bleeding symptoms**
62
What is the **first-line treatment** for **ITP patients without bleeding or severe thrombocytopenia**❓
➡️ **Outpatient management** with **single agent therapy:**
🔹 **Prednisone**
🔹 **Dexamethasone**
🔹 **IVIgG**
🔹 **Rh(D) immune globulin (only Rh-positive patients)**
63
How is **severe ITP** (platelets <5000) managed❓
➡️ **Hospitalization**
➡️ **Combined-modality therapy**
🔹 **high-dose glucocorticoids + IVIgG or Rh(D) immune globulin**
64
When is **Anti-D immunoglobulin** used in ITP❓
➡️ **Rh+ patients who haven’t had splenectomy**
65
When is **rituximab** used in **ITP treatment❓**
➡️ **Refractory cases** of ITP
66
When is **splenectomy** performed in **ITP❓**
🚩 In patients who **relapse after steroid tapering**
67
When are **TPO agonists** used in **ITP treatment**❓
➡️ **relapse after splenectomy**
➡️ **unresponsiveness to at least one other therapy**
68
Is **bone marrow biopsy** indicated for **ITP❓**
🙅**NO**
69
# Thrombotic Thrombocytopenic Purpura
What is the **classic pentad** of TTP❓
➡️ **Thrombocytopenia**
➡️ **Microangiopathic hemolytic anemia (MAHA)** (high LDH, schistocytes)
➡️ **Renal failure**
➡️ **Neurologic findings**
➡️ **Fever**
## Footnote
⚠️ 👉🏼 **Full pentad not required for diagnosis**
70
What is the **pathogenesis** of TTP❓
➡️ **Deficiency of the enzyme
ADAMTS13 or antibodies against it**→ uncleaved **VWF** → platelet & RBC aggregation in small vessels
71
Who is at **higher risk** for developing TTP❓
🔸**Women**
🔸 **HIV patients**
🔸 **pregnancy**
72
What **medications** can trigger TTP❓
🔸**Clopidogrel**
🔸 **Tacrolimus**
🔸 **Cyclosporine**
🔸 **Quinine**
73
What are the **characteristic lab findings** in TTP❓
➡️ **↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin**
➡️ **↑ reticulocyte count**
➡️ **Negative direct Coombs test**
74
What lab test helps confirm **TTP diagnosis**❓
➡️ **ADAMTS13 activity & antibody levels**
75
What is the **first-line treatment** for TTP❓
➡️ **Plasma exchange** until **platelet count normalizes & hemolysis resolves for ≥2 days**
76
What **medications** are used in **TTP treatment❓**
▪️**Glucocorticoids**
▪️ **rituximab**
▪️ **caplacizumab (anti-VWF nanobody)**
77
When are **glucocorticoids** used in **TTP treatment❓**
➡️ As **adjunct therapy**
78
Why is **von Willebrand disease NOT a differential** for TTP❓
❌ It **does NOT cause fever, confusion, or AKI**
79
What is the definition of **anemia based on Mean Corpuscular Volume (MCV)❓**
➡️ **Microcytic:** MCV < 80
➡️ **Normocytic:** 80 < MCV < 100
➡️ **Macrocytic:** MCV > 100
80
What are the **causes of microcytic anemia (MCV < 80)❓**
🔹 **Iron deficiency anemia**
🔹 **Thalassemia**
🔹 **Anemia of inflammation**
🔹 **Sideroblastic anemia**
81
What are the three **main mechanisms leading to iron deficiency anemia⁉️**
➡️ **Increased demand:**
🔹 Pregnancy
🔹 Rapid adolescent growth
➡️ **Increased loss:**
🔹 GI bleeding
🔹 Menses
🔹 Frequent phlebotomy
➡️ **Decreased intake/absorption:**
🔹 Inadequate diet
🔹 Crohn’s disease
🔹 Gastrectomy
82
What are the **clinical features of iron deficiency anemia⁉️**
🩸 Common signs include:
▪️ **Pallor, fatigue, weakness**
▪️ **Dyspnea, tachycardia**
▪️ **Cheilosis**
▪️ **Koilonychia (spoon-shaped nails)**
83
What are the typical **lab findings in iron deficiency anemia⁉️**
➡️ Iron panel shows:
🔹 **Low MCV**
🔹 **Low serum iron**
🔹 **Low ferritin**
🔹 **High transferrin**
84
What is the **most common cause of iron deficiency anemia in adults, and how should it be investigated⁉️**
🚩 **GI bleeding** is the most common cause
➡️ Requires evaluation with **endoscopy**
85
What are the **causes of macrocytic anemia (MCV > 100)❓**
🔹 **B12 deficiency**
🔹 **Folate deficiency**
🔹 **Alcoholic liver disease**
🔹 **Myelodysplastic syndrome (MDS)**
86
What are the **causes of normocytic anemia❓**
87
What is **megaloblastic anemia**❓
➡️ **Macrocytic anemia** caused by **ineffective erythropoiesis** due to **impaired DNA synthesis**, most commonly due to **vitamin B12 or folate deficiency**.
88
What **blood smear finding** is **characteristic of megaloblastic anemia❓**
🔬 **Hypersegmented neutrophils**
89
How does **vitamin B12 deficiency** differ from **folate deficiency**❓
➡️ **B12 deficiency causes neurological disturbances** (e.g., **subacute combined degeneration of the spinal cord**), while **folate deficiency does not**.
90
What foods are **rich in folic acid**❓
🥬 **Green leafy vegetables (spinach), liver, nuts**
91
What is the **daily adult requirement** of **folic acid**❓
➡️ **~100 micrograms per day**
92
What are the **causes** of **folate deficiency❓**
🔸 **Inadequate intake** (old age, alcoholics, poverty)
🔸 **Malabsorption** (celiac disease, Crohn’s disease, intestinal resection)
🔸 **Increased demand** (pregnancy, chronic hemolytic anemia)
🔸 **Antifolate drugs** (phenytoin, barbiturates, sulfasalazine)
93
What are the **clinical manifestations** of megaloblastic anemia due to **folate deficiency❓**
🔸 **Fatigue, weakness** (due to anemia)
🔸 **Glossitis, angular cheilosis**
🔸 **Thrombocytopenia** → **easy bruising**
🔸 **Leukopenia** → **recurrent infections**
94
What are the **laboratory findings** in **folate deficiency❓**
➡️ **Macrocytic anemia(MCV >100 fL/RBC)**
➡️ **Peripheral smear**
🔹**Oval macrocytes**
🔹**poikilocytosisand anisocytosis** 🔹**hypersegmented neutrophils (>5 lobes)**
➡️ **Bone marrow smear**
🔹 **Hypercellular marrow with large megaloblasts (ineffective erythropoiesis)**
95
**How is folate deficiency diagnosed⁉️**
➡️ **Measure:**
🔹 **Serum folate**
🔹 **Vitamin B12**
⚠️ **Methylmalonic acid ➡️ Elevated only in B12 deficiency, normal in folate deficiency**
96
What is the **treatment** for **folate deficiency anemia❓**
➡️ **Oral folate supplementation (5–15 mg/day) for 4 months**
97
How does **anemia of chronic disease** differ from **folate deficiency❓**
➡️ **ACD leads to normocytic/microcytic anemia, not macrocytic megaloblastic anemia**
98
How does **iron deficiency anemia** differ from **folate deficiency❓**
➡️ **Iron deficiency anemia is microcytic, not macrocytic megaloblastic anemia**
99
What are the **etiologies of B12 deficiency❓**
🔸 **Decreased intake** (e.g., vegans)
🔸 **Decreased absorption:** pernicious anemia, celiac disease, Crohn’s disease, post-gastrectomy
🔸 **Bacterial overgrowth**
100
What are special **clinical manifestations of B12 deficiency❓**
➡️ **Neurologic changes (subacute combined degeneration):**
🔹 **Paresthesia**
🔹 **Ataxia**
🔹 **Dementia**
101
What are the **lab findings in B12 deficiency anemia❓**
➡️ **Neutrophil hypersegmentation on smear**
➡️ **Ineffective hematopoiesis**
➡️ **Increased LDH**
➡️ **Increased indirect bilirubin**
102
What is the **main transport protein for iron in plasma⁉️**
➡️ **Transferrin**:
Binds and transports iron absorbed from the gut or released from stores
103
What is the **function of albumin in the body, and does it transport iron⁉️**
➡️ **Albumin does not transport iron**
🔹 **It maintains oncotic pressure** and transports hormones, drugs, and other molecules
104
What is the **role of haptoglobin in iron metabolism⁉️**
🩸 **Haptoglobin** binds **free heme**
⚠️ Levels decrease in **intravascular hemolysis** due to consumption
105
What happens to excess intracellular iron in **erythroid cells⁉️**
➡️ Excess iron binds to **apoferritin**
➡️ Forms **ferritin,** the intracellular **iron storage protein**
106
What are the **key clinical and lab features of autoimmune hemolytic anemia (AIHA)⁉️**
➡️ **Clinical signs:**
🩸 Rapid hemoglobin drop
🩸 Jaundice
🩸 Splenomegaly
➡️ **Lab findings:**
🔹 Positive direct Coombs test
🔹 Reticulocytosis
🔹 ↑ LDH
🔹 ↑ Indirect bilirubin
🔹 ↓ Haptoglobin
107
What are the **two main types of autoimmune hemolytic anemia (AIHA), and how are they classified⁉️**
⚠️ **AIHA is classified by antibody temperature:**
🔸 **Warm AIHA:** IgG active **at 37°C**
🔸 **Cold AIHA:** IgM active at **<37°C** (not discussed here)
108
What is the next best step to **confirm autoimmune hemolytic anemia (AIHA)⁉️**
➡️ **Direct Antiglobulin Test** (Direct Coombs test)
🔹 Detects **autoantibodies bound to RBCs**
109
What are **common causes of warm AIHA⁉️**
➡️ **Idiopathic**
➡️ **Secondary to:**
▪️ **Autoimmune diseases** (e.g. SLE)
▪️ **Lymphoproliferative diseases** (e.g. CLL, lymphoma)
▪️ **Drugs:** penicillin, cephalosporins, NSAIDs
110
**Which antibiotics are commonly associated with drug-induced immune hemolytic anemia⁉️**
➡️ Suspect after recent exposure to:
🔹 **Ceftriaxone**
🔹 **Azithromycin**
❗️ Can trigger autoantibody formation against RBCs
111
What is the **direct Coombs test result in warm AIHA⁉️**
➡️ **Positive for IgG antibodies bound to red blood cells**
112
What is the **first-line treatment** for **warm AIHA mild cases⁉️**
➡️ **Prednisone (1 mg/kg)**
➡️ **Rituximab** added to first-line
113
When is **blood transfusion** indicated in warm AIHA⁉️
🚨 **As needed, based on severity of anemia**
114
What is the **treatment for relapsed or refractory cases** in warm AIHA⁉️
➡️ **Splenectomy**
115
What is the **pathophysiology and antibody type in cold AIHA⁉️**
➡️ **Cold AIHA involves:**
🔹 Antibodies reactive **below 37°C**
🔹 Typically **IgM**
🔹 Direct Coombs test **positive for C3**
116
Where does **hemolysis predominantly occur in cold AIHA and why⁉️**
❄️ Hemolysis occurs **in the extremities**
➡️ Due to **colder temperatures enhancing IgM-mediated binding**
117
What are the common **triggers or associations of cold AIHA⁉️**
➡️ **Cold AIHA is linked to:**
🔹 **Monoclonal conditions:** MGUS, Waldenstrom’s macroglobulinemia
🔹 **Infections:**
▪️ Mycoplasma pneumoniae
▪️ Hepatitis C virus
🔹 **Lymphomas**
118
What is the **treatment approach for cold AIHA⁉️**
➡️ **Management includes:**
🔹 **Supportive care for mild cases**
🔹 **Rituximab for more severe or persistent cases**
⛔ **Steroids and splenectomy are not effective**
119
What are the **key features of Myelodysplastic Syndrome (MDS)⁉️**
➡️ **MDS is hematological disease characterized by:**
🔹 **Cytopenia**
🔹 **Dysmorphic blood cells & precursors**
🔹 **Bone marrow failure**
🔹 **High risk of progression to acute myeloid leukemia (AML)**
120
# Myelodysplastic Syndrome
What are the **causes** of **MDS⁉️**
🔹 **Idiopathic** (primary)
🔹 **Secondary:**
▪️ Radiation
▪️ Chemicals (e.g. benzene)
▪️ Chemotherapy (especially alkylating agents)
121
# Myelodysplastic Syndrome
What are the common **bone marrow findings in MDS⁉️**
🔬**Bone marrow shows:**
🔹 **Ringed sideroblasts**
🔹 **Dysmorphic blood cells**
🔹 **Evidence of ineffective hematopoiesis**
122
# Myelodysplastic Syndrome
What is the **most common peripheral blood finding in MDS⁉️**
➡️ **Macrocytosis with cytopenias** (most commonly anemia)
123
# Myelodysplastic Syndrome
What **cytogenetic abnormalities are associated with MDS⁉️**
➡️ **Chromosomal defects:**
🔹 Deletion of chromosomes **5q, 7q, 20q**
🔹 **Trisomy 8**
124
# Myelodysplastic Syndrome
What are the common **clinical features of MDS⁉️**
🩸 **Symptoms due to anemia:**
🔹 **Fatigue**
🔹 **Weakness**
🔹 **Dyspnea**
🔹 **Pallor**
🔻 **Some patients may be asymptomatic**
125
# Myelodysplastic Syndrome
What are the **key laboratory findings in MDS⁉️**
➡️ **Lab results show:**
🔹 **Pancytopenia**
🔹 **Macrocytosis**
🔹 **Peripheral smear:**
▪️ **Hypogranulated neutrophils**
▪️ **Hyposegmented or abnormally segmented (ringed) nuclei**
126
# Myelodysplastic Syndrome
What does **bone marrow biopsy reveal in MDS⁉️**
🔬 Bone marrow is usually **hypercellular**
⚠️ In up to **20% of cases,** it may be **hypocellular**
127
# Myelodysplastic Syndrome
What is the **only curative treatment for MDS⁉️**
➡️ **Hematopoietic stem cell transplantation (HSCT)**
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# Myelodysplastic Syndrome
What is the treatment of choice for **MDS with 5q- syndrome⁉️**
💊 **Lenalidomide** is effective in patients **with 5q deletion (5q- syndrome)**
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# Myelodysplastic Syndrome
**How can MDS be differentiated from AML⁉️**
🔻 **MDS vs AML:**
**AML = >20% blasts in marrow**
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# Myelodysplastic Syndrome
**How can MDS be differentiated from myelofibrosis⁉️**
🔻 **MDS vs Myelofibrosis:
Myelofibrosis = fibrotic marrow + extramedullary hematopoiesis**
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# Myelodysplastic Syndrome
Why must **B12 & folate deficiencies** be ruled out in suspected MDS⁉️
➡️ **Vitamin deficiency mimics MDS → must rule out first**
**B12 deficiency:**
▪️ **Hypercellular marrow**
▪️ **Megaloblastic erythroid hyperplasia**
▪️ **Hypersegmented neutrophils**
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What is the **effect of Factor V Leiden mutation**⁉️
➡️ **Activated factor Va** becomes **resistant to degradation** by activated protein C, leading to a **hypercoagulable state**
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What is the **clinical significance of Factor V Leiden mutation**⁉️
🚨 **Increased risk of venous thromboembolism (VTE)**
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Who is at **highest risk of VTE in Factor V Leiden mutation⁉️**
🚨 **Homozygous patients** have the **highest risk** of venous thromboembolism
⚠️ **Heterozygous carriers** still have **increased risk**
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Do patients with Factor V Leiden **always require anticoagulation⁉️**
⛔ **No treatment is required** for asymptomatic **carriers**
✅ **Avoidance of risk factors** (e.g. prolonged immobilization) is recommended
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What is the **most common lymphoid leukemia** and how does it usually present⁉️
➡️ **Chronic Lymphocytic Leukemia (CLL)**
🔹 Often **asymptomatic,** discovered via routine CBC
🔹 If symptomatic:
▪️ **Night sweats, weight loss, malaise**
🔹 physical examination may show:
▪️ **Lymphadenopathy**
▪️ **Hepatosplenomegaly**
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What are the key **diagnostic findings in CLL⁉️**
➡️ **CBC (initial clue):**
🔹 **Lymphocytosis** (↑ absolute lymphocyte count)
➡️ **Peripheral blood smear:**
🔬 **Smudge cells** (fragile lymphocytes)
➡️ **Flow cytometry (confirmatory):**
🔹 **Clonal B-cells expressing CD5+** (T-cell marker abnormally present on B cells)
➡️ **Lymph node biopsy:**
🔹 **Shows small, mature-appearing lymphocytes**
➡️ **Bone marrow biopsy:**
🔹 Reveals **monoclonal B-lymphocyte infiltration**
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When is **treatment indicated** for CLL⁉️
➡️ Only for **symptomatic patients with:**
🔹 **Progressive marrow failure**
🔹 **Massive/symptomatic splenomegaly**
🔹 **Symptomatic lymphadenopathy**
🔹 **Autoimmune anemia/thrombocytopenia resistant to standard therapy**
🔹 **Constitutional symptoms** (fatigue, fevers, night sweats)
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What is the **gold standard treatment** for CLL in patients **<65 years⁉️**
➡️ **FCR regimen:**
🔹 **Fludarabine**
🔹 **Cyclophosphamide**
🔹 **Rituximab**
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What is the **preferred treatment** for **older CLL patients⁉️**
➡️ **Rituximab + chlorambucil**, due to lower toxicity.
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What is the treatment for **refractory CLL**⁉️
➡️ **Allogeneic stem cell transplantation**
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What are the **safe anticoagulation options in pregnancy⁉️**
➡️ **Safe agents during pregnancy include:**
🔹 **Unfractionated heparin** (UFH)
🔹 **Low-molecular-weight heparin** (LMWH) – e.g. Clexane
🔹 **Fondaparinux** (used with caution)
## Footnote
⚠️ Warfarin and direct oral anticoagulants (DOACs) are contraindicated
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What is the recommended management for a **young patient with PE during pregnancy⁉️**
➡️ **Start anticoagulation immediately** (LMWH preferred)
➡️ **Evaluate for underlying VTE causes** (e.g. Antiphospholipid syndrome - APLA)
➡️ **Continue anticoagulation for at least several months** to reduce recurrence risk
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What is the **pathophysiology of acute myeloid leukemia (AML)⁉️**
➡️ AML results from:
🔹 **Failed differentiation of hematopoietic progenitor cells**
🔹 **Accumulation of blasts in bone marrow and blood**
🔹 **Decreased production of:**
▪️ Red blood cells
▪️ Neutrophils
▪️ Platelets
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What are the common **risk factors for AML⁉️**
➡️ Most cases are **idiopathic,** but known risks include:
🔹 **Hereditary syndromes**
🔹 **Radiation exposure**
🔹 **Chemical exposure** (e.g., benzene)
🔹 **Chemotherapy**
🔹 **Occupational exposures**
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**How is AML diagnosed⁉️**
➡️ **Diagnosis is made by:**
🔹 **>20% blasts** in bone marrow or peripheral blood
❗️ Exception: AML can be diagnosed **regardless of blast % if specific genetic abnormalities are present:**
▪️ **inv(16)**
▪️ **t(15;17)**
▪️ **t(8;21)**
▪️ **t(16;16)**
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How is the **prognosis of AML stratified cytogenetically⁉️**
➡️ **Favorable:**
🔹 t(15;17)
🔹 t(8;21)
🔹 inv(16)
➡️ **Intermediate:**
🔹 Normal cytogenetics
➡️ **Poor prognosis:**
🔹 t(6;9)
🔹 inv(3)
🔹 -7 (monosomy 7)
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How is **Down syndrome related to AML⁉️**
➡️ Children with Down syndrome have:
🔹 **Higher risk of early-onset AML**
🔹 Often have **excellent prognosis**
⚠️ Without genetic predisposition, >20% blasts are still required
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**Why is BCR-ABL not a diagnostic feature of AML⁉️**
➡️ BCR-ABL fusion gene is **characteristic of:
Chronic Myeloid Leukemia (CML)**
❗️**Not AML**
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