Hematology Flashcards
(520 cards)
1
Q
What is anemia?
A
Anemia is defined as a reduction in the number of circulating red blood cells, measured by hemoglobin (Hb) or hematocrit (Hct).
Hematocrit is the percentage of red blood cells in your blood, and hemoglobin helps carry oxygen throughout the body.
2
Q
What are the key indicators of anemia?
A
Anemia is characterized by low hemoglobin (Hb), low red blood cell (RBC) count, and low hematocrit.
3
Q
How does anemia affect tissue oxygenation?
A
Anemia affects tissue oxygenation because hemoglobin delivers oxygen from the lungs to tissues. Low Hb leads to low oxygen delivery, which may result in organ dysfunction.
4
Q
What factors influence the clinical consequences of anemia?
A
The clinical consequences depend on: 1) Hb level, 2) rapidity of anemia development, 3) age of the patient, and 4) compensatory mechanisms of the body.
5
Q
What compensatory mechanisms maintain oxygen delivery in anemia?
A
Compensatory mechanisms include: 1) Increased cardiac output, 2) Increased oxygen extraction ratio, 3) Rightward shift of the oxyhemoglobin curve, 4) Expansion of plasma volume.
6
Q
What are the general causes of anemia?
A
The general causes of anemia include: 1) Blood loss anemia, 2) Decreased production (nutritional deficiencies, marrow disease), 3) Increased destruction (hemolytic anemia).
7
Q
What are the symptoms of anemia?
A
Symptoms of anemia are variable and depend on severity, rate of development, and underlying oxygen demands. Rapid development leads to more symptoms, while gradual onset may result in minimal or absent symptoms.
8
Q
When is blood transfusion recommended for anemia?
A
Blood transfusion is generally not recommended unless the Hb concentration is less than 7 g/dL.
9
Q
A
10
Q
What is the general rule regarding blood transfusion?
A
Blood transfusion is not recommended unless either of the following is true:
1. The HB concentration <7 g/dL OR
2. The patient requires increased oxygen-carrying capacity.
11
Q
What are some clinical features of anemia?
A
Clinical features include:
1. Headache
2. Tachycardia
3. Pallor (most noted in the conjunctiva)
4. Signs and symptoms of the underlying cause.
12
Q
What are signs and symptoms of the underlying cause of anemia?
A
Signs and symptoms may include:
1. Orthostatic lightheadedness, syncope, or hypertension if acute bleeding
2. Jaundice if hemolytic anemia
3. Blood in stool if GI bleeding.
13
Q
What historical findings should be considered in patients with anemia?
A
Historical findings include:
1. Family history (e.g., hemophilia, G6PD deficiency, thalassemia)
2. Bleeding (e.g., recent trauma/surgery, hematemesis, melena)
3. Chronic illnesses (e.g., renal failure, autoimmune disease, malignancies)
4. Ingestions (e.g., alcohol, medications).
14
Q
What does a reticulocyte index < 2% indicate?
A
If the reticulocyte index is < 2%, it indicates inadequate bone marrow response.
Differential diagnosis includes microcytic anemia and macrocytic anemia.
15
Q
What are the differential diagnoses for microcytic anemia (MCV < 80)?
A
Differential diagnoses include:
1. Iron deficiency anemia
2. Anemia of chronic disease
3. Thalassemia
4. Sideroblastic anemia.
16
Q
What are the differential diagnoses for macrocytic anemia (MCV > 100)?
A
Differential diagnoses include:
1. Vitamin B12 or folate deficiency
2. Liver disease
3. Simulated erythropoiesis
4. Alcoholism
5. Hypothyroidism.
17
Q
What does a reticulocyte index > 2% indicate?
A
If the reticulocyte index is > 2%, it indicates an adequate bone marrow response.
Differential diagnoses include normocytic anemia.
18
Q
What are the differential diagnoses for normocytic anemia (MCV 80 to 100)?
A
Differential diagnoses include:
1. Aplastic anemia
2. Bone marrow fibrosis
3. Bone marrow infiltration
4. Anemia of chronic disease
5. Renal failure.
19
Q
What is normocytic anemia?
A
A type of anemia where the mean corpuscular volume (MCV) is between 80 to 100.
Differential diagnoses include bone marrow infiltration, anemia of chronic disease, and renal failure.
20
Q
What does a reticulocyte index >2% indicate?
A
An adequate bone marrow response.
Differential diagnoses include acute blood loss and hemolysis.
21
Q
What should be checked if the reticulocyte index is elevated?
A
Look for sources of blood loss or check for hemolytic anemia.
Check haptoglobin, LDH, and bilirubin levels.
22
Q
What are the characteristics of microcytic anemia?
A
MCV is less than 80.
Check iron studies.
23
Q
What are the characteristics of normocytic anemia?
A
MCV is between 80-99.
Differential diagnoses include aplastic anemia, bone marrow fibrosis, tumor, anemia of chronic disease, and renal failure.
24
Q
What are the characteristics of macrocytic anemia?
A
MCV is greater than 100.
Check vitamin B12 and folate levels.
25
What is nutritional anemia?
A condition where the hemoglobin content of blood is lower than normal due to deficiency of one or more essential nutrients.
26
What is nutritional anemia?
A condition in which the hemoglobin content of blood is lower than normal as a result of deficiency of one or more essential nutrients.
27
What are the types of nutritional anemia?
1. Microcytic anemia: iron deficiency anemia
2. Normocytic anemia: protein energy malnutrition
3. Macrocytic anemia: B12 deficiency, deficiency in folate.
28
What is microcytic anemia?
Iron deficiency anemia, which is the most common cause of anemia worldwide.
29
Why is iron important in anemia?
Iron is important for heme synthesis in hemoglobin molecules in red cells.
30
What is heme composed of?
Heme = protoporphyrin + iron.
31
What are the two types of iron?
1. Heme Iron (ferrous, Fe2+), from meat, better absorbed.
2. Non-Heme Iron (ferric, Fe3+), from vegetables & cereal.
32
How is iron transported in the body?
Transported in plasma bound to transferrin.
33
Where is iron absorbed in the body?
In the duodenum, upper part of the small intestine.
34
What happens to transferrin levels when serum iron increases?
Transferrin levels will be reduced because cells have enough iron.
35
What happens to transferrin levels when serum iron decreases?
Transferrin levels will be increased because more iron is needed to enter the cells.
36
What should be ruled out in elderly patients with iron deficiency anemia?
Colon cancer, as it is a common cause of GI bleeding in the elderly.
37
What is the most common cause of blood loss leading to iron deficiency anemia?
Menstrual blood loss is the most common source.
38
What is the most common cause of iron deficiency anemia?
Blood loss, primarily from gastrointestinal sources or menstrual bleeding.
39
What are the increased demand conditions for iron?
Growth (infants, toddlers, adolescents) and pregnancy.
40
What dietary deficiency is seen in infants and toddlers?
Iron deficiency, especially if the diet is predominantly human milk.
41
Why are adolescent women particularly at risk for iron deficiency?
Due to increased iron requirements from rapid growth and menstrual blood loss.
42
What are the signs and symptoms of iron deficiency anemia?
Fatigue, pallor, shortness of breath, tachycardia, brittle hair and nails, atrophic glossitis, angular stomatitis, koilonychia, and pica.
43
What might cause dizziness and fatigue after gastric bypass surgery?
Iron deficiency anemia due to blood loss.
44
What does CBC reveal in iron deficiency anemia?
Decreased Hb, microcytic RBCs, hypochromic RBCs, low reticulocytes, high RDW, and reactive thrombocytosis.
45
What does a blood film show in iron deficiency anemia?
Small hypochromic RBCs, anisocytosis, and poikilocytosis.
46
47
What is the most common cause of iron deficiency anemia?
Blood loss, primarily from gastrointestinal sources or menstrual bleeding.
48
What are the increased demand conditions for iron?
Growth (infants, toddlers, adolescents) and pregnancy.
49
What dietary deficiency is seen in infants and toddlers?
Iron deficiency, especially if the diet is predominantly human milk.
50
Why are adolescent women particularly at risk for iron deficiency?
Due to increased iron requirements from rapid growth and menstrual blood loss.
51
What are the signs and symptoms of iron deficiency anemia?
Fatigue, pallor, shortness of breath, tachycardia, brittle hair and nails, atrophic glossitis, angular stomatitis, koilonychia, and pica.
52
What might cause dizziness and fatigue after gastric bypass surgery?
Iron deficiency anemia due to blood loss.
53
What does CBC reveal in iron deficiency anemia?
Decreased Hb, microcytic RBCs, hypochromic RBCs, low reticulocytes, high RDW, and reactive thrombocytosis.
54
What does a blood film show in iron deficiency anemia?
Small hypochromic RBCs, anisocytosis, and poikilocytosis.
55
What are reticulocytes?
Immature RBCs that contain no nucleus but have residual RNA.
56
What is reactive thrombocytosis?
A condition characterized by an increase in platelet count.
57
What are the characteristics of small hypochromic RBCs in a blood film?
They appear pale and have a reduced hemoglobin content.
58
What is anisocytosis?
A condition where red blood cells are unequal in size.
59
What is poikilocytosis?
An increase in abnormal red blood cells of any shape that makes up 10% or more of the total population.
60
What are examples of poikilocytes?
Flat, elongated, teardrop-shaped, crescent-shaped, sickle-shaped, or those with pointy/thorn-like projections.
61
What do iron studies confirm in iron deficiency anemia?
Decreased ferritin, decreased transferrin saturation, increased TIBC, and increased transferrin receptor levels.
62
What does a bone marrow biopsy reveal in iron deficiency anemia?
Absence of stainable iron; it is the gold standard test.
63
What must be ruled out in elderly patients with iron deficiency anemia?
Colon cancer, as it is a common cause of gastrointestinal bleeding.
64
What are the treatment options for iron deficiency anemia?
Treat underlying cause, oral iron supplements, IV iron, and blood transfusion if severe.
65
How long should oral iron supplements be taken before determining response?
3 to 6 months.
66
What are common side effects of oral iron supplements?
Constipation, nausea, and dyspepsia.
67
When is IV iron indicated?
If unable to tolerate side effects, have a disease affecting absorption, or need to increase iron quickly before surgery.
68
When is blood transfusion recommended in iron deficiency anemia?
Not recommended unless anemia is severe or the patient has cardiopulmonary disease.
69
What is the serum ferritin level in iron deficiency anemia?
Low.
70
What is the serum ferritin level in anemia of chronic disease?
Normal/high.
71
What is the TIBC in iron deficiency anemia?
High.
72
What is the RDW in iron deficiency anemia?
High.
73
What is the most likely cause of microcytic hypochromic anemia in a 20-year-old male medical student with vague abdominal pain?
A. bleeding ulcer
## Footnote
This presentation is indicative of iron deficiency anemia, where bleeding is the most important cause of iron deficiency.
74
What would you find in a patient with dizziness, palpitations, and dyspnea on exertion who had gastric bypass surgery and a peripheral blood smear showed microcytic RBC?
A. low serum ferritin
## Footnote
This presentation is indicative of iron deficiency anemia, where low ferritin indicates iron deficiency.
75
What is sideroblastic anemia characterized by?
Defect in protoporphyrin synthesis.
76
What leads to the pathologic iron deposits in RBC mitochondria in sideroblastic anemia?
Abnormality in RBC iron metabolism (heme synthesis) leading to refractory anemia.
77
What are some causes of acquired sideroblastic anemia?
1. Myelodysplasia
2. Alcoholism
3. B6 deficiency
4. Lead poisoning.
78
What does sideroblastic anemia result in regarding iron and hemoglobin?
The body produces enough iron but is unable to incorporate it into hemoglobin.
79
What is sideroblastic anaemia?
Sideroblastic anaemia is a disorder where the body produces enough iron but is unable to utilize it effectively.
80
What are the types of sideroblastic anaemia?
Sideroblastic anaemia can be hereditary or acquired.
81
What are some acquired causes of sideroblastic anaemia?
Acquired causes include myelodysplasia, alcohol, lead toxicity, certain drugs (isoniazid, chloramphenicol), and vitamin B6 deficiency.
82
What is myelodysplastic syndrome?
Myelodysplastic syndrome is a group of cancers where immature blood cells in the bone marrow do not mature into healthy blood cells.
83
What are the blood film findings in sideroblastic anaemia?
Blood film shows hypochromic cells.
84
What are the bone marrow findings in sideroblastic anaemia?
Bone marrow shows ringed sideroblasts (erythroblasts with iron deposited in mitochondria) using Prussian blue stain.
85
What are the iron study findings in sideroblastic anaemia?
Iron studies show increased iron and ferritin, normal TIBC, and normal/elevated TIBC saturation.
86
What is the treatment for sideroblastic anaemia?
Treatment includes removing the causative agent, transfusing as necessary, and some patients respond to pyridoxine (vitamin B6).
87
How does sideroblastic anaemia differ from iron deficiency anemia?
Iron deficiency anemia and anemia of chronic disease will show low iron levels, while sideroblastic anemia will show increased protoporphyrin.
88
What is thalassemia?
Thalassemia is discussed under 'Hemolytic anemia' and is characterized by issues with globin production.
89
What are the types of macrocytic anemia?
Macrocytic anemia is divided into megaloblastic and normoblastic.
90
What characterizes megaloblastic anemia?
Megaloblastic anemia is characterized by impaired DNA synthesis.
91
What are the two types of macrocytic anemia?
Megaloblastic and normoblastic anemia.
92
What characterizes megaloblastic anemia?
Impairment of DNA synthesis.
93
What deficiencies lead to megaloblastic anemia?
Vitamin B12 or Folate deficiency.
94
What are the blood film findings in megaloblastic anemia?
Megaloblasts in bone marrow and hypersegmented neutrophils in blood film, +/- thrombocytopenia.
95
What is the role of Vitamin B12?
It serves as a cofactor in two important reactions for normal erythropoiesis and CNS functioning.
96
What are the two important reactions that Vitamin B12 is involved in?
1. Conversion of homocysteine to methionine. 2. Conversion of methylmalonyl-CoA to succinyl-CoA.
97
Where is Vitamin B12 found?
Only in meat and dairy products.
98
How is Vitamin B12 released from animal protein?
By acid and pepsin in the stomach.
99
What binds Vitamin B12 in the stomach?
R-binder (aka Transcobalamin) from saliva.
100
What happens to Vitamin B12 in the duodenum?
Pancreatic enzymes release it from the R-binder, and it binds to Intrinsic Factor (IF).
101
Where is the Vitamin B12 and IF complex absorbed?
In the terminal ileum.
102
How is Vitamin B12 transported after absorption?
By Transcobalamin II and then stored in the liver.
103
What can patients with Vitamin B12 deficiency experience?
Moderate to severe neurologic symptoms with little to no anemia.
104
What are the causes of Vitamin B12 deficiency?
1. Poor diet (vegan). 2. Malabsorption (e.g., celiac, tropical sprue). 3. Pernicious anemia.
105
What is pernicious anemia?
An autoimmune disease with autoantibodies against parietal cells and/or intrinsic factor.
106
What is the most characteristic neurologic lesion in B12 deficiency?
Subacute combined degeneration of the spinal cord (SCDC).
107
What is the most common neurologic feature in B12 deficiency?
Peripheral polyneuropathy (absent reflexes).
108
What are the signs of subacute combined degeneration of the spinal cord?
Weakness, ataxia, hyperreflexia, spastic paraplegia, increased deep tendon reflexes, spasticity, Babinski sign.
109
What autoimmune diseases may be associated with B12 deficiency?
Thyroid disease, Addison's disease, and vitiligo.
110
What is the most characteristic neuron lesion in B12 deficiency?
Subacute combined degeneration of the spinal cord (SCDC).
111
What is the most common neurological feature in B12 deficiency?
Peripheral polyneuropathy (absent reflexes).
112
What are the characteristics of subacute combined degeneration of the spinal cord?
Degeneration of the posterior & lateral columns, UMNL signs like weakness, ataxia, hyperreflexia, spastic paraplegia, increased deep tendon reflexes, spasticity, and Babinski sign.
113
What sensory losses occur in subacute combined degeneration of the spinal cord?
Loss of vibration and proprioception in lower extremities.
114
What type of signs do patients with B12 deficiency exhibit?
Both UMN signs and LMN signs (mixed picture; e.g., absent ankle reflexes with exaggerated knee reflexes).
115
What are some neurological symptoms associated with B12 deficiency?
Dementia and optic atrophy leading to visual disturbances.
116
Where is folate found and absorbed?
Found in green vegetables and offal (liver, kidney), absorbed in the duodenum.
117
What role does folate play in the body?
Folate plays an important role in DNA synthesis.
118
What are the common causes of folate deficiency?
Poor intake (most common), alcoholism, excess utilization (pregnancy, ICU, chronic hemolysis), malabsorption (celiac, tropical sprue), and drugs (methotrexate, phenytoin, trimethoprim, sulfasalazine).
119
What are the investigations for folate deficiency?
CBC shows low Hb, low Retics, macrocytic (high MCV); blood film shows hypersegmented neutrophils.
120
What are the vitamin B12 studies for deficiency?
Serum Vitamin B12 <50 ng/L (N>160), red cell folate may be low, anti-parietal cell antibodies, anti-IF antibodies, high homocysteine, and methylmalonic acid (MMA).
121
What is the treatment for B12 deficiency?
IM hydroxocobalamin or oral B12 2mg/day.
122
What is the treatment for folate deficiency?
Treat underlying cause; oral folic acid 5mg/day for 4 months.
123
What complication can arise from B12 and folate replacement?
Hypokalemia due to rapid cell production.
124
How can folate deficiency mask B12 deficiency?
After folate replacement, hematological symptoms may improve but neurological symptoms can deteriorate.
125
What can folate deficiency mask?
B12 deficiency
## Footnote
After replacement of folate, hematological symptoms may improve but neurological symptoms deteriorate.
126
What is macrocytic anemia with normoblastic bone marrow characterized by?
Macrocytosis without hypersegmented neutrophils.
127
What are some causes of macrocytic anemia?
1. Physiological (pregnancy, newborn)
2. Alcohol excess
3. Liver disease
4. MDS (myelodysplastic syndrome)
5. Hydroxyurea, azathioprine
6. Cold agglutinins
7. Hemolysis
8. High retics (hemorrhage, hemolysis)
128
What condition might a 65-year-old male vegetarian with peripheral neuropathy have?
Vitamin B12 deficiency
## Footnote
This can lead to megaloblastic anemia and neurological manifestations.
129
What might cause dizziness in someone who had ileum restriction surgery two years prior?
Megaloblastic anemia.
130
What is anemia of chronic disease?
Anemia of chronic disease is a hypoproliferative anemia that develops in response to systemic illness or inflammation.
131
What is the commonest cause of anemia among patients with chronic illness?
Anemia of chronic disease.
132
What cytokines are produced in chronic diseases that affect erythropoiesis?
Cytokines such as IL1, IL6, and TNF alpha.
133
How do cytokines affect hepcidin and erythropoietin?
Cytokines enhance the production of hepcidin in the liver and reduce erythropoietin in the kidney.
134
What are the characteristics of anemia of chronic disease?
May be normocytic normochromic or microcytic.
135
What causes anemia of chronic disease?
LOW iron release from BM, LOW erythropoietin response, and HIGH hepcidin.
136
What are some chronic inflammatory diseases associated with anemia of chronic disease?
Examples include Crohn's disease, Rheumatoid arthritis, and SLE.
137
What chronic infections can lead to anemia of chronic disease?
Tuberculosis and lung abscess.
138
What malignancies are associated with anemia of chronic disease?
Lung cancer, breast cancer, and Hodgkin disease.
139
What is the effect of inflammatory cytokines on erythropoietin?
The release of inflammatory cytokines has a suppressive effect on erythropoietin.
140
What lab findings are associated with anemia of chronic disease?
Hepcidin, serum iron, OTIBC, ferritin, hemoglobin, hematocrit, transferrin, transferrin saturation.
141
What is the treatment for anemia of chronic disease?
Treatment of the underlying cause and Erythropoiesis-Stimulating Agents.
142
When is recombinant erythropoietin used?
If anemia of chronic disease is due to chronic kidney disease.
143
What is Aplastic Anemia?
Aplastic Anemia is defined as bone marrow failure leading to pancytopenia (anemia, neutropenia, thrombocytopenia).
144
What are the key characteristics of Aplastic Anemia?
Key characteristics include pancytopenia and hypocellularity of bone marrow, along with a decreased number of pluripotent stem cells.
145
What are some hereditary causes of Aplastic Anemia?
Hereditary causes include Schwachman-Diamond syndrome and Fanconi's anemia, which is a DNA crosslink repair defect.
146
What are the classic features of Fanconi's anemia?
Classic features include abnormal thumbs, absent radii, short stature, and skin hyperpigmentation.
147
What is the most common cause of Aplastic Anemia?
Idiopathic causes account for 67% of Aplastic Anemia cases.
148
What drugs can cause Aplastic Anemia?
Drugs that can cause Aplastic Anemia include chemotherapy (dose-related) and idiosyncratic reactions to chloramphenicol, phenytoin, NSAIDs, and carbamazepine.
149
What chemicals are associated with Aplastic Anemia?
Chemicals such as benzene, insecticides, and radiation are associated with Aplastic Anemia.
150
What infections can lead to Aplastic Anemia?
Infections that can lead to Aplastic Anemia include EBV, HIV, TB, hepatitis C and B, parvovirus B19, CMV, Herpes, and varicella.
151
What are the signs and symptoms of Aplastic Anemia?
Signs and symptoms include fatigue, dyspnea, headache, palpitations, pallor, increased susceptibility to infections, and bleeding.
152
What is a potential complication of Aplastic Anemia?
Aplastic Anemia can transform into acute leukemia.
153
What are the diagnostic criteria for Aplastic Anemia?
Diagnosis includes pancytopenia, decreased or absent reticulocytes, and a peripheral blood smear revealing normocytic anemia with decreased neutrophils and platelets.
154
What does a bone marrow biopsy reveal in Aplastic Anemia?
A bone marrow biopsy shows hypocellularity with increased fat spaces.
155
What is the prognosis for Aplastic Anemia?
Prognosis is poor if neutrophils are < 0.5x10^9, platelets < 20x10^9, or reticulocytes < 40x10^9.
156
What is the definitive treatment for patients under 40 years?
Bone marrow transplantation (BMT) from HLA identical donor
157
What is the definitive treatment for patients above 40 years?
Immunosuppressive treatment (antilymphocyte globulin & cyclosporine)
158
What is the first step in treatment?
Discontinuation of offending agents or treatment of any known underlying causes
159
What is the second step in treatment?
Transfusion of PRBCs and platelets as necessary — use judiciously
160
What is the third step in treatment?
Bone marrow transplantation
161
What are hemolytic anemias?
Increased destruction of RBCs leading to decreased lifespan.
162
What is hemolysis?
Premature destruction or breakdown of red blood cells.
## Footnote
Hemolytic anemia is defined as the destruction of red blood cells before their normal 120-day lifespan.
163
What is compensated hemolysis?
Increase in erythropoiesis in bone marrow compensates for increased destruction (hemolysis without anemia).
164
What is uncompensated hemolysis?
Increased erythropoiesis can't compensate for excessive hemolysis, leading to hemolytic anemia.
165
What is the initial step to diagnose hemolytic anemia?
Reticulocyte count.
166
What are common clinical features of hemolytic anemia?
Signs/symptoms of anemia: fatigue, dyspnea, headache, palpitations, pallor, jaundice, dark urine, hepatosplenomegaly, cholelithiasis, lymphadenopathy.
167
What laboratory findings are associated with hemolytic anemia?
Low Hb/Hct level, elevated reticulocyte count, schistocytes, spherocytes, sickled RBCs, Heinz bodies, low haptoglobin, elevated LDH, elevated indirect bilirubin.
168
What does a low haptoglobin level indicate?
Decreased levels suggest hemoglobin release secondary to RBC destruction.
169
What does elevated LDH indicate?
LDH is released when RBCs are destroyed.
170
What does elevated indirect bilirubin indicate?
Due to degradation of heme as RBCs are destroyed.
171
What is a positive direct Coombs test indicative of?
A positive direct Coombs test indicates autoimmune hemolytic anemia (AIHA) if it detects antibody or complement on RBC membrane.
172
What does a positive osmotic fragility test indicate?
A positive osmotic fragility test indicates the presence of hemolysis.
173
What is the treatment for hemolytic anemia?
The treatment includes addressing the underlying cause, transfusion of PRBCs if severe anemia is present or the patient is hemodynamically compromised, and folate supplementation.
174
What happens to bilirubin levels in hemolysis?
Bilirubin levels increase, leading to dark urine (tea colored) due to extra hemolysis.
175
What does red urine indicate in hemolysis?
Red urine indicates intra hemolysis.
176
What is intravascular hemolysis?
Hemolysis occurring within the circulation, where red cells are rapidly destroyed in blood vessels, leading to hemoglobinemia (free Hb in circulation).
177
What are the consequences of intravascular hemolysis?
Hemoglobinemia, hemoglobinuria, and very low or absent haptoglobin due to saturation and removal of the Hb-haptoglobin complex by the liver.
178
What causes intravascular hemolysis?
Hemoglobinopathies (e.g., sickle cell, thalassemia), hereditary spherocytosis, warm autoimmune hemolytic anemia, hemolytic disease of the newborn, G6PD deficiency, red cell fragmentation (MAHA), mismatched transfusion, paroxysmal nocturnal hemoglobinuria, cold autoimmune hemolytic anemia, and malaria.
179
What is extravascular hemolysis?
Hemolysis that occurs outside the circulation, primarily in the spleen and liver, where RBCs are removed by macrophages in the reticuloendothelial system.
180
What are the characteristics of extravascular hemolysis?
Majority of hemolysis occurs here, leading to splenomegaly, production of bilirubin (direct or indirect), and normal haptoglobin levels.
181
What is the difference between inherited and acquired hemolytic anemia?
Inherited hemolytic anemia includes hereditary spherocytosis and hemoglobin abnormalities, while acquired hemolytic anemia can be due to infections, medications, or autoimmune responses.
182
What are some examples of inherited hemolytic anemia?
Hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria (PNH), hemoglobin C disease, thalassemias, and metabolic defects like G6PD deficiency.
183
What are some examples of acquired hemolytic anemia?
Malaria, clostridium infections, autoimmune hemolytic anemia, and drug-induced hemolysis.
184
What laboratory findings are associated with hemolysis?
Increased LDH, increased indirect bilirubin, decreased haptoglobin, and potential jaundice.
185
What is the significance of haptoglobin in hemolysis?
Haptoglobin binds free hemoglobin; in hemolysis, it becomes saturated and is removed, leading to low or absent levels in the blood.
186
What is the role of the spleen in extravascular hemolysis?
The spleen is primarily responsible for removing aged or damaged RBCs, leading to splenomegaly in cases of increased hemolysis.
187
What is cold autoimmune hemolytic anemia?
A type of anemia caused by the destruction of red blood cells due to the immune system attacking them in cold temperatures.
188
What is the main cause of hereditary spherocytosis?
A defect in the red blood cell membrane due to a deficiency in spectrin, leading to increased permeability to sodium and resulting in rigid, spherical red blood cells.
189
What are the causes of spherocytosis?
Hereditary spherocytosis, G6PD deficiency, ABO incompatibility, hyperthermia, and autoimmune hemolytic anemia (AIHA).
190
What are the signs and symptoms of hereditary spherocytosis?
Chronic conditions can lead to pigmented gallstones and folate depletion from hyperactivity of the bone marrow.
191
What does a complete blood count (CBC) show in hereditary spherocytosis?
Microcytic anemia (mild) and reticulocytosis.
192
What findings are observed in blood film (BF) for hereditary spherocytosis?
Presence of spherocytes and increased reticulocytes.
193
What is the significance of a negative direct Coombs test?
It helps to distinguish hereditary spherocytosis from autoimmune hemolytic anemia.
194
What is the purpose of eosin-5-maleimide (EMA) binding testing?
To assess the number of proteins present on the RBC membrane; spherocytes show decreased EMA binding.
195
What does osmotic fragility testing measure?
The ability of RBCs to swell in hypotonic solutions; spherocytes rupture earlier due to their reduced surface area to volume ratio.
196
What is the treatment for hereditary spherocytosis?
Chronic folic acid supplementation, splenectomy after childhood, and blood transfusions as necessary.
197
What is hereditary elliptocytosis?
A condition where RBCs are elliptical in shape, milder clinically, and does not require splenectomy.
198
What causes hereditary elliptocytosis?
Mutations in genes encoding RBC membrane proteins (e.g., spectrin, protein 4.1) lead to weakness of the cytoskeleton, causing cell deformation.
199
What are hemoglobin abnormalities?
Genetic conditions that can be autosomal recessive; if both parents are carriers, the offspring have a 25% chance of being affected.
200
What is thalassemia?
A condition characterized by a gene defect that leads to decreased synthesis of one or more globin chains, resulting in decreased normal Hb and cell damage.
201
What happens in alpha-thalassemia?
There is reduced alpha chain synthesis and excess beta chains.
202
What are the chromosomal locations for alpha-thalassemia?
Chromosome 16 with 4 loci.
203
What happens in beta-thalassemia?
There is reduced beta chain synthesis and excess alpha chains that bind to delta forming HbA2 and to gamma forming HbF.
204
What are the chromosomal locations for beta-thalassemia?
Chromosome 11 with 2 loci.
205
What is alpha-thalassemia trait & minor?
If 1 locus affected: asymptomatic trait; if 2 loci affected: asymptomatic + mild microcytic anemia. No treatment needed.
206
What are the lab results for alpha-thalassemia trait & minor?
Normal Hb on electrophoresis and normal HCT (97% HbA, 2% HbA2, 1% HbF). Peripheral blood smear reveals microcytic, hypochromic RBCs.
207
What characterizes HbH disease?
Anemias of varying severity with 3 loci affected.
208
What are bone abnormalities associated with ineffective bone marrow?
Enlarged maxilla and prominent frontal & parietal bones, leading to a 'crew-cut' appearance on skull X-ray.
## Footnote
Skull X-ray shows hair on end appearance.
209
What causes jaundice in this condition?
High unconjugated bilirubin and dark urine.
210
What is the consequence of untreated thalassemia major?
Death occurs within the first few years of life secondary to progressive CHF.
211
What are the key laboratory findings in thalassemia?
N/high RBCs, low MCV; Mentzer index helps differentiate between IDA and thalassemia.
## Footnote
If <13: thalassemia; If >13: IDA.
212
What does the blood film show in thalassemia?
Microcytic hypochromic RBCs, basophilic nucleated RBCs, target cells, and reticulocytes.
213
What is the purpose of electrophoresis in thalassemia?
To detect THbF and HbA2; normal HbA is decreased due to lack of b-globin production.
214
What are the iron studies findings in thalassemia?
Normal ferritin and iron studies.
215
What is the mainstay treatment for thalassemia major?
Blood transfusion; indicated if Hb <7-8 or marked clinical symptoms.
216
What is the goal of treatment in thalassemia major?
To keep Hb > 10 to suppress ineffective erythropoiesis and consider splenectomy.
217
What long-term supplementation is required in thalassemia major?
Long-term folic acid supplementation.
218
What is the benefit of splenectomy in thalassemia?
Beneficial in patients with severe splenomegaly.
219
What is a potential complication of iron overload in thalassemia?
Damage to heart, liver, and pancreas.
220
When are iron chelating agents indicated in thalassemia?
If serum ferritin >1000ug/L.
221
What are the options for iron chelation therapy?
Subcutaneous desferrioxamine, oral deferasirox, and oral deferiprone.
## Footnote
Desferrioxamine has skin reactions and hearing loss; deferasirox is not used in cardiac involvement; deferiprone is best for cardiac involvement.
222
What role does ascorbic acid play in iron overload?
Increases urinary excretion of iron.
223
What is sickle cell anemia?
An autosomal recessive disorder caused by inheritance of two HbS genes, replacing normal Hb A with mutant Hb S.
224
What mutation causes sickle cell anemia?
A nonconservative missense point mutation in the b-globin chain, changing glutamine to valine at position 6.
225
What happens to HbS when it is deoxygenated?
It becomes insoluble and polymerizes, increasing rigidity and causing sickling.
226
What are the consequences of sickling in sickle cell anemia?
Hemolysis, premature destruction of RBCs, and vaso-occlusion leading to tissue infarction.
227
What causes sickling when there is no oxygen?
When HbS is deoxygenated, it becomes insoluble and polymerizes, leading to increased rigidity and sickling.
228
What precipitates sickling?
Sickling is precipitated by anything that shifts the oxygen dissociation curve to the right: hypoxia, dehydration, infection, acidosis, and cold weather.
229
When do signs and symptoms of sickle cell disease start?
Signs and symptoms start after 6 months of age, as HbF is normal before then.
230
What are the clinical features of hemolytic anemia/crisis?
Jaundice, pallor, dark urine, and pigment gallstones.
231
What is a vasoocclusive crisis?
A painful crisis characterized by recurrent episodes of severe deep bone pain and dactylitis, often seen in children and adolescents.
232
What is dactylitis?
Painful swelling of the dorsa of hands and feet, usually in infancy and early childhood, often the first manifestation of sickle cell disease.
233
What is avascular necrosis?
Avascular necrosis, especially of the femoral head, is common in hip and shoulder joints.
234
What is auto-splenectomy?
Splenic atrophy from repeated infarction, making patients susceptible to infections with capsulated organisms.
235
What is acute chest syndrome?
A medical emergency requiring blood transfusion, characterized by fever, cough, shortness of breath, and pulmonary infiltrates.
236
What is priapism?
Prolonged painful erections lasting between 30 minutes and 3 hours, which usually subsides spontaneously.
237
What are the complications of sickle cell disease related to the brain?
CVA (cerebrovascular accident) is especially common in the young.
238
What are the ocular complications of sickle cell disease?
Retinal infarcts leading to visual disturbances, vitreous hemorrhage, proliferative retinopathy, and retinal detachment.
239
What is renal papillary necrosis?
A common condition affecting up to 20% of patients, characterized by hematuria, usually painless.
240
What is splenic sequestration?
Painful rapid enlargement of the spleen due to sudden pooling of blood, resulting in splenomegaly and hypovolemic shock.
241
What is an aplastic crisis?
A condition caused by parvovirus B19, reducing the bone marrow's ability to compensate for chronic hemolysis.
242
What infections are common in sickle cell disease?
Pneumonia, meningitis, osteomyelitis (especially from salmonella), and sepsis.
243
What is sickle cell nephropathy?
Includes renal papillary necrosis, pyelonephritis, chronic interstitial nephritis, isosthenuria, CKD, and ESRD.
244
What are the growth and maturation effects of sickle cell disease?
Delayed growth and maturation, especially in boys.
245
What cardiovascular complications can arise from sickle cell disease?
High-output heart failure and myocardial infarction.
246
What is the risk of stroke in sickle cell disease?
Stroke is primarily a concern in children.
247
What is the most common finding in sickle cell disease investigations?
+ Hb, N MCV, T retics (Anemia)
248
What is the best initial test for sickle cell disease?
Sickled RBCs on blood film
249
What is the most accurate test for sickle cell disease?
Hb electrophoresis → 80-90% HbSS, absent HbA
## Footnote
HbS travels slower on electrophoresis because of less charge.
250
What laboratory finding is inappropriately low in sickle cell disease?
ESR
251
What is a common finding during a sickle cell crisis?
Neutrophilia
252
What is the method for neonatal screening for sickle cell disease?
Cord blood or heel prick test
253
What type of screening is used for prenatal diagnosis of sickle cell disease?
DNA-based (PCR or allele specific hybridization)
254
What is the pH used in cellulose acetate strip for sickle cell testing?
pH 8.0
255
What is a key management strategy for sickle cell disease?
Chronic folic acid supplementation
256
When should blood transfusions be based on in sickle cell disease?
Patient's clinical condition and not on Hb levels
257
What medication decreases the occurrence of sickle cell crises?
Hydroxyurea
258
What should be administered for fever or high WBC in sickle cell disease?
Antibiotics (ceftriaxone or levofloxacin)
259
What prophylactic treatment is recommended until age 6 in sickle cell disease?
Penicillin
260
What is the management for a painful crisis in sickle cell disease?
Analgesia (NSAIDs or morphine)
261
What should be avoided to prevent precipitating a crisis?
High altitudes
262
What type of hydration is recommended for mild episodes of sickle cell crisis?
Oral hydration
263
What type of hydration is recommended for moderate/severe episodes of sickle cell crisis?
IV fluids (normal saline)
264
What vaccinations are recommended for sickle cell disease?
Pneumococcal, Influenza, Meningococcal, Hemophilus, Hepatitis B
265
In which situations is exchange transfusion needed for sickle cell disease?
Acute chest syndrome, Priapism, Stroke, Visual disturbance from retinal infarction, Splenic sequestration, Aplastic crisis, Before elective surgery, During pregnancy
266
What is the success rate of bone marrow transplantation for sickle cell anemia?
Bone marrow transplantation has been performed successfully to cure sickle cell anemia, but is not routinely performed due to matched donor availability and risk of complications.
267
What is the composition of hemoglobin in sickle cell trait?
Sickle cell trait consists of 60% HbA (normal) and 40% HbS.
268
What are the symptoms of sickle cell trait?
There are no symptoms except in extreme circumstances such as hypoxia.
269
What are the findings in a CBC and blood film for sickle cell trait?
The CBC and blood film are normal.
270
What is the only manifestation of sickle cell trait?
The only manifestation is isosthenuria, a defect in the ability to concentrate urine.
271
What is the prevalence of sickle cell trait among people of African descent?
1 in 12 people of African descent are carriers of sickle cell trait.
272
In which other populations can sickle cell trait appear?
Sickle cell trait also appears in individuals of Italian, Greek, and Saudi Arabian descent.
273
What is the life expectancy for patients with sickle cell trait?
Patients with sickle cell trait are not anemic and have a normal life expectancy.
274
What can screening for sickle cell trait identify?
Screening can identify asymptomatic individuals with sickle cell trait, for whom genetic counseling may be provided.
275
What is the median survival for sickle cell disease in the United States?
The median survival for sickle cell disease is 58 years in the United States.
276
What factors are associated with increased mortality rates in sickle cell disease?
Factors associated with increased mortality rates include greater frequency of hospitalization, acute chest syndrome, and renal insufficiency.
277
What are the most common causes of death in sickle cell disease?
The most common causes of death include acute chest syndrome and multiorgan failure.
278
What enzyme deficiency is mentioned in the context of sickle cell disease?
G6PD deficiency.
279
What is G6PD deficiency?
G6PD deficiency is an inherited intravascular hemolytic anemia caused by a deficiency in the G6PD enzyme, which is important for NADPH production.
280
How is G6PD deficiency inherited?
It is inherited in an X-linked recessive manner, affecting primarily men and rarely females due to X-chromosome inactivation.
281
In which populations is G6PD deficiency predominantly found?
It is predominantly found in African, Mediterranean, and Middle Eastern populations.
282
What is the role of G6PD enzyme?
The G6PD enzyme is crucial for NADPH production, which maintains reduced glutathione levels to protect against oxidative stress.
283
What happens in G6PD deficiency?
In G6PD deficiency, there is an inability to protect RBCs from oxidative stress, leading to increased oxidative stress and RBC lysis.
284
What are common triggers for G6PD deficiency symptoms?
Common triggers include infection, acidosis, fava beans, and certain drugs such as antimalarials and sulphonamides.
285
What are the clinical features of G6PD deficiency?
Most patients are asymptomatic but may experience dark urine and jaundice when exposed to triggers.
286
What does dark urine indicate in G6PD deficiency?
Dark urine indicates intravascular hemolysis due to hemoglobinuria.
287
What is the typical spleen size in G6PD deficiency?
Patients typically have a normal-sized spleen, as there is no organomegaly due to intravascular hemolysis.
288
What are the diagnostic features in a blood film for G6PD deficiency?
Diagnostic features include bite cells, Heinz bodies, helmet cells, and ghost cells.
289
What is the significance of NADPH in G6PD assay?
NADPH levels are measured in the G6PD assay to diagnose the deficiency.
290
Why might G6PD levels be normal during a hemolytic episode?
G6PD levels may be normal during a hemolytic episode because the RBCs most deficient in G6PD have already been destroyed.
291
What is the significance of G6PD level measurement?
It is diagnostic and can help facilitate diagnosis by repeating the test at a later date to find decreased G6PD enzyme in RBCs.
292
What are the treatment options for G6PD deficiency?
1. Avoid precipitants. 2. Ensure good hydration. 3. Transfusion only if necessary. 4. Full recovery after removal of stressors.
293
What is pyruvate kinase deficiency?
It is an autosomal recessive defect of pyruvate kinase leading to inherited extravascular hemolytic anemia.
294
What role does pyruvate kinase play in the body?
It catalyzes the last step of glycolysis, which is responsible for ATP energy generation.
295
What happens in the absence of pyruvate kinase?
There is ATP deficiency in RBCs, leading to rigid RBCs and extravascular hemolysis.
296
What are the symptoms of pyruvate kinase deficiency?
Typically presents in newborns with jaundice and hemolysis, and is associated with splenomegaly, pallor, fatigue, and weakness.
297
How is pyruvate kinase deficiency diagnosed?
Diagnosis is made by measuring pyruvate kinase enzyme activity and identifying PKLR gene mutation.
298
What are the treatment options for pyruvate kinase deficiency?
1. Phototherapy and/or exchange transfusions. 2. Splenectomy in cases of severe anemia or excessively enlarged spleen.
299
What is autoimmune hemolytic anemia?
Autoimmune hemolytic anemia (AIHA) occurs when your immune system mistakes red blood cells as unwanted substances, leading to the production of antibodies that destroy red blood cells, resulting in anemia.
300
What is warm autoimmune hemolytic anemia?
Warm autoimmune hemolytic anemia is the most common type of AIHA, accounting for 80% of cases, caused by autoantibodies that react with self RBCs at body temperature (37°C).
301
What type of antibodies are involved in warm autoimmune hemolytic anemia?
IgG autoantibodies are primarily involved, with rare cases involving IgE or IgA.
302
What is the mechanism of hemolysis in warm autoimmune hemolytic anemia?
It leads to sequestration in the spleen and extravascular hemolysis, where IgG-coated RBCs are engulfed by reticulo-endothelial macrophages of the spleen, causing splenomegaly.
303
What are the common symptoms of warm autoimmune hemolytic anemia?
Symptoms may range from mild to fulminant, typically including fatigue, dyspnea, and mild splenomegaly.
304
What are the causes of warm autoimmune hemolytic anemia?
Causes may be primary/idiopathic or secondary, with 50-60% of cases linked to chronic lymphocytic leukemia (CLL), lymphoma, systemic lupus erythematosus (SLE), and certain drugs.
305
What investigations are used for warm autoimmune hemolytic anemia?
Investigations include a blood film showing spherocytes and a Direct Coomb's test detecting IgG antibody on the surface of red blood cells.
306
What is the first-line treatment for warm autoimmune hemolytic anemia?
Glucocorticoids (prednisone) are the best initial therapy, achieving remission in 80% of cases.
307
What treatment is recommended for recurrent episodes of warm autoimmune hemolytic anemia?
Recurrent episodes may respond to splenectomy if the patient does not respond to glucocorticoids.
308
What treatments are available if warm autoimmune hemolytic anemia is not controlled?
If not controlled, options include rituximab and immunosuppression with azathioprine, cyclophosphamide, or cyclosporine.
309
What is cold agglutinin disease?
Cold agglutinin disease involves IgM autoantibodies that react with self RBCs at low temperatures (4 to 23°C), leading to complement activation and intravascular hemolysis.
310
What are the potential causes of cold agglutinin disease?
It may be primary, especially in the elderly, or secondary to infections (e.g., Mycoplasma pneumoniae, Epstein-Barr virus, CMV) or lymphoid/plasma cell malignancies (e.g., B-cell lymphomas, CLL, Waldenström macroglobulinemia).
311
What symptoms may present in cold agglutinin disease?
Symptoms may include cold-induced symptoms such as acrocyanosis, livedo reticularis, Raynaud phenomenon, and numbness/mottling of the extremities.
312
What is macroglobulinemia?
A condition that may present as cold-induced symptoms (acrocyanosis, livedo reticularis, Raynaud phenomenon, numbness/mottling of the nose/ears/fingers/toes) or as hemolysis (may range from mild to severe).
313
What are the investigations for macroglobulinemia?
1. Direct Coombs test: positive only for complement
2. Cold agglutinin titer: most accurate test (positive)
3. Blood film: red cell agglutination at room temperature (RBC aggregates)
314
What is the treatment for macroglobulinemia?
1. Treat the underlying condition
2. Keep the patient warm (avoid cold, warm blankets, blood warmer)
3. Steroids & splenectomy are not beneficial
4. Rituximab (+/- plasmapheresis or cyclophosphamide or cyclosporine)
315
What is Autoimmune Hemolytic Anemia (AIHA)?
A condition classified into warm and cold types based on antibody allotype and agglutination temperature.
316
What are the characteristics of Warm AIHA?
75-90% of cases, IgG antibody, agglutination at 37°C, positive for IgG and complement.
317
What are the causes of Warm AIHA?
Idiopathic or secondary to lymphoproliferative disorder (e.g., CLL, Hodgkin lymphoma).
318
What is the blood film finding in Warm AIHA?
Spherocytes.
319
What is the management for Warm AIHA?
Treat underlying cause, corticosteroids, immunosuppression, splenectomy, folic acid, Rituximab (2nd line to steroids).
320
What are the characteristics of Cold AIHA?
IgM antibody, agglutination at 4-37°C, positive for complement.
321
What are the causes of Cold AIHA?
Idiopathic, secondary to infection (e.g., mycoplasma pneumonia, EBV), or secondary to lymphoproliferative disorder (e.g., macroglobulinemia, CLL).
322
What is the management for Cold AIHA?
Treat underlying cause, warm patient/avoid cold, Rituximab regimens (1st line), plasma exchange (2nd line for high IgM levels), folic acid.
323
What are the potential treatments for Cold AIHA?
Low dose alkylating agents (chlorambucil, cyclophosphamide) or interferon may be useful but less effective.
324
What is Microangiopathic Hemolytic Anemia?
A type of hemolytic anemia associated with thrombotic microangiopathy.
325
What is Paroxysmal Nocturnal Hemoglobinuria?
An inherited X-linked hematologic disorder characterized by hemolytic anemia.
326
327
What is Paroxysmal Nocturnal Hemoglobinuria (PNH)?
An inherited X linked hematologic stem cell disorder resulting in nocturnal hemolysis, hemolytic anemia, bone marrow failure, and thrombosis.
328
What gene mutation is associated with PNH?
Mutation in the PIGA gene in hematopoietic stem cells.
329
What is the role of the PIGA gene?
PIGA is required for the synthesis of glycosylphosphatidylinositol (GPI) protein on the cell surface.
330
What is the function of GPI protein?
GPI anchors glycoproteins on the erythrocyte surface, protecting the cell from lysis by attenuating the activity of complement.
331
What occurs in the absence or deficiency of GPI protein?
Leads to high susceptibility to complement-mediated intra vascular hemolysis.
332
What are the general characteristics of PNH?
1. Acquired disorder affecting hematopoietic stem cells and all blood lineages.
2. Caused by a deficiency of proteins that anchor complement-inactivating proteins to blood cell membranes.
3. Results in unusual susceptibility to complement-mediated lysis of RBCs, WBCs, and platelets.
333
What is the overview of PNH?
Acquired intravascular hemolytic anemia due to a clonal stem cell defect from PIGA gene mutation, leading to deficiency of complement regulatory proteins CD55 and CD59, increased sensitivity of RBCs to complement in acidosis, hemolysis, and thrombosis.
334
What are the clinical features of PNH?
Hemolysis (episodic dark urine), cytopenias (may present with pancytopenia or iron deficiency anemia), venous thrombosis, and signs/symptoms of anemia (fatigue, dyspnea, headache, palpitations, pallor).
335
What are the signs/symptoms of chronic intravascular hemolysis?
Paroxysmal hemoglobinuria (dark urine), jaundice, abdominal, back, and musculoskeletal pain.
336
What are the diagnostic criteria for PNH?
Hemolysis: high LDH, low haptoglobin, high unconjugated bilirubin; urine: hemoglobinuria; direct Coombs test is negative; most accurate test: decreased level of CD55 and CD59.
337
What does PNH develop into?
Normocytic anemia with elevated reticulocyte count.
338
What are the complications of PNH?
Thrombosis (most common cause of death), infections (2nd most common cause of death), iron deficiency anemia (IDA), acute myeloid leukemia (AML).
339
Most common cause of death in Paroxysmal Nocturnal Hemoglobinuria (PNH)
Thrombosis, especially venous.
## Footnote
Second most common cause is infection.
340
Key treatments for hemolysis in PNH
Prednisone is the best initial therapy. Eculizumab is a monoclonal antibody to C5 that inhibits complement activation.
## Footnote
Must give meningococcal vaccine prior to eculizumab.
341
What is Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Acquired chronic hemolytic anemia due to a defect in myeloid stem cells, specifically the PIGA gene.
342
What does the PIGA gene encode?
An enzyme that synthesizes membrane-associated proteins that regulate the complement, including GPI and CD55 (DAF).
343
Consequences of no GPI in PNH
No complement regulatory proteins like CD59 (MIRL) are produced, leading to intravascular hemolysis.
344
Complications of PNH
Iron deficiency anemia, acute myeloid leukemia (AML), and various thromboses (hepatic, cerebral, dermal).
345
Clinical features of PNH
Hemolytic anemia, splenomegaly, fever of unknown origin, and esophageal spasm may coincide with hemoglobinuria.
346
Definition of myeloproliferative disorders
Clonal myeloid stem cell abnormalities leading to overproduction of one or more cell lines.
347
What is the only cure for PNH?
Allogeneic bone marrow transplant.
348
Common symptoms of aplastic anemia
Pancytopenia, infections, bleeding, and fatigue.
349
What are myeloproliferative disorders?
Clonal myeloid stem cell abnormalities leading to overproduction of one or more cell lines (erythrocytes, platelets, and other cells of myeloid lineage).
## Footnote
A heterogeneous group of clonal hemopoietic stem cell disorders characterized by uncontrolled proliferation of one or more of the myeloid lineages.
350
What is the pathogenesis of myeloproliferative disorders?
1- Abnormal activation of tyrosine kinase leading to constitutive activation of signal transduction pathways.
2- Increased transcription of genes that block apoptosis.
3- Cells are not dying, so they are accumulating progressively.
351
How are myeloproliferative disorders classified?
Based on lineage predominant proliferating cells, prominence of BM fibrosis, clinical features, and laboratory features (PBS, BM, cytogenetic & molecular studies).
352
What are the five categories of myeloproliferative disorders?
1- Chronic Myeloid Leukemia (CML)
2- Polycythemia (PV)
3- Essential Thrombocythemia (ET)
4- Primary myelofibrosis (PMF)
## Footnote
CML has excessive granulocytes, PV has excessive red blood cells, ET has excessive platelets, and PMF has increased fibrotic tissues in the bone marrow.
353
What are some shared characteristics of myeloproliferative disorders?
1- Happen at any age
2- Onset is insidious
3- Patients may suffer from hepatosplenomegaly due to extramedullary infiltration and sequestration.
354
What is the epidemiology of myeloproliferative disorders?
Mainly affects middle-aged and older patients, with a peak incidence between 60-80 years.
355
What is the prognosis for myeloproliferative disorders?
May develop marrow fibrosis with time, and all disorders may progress to Acute Myeloid Leukemia (AML).
356
What is Polycythemia Vera?
A type of myeloproliferative disorder characterized by IAK-2 kinase activation and a gain of function mutation.
## Footnote
Mutation 70761721.
357
What is Polycythemia Vera?
A myeloproliferative neoplasm characterized by JAK-2 kinase activation, leading to increased RBCs, hemoglobin, and hematocrit.
358
What mutation is commonly associated with Polycythemia Vera?
JAK-2 V617F mutation (gain of function mutation).
359
What are the main clinical presentations of Polycythemia Vera?
Hypervolemia, hyperviscosity, headache, dizziness, hypertension, thrombosis, and bleeding.
360
What is aquagenic pruritus?
Itching after a hot shower due to histamine release from T basophils.
361
What is erythromelalgia?
A pathognomonic microvascular thrombotic complication characterized by erythema, pallor, cyanosis, and burning pain in extremities.
362
What is the treatment for erythromelalgia?
Aspirin, cooling, and leg elevation.
363
What is the median survival with treatment for Polycythemia Vera?
About 9 to 14 years.
364
What are the major criteria for diagnosing Polycythemia Vera?
1. Elevated Hb (men >16.5 g/dL; women >16.0 g/dL)
2. Bone marrow biopsy showing trilineage hypercellularity
3. JAK2 V617F or JAK2 exon 12 mutation.
365
What are the minor criteria for diagnosing Polycythemia Vera?
Serum erythropoietin level below normal.
366
What are the common causes of death in Polycythemia Vera?
Thrombosis, progression to AML, myelofibrosis, and bleeding.
367
What is the target hematocrit after treatment for Polycythemia Vera?
Less than 45%.
368
What is the relationship between Polycythemia Vera and gout?
Increased risk of gout due to high cell turnover.
369
What are some physical signs of Polycythemia Vera?
Plethoric complexion, palmar erythema, red face, and red conjunctiva.
370
What are the hemoglobin (Hb) and hematocrit (Hct) levels in males and females for polycythemia?
Hb > 18.5 in males / >16.5 in females
## Footnote
Hct > 70% indicates treatment is required.
371
What laboratory findings may be present in polycythemia?
May have high platelet (Plt) and white blood cells (WBCs), high Vitamin B12 but low iron, and low MCV.
372
What is the most accurate test for polycythemia?
The most accurate test is JAK2 mutation (in 95% of patients).
373
What does a bone marrow biopsy reveal in polycythemia?
Bone marrow biopsy reveals hypercellularity with increased proliferation of erythrocyte, granulocyte, and megakaryocyte precursors.
374
What is the first line of treatment to prevent thrombosis in polycythemia?
Venesection and low-dose aspirin.
375
What is used to lower cell count in polycythemia?
Hydroxyurea: myelosuppressant (Others: busulfan, subcutaneous alpha-INF injection).
376
What is the treatment for pruritis in polycythemia?
Antihistamines.
377
How can uric acid levels be decreased in polycythemia?
Allopurinol or rasburicase.
378
What is Anagrelide used for in polycythemia?
Anagrelide is a phosphodiesterase inhibitor that inhibits megakaryocyte differentiation.
379
What is Ruxolitinab used for in polycythemia?
Ruxolitinab is a JAK-2 inhibitor used if hydroxyurea fails.
380
What is reactive polycythemia?
Hemoconcentration or an elevation of hemoglobin or hematocrit due to decrease in plasma volume alone (without an increase in RBC mass).
381
What are common causes of reactive polycythemia?
The most common causes are diarrhea, vomiting, and poor oral intake.
382
What is Gaisbock's syndrome?
Classically described as polycythemia in a tense/anxious patient with hypertension, no splenomegaly, and reduced plasma volume.
383
Who is typically affected by Gaisbock's syndrome?
Usually middle-aged obese men, smokers, with high alcohol intake.
384
What is secondary polycythemia?
Increased RBC mass due to elevated erythropoietin.
385
What are hypoxia-associated causes of secondary polycythemia?
Chronic pulmonary disease, right to left shunts, sleep apnea, obesity hypoventilation syndrome, high altitude, chronic carbon monoxide poisoning.
386
What are tumor-associated causes of secondary polycythemia?
Autonomous production of EPO by hepatocellular carcinoma, renal cell carcinoma, hemangioblastoma, pheochromocytoma, uterine myoma.
387
What characterizes primary myelofibrosis?
Myeloproliferation in the bone marrow and bone marrow fibrosis.
388
What is primary myelofibrosis?
Primary myelofibrosis is a disease characterized by myeloproliferation in the bone marrow, atypical megakaryocyte hyperplasia, and bone marrow fibrosis.
389
What causes primary myelofibrosis?
It is caused by a gene mutation within hematopoietic cells that activates the JAK-STAT pathway.
390
What happens to the bone marrow in myelofibrosis?
In myelofibrosis, fibrous tissue replaces normal hematopoietic activity in the bone marrow.
391
What is the main role of bone marrow?
The main role of bone marrow is to produce erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets).
392
What is extramedullary hematopoiesis?
Extramedullary hematopoiesis is the migration of hematopoietic cells to the liver, spleen, and lungs in response to myelofibrosis.
393
What are the consequences of extramedullary hematopoiesis?
It can lead to enlarged tissues such as hepatomegaly and splenomegaly, and may cause pulmonary hypertension.
394
What is pancytopenia?
Pancytopenia is a shortage of all blood cell lines that can occur due to the inability of extramedullary hematopoiesis to compensate for the loss of bone marrow hematopoiesis.
395
What symptoms can arise from anemia in myelofibrosis?
Anemia can lead to fatigue, while low white cell count (leukopenia) can result in frequent infections.
396
What can extramedullary hematopoiesis lead to?
Hepatomegaly, splenomegaly, and pulmonary hypertension.
397
What are the effects of anemia in myelofibrosis?
Leads to fatigue and low white cell count (leukopenia), which can cause frequent infections.
398
What complications can excess platelets cause?
Thrombotic complications like deep vein thrombosis and pulmonary thromboembolisms.
399
What is the typical blood cell count pattern in myelofibrosis?
Initial increase in blood cells, particularly platelets, followed by a drop leading to pancytopenia.
400
What are common presentations of myelofibrosis?
BM fibrosis, massive hepatosplenomegaly, severe fatigue, weakness, weight loss, lethargy, low-grade fever, bone pain, night sweats, and pulmonary hypertension.
401
What are the causes of death in myelofibrosis?
Transformation to AML, progression of myelofibrosis, cardiovascular disease, and infection.
402
What does a blood film show in myelofibrosis?
Leucoerythroblastic picture with myelocytes, teardrop RBCs, and immature nucleated RBCs.
403
What does a bone marrow biopsy reveal in myelofibrosis?
High fibrosis; aspiration may not be obtainable (dry tap).
404
What mutation is present in 50% of myelofibrosis cases?
JAK2 mutation.
405
Is the Philadelphia chromosome present in myelofibrosis?
The Philadelphia chromosome is absent.
406
What are the treatments for myelofibrosis?
Thalidomide & lenalidomide (TNF inhibitors), Ruxolitinab (JAK-2 inhibitor), transfusion for anemia, allopurinol or rasburicase to decrease uric acid, and allogenic BM transplantation for younger patients (<50-55).
407
What indicates a fibrotic bone marrow in myelofibrosis?
The presence of immature cells and nucleated RBCs gives a leukoerythroblastic picture.
408
What is the role of Ruxolitinib in myelofibrosis treatment?
It is a JAK-2 inhibitor that suppresses myelofibrosis and relieves symptoms.
409
What is the initial blood cell count pattern in early myelofibrosis?
An initial increase in blood cells.
410
What is the potential cure for myelofibrosis?
Hematopoietic stem cell transplantation.
411
What is essential thrombocythemia?
A condition characterized by the production of an excessive number of platelets (>1000x10^9) that can lead to bleeding or thrombosis.
412
What is the primary mutation associated with essential thrombocythemia?
It is related to the JAK2 gene mutation.
413
When should essential thrombocythemia be treated?
Only if the patient is over 60 years old and has thrombosis or platelets greater than 1.5 million.
414
What is the best treatment for essential thrombocythemia?
Hydroxyurea is the best treatment.
415
What are other treatment options for essential thrombocythemia?
Busulfan, anagrelide, or IFN-a.
416
What is the diagnosis process for essential thrombocythemia?
Diagnosis is of exclusion, requiring differentiation from other causes of high platelets.
417
What are some differential diagnoses for high platelets?
1. Reactive thrombocytosis
2. Autoimmune rheumatic disorders
3. Splenectomy/hyposplenism
4. IBD/chronic infections/malignancy
5. PV/myelofibrosis/myelodysplasia
418
What are common manifestations of erythromelalgia in essential thrombocythemia?
Thrombosis (e.g., CVA) or less frequently, bleeding due to defective platelet function.
419
What additional findings may be present in essential thrombocythemia?
Splenomegaly, pseudohyperkalemia, elevated bleeding time, and burning pain and erythema of the extremities due to microvascular occlusions.
420
What does a peripheral blood smear show in essential thrombocythemia?
Hypogranular, abnormally shaped platelets.
421
What does a bone marrow biopsy reveal in essential thrombocythemia?
An increased number of megakaryocytes.
422
What percentage of essential thrombocythemia cases show a JAK2 mutation?
JAK2 tyrosine kinase mutation is seen in 40% to 50% of cases.
423
What is the role of thrombopoietin in platelet production?
Thrombopoietin binds to hematopoietic cell receptors, activating the JAK2 gene, leading to division and maturation into megakaryocytes and platelets.
424
What happens to the platelets produced in essential thrombocythemia?
Many of the platelets are misshapen, being large and dysfunctional.
425
What happens to excess platelets?
Many excess platelets end up being misshapen - they're large and irregularly shaped.
426
What is the risk associated with excess platelets?
Excess platelets cause an increased risk of blood clots in the deep veins of the legs, lungs, and even sites where clots don't usually form, like the abdomen.
427
What are the potential health risks from excess platelets?
Increased risk of stroke, heart attack, and miscarriage.
428
What is the risk if platelet count is extremely high?
If the number of platelets is over 1.5 million, there's an increased risk of bleeding.
429
What condition is discussed under 'Chronic Leukemia'?
Chronic Myeloid Leukemia.
430
What syndrome is mentioned?
Myelodysplastic Syndrome.
431
What is Myelodysplastic Syndrome?
A heterogeneous group of clonal, acquired malignant hematopoietic stem cell disorders characterized by ineffective hematopoiesis, increased apoptosis, increased marrow cellularity, and peripheral blood cytopenias.
432
What are the common features of Myelodysplastic Syndrome?
Abnormal morphology (dysplasia) in one or more cell lines, with a generally poor prognosis and increased risk of developing acute myeloid leukemia.
433
What is the typical demographic affected by Myelodysplastic Syndrome?
Mostly affects the elderly, with a median age of 70, and is slightly more common in men. Unusual before 50 years unless related to treatment.
434
What are potential causes of Myelodysplastic Syndrome?
Usually idiopathic, may be primary or secondary to chemicals (like benzene), chemotherapy, radiation, immunosuppressive agents, or genetic abnormalities.
435
How does the WHO classify Myelodysplastic Syndrome?
Into 7 categories based on the presence or absence of dysplastic features and the percentage of myeloblasts in peripheral blood and bone marrow.
436
What are the MDS types based on blast percentages?
MDS type 1: blasts 5-9%, MDS type 2: blasts 10-19%, All other types: blasts < 5%.
437
What percentage of MDS cases have cytogenetic and molecular abnormalities?
Approximately 50% of MDS cases.
438
What are common symptoms of Myelodysplastic Syndrome?
Often asymptomatic in early stages; may present with symptoms of pancytopenia, such as anemia, leucopenia, and thrombocytopenia.
439
What is the typical blood count pattern in Myelodysplastic Syndrome?
Anemia (with decreased reticulocyte count), thrombocytopenia, and neutropenia.
440
What are the clinical features of Myelodysplastic Syndrome?
Due to bone marrow failure, they mimic those of aplastic anemia.
441
What is the typical blood film finding in Myelodysplastic Syndrome?
Dysplastic features in one or more cell lines, including nucleated red blood cells, Pelger-Huet cells, and other evidence of dysplasia.
442
What is required for a definitive diagnosis of Myelodysplastic Syndrome?
Bone marrow aspirate and biopsy with cytogenetic analysis to reveal chromosomal abnormalities or mutated oncogenes.
443
What are some dysplastic features observed in bone marrow?
Dysplastic marrow cells with blasts or ringed sideroblasts, dysmyelopoiesis, and dyserythropoiesis.
444
What are the characteristics of dysplastic marrow cells?
Dysplastic marrow cells may present with blasts or ringed sideroblasts (Prussian blue iron stain).
445
What is dysmyelopoiesis?
Dysmyelopoiesis is characterized by nuclear-cytoplasmic asynchrony, abnormal cytoplasmic staining, and hypogranulation.
446
What is dyserythropoiesis?
Dyserythropoiesis involves multinucleated erythroblasts and abnormal nuclear shapes.
447
What percentage of blast cells may be seen in MDS?
Blast cells may be seen in less than 20% of cases.
448
What cytogenetic abnormality is associated with a better prognosis in MDS?
5q deletion is associated with a better prognosis.
449
What paradox is observed in MDS?
The paradox of peripheral pancytopenia and a hypercellular bone marrow reflects premature cell loss by apoptosis.
450
What is a common treatment for MDS?
Transfusion support with blood products as needed (RBC and platelet transfusions).
451
What is the response rate of erythropoietin in MDS treatment?
Erythropoietin gives about a 20% response and may help reduce the number of blood transfusions necessary.
452
What treatment is indicated for patients with 5q deletion?
Lenalidomide is indicated for those with the 5q deletion.
453
What is the recommended treatment for patients under age 50?
Bone marrow transplant is recommended for patients under age 50.
454
What adjunctive treatment can be effective for neutropenic patients?
Granulocyte colony-stimulating factor can be an effective adjunctive treatment.
455
Why is vitamin supplementation important in MDS?
Vitamin supplementation (particularly B6, B12, and folate) is important due to the increased turnover of marrow cells.
456
What treatments may improve survival in some MDS patients?
Chemotherapy and immunosuppressive agents may improve survival in some patients.
457
What is acute leukemia characterized by?
Acute leukemia is characterized by blast/immature cells and requires a bone aspirate smear to confirm the diagnosis: >20% blasts in the bone marrow.
458
How is acute leukemia classified by the type of WBC affected?
If granulocytes or monocytes are affected, myelogenous leukemia is present. If lymphocytes are affected, lymphocytic leukemia is present.
459
What distinguishes acute leukemias from chronic leukemias?
Acute leukemias progress rapidly and affect immature cells, while chronic leukemias progress slowly and affect mature cells.
460
What are common electrolyte disturbances in acute leukemia?
Common electrolyte disturbances include hyperuricemia, hyperkalemia, and hyperphosphatemia.
461
What are the signs and symptoms of bone marrow failure in acute leukemia?
Signs include anemia, thrombocytopenia, neutropenia (even with normal WBC), and infections/fever (e.g., recurrent sore throat/pneumonia).
462
What causes bone pain in acute leukemia?
Bone pain is caused by the accumulation of blast cells in the bone marrow and invasion of the periosteum.
463
What are extramedullary organ infiltrations in acute leukemia?
Extramedullary organ infiltrations can lead to hepatosplenomegaly, lymphadenopathy, skin nodules, and involvement of eyes, gums, and gonads.
464
What metabolic effects may occur in acute leukemia?
Increased uric acid can lead to nephropathy and gout, while the release of phosphate can decrease Ca2+ and Mg2+.
465
What is tumor lysis syndrome?
Tumor lysis syndrome is a complication of chemotherapy characterized by rapid cell death with release of intracellular contents, causing hyperkalemia, hyperphosphatemia, and hyperuricemia. It is a medical emergency.
466
What is a specific symptom of acute myeloid leukemia (AML)?
Gingival hypertrophy is more specific to AML.
467
What are specific symptoms of acute lymphoblastic leukemia (ALL)?
Specific symptoms of ALL include testicular enlargement, lymphadenopathy, and bone pain.
468
What is the risk associated with neutropenia in acute leukemia?
Increased risk of bacterial infections, such as pneumonia, urinary tract infection, cellulitis, pharyngitis, and esophagitis, which can be life-threatening.
469
What are the signs of thrombocytopenia in acute leukemia?
Signs of thrombocytopenia include epistaxis, bleeding at puncture sites, petechiae/purpura, and ecchymoses.
470
What neurological dysfunction may occur in acute leukemia?
Diffuse or focal neurologic dysfunction may occur, such as meningitis and seizures, due to CNS involvement.
471
What is Acute Myeloid Leukemia (AML)?
Clonal expansion of immature myeloid cells in bone marrow/blood/tissues, causing bone marrow failure.
472
What percentage of adult acute leukemias does AML account for?
80% of adult acute leukemias.
473
What percentage of childhood leukemias does AML account for?
20% of childhood leukemias (under 15 years old).
474
How does the response to therapy in AML compare to acute lymphoblastic leukemia?
Response to therapy is not as favorable as in acute lymphoblastic leukemia.
475
What are some clinical features of AML?
Skin nodules, gingival hypertrophy, hepatosplenomegaly, excessive fibrinolysis, and DIC.
476
What is a key aspect of the pathogenesis of AML?
Loss of function of transcription factors needed for differentiation leads to a differentiation block.
477
What mutations contribute to AML pathogenesis?
Gain of function mutations of tyrosine kinases lead to enhanced proliferation.
478
What are some risk factors for developing AML?
Exposure to ionizing radiation, previous chemotherapy (e.g., alkylating agents), exposure to chemicals (e.g., benzene), myeloproliferative syndrome, Down syndrome, and viral infections.
479
What are common findings in a Complete Blood Count (CBC) for AML?
Uni/bi/pancytopenia with WBCs being high, normal, or low.
480
What is observed in a blood film for AML?
Blast cells characterized by high N:C ratio and fine chromatin.
481
What are Auer rods?
Intracytoplasmic eosinophilic inclusions within blast cells that are pathognomonic of AML.
482
What stains are positive in AML?
Sudan black and myeloperoxidase positive.
483
What does a bone marrow aspirate show in AML?
Increased cellularity with a high percentage of abnormal blast cells.
484
What is the purpose of immunophenotyping in AML?
To distinguish the lineage (i.e., AML vs. ALL) and differentiation of blasts.
485
What are the markers for myeloblasts?
CD13, CD33, and MPO.
486
What are the markers for megakaryoblasts?
CD41 and CD61.
487
What is the marker for erythroblasts?
Glycophorin A.
488
What is the marker for monoblasts?
CD14.
489
What does cytogenetic and genotyping analysis detect in AML?
Chromosomal abnormalities, clonality, and subclassification that affect treatment and prognosis.
490
What are some chromosomal abnormalities associated with AML?
t(8;21) → AML1, t(15;17) → PML/RARA, and inversion 16 → MYH-11/Cbfb.
491
What gene is associated with the chromosomal rearrangement t(8;21)?
RUNX1/RUNX1T1.
492
What gene is associated with the chromosomal rearrangement t(15;17)?
PML/RARA.
493
What gene is associated with the chromosomal rearrangement inv(16)?
MYH-11/CBFB.
494
What is Acute Promyelocytic Leukemia (APL)?
A variant of Acute Myeloid Leukemia (AML) accounting for 10-15% of cases, characterized by cytogenetics t(15;17).
495
What are common presentations of Acute Promyelocytic Leukemia?
May present with pancytopenia and is associated with coagulopathy (DIC) in almost all cases.
496
What is the major cause of early death in APL?
Coagulopathy (DIC) due to the release of procoagulant/profibrinolytic factors from blast cells.
497
What treatment must be combined with APL therapy?
All-trans-retinoic acid (ATRA) must be combined with the treatment.
498
What are the two main prognostic factors in AML?
Age and cytogenetics.
499
What are good prognostic factors in AML?
Favorable cytogenetics: t(15;17), t(8;21), inv(16), and NPM1 mutation with normal FLT3.
500
What are poor prognostic factors in AML?
Adverse cytogenetics (e.g., chromosome 5 del (5q), 7 del, complex karyotype), minimal residual disease positivity after chemotherapy, FLT3 mutation, secondary disease, age >60, male gender, and high WBC.
501
How is AML initially treated?
Treated with chemotherapy to induce remission, removing blasts from the peripheral blood smear and restoring normal hematopoiesis.
502
What is the complete remission rate for patients <60 y/o with intensive therapy?
80% of patients <60 years old achieve complete remission.
503
What is the treatment approach for good prognosis AML?
Induction chemotherapy (Daunorubicin & cytarabine) followed by consolidation chemotherapy.
504
What is the treatment approach for poor prognosis AML?
Induction of complete remission followed by allogenic transplantation, with no need for consolidation chemotherapy.
505
What is the overall cure rate for AML?
40% overall, with 60-70% in those with favorable cytogenetics and 10-20% in those with adverse cytogenetics.
506
What supportive treatments are necessary in AML?
Antibiotics for infection, blood transfusion for anemia, and platelet transfusion for bleeding.
507
What characterizes leukemia?
Neoplastic proliferation of abnormal WBCs that interfere with the production of normal WBCs, erythrocytes, and platelets, resulting in anemia and thrombocytopenia.
508
What characterizes leukemia?
Leukemias are characterized by neoplastic proliferation of abnormal WBCs, which interfere with the production of normal WBCs, erythrocytes, and platelets, resulting in anemia and thrombocytopenia.
509
How are leukemias classified?
Leukemias are classified by the type of WBC affected and by the maturity of the cell affected and the rapidity of disease progression.
510
What are the types of leukemia based on WBC affected?
1. Myelogenous leukemia (if granulocytes or monocytes are affected)
2. Lymphocytic leukemia (if lymphocytes are affected)
511
What are the types of leukemia based on cell maturity?
1. Acute leukemia (rapid progression, affects immature cells)
2. Chronic leukemia (slow progression, affects mature cells)
512
What characterizes acute leukemia?
Acute leukemia is characterized by the circulation of immature cells.
513
What characterizes chronic leukemia?
Chronic leukemia is characterized by the circulation of mature cells.
514
What are the three types of lymphocytes in lymphoid leukemia?
1. B-cells
2. T-cells
3. NK cells
515
What is Acute Lymphocytic Leukemia (ALL)?
ALL is characterized by clonal expansion of immature lymphoid cells, leading to an increase in lymphoblasts.
516
What is the pathogenesis behind ALL?
A mutation occurs in precursor T/B lymphocytes leading to maturation arrest of immature cells through:
1. Enhanced tyrosine kinase activity
2. Inactivation of tumor suppressor gene
3. Activation of proto-oncogenes into an oncogene.
517
What is the typical patient demographic for ALL?
ALL is mostly seen in children, is the most common type of malignancy in childhood, with a higher risk in males and those with Down syndrome.
518
What are the symptoms of ALL?
Symptoms include infections, lymphadenopathy, testicular enlargement, splenomegaly, bone pain, arthralgia, and may present with meningeal signs.
519
What are common investigation findings in ALL?
Common findings include increased leukocytes (>10x10^9/L), neutropenia, anemia, and thrombocytopenia.
520
How is ALL subdivided?
ALL is subdivided depending on the cell of origin into B-cell and T-cell.
