Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Med 1 UBC Winter 2020 > Week 23-4: Anemia, Bleeding Disorders and Hematologic Neoplasms > Flashcards

Week 23-4: Anemia, Bleeding Disorders and Hematologic Neoplasms Flashcards

1
Q

Most common causes of iron deficiency anemia (3)

A

BLOOD LOSS is #1

Iron-poor diet

Malabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Significance of iron deficiency anemia

A

most common nutritional deficiency in N America. Affects 20% of pre-menopausal women and 50% of pregnant women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Biochemical findings in iron deficiency

Serum Iron

Serum transferrin (TIBC)

%Saturation of transferrin

Ferritin

Free erythrocyte protoporphyrin

A

Serum Iron - low

Serum transferrin (TIBC) - high

%Saturation of transferrin - low

Ferritin - low

Free erythrocyte protoporphyrin - high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Hematologic findings in iron deficiency

Hemoglobin

MCV

MCH (mean corpuscular hemoglobin)

Peripheral blood smear

Platelet count

A
  • Hemoglobin - low
  • MCV - low
  • MCH (mean corpuscular hemoglobin) - low
  • Peripheral blood smear - small cells of varying sizes, hypochromatic; pencil cells
  • Platelet count - high
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cause of hemochromatosis and how does it work?

A
  • genetic disorder with autosomal recessive inheritance.
  • Caused by a mutation that reduces hepcidin expression.
  • This means that iron may more freely exit cells via ferroportin.
  • Iron builds up in parenchymal cells of liver, heart, pancreas and other tissues. Build up over time and symptoms arise later in life.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Lab findings for hemochromatosis Serum Iron Serum transferrin (TIBC) %Saturation of transferrin Ferritin

A

Serum Iron - High Serum transferrin (TIBC) - Low %Saturation of transferrin - High Ferritin - High

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Causes of B12 deficiency (4)

A

poor nutrition (vegans)

Pernicious anemia

Total or partial gastrectomy

Intestinal disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Causes of folate deficiency

A

poor nutrition (elderly, poverty, alcoholic)

Increased utilization of folate (pregnancy, lactation, malignancy, inflammation, hemolytic anemia)

Intestinal disease;

Drug Induced (i.e., anticonvulsants);

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 3 major components of the RBC?

A
  1. membrane (needs ot be tough and have a large SA) 2. Hb (responsible for on/offloading of oxygen) 3. Enzymes (need to have enough enzymes to look after the cell for its 120 day life because RBCs don’t have DNA to make more)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hemolytic Anemia - characteristics (3)

A
  • ANEMIA - decreased Hb concentration;
  • JAUNDICE - increased red cell breakdown (causing hyperbilirubinemia and cholelithiasis)
  • SPLENOMEGALY - increase bone marrow compensation (leading to reticulocytosis and splenomegaly)

should also see reticulocytosis if the BM is properly compensating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cause of hemolytic anemia

A

MALARIA is the major genetic driving force.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Causes and distribution of hereditary spherocytosis

A
  • mutations in RBC membrane support proteins: ankyrin, spectrin, Band 3, and protein 4.2.
  • Mostly autosomal dominant with some more serious autosomal recessive variants. More prevalent in N Europeans.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pathology in hereditary spherocytosis

A
  • Mutations to membrane support proteins (ankyrin, spectrin, Band 3, or protein 4.2) make RBCs fragile.
  • Cells are fragile and lose SA - become spherocytes.
  • RBCs experience ‘splenic conditioning’ which refers to progressive loss of membrane each time the spherocytes try to squeeze through splenic vasculature (EXTRAVASCULAR hemolysis). The spherocytes are rigid and lyse easily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Symptom triad in hereditary spherocytosis and critical symptoms that may occur

A

anemia, jaundice, splenomegaly

critical symptoms: aplastic crisis, choliesthasis, massive splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Diagnosis of hereditary spherocytosis

A
  • blood smear (for spherocytes and polychromasia)
  • osmotic fragility test (in vitro hemolysis with decreasing NaCl concentration)
  • Flow cytometry (best; most diagnostic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Management of Hereditary spherocytosis (2)

A
  • supportive treatment (folic acid, spleen protection)
  • splenectomy is a symptomatic cure but it comes with complications and must be met with immune prophylaxis because losing the spleen severely compromises the immune system.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the hemoglobinopathies?

A

Beta-Thalassemia Major and Sickle Cell Anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Distribution of hemoglobinopathies

A

High incidence in southern europe (italy, greece), middle east, south asia, south east asia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is B Thalassemia Major?

A
  • Mutation in the beta-globin gene. Decreased beta-globin production results in imbalanced alpha : beta globin pairing. Excess alpha chains precipitates damage to RBC membranes.
  • Ineffective erythropoiesis
  • Severe anemia, bone marrow expansion, and hepatosplenomegaly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

major characteristics of beta thalassemia major

A
  • Severe anemia
  • bone marrow expansion (characteristic changes to physical appearance of patients)
  • hepatosplenomegaly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

distribution of beta thalassemia

A

High numbers of carriers in S mediterranean, middle east, N Africa, S Asia, SE Asia, and S China.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Treatment of B-Thalassemia

A
  • Regular transfusions required for B Thal Major. Starting around 6-12 months old (after fetal Hb has dissipated).
  • Regular transfusions (ever 3-4 wks) lead to high iron deposition so iron chelation therapy begins after 10-20 transfusions.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Complications associated with B Thalassemia (5)

A
  • Bone marrow expansion (leads to osteoporosis)
  • Endocrine failure
  • Transfusion hemosiderosis (leads to CHF, liver cirrhosis and liver CA)
  • Transfusion-related complications (i.e., infections, transfusion reactions)
  • Psycho-social impact
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Diagnosis of B thalassemia

A

Hemoglobin electrophoresis;

HIgh performance liquid chromatography;

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Distribution of sickle cell anemia

A

Sub-saharan afric and also seen in middle east, south Europe and Indian subcontinent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Cause and pathology of sickle cell anemia (6)

A
  • SIngle gene mutation.
  • The mutated HbS polymerizes when deoxygenated, causing RBC to be stiff and deformed (sickled).
  • Sickle cells sludge in capillaries, leading to recurrent infarctions (especially in spleen, BM, kidneys).
  • Sickle cells lyse (intravascular hemolysis).
  • Damaged RBCs are adherent to vessels and can cause proliferative vasculopathy, which may lead to a stroke.
  • Drop in NO associated with hemolysis leads to increased vascular tone and HTN.
    *
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Complications of sickle cell disease (8)

A
  • Infections (hyposplenism, encapsulated bacteria)
  • Vaso-occlusive crises (very painful, common in long bones, back, abdomen)
  • Acute chest syndrome (due to sickling in lungs)
  • Stroke
  • Kidneys - hyposthenuria (refers to damage to countercurrent multiplier system that results in increased urination and dehydration)
  • pulmonary hypertension
  • aplastic crises (with parvovirus B19 infection)
  • spenic sequestration crisis (need urgen transfusion)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Diagnosing sickle cell disease (2)

A

Sickedex screen;

Hb electrophoresis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Management for sickle cell disease (5)

A
  • Supportive care (hydration and pain control);
  • Prevent and treat infections;
  • Drug (hydroxyurea) to elevate numbers of fetal hemoglobin.
  • Blood transfusions with care not to over transfuse because hyperviscosity can worsen pathology.
  • Gene therapy.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

The two major enzymopathies

A

GDPD (glucose-6-phosphate dehydrogenase) and PK (pyruvate kinase) deficiencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Pathology of G6PD deficiency

A

Shortened half-life of G6PD enzyme results in reduced glutathione availability. GLutathione is a major antioxidant. Without glutathione, Hb is oxidated and RBC membrane is subjected to oxidative damage, ultimately leading to hemolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Cause of G6PD deficiency

A

Sex-linked inheritance of the mutation - more common in boys.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

oxidative challenge in G6PD deficiency

A

Things that cause oxidative stress on cells exacerbate pathology of G6PD deficiency. Oxidative challenges include some infections, drugs, fava beans, moth balls.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What do RBCs look like in G6PD deficiency?

A
  • Bite cells and blister cells.
  • Intravascular hemolysis due to instability of the cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How may G6PD present?

A

Neonatal jaundice;

Episodic or chronic hemolysis.

  • especially with oxidative challenges (infections, drugs, fava beans)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Diagnosis of G6PD deficiency

A

Enzyme assay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

management of G6PD deficiency

A
  • avoid fava beans and oxidizing drugs
  • vigilance during severe infections
  • Treat acute hemolysis with hydration alkalinization and possibly packed RBC transfusion.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Pathology of pyruvate kinase deficiency

A
  • Pyruvate kinase is key in the rate-controlling step of glycolysis. Deficient PK undermines ATP production in RBCs.
  • ATP depletion in cells results in morphological changes to cells (they get spiky) and eventual hemolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Tolerance of anemia in PK deficiency

A

PK deficiency is associated with improved oxygen offloading from Hb, so pts with PK deficiency tolerate their anemia relatively well.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Symptoms of PK deficiency (3)

A
  • Neonatal jaundice;
  • life long anemia (but well tolerated);
  • Mild jaundice, cholelthiasis;
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Management of PK deficiency

A
  • Supportive;
  • Splenectomy not usually helpful;
  • Transfusion may be needed at times of BM suppression.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Senile Purpura

A
  • A bruising/bleeding problem of the vasculature - Age-dependent deterioration of the vascular supporting structure, leading to bruising on the Dorset of the hands and forearms - no serious bleeding - can also be induced by longterm endogenous or exogenous steroid exposure.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Von Willebrand Disease

A
  • A bleeding disorder caused by inherited defects in the concentration, structure or function of von Willebrand factor.
  • Type 1 (reduced VWF; common)
  • Type 2 (dysfunctional VWF protein; rare)
  • Type 3 (absolute deficiency of VWF; extremely rare).
  • mostly autosomal dominant with variable penetrance (can be recessive)
  • Prevalence 1:1000 to 1:10,000
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are the three types of VWF disease?

A
  1. Type 1 - reduced VWF protein (most common)
  2. Type 2 - dysfunctional VWF protein (uncommon)
  3. Type 3 - no VWF protein (Coagulation factor VIII suffers because it lacks protection from VWF carrier protein; extremely rare)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

How do each of the VW disease types present?

A

Type 1 & 2 - mucocutaneous bleeding

Type 3 - severe mucocutaneous bleeding. May see joint/muscle bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Hemophilia

  • what is it, what are the two types, and how is it acquired?
A
  • An inherited bleeding disorder with mild, moderate or severe deficiency of a coagulation factor.
  • Hemophilia A = Factor VIII deficiency (1:10,000 births)
  • Hemophilia B = Factor IX deficiency (more rare) X-linked recessive inheritance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Pathophysiology of hemophilia and how that will present in a pt

A
  • This is a coagulation factor problem.
  • Deficiency of Factor VIII (A) or IX (B) undermines the clotting cascade. So the Extrinsic pathway is still functional, but clotting cascade through the Intrinsic pathway is non-functional. This means that thrombin is only generated slowly
  • pt will experience prolonged bleeding after injury with weak, fragile clots that are prone to re-bleeding.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Explain the graded presentation of hemophilia

A

Hemophilia can present as mild to severe bleeding. The amount of coagulation factor protein made is directly linked to the severity of bleeding. At severe levels the pt experiences spontaneous bleeding starting at a young age. In mild presentation the bleeding my only arise with trauma or surgery and impairment may not be evident until adulthood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

3 coagulation factor problems that are acquired

A

Liver disease; Anticoagulants (i.e., heparin or warfarin); Vitamin K deficiency;

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

How does liver disease cause bleeding issues

A

It’s a coagulation factor problem because coagulation factors are produced in the liver. Patients will present with mildly exaggerated bleeding because the liver can compensate to an extent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How can anticoagulants lead to bleeding issues?

A

It’s a coagulation factor problem. Severe bleeding results from overdose, trauma, or procedures. The bleeding can be severe or life-threatening.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

How does Vitamin K deficiency lead to a bleeding disorder?

A

Vitamin K is an important cofactors in the synthesis of several coagulation proteins. Vit K deficiency will lead to mild bleeding disorder.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Treating senile/steroid purpura?

A

No specific treatment. Limit exposure to steroids; Caution with respect to the delicate skin; Recognize that aspirin, anti-inflammatories and anti-coagulants may worsen bleeding;

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Treatment for Von Willebrand Disease

A
  1. Administer DDAVP to promote release of endogenous VWF stores. This can usually yield a 3-5 fold rise in VWF and Factor VIII levels in Type 1 VWF, but is not effective in a qualitative and absolute VWF deficit (I.e., not helpful in Type 2 or 3).
  2. Administer exogenous VWF and Factor VIII. Plasma derived VWF-VIII concentrate of a VWF recombinant (lacking VIII). Given for Type 2 and 3 VWF disorder. Administered by IV with half life of 8-12 hours.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Two major ways that cancer kills

A

Systematically… by consuming nutrients and energy that the body needs to survive (“Cachexia”). Locally… by injuring or impairing critical organ functions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Derivatives of myeloid stem cells

A

Granulocytes, erythrocytes, monocytes, and megakaryocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Derivatives of lymphoid stem cells

A

B cells (plasma cells) and T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What are Lymphoid neoplasms?

A

Neoplasms arising in Lymphoid tissue Usually a lymph node, but can be in extranodal tissue or in the BM. Most often presents with an enlarged lymph node (lymphoma = lumps). Cannot be cured surgically. Requires chemotherapy +/- radiation. Hodgkin and Non-Hodgkin types. Non-hodgkin can be B or T cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Pathology of acute leukemia

A

The mutation leads to maturation arrest, relentless cell division and immortality of cells. Malignant blasts fill the marrow space and spill out into the peripheral blood. Leads to suppression of normal hematopoiesis, which causes cytopenias or pancytopenia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

How might acute leukemia present in patients?

A

Acute leukemia lead to various cytopenias. Patients will have complaints related to low cells counts. Ex: anemia –> fatigue thrombocytopenia –> weird bruises, petichiae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

“acute” leukemia refers specifically to what feature of the cancer?

A

The fact that all of the cells are blasts (whether they are myeloid or lymphoid blasts)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

If a 1:1 mixing study comes back with a normal INR, what does that suggest?

A

It suggests that the pt has a coagulation factor deficiency rather than an issue with inhibition of a coagulation factor. Usually it’s Factor 8 that is deficient, because that is more common (Hemophilia A).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

If a 1:1 mixing study comes back with a prolonged INR, what does that suggest?

A

It suggests that the prolonged INR is due to some form of inhibition of coagulation factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is a 1:1 mixing study used for?

A

To determine if a prolonged INR is due to a deficiency of coagulation factors or inhibition of coagulation factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Presentation of AML

A

Symptoms related to pancytopenia (fatigue, bruising/bleeding, infections, etc) Constitutional (“B” symptoms), which include: fevers, drenching night sweats, weight loss >10% in 6 mo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

How does Warfarin increase clotting time?

A

Warfarin is a vitamin K antagonist. Vitamin K is a critical cofactor in production of many coagulation factors. Warfarin therefore interferes with both the intrinsic and extrinsic coagulation pathways, leading to increased clotting time.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Tumor Lysis Syndrome When does it occur? What is it?

A

An emergent presentation of AML. Can also occur when you start chemo. As cells start breaking down, they release DNA into the blood. Purines from DNA release uric acid, which is toxic to the kidneys at high levels and can lead to renal failure. Protein breakdown can also contribute to the renal failure. Further, K release from the cells can lead to cardiac arrhythmias and neuromuscular irritability.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Definition of Leukemia

A

A malignancy of hematopoietic stem cells arising in the bone marrow, in which the (normal) bone marrow is almost entirely replaced. Leukemia can be acute or chronic. In acute all cells are blasts and in chronic the leukemia cells are more mature.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What is acute myeloid leukemia?

A

A myeloid malignancy of WBCs, in which all malignant cells are blasts. It is the result of mutations in a hematopoietic stem cell. Classified based on what mutation is present.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

In whom is AML more common?

A

More common in adults than children

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is the prognosis for AML

A

prognosis depends on the mutations that are present.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Cause of acute leukemia

A

Mutation in a hematopoietic stem cell, usually idiopathic, but can be due to radiation or chemical exposure. Rarely there is a genetic predisposition.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Prognosis for acute myeloid leukemia (AML)

A

generally worse than ALL (acute lymphoid leukemia). It is worse for older patients and more complex mutations. Cure is about 40% with intensive chemotherapy +/- stem cell transplant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

pancytopenia

A

Low RBCs, neutrophils, and platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Lab findings in Acute Myeloid Leukemia

A

Pancytopenia (low RBCs, low neutrophils, low platelets) ; HIGH WBC count due to many circulating blasts;

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What are Auer rods (on blood film)

A

Red needle-like includion within the cytoplasm of some acute myeloid leukemia blasts. These are pathognomic of AML!! But now every AML case has them. So if we see Auer rods it’s definitely AML, but if we don’t seem them it still could be AML.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Clinical Presentation of ALL

A

Very similar to AML. - Symptoms of pancytopenia (fatigue, bruising/bleeding, infections, etc) - Constitutional (“B” Symptoms): fevers, drenching night sweats, weight los > 10% in 6 mo ALSO (unique to ALL) - palpable lymph nodes - CNS involvement (headaches, numbness)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Prognosis of ALL

A

Very good in children! 85% cure rate with intensive chemo over 2 years. Must consider long term treatment effects (CNS radiation). Adults are harder to treat. Cure rate is less than 40% even with stem cell transplant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Presentation of AML

A

Symptoms related to pancytopenia (fatigue, bruising/bleeding, infections, etc) Constitutional (“B” symptoms), which include: fevers, drenching night sweats, weight loss >10% in 6 mo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Emergency Presentation of AML

A
  • Tumor lysis syndrome (TLS) - Hperviscosity Febrile neutropenia DIC (disseminated intravascular coagulation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Workup for MDS

A

CBC (normal to low cell counts due to cells being held in BM);

Peripheral blood smear (bilobed neutrophils, large and dysplastic RBCs);

Rule out other causes of macrocytosis (B12, folate, TSH);

Bone marrow aspirate and biopsy: Bone marrow is hypercellular with dysplastic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Hyperviscosity

A

An emergent complication of AML. This happens when the blast count is very high. Blasts are BIG so they are good at clogging blood vessels. The pt may experience mucosal bleeding, visual changes, neurologic symptoms (headache, decreased LOC), dyspnea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

How would you respond to hyperviscosity presentation of AML?

A

Urgent chemotherapy, avoid RBC transfusion, may need leukapheresis (remove WBCs). ALl with the goal of decreasing blood viscosity asap.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Prognosis of MDS

A

Possible transformation to AML - worst possible complication because the AML that arises from MDS is worse and harder to treat than de novo AML.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Acute Promyelocytic Leukemia

A

An acute myeloid leukemia with a translocation at t(15 ; 17). This one has a good prognosis but also is prone to complication with DIC, which has a high mortality rate in first 48 hours.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Treatment for AML

A

Depends on their age and how sick they are. For younger/fit pts: multiple rounds of intensive chemo +/- stem cell transplant aiming for cure Older/unfit pts: palliative treatment such as gentler chemo, novel drugs, clinical trials Supportive care (RBC and platelet transfusions, treat infections, lower blast count

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

HLA tissue typing

A

We look for a 10/10 match when donating bone marrow. Full siblings have a 25% chance of being a match. Parents can only ever be a 50% match. There are also stem cell drives that have tons of people tested to see if there is an unrelated donor match out there. The chance of finding a match is much better for caucasian people.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Define Acute Lymphoid Leukemia (ALL)

A

A lymphoid malignancy arising in WBCs, in which all malignant cells are blasts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

In whom is ALL more common?

A

More common in children than adults, and is THE MOST COMMON MALIGNANCY IN CHILDREN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Pathology of ALL

A

A lymphoid stem cell undergoes a mutation in the bone marrow that makes it immortal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Clinical Presentation of ALL

A

Very similar to AML. - Symptoms of pancytopenia (fatigue, bruising/bleeding, infections, etc) - Constitutional (“B” Symptoms): fevers, drenching night sweats, weight los > 10% in 6 mo ALSO (unique to ALL) - palpable lymph nodes - CNS involvement (headaches, numbness)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Prognosis of ALL

A

Very good in children! 85% cure rate with intensive chemo over 2 years. Most consider long term treatment effects.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Define Myelodysplastic Syndromes

A

These are clonal disorders that lead to: - Ineffective myeloid hematopoiesis - Dysplasia Must have <20% balsts in blood ( >20% is automatically AML) Has the potential to transform into AML. Often considered a pre-leukemia state, but not all AMLs start with MDS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

Lab findings for MDS

A

Pancytopenia: cells are being produced but they can’t exit BM into peripheral blood. Dysplasia: found on peripheral blood smear; super odd neutrophils (bilobed; John Lennon); RBC macrocytosis and dysplasia.

95
Q

Workup for MDS

A

CBC (normal to low cell counts due to cells being held in BM); Peripheral blood smear (bilobed neutrophils, large and dysplastic RBCs); Rule out other causes of macrocytosis (B12, folate, TSH); Bone marrow aspirate and biopsy: Bone marrow is hypercellular with dysplastic cells

96
Q

Risk factors for MDS

A

Older age (rare under age 50); Exposure to organic compounds (e.g., benzene); Exposure to prior chemo or radiation therapy; Cigarette smoking;

97
Q

Presentation of MDS

A

Fatigue, bleeding, infections due to pancytopenia.

98
Q

Prognosis of MDS

A

Possible transformation to AML - worst possible complication because the AML that arises from MDS is worse and harder to treat than de novo AML.

99
Q

Where can stem cells be sourced?

A

Bone marrow (harvested in the OR); Peripheral blood (more common now); Umbilical cord (public and private cord banks);

100
Q

The two kinds of stem cell transplants

A

Autologous (from own blood); Allogenic (another person’s blood, umbilical cord)

101
Q

HLA tissue typing

A

We look for a 10/10 match when donating bone marrow. Full siblings have a 25% chance of being a match. Parents can only ever be a 50% match. There are also stem cell drives that have tons of people tested to see if there is an unrelated donor match out there. The chance of finding a match is much better for caucasian people.

102
Q

What would a PT and PTT show in a hemophilia?

A

The PTT would be abnormal but a PT/INR would be normal. This is because the PTT tests the intrinsic pathway, which includes Factor 8 and 9. PT only tests the extrinsic pathway.

103
Q

4 stages of RBC development (after hematopoietic stem cell)

A

Proerythroblast: committed to being an RBC; wearing EPO receptors

Normoblast: last nucleated stage

Reticulocytes: Expel nucleus and then move into the peripheral blood 2 days later, where they extrude other organelles

Mature RBC: 24 hours after going into the peripheral blood

104
Q

Erythropoietin

A
  • Regulates formation and release of RBCs
  • Secreted by the kidney >> liver
  • Increases at high altitude
  • Interacts with receptors on proerythroblasts
105
Q

3 major components of RBCs

A
  • membrane
  • hemoglobin
  • enzymes
106
Q

Membrane proteins on RBCs (5)

A

Integral membrane proteins:

  • Glycophorin C - maintains cell shape
  • Band 3 - prevents membrane surface loss/damage during travels

Peripheral membrane proteins:

  • Spectrin - maintains cell shape
  • Protein 4.2 - anchor cytoskeleton to integral membrane proteins
  • Ankyrin - anchor cytoskeleton to integral membrane proteins (band 3)
107
Q

How is hemoglobin synthesized?

A

Synthesized by reticulocytes before they go into peripheral blood. They make almost all of the Hb they’re ever going tohave at this time, with some residual rRNA making a little more birefly after entering vasculature.

108
Q

Structure of hemoglobin

A

4 globins and 4 hemes

globins surround and protect the heme. Globins are usually 2alpha and 2beta (HbA).

heme is a porphyrin ring that contains Fe, which reversibly binds O2.

109
Q

Describe erypoptosis and parts recycling

A
  • RBCs die after about 4 months because their membranes get too old
  • SPlenic macrophages phagocytose old RBCs in the spleen and liver.
  • Globins broken into AAs that are reused
  • Heme extremed with bilirubin
  • Iron brought back to BM by transferring to be reuused in synthesis of more Hb
110
Q

What is the pentose phosphate pathway and its significance in anemia

A
  • The process of RBC taking up glucose and converting it to 6-phosphogluconate. The process produces reduced glutathione, which is a key antioxidant in the RBC.
  • The process requires the enzyme G6PD
  • People who are G6PD deficient will have hemolytic anemia due to inability of RBCs to withstand oxidative stress
111
Q

G6PD deficiency

A
  • Most common cause of enzyme-deficienct hemolytic anemia
  • x-linked, variable expression
  • Pt unable to produce as much reduced glutathione (antioxidant), which causes RBCs to be prone to lysis in states of oxidative stress (aspirin, fava beans)
112
Q

Describe the importance of pyruvate kinase in RBCs and what happens when it is deficient

A
  • Pyruvate kinase is a key enzyme in glycolysis. RBCs don’t have mitochondria so they rely on glycolysis for ATP production.
  • In pyruvate kinase deficiency, RBCs can’t make enough ATP so they lyse –> hemolytic anemia
    *
113
Q

A high reticulocyte count suggests what kind of anemia?

A

A blood loss or hemolytic anemia (not an anemia due to decreased RBC production)

114
Q

explain what is meant by an inappropriately normal reticulocyte count in the context of anemia?

A

the BM can compensate for reduction in RBCs due to blood loss or hemolysis. The BM should compensate by making more RBCs, which should increase peripheral reticulocyte counts. A normal retic count suggests that the body isn’t compensating - worrying.

In an inappropriately normal retic count (i.e., normocytic but no increased reticulocytes), we suspect decreased RBC production in BM.

  • intrinsic issue:
    • nutrient deficiency: B12, ferritin, iron, folate
    • Trophic factor deficiency: EPO androgen (check creatinine)
    • suppression: Inflammation (check CRP)
  • Extrinsic BM limitation: Do a BM biopsy
    • Abnormal cell development (MDS, leukemia, aplastic anemia, RBC aplasia)
    • Marrow replacement (malignancy, myelofibrosis, infection)
115
Q

Absorption of Iron and 4 important proteins involved in its absorption and transport

A
  • Fe absorbed in intestine
  • Ferric reductase converts Fe3+ to Fe2+ so that it can be taken in at the apical surface
  • Ferroportin transports Fe2+ on the basolateral surface so that iron can get into the blood
  • Hephaestin is a basolateral membrane protein that converts Fe 2+ back to Fe3+ before it heads off to the BM via transferrin
116
Q

Iron storage in the body: Where is it and 2 important proteins

A
  • 2/3 body iron stored in Hb
  • The rest of the body’s iron is in the liver, BM, and spleen and other tissues
  • Ferritin is a holow protein ball that can hold up to 4500 Fe atoms. Low ferritin is therefore diagnositc for iron deficiency
  • Hemosiderin is an insoluble complex or iron. This means it lasts longer, but it is more difficult to liberate iron from hemosiderin.
117
Q

Major causes of anemia in developing countries and at-risk populations in canada

A

Iron, folate, and B12 deficiences

118
Q

How does B12 or folate deficiency cause anemia?

A
  • B12 is a cofactor for turning folate into its usable form (THF) in cells. We need that usable form of folate for RBCs to synthesize DNA
  • In B12/folate deficiency, erythroblasts in BM have delayed nucleus maturation because DNA synthesis is defective
  • The ultimate result is megaloblastic anemia
119
Q

megaloblastic anemia

A
  • caused by B12 or folate deficiency
  • Cells can’t make enough DNA to divide so RBCs get really big and variable in size/shape
  • ANemia because there just aren’t enough RBCs out there.
120
Q

What is the role of malaria in RBC disorders?

A

It is the driving force for inherited RBC disorders

121
Q

What might you see on a blood smear of B Thalassemia Major

A
  • Microcytic, hypochromatic RBCs
  • Target cells
  • Basophilic stippling of RBCs
122
Q

What are the cardinal symptoms of anemia

A
  • Fatigue
  • Dyspnea/chest pain on exertion
  • Jaundice (hemolytic)
  • Splenomegaly (hemolytic)
123
Q

What are the characteristics of all microcytic anemias?

A
  • RBC underfilling due to abnormalities in iron, heme, or globin
  • Cells are hypochromic and microcytic (MCV < 80)
124
Q

What is the differential for microcytic anemia and how can we tell them apart?

A

we always need to rule out occult bleeding

  • Thalassemia Trait - results from reduced globin production
    • Ferritin is normal
    • Diagnose with serum protein electrophoresis
  • Iron deficiency - results from low iron availability
    • Ferritin < 15
  • anemia of chronic disease - results from reduced iron availability
    • Cardinal feature: MCV is only slightly reduced and anemia tends to be mild
    • Ferritin is normal to high
    • CRP for diagnosis
125
Q

What may schistocytes mean?

A

microangiopathic hemolytic anemia (related to DIC);

126
Q

What tests would you do for a normocytic anemia with a high reticulocyte count?

A

We suspect bleeding or hemolysis.

For bleeding check

  • ferritin
  • GI
  • urinalysis

For hemolysis check

  • bilirubin (total, direct)
  • LDH
  • DAT
  • Haptoglobin
127
Q

If you see macrocytosis with high retic count, what are you thinking?

A

It’s probably a hemolytic anemia. The reiculocytes are making the MCV look high because retics are so large.

128
Q

2 categories of macrocytic anemia and how to differentiate them on blood smear

A
  • Megaloblastic anemia (will have polynuclear neutrophils - lots of lobes in the nuclei because not enough DNA to divide!)
  • Non-megaloblastic anemia (will have pgeroid neutrophils aka John Lennon neutrophils with 2 lobes).
129
Q

3 causes of megaloblastic anemia

A
  • B12 deficiency
  • folate deficiency
  • Drugs that interfere with DNA synthesis
130
Q

5 causes of non-megaloblastic macrocytic anemia

A
  • Liver disease/chronic EtOH
  • HIV infection/therapy
  • Myelodysplastic syndrome
  • Myeloma
  • Hypothyroidism
131
Q

Direct vs indirect bilirubin testing

A

Direct bilirubin is conjugated

Indirect bilirubin is unconjugated - this is released by RBCs during hemolysis so it makes a good test for hemolysis.

132
Q

LDH test

A

Enzyme in RBCs that is released in hemolysis

133
Q

Purpose of DAT testing

A

Direct antiglobulin. A positive result shows that the anemia is immune-mediated. It also tells you if the anemia is dependent on cold temperature. Warm anemia is IgG mediate and cold anemia is IgM mediated.

134
Q

Warm vs cold anemia

A

Distinction important in immune-mediated hemolytic anemia.

Warm - IgG; Phagocytosis by reticuloendothelial cells in the spleen

Cold - IgM (flare ups in cold temp); Intravascular hemolysis and RE-mediated phagocytosis in the spleen.

135
Q

What does a low haptoglobin result mean in anemia?

A

Haptoglobin is busy transporting globins from broken down RBCs - this is a hemolytic anemia.

136
Q

Explain the process of normal hemostasis

A
  1. Primary Hemostasis (Platelets and VWF)
    • Von Willebrand Factor is activated by exposure to tissue factors in damaged vessel wall –> VWF uncoils and divides
    • VWF grabes platelets –> primary platelet plug
  2. Secondary Hemostasis (clotting factors)
    • Propagation of clotting process
    • Platelets are activated - membranes coated in -ve charge that is necessary to active coagulation protein zymogens
    • Results in a stable fibrin clot
  3. Termination of Clotting via anti-thrombotic control mechanisms
  4. Fibrinolysis (removal of the clot and wound healing)
137
Q

describe the coagulation cascade

A
  • Extrinsic Pathway involves tissue factor and factor 7.
  • Intrsinsic pathway involves factors 12, 11, 9, 8
  • Common pathway starts at factor 10, 5, 2, 1 and leads to thrombin, which mediated generation of fibrin from fibrinogen, which is key in the stable fibrin clot.
138
Q

How might a vitamin K deficiency affect bleeding?

A
  • Vitamin K is central in the production of coagulation factors 10, 9, 7, 2 (1972 was a good year to have a kid) and protein C and protein S
  • A Vitmain K deficiency will therefore lead to a deficiency in these factors and related bleedings disorders.
139
Q

How does warfarin work?

A

It’s a Vitamin K antagonist - it interferes with Vitamin K’s role in the production gof clotting factors (10, 9, 7, 2). If you exceed therapeutic dose of Warfarin, you may present with a bleeding disorder associated with a deficiency in those clotting factors.

140
Q

How may a therapeutic dose of warfin become a toxic dose in the context of bleeidng disorders

A
  • Changes in diet - must take in a stable amount of vitamin K because warfarin is a Vit K antagonist and we need a certain amount of Vit K available to produce clotting factors
  • Antibiotic usage may affect productiong of Vitamin K by gut bacteria
  • Medications that affect the metabolism of warfarin by cytochrome P450
141
Q

How does liver disease cause coagulopathy

A
  • A production issue
142
Q

what is the role of an immediate 50:50 mix in diagnosing bleeding disorders

A

Rules out an inhibitor of coagulation factor and points toward a deficiency in coagulation factors.

The pt blood is mixed with control blood.

  • If mixing results in coagulation then there is likely a factor deficiency (often hemophilia B; but it could be VW disease because VWF protects factor 8 from degradation).
  • If mixing does not result in coagulation, then it is likely that a coagulation inhibitor is at play (lupus, anticoagulant)
143
Q

PT/INR vs PTT tests

A

PTT tests the intrinsic coagulation pathway

PT/INR tests the extrinsic pathway

neither of them test platelet function!

144
Q

Vessel-related causes of bleeding

A

Senile pupura;

Disseminated intravascular coagulopathy;

145
Q

platelet/VWF-related causes of bleeding

A

Von Willebrand disease;

Congenital thrombocytopenia;

Immune/non-immune thrombocytopenia

146
Q

Coagulation factor problems that cause bleeding disorders (4)

A
  1. Hemophilia (A or B)
  2. Liver disease
  3. ANticoagulants
  4. Vitamin K deficiency
147
Q

How is Von Willebrand Disease Diagnosed?

A

VWF levels and functionality testing

148
Q

Management of von Willebrand disease

A

Type 1: treat with DDAVP, which releases VWF stores from cells. This won’t work for the other types because there is an absolute deficiency or the VWF is no good to begin with.

Type 2 & 3: Provide exogenous VWF by IV (may be recombinant or plasma derived)

149
Q

Diagnosis of Hemophilia A or B

A

Factor VIII and IX assay

150
Q

Key things to ask on history from a pt with abnormal bleeding

A
  • Their bleeding history (when, how much, what kind, rashes)
  • Family history
  • Use of medications
151
Q

Lab assessment of platelet-type bleeding (4)

A
  • CBC - low platelet count much more common
  • Peripheral blood smear
  • VWF testing (INR/PTT)
  • Platelet function testing (PFA-100)
    • if platelets are dispersed then light won’t pass through
    • add reagent and platelets should clump up and allow light to pass through.
    • this test is affected by ASA / NSAIDs
152
Q

Qualitative platelet disorders

A
  • Less common than quantitative platelet disorders. Acquired.
  • Could be due to
    • Drugs: NSAIDs, aspirin, heparin
    • Systemic conditions: renal failure, cardiopulmonary bypass
    • Hematologic disease: MDS, myeloproliferative disease, apraproteinemia
153
Q

Treatment for hemophilia

A
  • Give recombinant coagulation factor proteins (factor VIII and IX deficiency)
  • Desmopressin for a mild factor VIII deficiency
154
Q

Treament for vessel disorders that are causing bleeding

A

No specific treatment

  • limit steroid exposure and recognize that aspirin, anti-inflammatory and anti-coagulants may worsen bleeding and bruising
  • Caution about the fragility of the tissues
155
Q

What is the bleeding like for different categories of bleeding disorders?

A
  • Non-hematologic (vessel-related) and platelet/VWF defects will present with petechiae, bruising, mucosal bleeding, and menorrhagia
  • Coagulation factor deficiencies undermine secondary hemostasis so the bleeding is more severe
    • joint/muscle bleeding, GIT bleeding, excess surgical bleeding.
156
Q

Causes of reduced platelet production

A
  • Congenital (rare)
    • Look for FHx and giant platelets on smear
  • Acquired
    • Nutritional (B12 or folate deficiency)
    • Infiltrative (cancer)
    • BM failure (aplastic anemia, myelodysplastic syndrome)
    • Medication (chemo)
157
Q

When to give a platelet transfusion

A

When platelets are < 10

158
Q

When would splenic platelet sequestration occur?

A

The spleen holds 1/3 of circulating platelet pool. Any cause of splenomegaly will sequester more platelets.

Possible causes

  • congestive (cirrhosis, portal HTN)
  • Infiltrative (blood cancers)
  • Work hypertrophy (infections, some autoimmune diseases)
159
Q
A
160
Q

What is Immune Thrombocytopenia? What is its course?

A
  • Platelet equivalent of autoimmune hemolytic anemia
  • Reticulo-endothelial/spleen-mediated clearance of antibody coated platelets (spleen not enlarged)
  • Platelet count variable
  • Usually post-viral and self-limiting in children
  • Usually more chronic in adults (more common in women)
161
Q

Symptoms of Immune Thrombocytopenia

A
  • platelet count variable - rarely has clinical manifestations unless plt < 30
  • Easy bruising, mucosal bleeding, petechiae
162
Q

Causes of immune thrombocytopennia

A
  • Usually post-viral in children
  • More common in adult women
    • Associated with connective tissue disease (i.e., SLE) or lymphoproliferative disease (i.e., CLL)
    • Can be triggered by meds
163
Q

Treatment for immune thrombocytopenia

A

Usually self-limiting in children.

In adults - immune suppression. Platelet transfusions are not helpful.

164
Q

What is thrombotic microangiopathy?

A

It’s a clinicopathological syndrome that results from a number of etiologies (I’m pretty sure this is the same as DIC)

  • Key features:
    • Endothelial injury
    • MAHA (microangiopathic hemolytic anemia)
    • low platelets
    • Organ injury from small vessel ischemia
  • Causes microvascular occlusion, causing organ injury
  • Results in consumptive thrombocytopenia
165
Q

Causes of thombotic microangiopathy

A

It’s a clinicopathological syndrome that results from a number of etiologies (I’m pretty sure this is the same as DIC)

  • hypertensive meregency
  • midications and illicit drugs
  • toxin-mediated endotheliul damage (HUS)
  • autoimmunity against ASAMTS13
166
Q

What is the classic pentad of symptoms for thombotic thrombosytopenic purpura?

A
  1. Thrombocytopenia **
  2. Microangiopathic hemolytic anemia**
  3. Fever
  4. Seurologic symptoms and signs
  5. Renal impairment

**consider this as a diagnosis if you see low platelets and evidence of hemolysis

167
Q

Treatment for thrombotic thrombocytopenic purpura (TTP)

A
  • MEDICAL EMERGENCY - mortality 90% without treatment
  • Plasma exchange (remove autoantibody if it is autoimmune)
    • Daily treatments until platelet count normalizes
  • Aspirin (reduce microthrombosis)
  • Corticosteroids for most cases
  • Platelet transfusions are contraindicated
168
Q

when you see bite cells and blister cells, what are you thinking is the cause of hemolysis?

A

Oxidative stress in a patient with G6PD deficiency. Various drugs can lead to xoidative injury

169
Q

Immune Hemolytic Anemia

Presentation

Diagnosis

Causes

A
  • Presentation: typical anemia
  • Diagnosis
    • Positive DAT (direct antiglobulin test)
    • Spherocytes on blood film
  • Causes
    • Many drugs (cephalosporins, penicillins)
170
Q

*****Heparin Induced Thrombocytopenia: Mechanism

A
  • Heparin binds platelet factor 4 (released from platelets)
  • The heparin-PF4 complex is bound by IgG and marks it for clearance
  • Platelet clearance AND activation occur - therefore VERY STRONG CLOTTING TENDENCY (=v dangerous)
171
Q

Diagnosing heparin-induced thrombocytopenia

A

First do an immunoassay for the HIT antibody. If it is present, then send to hamilton for the more accurate platelet activation assay

172
Q

When should you proceed with heparin-induced thrombocytopenia testing?

A

4 Ts

  • Thrombocytopenia is present
  • Timing of fall in platelets aligns with starting heparin.
  • Thrombotic signs and symptoms
  • AnoTher cause of platelet drop is not evident
173
Q
A
174
Q

What drug is famous for causing neutropenia?

A

CLOZAPINE

175
Q

Drug induced myelosuppression

A

Commonly occurs with chemotherapy.

The myelosuppression is predictable and blood counts have an expected nadir, then recovery.

Usually a pancytopenia.

176
Q

More common drug-induced anemias (3)

A

Oxidant hemolysis (for a pt w G6PD deficiency)

Immune hemolytic anemia

Worsened bleeding with an anticoagulant

177
Q

4 drug-induced thrombocytopenias

A

Heparin-induced thrombocytopenia

Drug-induced immune thromboctopenia

Thrombotic microangiopathy (and also anemia)

Bone marrow suppression

178
Q

Drug induced pancytopenia may be the result of what mechanism?

A

Myelosuppression

179
Q

Vitamins we need to make RBCs (3)

A

Iron, B12, folic acid

180
Q

b12 supplementation in pernicious anemia

A

Because oral absorption is impaired, intramuscular preparation is standard or a high oral dose overcome the impairment

181
Q

Circumstances where folic acid supplementation may be a good idea?

A

Hemolytic anemia

pregnancy

(also check and treat a comborbid B12 deficiency)

182
Q

What is th ebig concern with B12 deficiency?

A

neurologic damage

183
Q

What are some situations when using erythropoiesis stimulating agents would be appropriate? (5)

A
  • Chronic Kidney Disease *** most common and most important
    • Used in almost all dialysis and predialysis patients with low hemoglobin
    • Must ensure that iron stores are replete
  • Low risk MDS (anemia bc low RBC production)
  • Chemo-induced anemia (rarely)
  • Prior to surgery to reduce transfusions
  • Jehova’s witness with anemia
184
Q

when to use thrombopoietin receptor agonists

A
  • Effective for immune thrombocytopenia
185
Q

4 paths of lymphomagenesis

A
  1. Random genetic transformation
  2. Oncogenic viruses (i.e., EBV)
  3. Antigen OVer-stimulation (T cells proliferate to manage an antigen and then forget to die down)
  4. Immunosuppression (iatrogenic, HIV, age)
186
Q

3 ways to classify lymphoid neoplasms

A
  1. Historical (hodgkin vs nonhodgkin)
  2. by cell type (B or T or NK)
  3. clinical behaviour (high grade low grade)
187
Q

hodgkin vs nonhodgkin lymphoma

A

Hodgkin has reed sternberg cells (owl cells) and swollen lymph nodes that are busy repsonding to these weird malignant cells.

Non Hodgkin - all of the cells in the tumor are malignant lymphocyte

188
Q

Low grade vs high grade lymphomas

A

Low grade = Indolent lymphoma

  • Tumor grows slowly over the course of lears
  • Lymphocyte accumulation due to defective apoptosis
  • Malignant lymphocytes are usually small
  • Treatment often not required at the time of diagnosis
  • Incurable

HIgh grade = aggressive lymphoma

  • tumor grows rapidly over the cours of hours-weeks
  • Lymphocyte accumulation due to uncontrolled cellular proliferation
  • Malignant lymphocytes are usually large and agly
  • Treatment required at the time of diagnosis
  • Potentially curable
189
Q

Most common lymphomas in the western world

A

1 Diffuse large B cell lymphoma

190
Q

Treatment for non-hodgkin lymphomas

A

All involve some sort of systemic therapy

  • Non-targeted therapies
    • Chemo (inhibit cell proliferation)
    • Radiation (damage dividing cells)
    • Immunotherapy (kill malignant cells)
  • Targeted molecular therapies - antibodies directed against particular proteins that are critical in the growth and survival of the lymphoma cells // Other proteins that interfere with cell growth and survival of the lymphoma cells.
191
Q

Lytic lesions and hypercalcemia in Multiple Myeloma

A
  • Malignant cells produce substances that promote bone trabeculae destruction and “lytic” lesions
  • Loss of bone leads to
    • pathological fractures
    • release of Ca from bone and intro blood –> hypercalcemia
192
Q

Acronym for clinical findings in multiple myeloma

A
  • Calcium elevated: from bone lysis
  • Renal insufficiency: monoclonal immunoglobulins (esp light chains) and hypercalcemia damage the kidney
  • Anemia: from marrow suppression by malignant plasma cells, and from renal failure (low erythropoietin)
  • Bone pain and pathological fractures: from bone lytic lesions seen on X-ray (not bone scan)
    • **most common presentation is back pain not responding to rest/physio or a vertebral compression fracture
  • infections: suppressed normal antibody (immunoglobulin) production
193
Q

classic presenting symptom for plasma cell myeloma

A

back pain that doesn’t get better with rest/physio or a compression fracture

194
Q

Hypercalcemia is a sx of what cancer and how can it present

A

Symptom of plasma cell myeloma.

Presents as nausea, constipation and difficulty urinating.

195
Q

Common sx of myeloproliferative neoplasms

A
  • fatigue
  • wt loss
  • night sweats
  • abdominal fullness (due ot massive splenomegaly)
  • anorexia
196
Q

evaluation for an incidental finding of increased WBC counts

A

We worry that it is a myeloproliferative neoplasm

  • Complete history and exam
  • CBC and differential
  • Bone marrow aspirate and biopsy
  • chromosome analysis “cytogenetics”
  • serum EPO and JAK 2 mutation
  • abdominal ultrasound - splenomegaly
197
Q

What is meant by a ‘left shift’

A

Presence of immature myeloid lineage cells… Characteristic of myeloproliferative neoplasms but could be due to other disease or infection.

198
Q

Significance of the Philadelphia chromosome

A

the first cytogenic abnormality identified that leads to chromic myeloid leukemia.

Result of t(9;22), which affects the BCR and ABL.

199
Q

Treatment for chromic myeloidleukemia; how effective is it?

A

Tyrosine kinase inhibitors specifically targeted at the problem mutation (BCR-ABL);

Imatinib and other mAbs.

These improve life expectancy a lot compared to previous therapies.

Always new drugs emerging though!

200
Q

What is polycythemia?

A

It just means elevated hemotocrit (too many RBCs).

201
Q

What are the different causes of polycythemia?

A
  • Spurious Polycythemia: occurs in dehydration; RBC levels/hematocrit look high because of reduced plasma volume
  • True polycythemia:
    • Secondary Polycythemia: BM response to hypoxia or high EPO is to make more RBCs. May occur in chronic hypoxia due to lung disease or in renal cell CA (high EPO)
    • Polycythemia Vera: Excessive RBC production from abnormal BM, without EPO stimulation
202
Q

what is the key mutation behing polycythemia vera?

A

JAK 2 mutation.

The mutated JAK2 protein binds to the EPO-receptor. The binding promotes signaling independent of APO stimultion and hypersensitivity to cytokin.

203
Q

Common challenges in phlebotomy

A

Venous access;

Lightheadedness and fatigue afterwards;

Vasovagal response;

204
Q

What must be ruled out before making an essential thrombocytopenia diagnosis

A

Iron deficiency;

Reactive changes - infection, inflammation, malignancy;

205
Q

Complications of essential thrombocythemia

A
  • The platelets may be functional or dysfunctional, which means that pt may clot or bleed
    • Thrombotic complications:
      • venous thrombosis (DVT, PE)
      • Arterial thrombosis (MI)
    • Bleeding complications: bruising, GI bleeding
206
Q

Imatinib

A

A TK inhibitor targetting the mutant gene in chronic myeloid leukemia.

207
Q

What is the mutation in chronic myeloid leukemia?

A

t(9;22)

208
Q

blood smear shows many large red blood cells with a bluish cytoplasm. Why??

A

Reticulocytes - retained RNA in their cytoplasm

209
Q

longstanding anemia in a chinese canadian with a family history is most likely to be due to…

A

B thalassemia major

210
Q

blood smear for b thalassemia major shows

A

microcytic, hypochromatic RBCs with target cells and basophilic stippling

211
Q

pencil cells are characteristic of

A

iron deficiency anemia

212
Q

in hereditary hemochromatosis, where is most of the excess iron located?

A

Present in tissues bound to ferritin and hemosiderin

213
Q

What are we likely to see on blood film of a non-cancer macrocytic anemia?

A

Oval macrocytes and hypersegmented neutrophils

214
Q

why do pts with sick cell anemia get infections a lot?

A

Most of them have infarcted their spleens by adulthood

215
Q

what supplement would you recommend to a patient with warm immune hemolytic anemia

A

Folic acid, because folic acid stores can be depleted quickly with increased erythropoiesis.

216
Q

how common is g6pd deficiency and how is it acquired?

A
  • Most common cause of enzyme-deficienct hemolytic anemia
  • x-linked, variable expression
217
Q

What would a blood smear for PK deficiency show?

A

spiky RBCs

218
Q

Chronic Lymphocytic Leukemia

A

Also called B cell small cell lymphocytic leukemia

Small, mature B cells that proliferate into BM, blood, lymph nodes;

219
Q

Diagnositics for chronic lymphocytic leukemia

A

Blood film –> Soccer ball cells;

lymph node biopsy –> extensive infiltration;

+/- immunophenotyping.

220
Q

Prognosis and treatment for chronic lymphocytic leukemia

A

Indolent - incurable;

Patients liv emany years with the disease;

Non-hodgkins treatments (systemic therapies and immunotherapy)

221
Q

Follicular Lymphoma: What is it and prognosis/treatment

A

Low grade B cell lymphoma with a follicular growth pattern

T(14;18)

Non-hodgkins treatment;

Indolent/incurable, but most patients live for many years with it

222
Q

Diffuse large B cell lymphoma

A

High grade B cell lymphoma in lymph nodes and extranodal lymphoid tissues;

Diffuse growth pattern;

Aggressive, but some are curable;

If cure isn’t achieved relatively quickly, patients die within months to years;

Non-hodgkin treatment

223
Q

Plasma cell myeloma

A

Aka multiple myeloma;

Malignancy of plasma cells that secrete a clonal immunoglobulin;

224
Q

Diagnosis of plasma cell myeloma

A
  • Blood smear - perinuclear halo;
  • Serum protein electrophoresis - thick single band representing presence of “M protein”
  • BM biopsy/aspirate - increased plasma cells
225
Q

treatment and prognosis for plasma cell myeloma

A
  • survival ~5-7 years with modern treatments;
  • The goal is to reduce mAbs
  • Stem cell transplant and chemo for pt under 70 years;
  • Novel treatments are significantly improving outcomes
226
Q

Chronic myeloid leukemia

A

Malignancy of pluripotent stem cells resulting in overproduction gof granulocytes, often accompanies with high RBCs and platelets.

227
Q

Diagnostics for chronic myeloid leukemia

A

hypercellular BM;

Cytogenetics - philadelphia chromosome (one abnormality that is implicated in some cases)

228
Q

Treating chronic myeloid leukemia

A

TK inhibitor - imatinib

229
Q

Progression of chronic myeloid leukemia

A

chronic phase of stability for 5-6 years;

Accelerated phase 6-9 mo;

Blast crisis phase 3-6 mo before death;

230
Q

Polycythemia vera

A

Excessive RBC production from abnormal BM without EPO stimulation.

Results from a mutation in JAK2, which causes inappropriate stimulation of EPO receptor resulting in RBC proliferation.

231
Q

Complications of polycythemia vera

A
  • Facial plethora, erythromelalgia
  • incresed blood viscosity –> thrombus
  • Platelet dysfunction –> bleeding
  • Increased histamine –> pruritis and peptic ulcers
  • Increased uric acid –> gout
232
Q

Treatment and prognosis of polycythemia vera

A

May progress to myelofibrosis or AML;

Phlemotamy to maintain hematocrit < 45%;

ASA 81 mg/day;

Hydroxyurea to control excessive platelet counts and decrease needs for phlebotamy;

233
Q

Essential thrombocythemia

A

Very high platelet count;

Platelets may be functinal or dysfunctional (so patient may clot or bleed)

No philadelphia chromosome, but pt may be JAK2 positive;

See megakaryocytes and hyperplasia on testing;

234
Q

Idiopathic myelofibrosis

A

Fibrosis fills the bone marrow resulting in pancytopenia

Med 1 UBC Winter 2020 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions