Hematology and Oncology Flashcards
(273 cards)
1
Q
Definition of Anemia
A
Reduction in Hct or Hgb
2
Q
Compensatory Mechanisms to Maintain O2 Delivery to Tissue
A
- ) Increased SV or CO/HR
- ) Increased Extraction Ratio
- ) Rightward shift on oxyhemoglobin curve
- ) Expansion of Plasma Volume
3
Q
When is a transfusion needed?
A
- Hgb <7
2. Patient requires increased O2 carrying capacity (CAD or cardiopulmonary disease)
4
Q
Symptoms of anemia (specific and nonspecific)
A
Nonspecific: fatigue, poor concentration, diarrhea, headache, nausea, vague abdominal discomfort, hypotension, tachycardia, pallor (best if seen in conjunctiva)
Specific: jaundice if hemolytic anemia, blood in stool if GI bleed
5
Q
1 unit of PRBCs increases Hgb by?
A
1 point of Hgb, 3 points of Hct
6
Q
If H/H reveals anemia, what is the next best step?
A
Get a retic count and MCV
7
Q
Effective Erythropoeisis Depends on:
A
- ) Adequate raw materials: folate, B12, Iron
- ) Absence of intrinsic bone marrow disease
- ) Adequate EPO release from kidney
- ) Survival of reticulocytes (no destruction prior to leaving the bone marrow).
8
Q
What does it mean if retic count is >2%
A
excessive RBC production or blood loss. The bone marrow is responding adequately to the cause of anemia.
9
Q
What does it mean if retic count is <2%
A
Inadequate RBC production by bone marrow
10
Q
Why do you mix PRBCs with Normal Saline and not Lactated Ringers?
A
Because the calcium in LR causes coagulation within the IV lines.
11
Q
What should you check after a transfusion of PRBCs is completed?
A
CBC
12
Q
What does FFP contain?
A
All of the clotting factors and no WBCs/RBCs.
13
Q
Why do you give FFP?
A
Coagulopathy, high PT/PTT, deficiency of clotting factors, liver failure (since vitamin K won’t work)
14
Q
What should you check after infusion of FFP?
A
PT/PTT
15
Q
What does cryoprecipitate contain
A
Factor VIII and Fibrinogen
16
Q
Why do you give cryoprecipitate?
A
Hemophilia A, von Willebrand Disease, or DIC (due to decreased fibrinogen)
17
Q
How much will 1 unit of platelets raise the platelet count by?
A
10,000
18
Q
Is acute hemolytic reaction intravascular or extravascular hemolysis?
A
Intravascular: Caused by ABO mismatched blood transfused into the patient. IgM antibodies attach to the infused RBCs, activate a complement pathway, and produce a massive intravascular hemolysis as C9 punches holes in the RBC membrane.
19
Q
Symptoms of Acute Hemolytic Reaction
A
N/V, fever, chills, pain in flank/back, chest pain, dyspnea
20
Q
Complications of Acute Hemolytic Reaction
A
DIC, renal failure w/ hemoglobinuria, hypovolemic shock with hypotension and tachycardia
21
Q
How do you treat/manage Acute Hemolytic Reaction?
A
- Stop the transfusion!!!
- Aggressive fluid replacement to prevent renal failure and shock
- Epinephrine for anaphylaxis
- Dopamine/NE as needed for pressors/to maintain BP
22
Q
Is delayed hemolytic transfusion reaction intravascular or extravascular?
A
Extravascular.
23
Q
What causes a delayed hemolytic transfusion reaction
A
Can occur 3-4 days after transfusion. It occurs when one of the minor RBC antigens is found in the transfusion. Reexposure of memory B cells to the antigen on RBCs after prior exposure results in the synthesis of IgG anti-Kell (for ex) antibodies. These antibodies coat the antigen positive RBC donor cells which will be removed extravascularly by macrophages in the liver and bone marrow.
24
Q
Symptoms of delayed hemolytic transfusion reaction
A
fever, jaundice anemia
25
How do you treat/manage delayed hemolytic transfusion reaction?
Don't do anything. The prognosis is good and is usually self limited.
26
Definition of Microcytic Anemia
MCV <80
27
What is in the differential diagnosis of a microcytic anemia?
1. ) Iron deficiency anemia
2. ) Anemia of Chronic Disease
3. ) Thalassemias
4. ) Ring Sideroblastic Anemias (lead poisoning, pyridoxine deficiency, toxic effects of alcohol)
28
Definition of Macrocytic Anemia
MCV >100
29
What is in the differential diagnosis of macrocytic anemia?
1. ) Nuclear defect: Folate or B12 deficiency
2. ) Liver disease
3. ) Stimulated erythropoiesis
30
How does liver disease lead to a macrocytic anemia?
MCV can get up to 115! This is due to altered metabolism of plasma lipoproteins into their membranes altering the shape of RBCs and therefore their volume.
31
What is in the differential diagnosis of a normocytic anemia?
1. ) Aplastic anemia
2. ) Bone marrow fibrosis
3. ) tumor
4. ) Anemia of Chronic Disease
5. ) Renal Failure 2/2 to decreased EPO production
32
If the Retic index is >2% what should you do?
1. ) Consider blood loss and look for the source.
| 2. ) Consider hemolysis and check: LDH, haptoglobin, bilirubin levels
33
What are the 2 most common causes of iron deficiency anemia worldwide?
1. ) Chronic blood loss
| 2. ) Increased iron requirements/dietary deficiency
34
What are the 2 most common causes of chronic blood loss leading to anemia?
1. ) Menstrual blood loss
| 2. ) GI bleeding
35
What populations require increased iron or are at risk of dietary deficiency of iron?
1. ) Infants and toddlers, particularly those who are on human breast milk
2. ) Teenagers, especially menstruating girls
3. ) Pregnant women
36
```
Diagnostic values of the following for iron deficiency anemia:
Ferritin
TIBC/Transferrin levels
TIBC Saturation
Serum Iron
Peripheral blood smear
```
```
Ferritin: decreased
TIBC/Transferrin levels: increased
TIBC Saturation: decreased
Serum Iron: decreased
Peripheral blood smear: microcytic hypochromic RBCs
```
37
Treatment of Iron Deficiency Anemia:
1. ) In menstruating females try a trial of oral ferrous sulfate.
2. ) in men and postmenopausal women attempt to determine the source of bleeding
38
Describe the pathophysiology of beta-thalassemia
beta chain production is deficient but alpha chain production is normal. Excess alpha chains bind to and damage the RBC membrane.
39
Describe the pathophysiology of alpha thalassemia
There is a decrease in the alpha chain production. The excess beta chains form tetramers which are abnormal hemoglobins.
40
What is a complication of the treatment of thalassemia major?
Iron overload because these patients are often transfusion dependent
41
If iron deficiency anemia is suspected but it does not respond to oral iron therapy, what is the next best step?
obtain a hemoglobin electrophoresis to rule out alpha or beta thalassemia
42
What are the clinical features of thalassemia major/Cooley anemia/homozygous beta-chain thalassemia?
- Severe anemia that is microcytic and hypochromic
- Massive hepatosplenomegaly
- Expansion of the marrow space which can cause distortion of bones
- Growth retardation and FTT
- Progressive CHF if left untreated
- Crew cut appearance of skull on XR.
43
What is seen on the hemoglobin electrophoresis of a patient with thalassemia major? Peripheral blood smear?
1. Elevated HbF and HbA2.
| 2. Hypochromic microcytic cells; target cells
44
What are the clinical features of thalassemia minor/heterozygous beta-chain thalassemia?
these patients are usually asymptomatic and usually require no treatment.
45
What is the genotype of a silent carrier of alpha thalassemia?
These patients have a mutation/deletion of only ONE of the alpha-locus.
They are asymptomatic with a normal H/H and require no treatment.
46
What is the genotype of alpha-thalassemia trait or alpha thalassemia minor?
These patients have a mutation/deletion of TWO of the alpha locus.
They may have a microcytic hypochromic anemia and usually require no treatment. Common in AAs.
47
What is the genotype of HbH disease?
This is hemoglobin Barts disease. These patients have mutation/deletion of THREE of the alpha loci.
Hemoglobin electrophoresis will show HbH. Treatment is transfusion, sometimes splenectomy is helpful.
48
What is the genotype of alpha thalassemia major?
This is a mutation/deletion of all FOUR alpha loci. These patients often have hydrops fetalis and die shortly after birth.
49
What is the most common type of thalassemia?
Thalassemia minor. Beta-thalassemia minor is more common than alpha-thalassemia minor.
50
```
What are the lab results of the following for sideroblastic anemia?
Ferritin
TIBC/Transferrin
TIBC Saturation
Serum iron
```
Ferritin: increased
TIBC/Transferrin: normal TIBC
TIBC Saturation: normal/elevated
Serum iron: increased
Ringed sideroblasts in bone marrow
51
What is the treatment for sideroblastic anemia
1. ) Remove the offending agent
| 2. ) Consider pyridoxine
52
What are some of the acquired causes of sideroblastic anemia
1. ) Drugs: chloramphenicol, INH, alcohol
2. ) Lead exposure
3. ) Collagen vascular disease
4. ) Neoplastic disease: myelodysplastic syndromes.
53
What is the pathophysiology of sideroblastic anemia?
It is caused by an abnormality of iron metabolism in RBCs.
54
Why does chronic inflammation lead to anemia?
It is thought that inflammatory cytokines have a suppressive effect on erythropoiesis
55
```
What are the lab results of the following for anemia of chronic disease?
Ferritin
TIBC/Transferrin
TIBC Saturation
Serum iron
```
```
Ferritin: increased
TIBC/Transferrin: low
TIBC Saturation: high
Serum iron: low
Normocytic and normochromic
```
56
What are the causes of aplastic anemia?
1. ) Idiopathic
2. ) Viral: parvovirus, Hep C, Hep B, EBV, CMV, Herpes zoster varicella, HIV.
3. ) Malignancy
4. ) Radiation exposure
5. ) Medications: chloramphenicol, sulfonamides, gold, carbamazepine
6. ) Chemicals: benzene, insecticides.
57
What are the clinical features of aplastic anemia?
1. ) fatigue and dyspnea due to anemia
2. ) Increased risk of infection due to neutropenia
3. ) Petechiae, bruising due to thrombocytopenia
58
What is a feared complication of aplastic anemia?
Transformation into an acute leukemia
59
How do you make the diagnosis of aplastic anemia?
1. ) The peripheral smear will show a normochromic normocytic anemia.
2. ) Bone marrow biopsy will show hypocellular marrow and the absence of progenitor cells for all 3 cell lines.
60
What are the two reactions in which B12 is an important cofactor?
1. ) Homocysteine to Methionine
| 2. ) Methylmalonyl CoA to Succinyl CoA.
61
Where is vitamin B12 absorbed?
In the terminal ileum while bound to intrinsic factor (produced by gastric parietal cells).
62
What are the causes of vitamin B12 deficiency?
1. ) Pernicious anemia
2. ) Gastrectomy
3. ) Poor diet (vegetarianism, alcoholism)
4. ) Crohn's Disease, Ileal resection
5. ) Organisms competingg for B12--> Diphyllobothrium latum (fish tapeworm), blind loop syndrome (bacterial overgrowth).
63
Define pernicious anemia
An autoimmune condition resulting in inadequate production of intrinsic factor by the gastric parietal cells. This leads to impaired absorption of vitamin B12 in the terminal ileum.
64
Clinical features of vitamin B12 deficiency:
1. Anemia
2. Sore tongue
3. Neuropathy
65
What are the neurologic manifestations of vitamin B12 deficiency?
1. ) Neuropathy secondary to demyelination of the posterior columns, the lateral CST< and the spinocerebellar tracts
2. ) Impaired proprioception
3. ) Ataxia
4. ) UMN signs, hyperreflexia, spasticity, weakness, upgoing Babinski.
5. ) Urinary and fecal incontinence
6. ) Dementia
66
What are 2 things you would see on a peripheral smear to diagnose B12 deficiency?
1. ) Macrocytic RBCs (MCV >100)
| 2. ) Hypersegmented neutrophils
67
What two values in the serum will be elevated with vitamin B12 deficiency?
1. ) Elevated methylmalonic acid
| 2. ) Elevated homocysteine levels
68
What is the treatment for vitamin B12 deficiency?
Cyanocobalamin (vitamin b12) IM once per month.
69
How long does it take to become deficiency in folate? in B12?
Folate--> 3 months
| B12--> 3+ years
70
What are the causes of folate deficiency?
1. ) Inadequate dietary intake "tea and toast" diet
2. ) Alcoholism
3. ) Long term use of antibiotics
4. ) Increased demand
5. ) Pregnancy
6. ) hemolysis
7. ) Use of folate antagonists like methotrexate
8. ) Anticonvulsant medications (phenytoin)
9. ) Hemodialysis
71
What is the treatment for folate deficiency?
Daily oral folic acid replacement
72
What are the serum levels of methylmalonic acid and homocysteine in folate deficiency compared to B12 deficiency.
In folate deficiency, serum levels of homocysteine are high but methylmalonic acid levels are normal. Therefore if both are elevated, it must be a vitamin B12 deficiency.
73
Hemolysis due to external RBC defects can be caused by?
1. ) Immune hemolysis
2. ) Mechanical hemolysis (prosthetic heart valves, MAH)
3. ) Medications, burns, toxins
Most of these are ACQUIRED cases of hemolysis.
74
Hemolysis due to internal RBC defects can be caused by?
1. ) Hemoglobin abnormality like sickle cell dz, HbC dz, thalassemia
2. ) Membrane defects like hereditary spherocytosis, PNH
3. ) Enzyme defects like G6PD deficiency, pyruvate kinase deficiency
75
Where does intravascular hemolysis occur? extravascular?
Intravascular--> within the circulation
| Extravascular--> within the reticuloendothelial circulation, the spleen.
76
What are the clinical features of hemolytic anemias?
1. Signs and symptoms of anemia
2. Jaundice
3. Signs and symptoms of whatever underlying disease they have
4. Dark color of urine (due to hemoglobinuria)
5. Hepatosplenomegaly, cholelithiasis, lymphadenopathy
77
Does hemoglobinuria indicate intra or extravascular hemolysis?
Intravascular hemolysis.
78
What are the typical lab values/findings seen in hemolytic anemia?
1. ) Anemia
2. ) Elevated retic count
3. ) Elevated LDH
4. ) Decreased haptoglobin
5. ) Decreased hemoglobin and hematocrit
6. ) Elevated indirect bilirubin
79
G6PD Deficiency peripheral smear
Heinz Bodies
80
Extravascular hemolysis on peripheral smear
Helmet cells or spherocytes
81
Intravascular hemolysis on peripheral smear
Schistocytes
82
Why is haptoglobin low in hemolytic anemias?
Haptoglobin binds to hemoglobin so when haptoglobin is low it indicates that hemoglobin has been destroyed.
83
What is the specific mutation that causes sickle cell disease?
Uncharged valine is substituted for a negatively charged glutamic acid at the sixth position of the beta-chain.
84
What type of conditions cause sickling?
Decreased oxygen conditions: acidosis, hypoxia, changes in temperature, dehydration, and infection.
85
Patients with sickle cell trait often have this unique finding in their urine:
Isothenuria. This is the inability to concentrate or dilute the urine. Patients have a constant osmolality on urine testing.
86
What causes hand foot syndrome/dactylitis in SCD?
Avascular necrosis of the metacarpal and metatarsal bones. This is often the first manifestation of sickle cell disease. Causes painful swelling of the dorsa of the hands and feet seen in infancy and early childhood.
87
What are 3 medical interventions that can be done to prevent complications of sickle cell disease.
1. ) Early vaccination against S. Pneumo, H. Flu, and N. Mening
2. ) Prophylactic PCN from 4 mos to 6 yrs old.
3. ) Folate supplementation due to chronic hemolysis
88
Hereditary Spherocytosis:
- Inheritance pattern
- Pathology
1. Autosomal dominant
2. Defect in the gene coding for spectrin and other RBC proteins. There is a loss in RBC surface area without a reduction in RBC volume, necessitating a spherical shape. The spherical RBCs become trapped and destroyed in the spleen by macrophages--> extravascular hemolysis.
89
What are the causes of spherocytosis? There are 5.
1. Hereditary spherocytosis
2. G6PD deficiency
3. Hyperthermia
4. ABO incompatibility (but not Rh incompatibility)
5. Autoimmune hemolytic anemia
90
What are the clinical features of hereditary spherocytosis?
- Hemolytic anemia
- Jaundice
- Splenomegaly
- Gallstones
- Occasional hemolytic crises
91
What is the treatment of choice for hereditary spherocytosis?
Splenectomy
92
Describe the osmotic fragility test as it relates to hereditary spherocytosis.
The osmotic fragility test tests the ability of RBCs to swell in a graded series of hypotonic solutions. Because of their shape, spherocytes tolerate less swelling before they rupture; thus they are osmotically fragile. The RBCs undergo lysis at a higher/earlier oncotic pressure.
93
G6PD Deficiency:
- Inheritance pattern
- Pathology
1. X-linked recessive
| 2. defect in glucose-6-phosphate dehydrogenase that results in hemolytic episodes caused by precipitating factors.
94
Known precipitants to G6PD:
- fava beans
- sulfonamides
- nitrofurantoin
- primaquine (anti-malarials)
- dimercaprol
- infection
95
What are the clinical features of G6PD deficiency?
- Episodic hemolysis
| - Jaundice and dark urine on examination
96
What does a peripheral blood smear show in a patient with G6PD?
- Bite Cells
| - Heinz Bodies
97
What are bite cells
Bite Cells are RBCs after the removal of Heinz bodies by phagocytes like splenic macrophages.
98
What are Heinz bodies?
Heinz bodies are abnormal hemoglobin precipitates within the RBCs.
99
How do you treat G6PD?
- Transfuse as necessary
- Avoid precipitants of hemolysis
- Maintain hydration
100
Define the pathology of AIHA (autoimmune hemolytic anemia).
This is caused by the production of autoantibodies that target RBC membrane antigens, leading to the destruction of these RBCs.
101
Which autoantibody class is produced in WARM AIHA?
IgG
102
What is the pathology of Warm AIHA?
IgG autoantibodies bine to RBC membranes optimally at 37 degrees C. This results in EXTRAVASCULAR hemolysis therefore Splenomegaly is a common feature.
It's WARM OUTside
103
What are some causes of warm AIHA?
- Idiopathic
- SLE
- Alpha methyldopa
- leukemias, lymphomas
- Collagen vascular disease
104
What autoantibody is produced in COLD AIHA?
IgM
105
What is the pathology of Cold AIHA?
IgM antibodies are produced and bind optimally to the RBC membranes at cold temperatures like 0 degrees celsius. This produces complement activation and results in intravascular hemolysis. The primary site of RBC sequestration in cold AIHA is the liver.
106
What are some causes of Cold AIHA?
- Mycoplasma Pneumonia
- Mononucleosis
- Idiopathic
107
In a direct coombs test, if the RBCs are coated with IgG, what is the diagnosis?
The diagnosis would be Warm AIHA. This is a positive direct coombs test. Spherocytes may be present in Warm AIHA.
108
In a direct coombs test, if the RBCs are only coated with complement, what is the diagnosis?
The diagnosis would be Cold AIHA. Also, if there is a positive cold agglutinin titer, then the diagnosis is cold AIHA.
109
Treatment of Warm AIHA
- Glucocorticoids
- Splenectomy if non-responsive to glucocorticoids
- Immunosuppression with azathioprine or cyclophosphamide
- RBC transfusions if absolutely necessary
- Folic acid supplements
110
Treatment of Cold AIHA
- Avoid cold exposure
- RBC transfusions if absolutely necessary
- Various chemotherapeutic agents
- Steroids are NOT helpful for COLD AIHA
111
What is the pathophysiology of paroxysmal noctural hemoglobinuria?
This is caused by a deficiency of anchor proteins that link complement-inactivating proteins to blood cell membranes. The deficiency of this anchoring mechanism results in an unusual susceptibility to complement mediated lysis of RBCs, WBCs, and platelets.
112
What are the clinical features of PNH?
1. Chronic intravascular hemolysis
2. Normochromic normocytic anemia
3. Pancytopenia
4. Thrombosis of venous system (look for Budd Chiari)
5. Abdominal, back, and MSK pain
6. May evolve into aplastic anemia, myelodysplasia, myelofibrosis, and acute leukemia.
113
What 3 tests can you do to diagnose PNH?
1. Ham Test
2. Sugar water test
3. Flow cytometry looking for CD59 and CD55.
114
Describe the Ham Test
The patient's cells are incubated in acidified serum, triggering the alternative complement pathway, resulting in lysis of PNH cells but not normal cells.
115
What is the treatment for PNH?
1. Glucocorticoids like prednisone. Many patients will not respond.
2. Bone marrow transplant.
116
Heparin Induced Thrombocytopenia Type 1
Heparin directly causes platelet aggregation. Seen <48 hours after initiating heparin. No treatment is needed.
117
Heparin Induced Thrombocytopenia Type 2
Heparin induces antibody-mediated injury to platelets; seen 3-12 days after initiating heparin; heparin should be discontinued immediately.
118
Describe the pathology of ITP
Immune (Idiopathic) Thrombocytopenic Purpura: This results from autoimmune antibody formation against host platelets. These antiplatelet antibodies are IgG antibodies that coat and damage the platelets which are then removed by splenic macrophages.
119
Acute Form of ITP
- occurs in children
- follows a viral infection
- self-limited
120
Chronic Form of ITP
- occurs in adults, women of childbearing age
| - spontaneous remission is rare.
121
At what platelet count do you get major spontaneous bleeding like intracranial bleeding or heavy GI bleeding?
<5000
122
At what platelet count do you see minor spontaneous bleeding like easy bruising, petechiae, epistaxis, menorrhagia or bleeding gums?
<20,000
123
Describe the clinical features of ITP
- petechiae and ecchymosis on the skin
- bleeding of mucus membranes
- NO splenomegaly
124
How do you diagnose ITP?
- Platelet count <20,000
- Blood smear normal aside from thrombocytopenia
- Bone marrow aspirate shows increased megakaryocytes
- Increased amount of platelet IgG
125
How do you treat ITP?
1. Adrenal corticosteroids
2. IVIG
3. Splenectomy (chronic ITP)
4. Romiplostim and Eltrombopag--> both are drugs that work as thrombopoietin receptor agonists to increase platelet production.
126
Describe the pathology of TTP.
Thrombotic Thrombocytopenic Purpura: a rare disorder of platelet consumption. Patient with TTP lack a functional ADAMTS13, which is a protease that cleaves vWF. Ultralarge vWF multimers buildup in the blood as a result of this deficiency. Microthrombi (mostly platelet thrombi) occlude small vessels leading to microangiopathic hemolytic anemia.
127
How are PT/PTT changed with TTP?
PT and PTT are normal in TTP because there is no consumption of clotting factors.
128
Compare TTP and HUS.
TTP = HUS + fever + AMS
129
Describe the clinical features of TTP:
```
FAT RN:
Fever
Anemia (microangiopathic hemolytic)
Thrombocytopenia
Renal failure (acute/mild)
Neurologic changes (fluctuating)
```
130
What is the treatment for TTP?
1. Plasmapheresis
| 2. Corticosteroids and splenectomy
131
Should you give platelets for TTP?
NO
132
In HIT, what are the antibodies formed against?
Autoantibodies are formed against heparin-platelet factor 4 complex.
133
Which type of heparin has a much lower risk of HIT?
LMWH
134
What is the feared complication of HIT?
A DVT or PE
135
A decrease in platelet count by what percentage indicates the possibility of HIT?
If platelets drop to 50% of initial value, consider HIT
136
How do you diagnose HIT?
1. Antiplatelet factor IV antibody
| 2. Serotonin release assay
137
How do you treat HIT?
1. STOP Heparin
2. give thrombin inhibitor such as Dabigatran, Argatroban, or Lepirudin.
3. Avoid heparin in the future in any patient that developed HIT.
138
Bernard-Soulier Syndrome:
- Inheritance Pattern
- Pathology
1. Autosomal Recessive Disease
| 2. Disorder of platelet adhesion to the subendothelium due to a deficiency of thee platelet glycoprotein GpIb-IX
139
What is seen in lab/smear in Bernard-Soulier Syndrome?
- Platelet count is low
| - Platelets are abnormally large
140
Glanzmann Thrombasthenia:
- Inheritance pattern
- Pathology
- Autosomal Recessive Disease
| - Disorder of platelet aggregation due to deficiency in platelet glycoprotein GPIIb-IIIa
141
What is seen in lab/smear in Glanzmann Thrombasthenia?
- Bleeding time is prolonged
| - Platelet count is normal
142
Reversible causes of sideroblastic anemia
Lead, EtOH, INH
143
Irreversible causes of sideroblastic anemia
Metabolic disease of B6, AML/Myelodysplasia
144
How do you confirm the diagnosis of G6PD?
Get a G6PD level 6-8 weeks after the attack. Levels will be normal during the attack because young cells have G6PD.
145
What is the best test for diagnosing hereditary spherocytosis?
Osmotic fragility
146
Inheritance of vWD
autosomal dominant
147
What is the role of vWF?
vWF enhanced platelet aggregation and adhesion by binding to Gp1B-IX on platelets. It also acts as a carrier of factor VIII in the blood.
148
Where is vWF made?
the endothelial cells and megakaryocytes.
149
How do you diagnose vWF?
Prolonged bleeding time, normal platelet count, PTT may or may not be prolonged, decreased plasma vWF, decreased factor VIII, reduced ristocetin induced platelet aggregation.
150
What medication can you give for vWD and how does it work?
DDAVP, it induces endothelial cells to secrete vWF.
151
Why should you not give cryoprecipitate for vWD?
Because of the risk of viral transmission.
152
What is the inheritance pattern of Hemophilia A?
X-linked Recessive
153
What clinical features are unique to hemophilia A or factor abnormalities as compared to platelet abnormalities?
Hemarthroses which can lead to progressive joint destruction.
154
What value is prolonged in Hemophilia A?
PTT
155
How do you treat hemarthroses associated with Hemophilia A?
Analgesics (not aspirin or NSAIDs), joint immobilization, ice packs, nonweight bearing.
Treat Hemophilia A in general with factor VIII replacement.
156
PT
represents the extrinsic pathway, prolonged by warfarin
157
PTT
represents the intrinsic pathway, prolonged by heparin
158
Thrombin Time
Measurement of the fibrinogen concentration
159
Bleeding Time
Reflects platelet function
160
Normal PT
11-15 seconds
161
Normal PTT
25-40 seconds
162
Normal bleeding time
2-7 minutes
163
What is DIC?
Abnormal activation of the clotting system, leading to the formation of microthrombi throughout the microcirculation. This causes consumption of platelets, fibrinogen, and coagulation factors. Fibrinolytic mechanisms are activated thus leading to hemorrhage. Therefore, bleeding and thromboses are occurring simultaneously.
164
List some causes of DIC
- Infection
- Malignancy
- Pregnancy (placental abruption, amniotic fluid emboli, retained POC)
- Major Tissue Injury from trauma or burns
- APL
- Shock
- Snake Venom
165
What levels are elevated in DIC?
PT, PTT, Bleeding Time, Fibrin split products, D-dimer
166
What levels are decreased in DIC?
Platelets, fibrinogen
167
What is seen on a peripheral smear in DIC?
Schistocytes
168
Tx of DIC?
Supportive, O2, IVF, BP support, treat the underlying cause
169
What factors depend on vitamin K for synthesis?
II, VII, IX, X, protein C and S.
170
What are some complications of DIC?
Intracranial bleeding, stroke, PE, bowel infarction, acute renal failure
171
What are some causes of Vitamin K Deficiency?
- Prolonged Abx Use and NPO
- Patients on TPN
- Malabsorption of fat soluble vitamins
- Warfarin
172
Which factor has the shortest half life?
VII
173
What lab value will be the first to be prolonged after initiation of warfarin?
PT because VII has the shortest half life.
174
What are the 3 reasons why coagulopathy develops in liver disease?
1. Clotting factors are made in the liver, so there is decreased synthesis
2. Cholestasis leads to decreased absorption of vitamin K
3. Hypersplenism/splenomegaly due to portal hypertension causes thrombocytopenia.
175
What are some treatment options for liver coagulopathy?
- FFP
- Platelet transfusion
- Vitamin K
- Cryoprecipitate
176
Antithrombin III Deficiency inheritance pattern
autosomal dominant
177
What is the MOA of AT3?
Antithrombin III inhibits thrombin. Therefore, when there is a deficiency of AT3, thrombin has free reign and keeps on making clots.
178
What are some clinical features of antiphospholipid antibody syndrome?
- Recurrent fetal loss
- arterial or venous thromboembolism
- thrombocytopenia
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Protein C Deficiency Inheritance Pattern
Autosomal dominant
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what is the MOA of protein C?
Protein C inhibits factor V and VIII which are both part of the clotting cascade. Therefore when protein C is deficient, clots continue to form.
181
What is the MOA of protein S/protein S deficiency?
Protein S is a cofactor for protein C. When protein S is deficient, protein C can't adequately inhibit factor V and VIII.
182
What is the MOA of factor V leiden mutation?
This leads to a mutation in factor V which results in the inability of protein C to inactivate factor V therefore there is continuous clotting.
183
In what clinical scenarios should you consider that someone has an inherited hypercoagulable disorder?
- Recurrent thromboses
- Family hx of recurrent thromboses
- First thrombotic event occurs before the age of 40.
- Patient experiences thromboses in unusual sites.
184
When should someone be permanently anticoagulated? (in reference to hypercoagulable disorders)
When they have had 2 or more thrombotic events.
185
What is the MOA of heparin?
Heparin potentiates the action of antithrombin III to inhibit factor IIa and Xa
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What are some adverse effects of heparin?
- Bleeding
- HIT
- Alopecia
- Osteoporosis
- Rebound hypercoagulability after stopping drug
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What are the contraindications to heparin
- Active bleeding, intracranial or GI
- Recent surgery on spine, brain, or eyes
- Severe HTN
- Previous HIT
- Hemophilia or thrombocytopenia
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What is the MOA of LMWH
LMWH mostly inhibits factor Xa but has less inhibition of factor IIa and platelet aggregation.
189
What are the drugs that are LMWH
enoxaparin, dalteparin, and tinzaparin
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What is the benefit of LMWH?
Less side effects, given SC, don't have to monitor PTT
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How is LMWH excreted and in which population should you use caution?
Renally excreted, use caution in those with renal failure
192
What is the MOA of warfarin?
Vitamin K antagonist
193
How long does it take for the anticoagulant effect of warfarin to occur?
4-5 days--> bridge w/ heparin
194
What is the target INR for people with mechanical heart valves?
2.5-3.5
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Adverse effects of warfarin?
- Hemorrhage
- Skin Necrosis
- Teratogenic
- DON'T GIVE TO PEOPLE AT RISK FOR FALLS (elderly, alcoholics)
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Why does skin necrosis occur with warfarin?
It is caused by a rapid decrease in protein C and S, (which actually increases clotting).
197
What is the MOA of clopidogrel
It blocks the binding of ADP to the PY12 receptor which reduced platelet activation and aggregation.
198
What are the direct factor Xa inhibitors?
Rivaroxaban, Apixaban, Edoxaban
199
What are the direct thrombin (IIa) inhibitors?
Dabigatran, argatroban, lepirudin
200
Define monoclonal gammopathy of undetermine significance
It is an asymptomatic premalignant clonal plasma cell proliferation.
201
How do you treat MGUS?
Don't do anything, just closely observe them to monitor for transformation to multiple myeloma.
202
How do you make the diagnosis of MGUS?
- IgG spike
- Bence-Jones Proteinuria
- NO end organ damage
203
Define multiple myeloma
A neoplastic proliferation of a single plasma cell line that produces monoclonal immunoglobulin.
204
Define CRAB in terms of multiple myeloma
C-Hypercalcemia
R-renal failure
A-anemia
B-bone lesions (lytic)
205
List 5 clinical features of Multiple Myeloma
1. ) Skeletal manifestations
2. ) Increased risk of infection
3. ) Renal failure
4. ) Anemia
5. ) Cord compression
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How does renal failure develop in Multiple Myeloma?
Myeloma Nephrosis-immunoglobulin precipitation in the renal tubules leads to tubular casts of Bence Jones proteins.
Also hypercalcemia contributes to the renal decompensation.
207
Why are patients with multiple myeloma at risk for recurrent infections?
because they are only producing one type of immunoglobulin and there is deprivation of normal immunoglobulins therefore humoral immunity is compromised.
208
How does cord compression occur in multiple myeloma?
1. Plasmacytoma
| 2. Fracture from bone fragment
209
What are some lab findings of multiple melanoma?
- Hypercalcemia
- Elevated ESR
- Rouleaux formation
- Increased total protein
- Bence Jones protein in urine
- Elevated Creatinine
- Leukopenia, thrombocytopenia, and anemia.
210
How do you make the diagnosis of multiple melanoma?
- Serum and urine protein electrophoresis will show M-protein (monoclonal protein)
- Bone scan to detect lytic lesions
- Bone marrow biopsy
211
What causes the osteolytic lesions of multiple myeloma?
Osteolytic lesions are secondary to the release of osteoclast-activating factor by the neoplastic plasma cells
212
What is the preferred treatment for multiple myeloma?
Hematopoietic cell transplantation. Usually reserved for younger and relatively asymptomatic patients.
213
What are other treatment options for multiple myeloma?
- Chemotherapy --> alkylating agents
| - Radiation therapy
214
What is Waldenstrom Macroglobulinemia
A malignant proliferation of plasmacytoid lylmphocytes. These lymphocytes produce IgM paraprotein which causes a hyperviscosity syndrome.
215
Are there bone lesions in Waldenstrom Macroglobulinemia?
NO
216
What are the clinical features of Waldenstrom Macroglobulinemia?
Fatigue, weight loss, neurologic symptoms, lymphadenopathy, splenomegaly, anemia, abnormal bleeding, hyperviscosity syndrome which can cause retinal vessel dilation with hemorrhage and blindness.
217
What mutation is commonly found in polycythemia vera?
JAK2 kinase
218
What are symptoms of hyperviscosity associated with PV?
Headache, dizziness, weakness, pruritus (esp. after taking a shower), visual impairment, dyspnea
219
What other clinical manifestations in addition to hyperviscosity can be seen with PV?
- Thrombotic phenomenon: DVT, CVA, MI, portal vein thrombosis
- Bleeding
- Splenomegaly, hepatomegaly
- HTN
220
What are some secondary causes of polycythemia?
CO poisoning, hypoxemia
221
What lab values are seen with PV? Hgb, Hct, leuks etc.
```
RBC-elevated
Hgb-elevated
Hct-elevated (often >50)
Thrombocytosis
Leukocytosis
Decreased serum levels of EPO
Elevated B12
Hyperuricemia
```
222
How do you confirm the diagnosis of polycythemia vera?
Bone marrow biopsy
223
Treatment for PV?
Repeated phlebotomy to lower the Hct
224
How do you make the diagnosis of a myelodysplastic syndrome?
- Normal or mildly elevated MCV
- Low retic count (BM isn't able to respond!)
- Howell Jolly Bodies
- Basophilic stippling
- Nucleated RBCs
- Large agranular platelets
225
Treatment of myelodysplastic syndrome
- RBC and platelet transfusion
- EPO
- Granulocyte CSF
- Vitamin Supplementation (B6, B12, Folate)
- BMT is the only potential cure
- Chemo, immunosuppressive agents have variable results
226
Define essential thrombocytosis
Platelet count >600,000
227
How does essential thrombocytosis usually manifest?
As a thrombotic event such as CVA. Could also present with paradoxical bleeding due to defective platelet function.
228
What are some other clinical findings seen with ET?
Splenomegaly
Pseudohyperkalemia
Elevated bleeding time
Erythromelalgia (burning pain and erythema of the extremities due to microvascular occlusions.
229
What will a peripheral smear in ET show?
Hypogranular abnormally shaped platelets
230
What will a bone marrow biopsy show in ET?
An increased number of megakaryocytes
231
Treatment of ET?
- Antiplatelet agents like: Anagrelide, low dose aspirin
| - Hydroxyurea
232
Which type of lymphoma has the worst prognosis?
Lymphocyte depleted type
233
What are the four subtypes of Hodgkin lymphoma?
- Nodular sclerosing
- Lymphocyte predominant
- Mixed Cellularity
- Lymphocyte Depleted
234
What cell is associated with HL?
Reen Sternberg
235
Describe the Ann Arbor Staging System
Stage 1: Confined to single lymph node
Stage 2: involvement of >/= 2 lymph nodes but on the same side of the diaphragm
Stage 3: Both sides of the diaphragm involved
Stage 4: metastatic disease to extralymphatic sites
236
Subtypes of HL-define A and B
A-no B symptoms
| B-B symptoms present (fever, weight loss, night sweats)
237
What is the most common symptom of Hodgkin Lymphoma
Painless lymphadenopathy
238
How does Hodgkin Lymphoma Spread?
Anatomically, from one lymph node to the next
239
What are 2 unique clinical signs associated with HL?
- Pel Epstein Fevers
| - Etoh lymphadenopathy
240
What 2 chemo regimens are used for HL?
BEACOPP and ABVD
241
How do you make the diagnosis of HL? There are 4 things
1. Lymph node biopsy w/ the presence of Reed-Sternberg Cells
2. Presence of inflammatory cell infiltrates (distinguishes HL from NHL, these are reactive to the Reed-Sternberg cells)
3. CXR and CT scan to determine extent of involvement
4. Bone marrow biopsy to evaluate bone marrow involvement
242
Stages I, II, and IIIa of HL can be treated with?
Radiotherapy alone to the involved field.
243
Stages IIIb and IV of HL are treated with?
Chemotherapy
244
How does NHL spread?
Non-contiguously to blood and bone marrow.
245
Where can a primary tumor in NHL be found?
GI tract
246
Which disease is more common? HL and NHL and who usually presents with more advanced disease?
NHL is twice as common as HL. NHL typically presents with more advanced disease, stage IIb or greater.
247
What are some risk factors for NHL?
- Immunosuppression
- HIV/AIDs
- EBV, HTLV-1 viral infections
- H. Pylori infection (increases risk of gastric associated lymphoma)
- Autoimmune disease like Sjogrens or Hashimotos that increases risk of mucosa associated lymphoid tissue (MALT).
248
What are some of the presenting signs of NHL?
- Lymphadenopathy (painless, firm, and mobile)
- HSM and early satiety/fullness
- B Symptoms (less common than in HL)
- Recurrent infections, symptoms of anemia or thrombocytopenia due to bone marrow involvement
- other findings include SVC syndrome, bone pain, respiratory involvement, skin lesions etc.
249
How do you diagnose HL?
- LYMPH NODE BIOPSY
- Other tests that may help: CXR and CT to determine extent of spread, serum LDH and beta-2 microglobulin are indicators of tumor burden, if alk phos is elevated, liver or bone involvement is likely. If LFTs or Bili is elevated liver involvement is likely; CBC, serum electrolytes, renal function tests, bone marrow biopsy
250
What is the diagnostic criteria or guideline for biopsy a lymph node?
ANY LYMPH NODE >1 CM PRESENT FOR MORE THAN 4 WEEKS THAT CANNOT BE ATTRIBUTED TO INFECTION SHOULD BE BIOPSIED
251
What is the chemo regimen for NHL?
R-CHOP
Rituxumab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
252
Risk factors for AML?
Exposure to radiation, myeloproliferative syndromes, down syndrome and chemotherapy
253
Translocation for APML?
t(15;17)
254
Treatment for APML
ATRA
255
Complications of APML
DIC 2/2 Auer Rods
256
What is the most common malignancy in children under age 15 in the US?
ALL-neoplasm of early lymphocytic precursors.
257
What is the feared complication of ALL and what do you do about it?
CNS involvement, prophylactically treat w/ intrathecal chemo
258
Which leukemia involves the testicles?
ALL
259
Which leukemia involves a mediastinal mass?
T-cell ALL
260
Which leukemia involves skin nodules?
AML
261
Lab abnormalities seen in tumor lysis syndrome?
```
Hypocalcemia
Hyperphosphatemia
Hyperkalemia
Hyperuricemia
This is a medical emergency!
```
262
What is the most common leukemia after age 50?
CLL
263
Is CLL scary?
No. They are more likely to die with it than from it.
264
How does CLL present?
Usually asymptomatic but picked up on a routine CBC as lymphocytosis. May have generalized painless lymphadenoptahy, splenomegaly, infections etc.
265
What is the CBC leukocyte range in CLL?
50k-200k. HIGH
266
What is the classic cell seen on a peripheral smear in CLL?
Smudge cell. These are fragile leukemic cells that are broken when placed on a glass slide.
267
Is CLL lymphocytic or myelogenous?
It is a monoclonal proliferation of lymphocytes that are morphologically mature but functionally defective meaning they do not differentiate into antibody manufacturing plasma cells.
268
How do you differentiate CML from a Leukemoid reaction?
In a leukemoid reaction:
- Usually no splenomegaly
- Leukocyte alkaline phosphatase is HIGH
- precipitating event like infection
269
That is the pathogenesis of CML?
Translocation between t(9:22) resulting in BCR-ABL constituitively active tyrosine kinase that result in neoplastic clonal proliferation of myeloid stem cells.
270
What is the feared complication of CML?
Transformation to an acute phase or blast crisis
271
What do we treat CML with?
TKIs: Imatinib, Dasatinib, or Nilotinib.
272
What are some of the presenting signs of CML?
fevers, night sweats, fatigue, weight loss, recurrent infections, easy bruising/bleeding, anemia symptoms.
splenomegaly, hepatomegaly, LAD.
273
What lab findings allow you to make the diagnosis of CML?
- LOW LAP
- Marked leukocytosis
- small number of blasts
- leukemic cells in the peripheral blood
- Thrombocytosis
- Bone marrow biopsy will show leukemic cells.
