USMLE Heme Flashcards
1
Q
Primary fibrinolysis
A
Plasmin overactive
Causes increase in fibrin degradation products with normal D-dimer (no clot or crosslinked fibrin)
Plasmin can deplete clotting factors, therefore increased PT/PTT with bleeding
2
Q
What does warfarin do? MOA
A
Antagonizes vitamin K
3
Q
Where are vWF stored in?
A
Stored in Weibel-Palade bodies in endothelial cells
vWF is synthesized by endothelial cells and megakaryocytes
4
Q
What do alpha granules contain?
A
Fibrinogen, vWF, platelet factor 4
5
Q
What do dense granules contain?
A
ADP, calcium, serotonin
6
Q
Heparin induced thrombocytopenia
A
Platelet factor 4 is released from alpha granules
Antibodies formed to PF4 complexed with heparin, causing platelet activation
Diffuse thrombosis
7
Q
Phosphodiesterase inhibitors
A
Increase cAMP levels
Can inhibit platelet activation
8
Q
P2Y12
A
Increases platelet aggregation
P2Y12 receptor blocking drugs include clopidogrel, prasugrel, ticlopidine, ticagrelor
9
Q
Thromboxane A2
A
Powerful platelet activator
Basis for ASA therapy
10
Q
Arachidonic acid
A
Released at sites of energy
AA converted to TXA2 by cyclooxygenase (COX)
11
Q
Bleeding time is a test of
A
platelet function
12
Q
Virchow’s triad
A
3 elements that lead to formation of thrombus
Endothelial damage, stasis of blood and hypercoagulability
13
Q
Elevated homocysteine
A
Hypercoagulable state
Levels lowered by folate
14
Q
Antithrombin
A
Inhibits activated forms of factors II, VII, IX, X, XI and XII
Heparin enhances activity of antithrombin
15
Q
Factor V Leiden mutation
A
Most common cause of inherited hypercoagulability in Caucasians
Resistant to degradation by activated protein C
Point mutation
Arg506Gln
16
Q
Protein C or S inactivate what?
A
Factors Va and VIIIa
17
Q
What is associated with warfarin skin necrosis?
A
Protein C or S deficiency
18
Q
Antiphospholipid syndrome
A
Increased risk of venous and arterial thrombosis
Recurrent fetal loss
Prolonged PTT
19
Q
What can cause false positive of VDRL/RPR?
A
Anticardiolipin antibodies in antiphospholipid syndrome
20
Q
Three antibodies in antiphospholipid syndrome
A
Anti-cardiolipin -> false + RPR/VDRL
Lupus anticoagulant -> high PTT
Anti-beta 2 glycoprotein
21
Q
Tx of hemophilia
A
Desmopressin
Increases vWF and factor VIII
22
Q
Aminocaproic acid
A
Antifibrinolytic drug
Inhibits plasminogen activation
Therefore less breakdown of formed clots
23
Q
Cryoprecipitate
A
Precipitate that forms when FFP is thawed
Contains factor VIII, fibrinogen
Source of fibrinogen for DIC and massive trauma
24
Q
Vitamin K dependent factors
A
II, VII, IX, X and proteins C and S
25
Vitamin K deficiency
Increased PT, increased INR and increased PTT
26
Glanzmann thrombasthenia
Defect in platelet integrin alphaIIbbeta3 (GpIIb/IIIa)
27
Bernard-Soulier syndrome
Decrease in Gp1b therefore defect in platelet to vWF adhesion
Giant platelet
28
Wiskott-Aldrich syndrome
XR; mutation in WASp gene where leukocytes and platelets unable to reorganized actin cytoskeleton -> defective antigen presentation
WATER: Wiskott-Aldrich: thrombocytopenia, eczema, recurrent pyogenic infections
29
Idiopathic thrombocytopenic purpura
Disorder of decreased platelet survival
Commonly caused by anti-GPIIB/IIIA antibody
Consumption by splenic macrophages
30
Tx of ITP
Steroids (decrease inflammation to decrease macrophage activation)
IVIG (competitive inhibition of Fc receptors on macrophages)
Splenectomy
31
TTP
Decreased activity of vWF cleaving protease ADAMTS13
FAT RN: fever, hemoangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic symptoms
Normal PT and PTT
32
Hemolytic uremic syndrome
Commonly seen in children
~TTP but no neurological deficits
Commonly follow GI infection E. coli O157:H7
33
Common presentation of vW dz
Mild, non-life-threatening
```
Easy bruising
Skin bleeding
Prolonged BT
Severe nosebleeds
Menorrhagia
```
34
What kind of test do you do for vW dz?
Ristocetin cofactor activity assay
35
Tx of vW dz
Desmopressin - increases vWF and factor VIII
Aminocaproic acid - inhibits plasminogen activation
36
One common side effect of ASA
Tinnitus (caused by salicylate which interferes with cochlear nerve function)
37
Reye's syndrome
Liver failure and encephalopathy in children
OK to use in Kawasaki syndrome
38
ADP receptor inhibitors
Clopidogrel
Prasugrel
Ticagrelor (reversible)
Ticlopidine
All can cause TTP
39
Phosphodiesterase inhibitors
Cilostazol, dipyridamole
| Causes increased cAMP therefore inhibition of platelet aggregation
40
Abciximab, eptifibatide, tirofiban
IIB/IIIA receptor blockers
Preventing aggregation
AE: thrombocytopenia
41
Unfractionated heparin increases what lab value?
Increases PTT
42
Reversible agent for heparin
Protamine
43
Significant drop in platelets can mean what?
Heparin induced thrombocytopenia
44
LMWH will only affect
Factor Xa
45
Benefits of direct factor Xa inhibitors
Do not need to monitor PT/INR vs heparin
46
What time should you monitor in warfarin pts?
PT (should be increased)
VII has the shortest half life
47
Prothrombotic effects of warfarin
Due to protein C (short half life)
Initial warfarin Rx = protein C to be deficient, thus pro-thrombotic
48
Major side effect of warfarin?
Wafarin skin necrosis
49
Reversal agent of warfarin
Vitamin K, FFP
50
Key blood test in normocytic anemias
Reticulocyte count
```
Low = underproduction
High = increased destruction/hemolysis
```
High LDH too
51
Correct for reticulocyte count
Correct RC = new RC% x (new Hct/old Hct)
52
Haptoglobin
Plasma protein that binds free hemoglobin
Resulting complex is removed by liver
Decreased serum haptoglobin with intravascular hemolysis
53
Classic findings of hemolysis
```
Normocytic anemia
Inc LDH
Inc indirect bilirubin
Inc reticulocyte count
Dec haptoglobin
Urine Hgb and hemosiderin (intravascular)
```
54
Parvovirus B19
Worsening anemia with low reticulocyte count
55
Warm autoimmune hemolytic anemia is associated with what type of antibody?
IgG antibodies against RBC surface antigens
56
What is the diagnostic finding of warm autoimmune hemolytic anemia?
Spherocytes (smaller than normal RBCs) - spherical
57
Which drug is associated with warm AIHA?
Alpha methyldopa
Also penicillin
58
Cold AIHA is positive for?
C3
59
What infections/conditions are cold AIHA associated with?
Chronic lymphocytic leukemia
Mycoplasma pneumonia
EBV - infectious mono
60
Blood smear findings of MAHA
Schistocytes
61
Which two infections are associated with hemolytic anemia?
Malaria
| Babesia
62
Paroxysmal nocturnal hemoglobinuria
RBC destruction via complement system
Acquired genetic mutation in SC; loss of GPI anchor
Leads to loss of DAF/CD59 that protect RBC membrane from complement
63
What is also common with PNH?
Fe deficiency
AP
Thrombosis - usually venous clots
Increased incidence of acute myeloid leukemia
64
Eculizumab
Anti-complement therapy
Antibody that binds to complement component C5 (prevents cleavage to C5a and C5b); blocks formation of MAC (depends on C5b)
65
Tx of PNH
Eculizumab
66
Pyruvate kinase deficiency
RBCs most affected
No mitochondria
Require PK for anaerobic metabolism
Therefore there is membrane failure, resulting in phagocytosis in spleen
67
HMP shunt is necessary for generation
NADPH
NADPH protects RBCs from oxidative damage
G6PD is a key enzyme in this shunt
68
What are some triggers of G6PD deficiency?
These trigger the production of H2O2
Sulfa drugs, antimalarials (primaquine), infections and fava bean
69
Blood smear findings of G6PD deficiency
Heinz bodies and bite cells
70
G6PD deficiency protects against
malaria
71
Hereditary spherocytosis
Cytoskeleton abnormality
Proteins include spectrin, ankyrin, band 3, protein 4.2
Dz from chronic destruction in the spleen
72
What infection is associated with hereditary spherocytosis?
Risk of aplastic crisis with parvovirus B19 infection
73
Tx of hereditary spherocytosis
Splenectomy
Howell-Jolly bodies appear (normally cleared by spleen)
74
What will you see if the spleen has been removed?
Howell-Jolly bodies
75
What type of cell regulates iron?
Enterocytes
Fe transporter = ferroportin
76
Two types of protein in Fe metabolism
Transport protein: transferrin
Storage protein: ferritin (stored intracellularly as ferritin; stored in macrophages of liver and bone)
77
TIBC is a measure of
Amount of transferrin in the serum
78
Who can develop iron deficiency very easily?
Babies
Fe stores depleted ~ 6 months
79
Where is Fe absorbed?
Duodenum
80
Adult or post-menopausal female with Fe deficiency must have a work-up for?
Colon CA
81
Rare causes of Fe deficiency
Hookworms, which consume blood in intestines (Ancylostoma
82
Plummer-Vinson syndrome
Fe deficiency
Beefy red tongue
Esophageal webs
83
Key findings of Fe deficiency
Decreased serum iron, ferritin and % sat
Increased transferrin, RDW, protoporphyrin
84
Increased RDW
Iron, B12/folate deficiency
85
Anemia of chronic dz
Increased hepcidin, increased ferritin
Associated with RA, SLE, neoplastic disorders and CKD
86
Lead poisoning
Microcytic, hypochromic anemia
Inhibition of ferrochelatase and ALA dehydratase
Decreased heme synthesis
87
What are increased in lead poisoning?
Plasma lead level, delta-ALA and protoporphyrin
88
Blood smear finding in lead poisoning
Basophilic stippling
| Also seen in thalassemias and other anemias
89
Symptoms of lead poisoning
AP, constirpation, HA
"Lead lines" - blue pigment on gum-tooth line
Nephropathy - injury to proximal tubules (Fanconi type syndrome)
Neuropathy - drop wrist and foot
90
Tx of lead poisoning
Dimercaprol
Calcium diosium
DMSA
91
Common cause of sideroblastic anemia
Alcohol
Isoniazid (vit B6 deficiency)
(typically 2/2 toxin)
92
Sideroblastic anemia can be be genetic. What is the tx?
Vitamin B6 (will activate whatever ALA synthase is available)
X-linked
Rare deficiency of ALA synthase
93
Lab findings in sideroblastic anemia
Increased serum iron, ferritin
Low TIBC, erythrocyte protoporphyrin
94
Basic difference between alpha and beta thalassemias
Alpha is due to gene deletion
Beta is due to point mutation
95
Alpha thalassemia minor: diff b/w Asians and Africans
Asians have cis
Africans have trans
More severe in Asians
96
HbH dz
Very little alpha globin production
Therefore beta globin; HbH forms 4 beta chains
Very high affinity for oxygen
97
How to dx beta thalassemia minor
Electrophoresis
Increase in HgbA2 (alpha2gamma2 = no beta chains)
98
Anisocytosis and poikilocytosis
Abnormal size and shapes associated with beta thalassemia major
99
Which condition do you find target cells?
Beta thalassemia
100
Pathophys of sickle cell anemia
Single base substitution (glutamic acid to valine)
101
Chipmunk facies and crew cut appearance
Beta thalassemia
Sickle cell anemia
102
Aplastic crisis
Seen in spherocytosis, thalassemia, parvovirus B19
103
Sickle cell anemia symptoms
Dactylitis
Avascular necrosis of femoral head
Painful crises
Splenic infarct/failure
Osteomyelitis from Salmonella
Chest syndrome
Renal dysfunction
104
Which bug is associated with sickle cell anemia?
Salmonella (encapsulated), causing osteomyelitis
105
Tx of sickle cell anemia
Immunizations, hydroxyurea to raise the amount of HbF, transfusions
106
Blood smear on hemoglobin dz
Glutamic acid to lysine
Crystals in RBCs
107
EPO produced in which part of the kidneys?
Interstitial cells peritubular capillary (cortex)
108
What condition should you consider in anemia of chronic dz?
CKD
Decrease in EPO
Therefore tx = EPO injections
109
Causes of aplastic anemia?
Still widely thought of as idiopathic, but potentially immune mediated with T cell mediated destruction
Radiation, benzene, chloramphenicol, methimazole, propylthiouracil, acute viral hepatitis, Fanconi anemia
110
Tx of aplastic anemia
Antithymocyte globulin and cyclosporine
111
Fanconi anemia
Inherited aplastic anemia
AR or XL; usually in children < 16 years old with physical deformities
High risk of malignancies
112
Pure red cell aplasia
Key association = thymoma
Absence of erythroid precursors in BM
113
Hypersegmented neutrophils is seen in...?
Megaloblastic anemia
114
Tx of newborn hemolytic dz
Anti-D immune globulin (RhoGAM) = IgG antibodies to D antigen
Rapid macrophage clearance of D+ RBCs
115
When would FFP be administered?
To replenish clotting factors
116
Anaphylaxis of blood transfusion rxns
May occur in IgA deficient individuals
Produce anti-IgA antibodies
Tx: stop transfusion, epinephrine and anti-histamines
117
Transfusion-related acute lung injury
Sudden onset hypoxemia during transfusion
Infiltrates on CXR
Results from neutrophil activation by blood products
118
Acute lymphoblastic leukemia
Usually pre-B cell malignancy
CD10
(Note that TdT is found on both pre-T and pre-B cells)
119
Which two sites may ALL spread to?
CNS and testes
120
Chr for ALL
t(12;21)
121
T-cell ALL may present as a
Mediastinal mass (thymus)
Causing SVC-like syndrome
122
AML
Malignancy of myeloblasts
Common in adult males
Symptoms from BM suppression
Myeloperoxidase positive (Auer rods)
123
Chr for APML
t(15;17)
Creates fusion gene PML-RARA
RARA = retinoic acid receptor alpha (chr 17)
124
Pathophys for APML
Abnormal retinoic acid receptor
DIC
125
Myelodysplasia (myelodysplastic syndrome)
Abnormal myeloid progenitor cells
Leads to ineffective hematopoiesis
Can progress to AML
126
RF for myelodysplasia
Environmental factors such as radiation, chemotherapy and usually years after exposure
127
How to distinguish CML from left shift (leukemoid rxn)
LAP (leukocyte alk phos)
Low in CML
High in leukemoid
128
Chr for CML
t(9;22) and BCR-ABL (22-9), which codes for tyrosine kinase
129
Immune marker for CLL
CD5+ B cell (unusual since it is usually in T cells)
130
CLL/SLL can progress to
Diffuse large B cell lymphoma
131
Three notable features of hairy cell leukemia
Dry tap
Massive splenomegaly
TRAP
132
Tx of hairy cell leukemia
Cladribine
133
Reed-Sternberg cells seen in what condition
Hodgkin lymphoma
134
Two markers of Reed-Sternberg cells
CD15 and CD30
135
Nodular sclerosing Hodgkin lymphoma
Often presents with mediastinal mass on CXR
More common in women
Hodgkin lymphoma (common in males)
136
Different subtypes of Hodgkin lymphoma
Nodular sclerosis
Common in females
Lymphocyte rich
Good prognosis
Mixed cellularity
Eosinophilia
Lymphocyte depleted
Bad prognosis
137
What lymphoid tissue is often involved in non-Hodgkin lymphoma?
Waldeyer's ring
138
Diffuse large B-cell lymphoma occurs in what condition?
HIV-AIDS defining malignancy
139
Tx for diffuse large B-cell lymphoma and follicular lymphoma
Rituximab
140
Chr in follicular lymphoma
t(14;18)
| BCL2 (18) - blocks apoptosis
141
Chr in mantle cell lymphoma
t(11;14)
| CD5
142
Marginal zone lymphoma
Lymphoma associated in chronic inflammatory disorders
Salivary glands in Sjogen's, thyroid in Hashimoto, stomach in H Pylori (MALToma)
143
Burkitt lymphoma - endemic form and sporadic form
Endemic form - jaw lesion
Sporadic form - abdomen
144
Epstein Barr virus (EBV)
Express CD21
145
T-cell leukemia/lymphoma
CD4 T cell malignancy
Occurs with HTLV-1 infection (RNA virus infecting CD4 T cells)
Dx: anti-HTLV1 antibodies
Present with skin lesions (ulcers, nodules, papular rash)
146
A specific finding on adult T cell lymphoma that is similar to multiple myeloma
Lytic bone lesions with hypercalcemia
147
Cutaneous T cell lymphoma (localized and diffuse)
Localized: mycosis fungoides
Diffuse: Sezary syndrome
148
Mycosis fungoides
Neoplasm of mature T cell
Pautrier microabscesses (epidermal aggregates)
Lymphoid cells on biopsy
149
Multiple myeloma is dependent on which cytokine
IL-6
150
What do you see on serum protein electrophoresis for multiple myeloma?
Gamma spike (M spike)
151
Light chains found in urine of multiple myeloma patients?
Bence Jones proteins
152
Findings of multiple myloma
CRAB
Hypercalcemia
Renal failure
Anemia - normocytic, normochromic
Bone lytic lesions/back pain
153
Waldenstrom macroglobulinemia
No osteolytic bone lesions, no CRAB
Hyperviscosity syndrome with visual impairment
M spike
154
Protein in primary amyloidosis vs secondary amyloidosis
Ig light chains
| vs serum amyloid AA (AA)
155
Amyloid protein in dialysis related amyloidosis, age-related systemic amyloidosis
Beta-2 microglobulin (dialysis)
Transthyretin (age related systemic)
156
Secondary amyloidosis
Serum amyloid A is an acute phase reactant therefore seen with a lot of chronic inflammatory conditions such as RA, IBD and familial Mediterranean fever
157
Familial Mediterranean fever
Inflammatory dz involving neutrophils with recurrent episodes of fever and inflammatory pain
Secondary AA amyloidosis is a major cause of death
Tx = colchicine
158
Dialysis related amyloidosis can cause what?
Shoulder pain, CTS
159
Systemic senile (age-related) amyloidosis
Normal transthyretin
Seen predominantly in cardiac ventricles
160
Clinical features of amyloidosis
Heart - restrictive cardiomyopathy, arrhythmias
Renal - nephrotic syndrome
161
Genetics of myeloproliferative disorders
JAK2 mutation, which codes for a tyrosine kinase
162
EPO level in polycythemia vera
Decreased EPOs
163
Tx of polycythemia vera
Phlebotomy, hydroxyurea
164
Teardrop RBC is associated with what condition?
Myelofibrosis
165
CD markers of Langerhans cell histiocytosis
S100, CD1a, CD207
166
Three types of Langerhans cell histiocytosis
Eosinophilic granulosa
Hand-Schuller-Christian dz
Letterer Siwe dz (most severe) - < 2 yo, FTT, rapidly fatal)
