Ch. 9 Heme/Onc, Allergy, Immunology Flashcards
What are 5 causes of microcytic anemia?
- Iron deficiency
- Thalassemia
- lead poisoning
- sideroblastic anemia
- chronic disease
What are 5 causes of normocytic anemia?
- hemorrhage
- hemolysis
- aplastic anemia
- sickle cell disease
- anemia of chronic disease/renal disease
What are 4 causes of macrocytic anemia?
- Vitamin B12 deficiency
- Folate deficiency
- Sulfa drugs
- EtOH abuse
What are normal fasting serum iron levels?
60-180 ug/dL
How will TIBC be changed in iron deficiency anemia?
increased, >400 ug/dL
What route causes lead poisoning in adults?
inhalation
(whereas in children, it is ingestion)
What causes sideroblastic anemia?
acquired or congenital defect in porphyrin synthesis.
Often related to toxins (like chloramphenicol,
isoniazid, cycloserine, lead); infections; malignancy; rheumatologic disease;
or hemolytic anemia.
What congenital disorder commonly causes aplastic anemia?
Fanconi anemia
What medications commonly cause aplastic anemia?
NSAIDs, chloramphenicol, sulfonamides, antiepileptics drugs, nifedipine
What viral infection most commonly causes aplastic anemia?
Parvovirus B19
(HIV and hepatitis also implicated)
Dark urine related to hemoglobinuria usually indicates ______ hemolysis
intravascular
Splenomegaly is more common in _______ hemolysis
extravascular
In _______ hemolysis, look for increased LDH, decreased haptoglobin,
hemoglobinuria, and schistocytes.
intravascular
In _______ hemolysis, look for indirect hyperbilirubinemia, increased
LDH, and spherocytes.
extravascular
Autosomal dominate disease caused by a defect in red cell membrane protein.
Hereditary spherocytosis
What is a risk factor for hereditary spherocytosis?
More common among persons of Northern European decent
What causes anemia in Hereditary Spherocytosis?
RBCs take on a microspherocytic shape that is unable to pass through the spleen leading to RBC destruction
How is Hereditary Spherocytosis diagnosed?
■ Peripheral smear with spherocytes.
■ Negative Coombs test (to rule out autoimmune hemolytic anemia).
■ Osmotic fragility test is confirmative.
What is the treatment for Hereditary Spherocytosis?
Folic acid supplementation in mild-moderate disease; splenectomy is curative
and indicated for severe anemia.
This X-linked recessive disorder results in RBCs that are more susceptible to oxidant stress.
G6PD Deficiency
What are risk factors for G6PD?
African, Asian, and Mediterranean descent
How does G6PD lead to anemia?
Oxidant stress leads to hemoglobin precipitation within the RBC and subsequently both intravascular cell lysis and removal of cell from circulation via spleen
What drugs/oxidizing agents commonly precipitate hemolysis in G6PD deficiency?
Dapsone, methylene blue, nitrofurantoin, phenazopyridine (Pyridium), primaquine sulfonamides, antimalarials
What are signs and symptoms of hemolytic crisis in G6PD deficiency?
severe hemolysis with dark urine (hemoglobinuria), jaundice, pallor, splenomegaly, dyspnea, and possible vascular collapse
How is G6PD diagnosed?
■ Laboratory findings of both intravascular and extravascular hemolysis.
■ Peripheral smear showing Heinz bodies (RBCs with precipitated hemoglobin) and degmacytes (aka “bite cell”)
Heinz bodies appear similar to Howell-Jolly bodies, but Heinz bodies will be stained with methylene blue and therefore be bluer in color rather than red/pink
■ Confirm diagnosis with G6PD enzyme activity; should delay testing by 3 weeks after acute event because reticulocytes have more normal levels of G6PD enzyme.
anemia caused by antibodies formed against native RBC antigens
Autoimmune (warm and cold antibody) hemolytic anemia
Which type of Autoimmune hemolytic anemia is caused by IgG antibodies form against native RBC antigens?
Warm antibody – bind at body temperature
Which type of Autoimmune hemolytic anemia is caused by IgM antibodies form against native RBC antigens?
Cold antibody – bind at cool temperatures
What commonly triggers Warm antibody autoimmune hemolytic anemia?
lymphoproliferative disorders?
What commonly triggers Cold antibody autoimmune hemolytic anemia?
Acute: mycoplasma pneumonia or Epstein-Barr infection
Chronic: Lymphoma or Waldenstrom macroglobulinemia
What do you call anemia caused by Antibodies form in response to foreign RBC antigens?
Alloimmune hemolytic anemia
What medications commonly cause auto-immune hemolytic anemia?
Cephalosporins, levodopa, methyldopa, penicillin, sulfa, quinidine, oral hypoglycemic agents, some NSAIDs
What is the pathophysiology for Drug-induced hemolytic anemia?
Antibody, hapten, or immune complex binding to RBCs leads to rapid cell destruction via complement fixation and/or sequestration by the spleen where affected portions of the RBC membrane are digested by macrophages leading to development of microspherocytes.
_________ on peripheral smear suggest splenic sequestration.
Microspherocytes
______ Coombs test measures immunoglobulin G [IgG]-mediated reactions like warm antibody
hemolytic anemia
direct
_____ Coombs test measures immunoglobulin M [IgM] or complement mediated reactions like cold antibody hemolytic anemia).
indirect
What are 6 causes of microangiopathic hemolytic anemia?
DIC
TTP
HUS
Pregnancy
Malignant HTN
Malignancies
Occurs in children and is recognized as microangiopathic anemia, thrombocytopenia, and renal dysfunction following a diarrheal illness
HUS
What bacteria are implicated in HUS?
classically caused by Shiga toxin–producing bacteria-like Escherichia coli, Shigella, Salmonella
What causes classic TTP?
congenital or acquired deficiency in ADAMTS13 protein activity
Besides bacteria, what are some other known causes of TTP-HUS in adults?
drugs (quinine, antiplatelet agents, chemotherapeutic agents); malignancy; and pregnancy
How does HUS-TTP cause anemia and thrombocytopenia?
Fibrin deposition and platelet aggregation in capillaries and arterioles lead to intravascular
hemolysis (microangiopathic hemolytic anemia) and thrombocytopenia
How does HUS-TTP lead to renal failure?
microthrombi in renal vasculature
How does HUS-TTP lead to neurologic symptoms?
microthrombi in CNS
What is the classic pentad of TTP?
fever, anemia, thrombocytopenia, renal failure,
and neurology problems
What are the three lab findings of microangiopathic hemolytic anemia?
anemia with:
1. decreased haptoglobin
2. elevated LDH
3. presence of schistocytes on peripheral smear
What is the treatment for typical HUS?
supportive care
What is the treatment for TTP or severe HUS?
plasma exchange therapy
What defines a-thalassemia?
≥ 1 of the 4 α-globin chain genes fail to function
What defines a-thalassemia carrier state?
one mutated gene; asymptomatic, normal CBC
What defines α-Thalassemia minor?
two mutated genes; usually asymptomatic, mild
microcytic anemia
What defines Hemoglobin H disease?
three mutated a chain genes; splenomegaly, jaundice,
chronic microcytic anemia
(most severe non-fatal form of alpha thalassemia)
What defines α-Thalassemia major/hydrops fetalis?
four mutated genes; fetal demise
How is B-Thalassemia minor defined?
one mutated gene; asymptomatic, hypochromic,
microcytic anemia
How is B-Thalassemia major/Cooley anemia defined?
two mutated genes; severe anemia,
splenomegaly, frontal bossing
What is the treatment for B-Thalassemia major?
Patients require transfusions to sustain life
and iron chelation therapy to prevent complications from chronic transfusions.
Splenectomy may reduce transfusion requirements
How is Sickle cell trait defined?
caused by defect in only one β-globin chain and produces a less severe form of the disease with sickling only under conditions of severe hypoxia
How is sickle cell disease defined?
This autosomal recessive disease is caused by an abnormal structure to BOTH β-globin chains of hemoglobin, resulting in sickling of deoxygenated RBC.
What is the most common manifestation of sickle cell crisis?
Vaso-Occlusive pain crisis
How long does pain from vaso-occlusive pain crisis typically last?
5-7 days
What is the treatment for vaso-occlusive pain crisis?
analgesia +/- IV/PO hydration if dehydrated
When are antibiotics implicated in vaso-occlusive pain crisis?
any age with concern for infection
and empirically in children < 2 years old with a temperature ≥ 39.5°C/103.1°F or white blood cells (WBCs) >20,000/μL
When are exchange transfusions indicated for sickle cell patients?
cardiopulmonary collapse, acute CNS event, acute chest syndrome, and priapism
What causes acute chest syndrome in sickle cell patients?
a combination of pulmonary vascular infarction
and/or infection
What pathogens are most commonly implicated in acute chest syndrome?
Chlamydia, Mycoplasma, respiratory syncytial
virus (RSV), Staphylococcus aureus, and Streptococcus pneumoniae
What is the treatment for acute chest syndrome?
supportive with O2, IV hydration, analgesia
+Abx (Azithromycin and Cefotaxime)
When is exchange transfusion indicated in acute chest syndrome?
multiple lobe involvement, severe
hypoxia, and disease refractory to antibiotics and supportive care
What is splenic sequestration Crisis?
Rapid sequestration of RBCs in spleen causing splenomegaly and severe anemia;
(usually 6 months-6 years old in setting
of viral illness)
How is Splenic Sequestration Crisis diagnosed?
Very low hemoglobin with evidence for reticulocytosis and palpable splenomegaly
What is aplastic crisis in sickle cell patients?
Sudden decrease in hemoglobin production by bone marrow resulting in severe anemia; usually precipitated by infection (parvovirus B19).
What is the treatment for stroke caused by Sickle Cell disease?
Exchange transfusions to HbS < 25%.
How is aplastic crisis diagnosed?
Hemoglobin fall > 2 g/dL from baseline without reticulocytosis (< 2%)
How is polycythemia defined?
an increase in RBC count to:
Women: Hgb > 16.5 g/ dL (Hct > 48%)
Men: Hgb > 18.5 g/dL (Hct > 52%)
What are some causes of secondary polycythemia?
conditions that increase erythropoietin levels such as:
lung disease, heart disease, high altitude, and erythropoietin-secreting tumors.
What are symptoms of polycythemia?
pruritus, headache, dizziness, blurry vision, plethora
How is primary polycythemia (vera) differentiated from secondary polycythemia?
primary polycythemia will have decreased serum EPO level, whereas it will be elevated in secondary polycythemia
What is the treatment for polycythemia? Treatment goal?
Phlebotomy
Goal Hct of 55%
How is methemoglobinemia defined?
Hemoglobin-containing ferric iron (Fe3+) – wont bind O2
What are common causes of methemoglobinemia?
Nitrates (in well water or vegetables)
Medications: Lidocaine, benzocaine, nitrates, nitroglycerin, nitroprusside, sulfonamides, dapsone, phenazopyridine (Pyridium), inhaled nitric oxide
Describe pulse ox in context of methemoglobinemia?
Classically see pulse oximetry of 80%-85% without response to supplemental O2
What causes classic chocolate brown blood on venipuncture?
methemoglobinemia
At what methemoglobin levels do you become symptomatic?
levels >20%;
levels >40% leads to significant mortality
What is the treatment for methemoglobinemia?
Methylene blue (1-2 mg/kg IV) facilitates the reduction of Fe3+ to Fe2+
BUT IS CONTRAINDICATED IN G6PD PATIENTS (bc may cause hemolysis and worsen symptoms)
Methemoglobinemia causes a ____ shift in the oxygen dissociation curve.
Leftward (cannot bind O2, therefore decreased delivery/dissociation)
How is leukemoid reaction differentiated from CML?
leukemoid reaction = normal leukocyte alkaline phosphatase (LAP) level
CML = low LAP
In which form of leukemia is the Philadelphia chromosome uniformly present (translocation between chrom. 9 and 22)?
CML
What is the most common ACUTE leukemia in adults?
AML
What is the most common leukemia in adults?
CLL (aka SLL)
How are AML and ALL diagnosed?
Bone marrow biopsy
How is CLL diagnosed?
flow cytometry
Which leukemia is known for being a malignancy of childhood with most cases occurring in children from 2-5 years old?
ALL
Malignant proliferation of a single plasma cell clone with subsequent uncontrolled
production of a single immunoglobulin
Multiple myeloma
How is multiple myeloma diagnosed?
anemia + renal failure
elevated protein:albumin ratio
Confirmation: serum/urine electrophoresis
A group of lymphoid malignancies characterized by the presence of Reed-Sternberg cells (owl eye cells) contained within a reactive cellular background
Hodgkin Lymphoma
What is the age distribution for Hodgkin Lymphoma?
bimodal: young adults (20s-30s) and adults >50 yrs old
Heterogeneous group of B-cell and T-cell malignancies that range from indolent
to highly aggressive and rapidly fatal. This is generally a disease of the elderly.
Non-Hodgkin Lymphoma (NHL)
Which type of lymphomas often have extranodal disease (GI and skin)?
Non-Hodgkin Lymphomas
What is the treatment for aggressive NHL?
Chemo: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
+/- rituximab (an anti-CD20 monoclonal antibody)
How is the intrinsic pathway of coagulation measured?
activated partial thromboplastin time (aPTT).
How is the extrinsic pathway of coagulation measured?
prothrombin time (PT).
What causes prolonged PT?
vitamin K deficiency
Warfarin
DIC
factor deficiency
liver disease
What causes prolonged PTT
Hemophilia A (Factor VIII)
Hemophilia B (Factor IX)
von Willebrand disease
Heparin
Factor deficiency
Liver disease
What is the mechanism of action of tPA?
released from endothelial cells, activates
plasminogen to plasmin leading to breakdown of fibrinogen and cross-linked fibrin (creating the degradation product d-dimer)
What should you be thinking about in a patient with petechiae, epistaxis, gum bleeding, or vaginal bleeding?
think platelet problems not coagulation factor disorders
What are some disorders of increased platelet destruction?
ITP, TTP, HUS, DIC, HELLP
At what platelet count should you transfused platelets in non-bleeding patient?
<10,000/uL
At what age(s) is peak incidence of ITP?
children 2-6 years old and adults 20-50 years old
What are common signs and symptoms of ITP?
Petechiae, gingival bleeding, epistaxis, menorrhagia, and GI bleeding
How is ITP diagnosed?
diagnosis of exclusion
isolated thrombocytopenia on CBC, and peripheral smear with a small
number of well-granulated platelets.
What is the treatment for ITP?
Children –> avoid physical activity and NSAIDs
Adults –> Prednisone 1-1.5 mg/kg/d PLUS IVIG or anti-D Ig
(platelets if hemorrhaging)
What is the treatment for TTP?
Exchange transfusions
What are the most common causes of DIC?
Infection; specific pathogens
gram- positive and gram-negative sepsis,
meningococcemia, typhoid fever, and
Rocky Mountain spotted fever
What is purpura fulminans?
protein C deficiency, often seen with meningococcemia
treat with protein C concentrate
What is the most common hereditary bleeding disorder?
von Willebrand disease
Bleeding disorder with normal platelet
count, PT, and PTT, but INCREASED bleeding time
Von Willebrand disease
How is von Willibrand diagnosed?
Abnormal assay of vWF activity, vWF antigen, or factor VIII coagulant (C) activity.
How is von willebrand disease treated?
DDAVP
and/or vWF concentrate
+/- Cryoprecipitate
What is the mechanism of action of DDAVP in the treatment of von willebrand disease?
Stimulates release of vWF (and factor VIII) stored in vascular endothelial cells
What are signs and symptoms of Hemophilia A and B?
Easy bruising, hemarthrosis, hematuria, and muscle hematoma are most common. May also see excessive bleeding after procedures, severe and/or delayed bleeding after apparent minor trauma (including intracranial hemorrhage and retroperitoneal hematoma formation).
How are hemophilia A and B diagnosed?
Prolonged PTT, normal PT, abnormal factor specific assay.
What is the treatment for Hemophilia A?
DDAVP (–>release of vWF and Factor VIII from endothelial cells)
and
Factor VIII replacement
What is the treatment for Hemophilia B?
Factor IX replacement
What should be given to Hemophilia A or B patients with bleeding refractory to first line treatments?
PCCs or Factor VIIa (to overcome inhibitors)
What anticoagulant primarily works through antithrombin III to inhibit thrombin and factor Xa (to prevent clot propagation)?
Unfractionated Heparin
What is the therapeutic range of unfractionated heparin?
aPTT (1.5-2.5x normal)
What should be administered in someone on Heparin with major bleeding?
Protamine Sulfate
(1 mg for every 100 unit of heparin administered over the previous 4 hours, max 50 mg)
When is the typical onset of HIT Syndrome?
within 5-7 days of initiating heparin therapy
What is the treatment in HIT SYndrome?
anticoagulation with direct thrombin inhibitors (eg bivalirudin) or heparinoids
Anticoagulant that works by primarily inhibiting factor Xa activity
LMWH (enoxaparin, dalteparin,
and ardeparin)
What must be considered in dosing LMWH?
renal function – renally cleared
What anticoagulant is a synthetic heparin derivative; inhibits activated factor X?
Fondaparinux
How should bleeding while on Fondaparinux be treated?
if severe, recombinant Factor VIIa
What medications are the traditional direct thrombin inhibitors? (list 4)
lepirudin, desirudin, argatroban, and bivalirudin
What is the primary use for direct thrombin inhibitors?
in patients with HIT
Argatroban is _____ metabolized so should be used with caution in patients with _____ failure.
hepatically, liver
Lepirudin and desirudin are_____ cleared so should be used with caution in patients with___ failure.
renally, renal
Oral anticoagulant that inhibits formation and activation of vitamin K–dependent coagulation factors
Warfarin
What coag factors are Vitamin K dependent?
II, VII, IX, X; also the anticoagulant factors protein C and protein S
What are contraindications to Warfarin?
Medication allergy, active bleeding, pregnancy, liver failure.
What INR is considered therapeutic for Warfarin?
2.0 - 3.0; for mechanical valves it is 2.5-3.5
What medications/supplements commonly increase INR?
Acetaminophen, amiodarone, amoxicillin,
antifungals, cimetidine, doxycycline,
fluoroquinolones, macrolides,
metronidazole, sulfonamides, SSRIs, garlic,
ginger, ginkgo biloba
What medications/supplements commonly decrease INR?
Carbamazepine, phenytoin, phenobarbital,
cholestyramine, dicloxacillin, griseofulvin,
haloperidol, nafcillin, ranitidine, rifampin
When is warfarin-induced skin necrosis most common?
2-10 days after initiation of warfarin
What is the treatment for Warfarin use, INR 5-9 without major bleeding?
Hold dose, consider oral vitamin K 1-2.5 mg PO, recheck INR in 24 h
What is the treatment for Warfarin use, INR >9 without major bleeding?
Hold dose, vitamin K 2.5-5 mg PO, recheck INR in 24 h
What is the treatment for any INR with major bleeding in context of Warfarin use?
Hold dose, vitamin K 10 mg slow IV or sub Q, administer FFP, PCC, or recombinant factor VIIa
What side effect/reaction does IV Vitamin K commonly produce?
anaphylaxis
What is the mechanism of action of ASA?
irreversibly inhibits cyclooxygenase (COX-1), which prevents synthesis of thromboxane A2 and associated platelet aggregation
What medications fall under the drug class, thienopyridines?
clopidogrel (Plavix), prasugrel (Effient), and ticlopidine (Ticlid)
What is the mechanism of thienopyridines, aka Plavix?
Irreversibly inhibit platelet aggregation via adenosine diphosphate receptor antagonism
What medications are GP IIb/IIIa inhibitors?
abciximab, tirofiban, and eptifibatide
What is the Hct of PRBC units?
55-80%
How many mLs are in 1 adult unit of PRBCs?
350mL
How many mLs are in 1 pediatric unit of blood?
60 mL
How is massive transfusion defined?
> 10 units of PRBCs in 24 hours for adult patients
What causes hypocalcemia in MTP?
binding to citrate preservative
If massive transfusion and INR >1.5, how many units of FFP be should be transfused?
2-4 units
If MTP and platelets <50,000, how many units of platelets should be transfused?
1 unit
If MTP and fibrinogen <100mg/dL, how many units of cryoprecipitate should be transfused?
10 units
In MTP, how is symptomatic hypocalcemia treated?
calcium gluconate
Most common transfusion reaction; characterized by fevers/chills, malaise.
Treatment is symptomatic, usually with Tylenol
Febrile transfusion reaction
Most serious transfusion reaction, typically due to clerical error. ABO incompatibility leads to lysis of transfused RBCs with associated hemoglobinemia and hemoglobinuria.
Acute hemolytic transfusion reaction
What is the treatment for Acute hemolytic transfusion reaction?
stopping the transfusion, immediate vigorous
crystalloid infusion, and diuretic therapy to maintain urine output at 1-2 mL/kg/h.
Usually urticaria or hives only (rarely anaphylaxis). Treatment is symptomatic,
usually with Benadryl.
Allergic reaction
Can occur with any plasma-containing blood transfusion, however is most common with FFP or platelets. Usually occurs within 6 hours
of transfusion. Signs and symptoms are indistinguishable from acute respiratory distress syndrome.
Transfusion-related acute lung injury (TRALI)
What is the treatment for Transfusion-related acute lung injury (TRALI)?
Stop transfusion. Treatment is otherwise primarily supportive, no evidence
for use of steroids, antihistamines, or diuretics
Characterized by delayed extravascular hemolysis due to presence of small amounts of RBC antibodies (not detected on blood-type screening) directed against transfused RBC antigens.
Delayed transfusion reaction
What is the treatment for Delayed transfusion reaction?
supportive
Occurs when immunocompromised patients are transfused with PRBC containing immunocompetent T lymphocytes, effectively resulting in an unintentional bone marrow transplant. Carries 80% mortality.
Transfusion-associated graft-versus-host disease
How can Transfusion-associated graft-versus-host disease be prevented?
use irradiated blood products in immunocompromised patients
One unit of platelets is sufficient to raise platelet count by ______/μL.
30,000
One unit of fresh frozen plasma (FFP) contains __ U/mL of each clotting factors in addition to
__-__mg/mL of fibrinogen.
1, 1-2
How is FFP typically dosed?
It must be ABO compatible
and is typically dosed as 4-6 units (200-250 mL volume per unit) in adults or
15 mL/kg in children.
What 4 things does cryoprecipitate contain?
Factors VIII, XIII, fibrinogen, and vWF
What is the standard dose of cryoprecipitate?
Standard dosage is 6-10 units (10-40 mL volume per unit). Does not require ABO matching.
What is contained in PCC?
vitamin K–dependent factors II, VII, IX, and X.
When is recombinant factor VIIa indicated?
approved only for the control of bleeding in hemophiliacs with inhibitors
What are the symptoms of hypercalcemia of malignancy?
anorexia, abdominal pain, nausea and vomiting,
constipation, polyuria/polydipsia, hypertension, weakness, confusion, and generalized itching
What ECG finding is consistent with hypercalcemia?
shortened QT interval
How is hypercalcemia of malignancy treated?
aggressive rehydration
bisphosphonates (pamidronate, zoledronate)
Calcitonin
avoid – thiazide diuretics or lithium
What are common causes of hyperviscosity syndrome?
Waldenström macroglobulinemia
(increased IgM), multiple myeloma (increased IgG or immunoglobulin A [IgA]), leukemias with blast transformation, or polycythemia vera
How does hyperviscosity syndrome classically present?
Blurred vision, mucosal bleeding, and neurologic
symptoms (headache, dizziness, AMS, dyspnea)
What might you see on peripheral smear in hyperviscosity syndrome?
rouleaux formation
What is the treatment for hyperviscosity syndrome?
■ Two units of phlebotomy with IV fluids hydration can be temporizing measure (and is definitive therapy for polycythemia).
■ Emergent plasmapheresis for dysproteinemias.
■ Emergency leukapheresis for blast transformations.
■ Chemotherapy.
How is neutropenic fever defined?
sustained temperatures > 38.0°C/100.4°F
or single temperature > 38.3°C/101.0°F in the presence of neutropenia (ANC < 500 cells/μL).
What is the treatment for neutropenic fever?
empiric broad-spectrum antibiotic:
Monotherapy with cefepime (or equivalent).
Add vancomycin if methicillin-resistant Staphylococcus aureus (MRSA) suspected or in presence of vascular catheter or soft tissue
infection.
Add other agents depending on clinical suspicion regarding source of infection.
What is the most common site of spinal cord compression due to malignancy (Rubin Syndrome)?
thoracic spine
What is superior vena cava syndrome?
Obstruction may be due to external pressure on the SVC or invasion of the SVC by tumor and resultant thrombosis
What is a risk factor for tumor lysis syndrome?
pre-existing renal failure
What metabolic derangements are commonly seen in tumor lysis syndrome?
Hyperuricemia, hyperkalemia, hyperphosphatemia, and associated
hypocalcemia
How does tumor lysis syndrome lead to renal failure?
Oliguric renal failure results from uric acid precipitation in the renal tubules.
How is hyperuricemia treated in Tumor Lysis Syndrome?
vigorous IV hydration and allopurinol
(to reduce production of uric acid).
Many sources recommend alkalization of urine to pH > 7, but this should be done with caution because it can exacerbate other metabolic abnormalities
For what uric acid level might hemodialysis be necessary?
> 10mg/dL
For what phosphate level might hemodialysis be necessary?
> 10 mg/dL
What malignancies are associated with acanthosis nigricans?
Gastrointestinal (GI) malignancies primarily, lung and breast cancer
What malignancies are associated with Dermatomyositis?
Breast, ovarian, stomach, colon, and lung cancer
What malignancies are associated with Erythema multiforme?
Leukemias and Hodgkin lymphoma
What malignancies are associated with Erythema nodosum?
Leukemia, Hodgkin lymphoma, and metastatic cancer
What is erythroderma?
Diffuse erythema of the skin. Associated with intractable pruritus
What malignancies are associated with erythroderma?
Hodgkin lymphoma, leukemia, and mycosis fungoides
What is icthyosis?
Diffuse, dry scaling lesions; hyperkeratosis of palms and soles
What malignancies are associated with acquired icythyosis?
Hodgkin lymphoma; breast, cervical, lung, and colon cancer
What malignancies are associated with pruritus?
Hodgkin lymphoma, leukemia, multiple myeloma, polycythemia vera, adenocarcinoma, carcinoid syndrome
What malignancies are associated with Sister mary joseph nodule?
Advanced adenocarcinoma (gastric or ovarian)
What malignancies are associated with Urticaria?
Hodgkin lymphoma, leukemia, internal malignancy, multiple myeloma
What malignancies are associated with Purpura?
Hodgkin lymphoma, leukemias, lymphoma, multiple myeloma, polycythemia vera
What is the mechanism of a Type I hypersensitivity reaction?
IgE-mediated degranulation of mast
cells with release of mediators
What is the mechanism of a Type II hypersensitivity reaction?
IgG or IgM antibodies react with
cell antigens with resultant
complement activation
What is the mechanism of a Type III hypersensitivity reaction?
Immune complex deposition and
subsequent complement activation
What is the mechanism of a Type IV hypersensitivity reaction?
Activated T cells against cell surface
bound antigens
Anaphylaxis is an example of which type of hypersensitivity reaction?
Type I
Angioedema is an example of which type of hypersensitvity reaction?
Type I
Autoimmune hemolytic anemia is an example of which type of hypersensitvity reaction?
Type II
SLE is an example of which type of hypersensitvity reaction?
Type III
Contact Dermatitis is an example of which type of hypersensitvity reaction?
Type IV
What is pediatric dosing for epinephrine in anaphylaxis?
0.01 mg/kg, max 0.5mg
_____ can be used for anaphylaxis patients on β-blockers with symptoms refractory to fluids and epinephrine
Glucagon
What causes hereditary angioedema?
an autosomal dominant hereditary disorder
associated with C1-inhibitor deficiency
What causes medication-related angioedema?
Mediated through bradykinin and substance P.
Hereditary Angioedema is clinical diagnosis but what lab value may be diagnostic?
Low C1 level
How is angioedema treated?
supportive & stop offending med
(Limited benefit: antihistamines, epi, steroids)
Severe attacks: purified human C1 inhibitor, icatibant (a bradykinin B2-receptor agonist),
or ecallantide (a kallikrein inhibitor).
FFP contains C1 inhibitor and is an alternative when these medications are not available
What type of hypersensitivity reaction is serum sickness?
type III (immune complex)
What is serum sickness?
when injection of an offending agent results in antigen-antibody complex formation. These complexes deposit in vessel walls and
result in activation of the complement cascade.
When does serum sickness typically occur?
7-10 days after exposure to causative agent
What are signs and symptoms of Serum SIckness?
a pruritic rash and flulike symptoms (fever, malaise, arthralgia, myalgia)
How is Serum Sickness diagnosed?
clinically; C3, C4 levels will be decreased
What is the treatment for Serum Sickness?
Generally self-limited – stops within 1-2 weeks of stopping offending agent.
Can give: antihistamines, NSAIDs, and steroids.
Plasmapheresis has been used for severe cases with symptoms that are not responsive to other treatments or when causative agent cannot be
withdrawn.
What medications are known to cause serum sickness?
Abx– PCN, sulfonamides
phenytoin
thiazide diuretics
barbiturates
Horse serum antivenom
What type of rash is seen in Drug hypersensitivity reaction?
widespread, symmetrical maculopapular rash
affects mucous membranes
What is treatment for Drug Hypersensitivity reaction?
withdraw offending agents
+antihistamines
+/- steroids
What type of rash is seen in DRESS?
Widespread rash, mucous membranes spared
How is DRESS diagnosed?
clinically based on rash, eosinophilia, and end organ damage
How is DRESS treated?
withdraw offending agent
antihistamines, glucocorticoids
How is DRESS treated?
withdraw offending agent
antihistamines, glucocorticoids
Which medications are commonly implicated in DRESS?
allopurinol, antiepileptic medications (carbamazepine, lamotrigine, phenytoin), sulfasalazine, vancomycin, minocycline, dapsone, and sulfamethoxazole
Describe the rash of SJS-TENS
Severe, acute, widespread blistering rash that often includes mucous membrane
lesions.
SJS is defined by sloughing of < 10% total body surface area, and TENS is defined by sloughing of > 10% of total body surface area
How is SJS differentiated from TENS?
SJS is defined by sloughing of < 10% total body surface area, and TENS is defined by sloughing of > 10% of total body surface area
What medications are commonly implicated in SJS-TENS?
allopurinol, antiepileptic medications, sulfa
medications
How is SJS-TENS treated?
withdraw offending agent
wound management, fluid and electrolyte management, infection prevention
(steroids, IVIG, immunomodulators controversial)
What prevention advice should be given to those with reynauds?
cold avoidance, smoking cessation, maintaining whole body warmth, and avoiding sympathomimetic medications.
How are acute Reynauds attacks treated?
rewarming
What typically causes reactive arthritis?
usually preceded by 1-4 weeks by a GI or GU infections caused by Chlamydia, Yersinia,
Shigella, Salmonella, Campylobacter, or Clostridium difficile
What are signs/symptoms of Reactive arthritis?
Asymmetric oligoarthritis, predominantly of weight bearing joints of lower extremities, including hips, knees, and heels (“lover’s heels”).
+/- urethritis, conjunctivit, and/or uveitis, mucocutaneous lesions, fever, malaise
Describe joint involvement in rheumatoid arthritis.
typically symmetric and starts with small joints, including MCP and PIP joints
What hand deformities are classically seen in RA?
Swan-neck deformities, Boutonniere deformity
How is RA diagnosed?
inflammatory arthritis involving >/= 3 joints
Elevated CRP or ESR
+RF and anti-CCP antibodies
What is treatment for RA?
NSAIDs and low dose oral prednisone for arthritis, arthralgias, serositis
Additional disease-modifying antirheumatic drugs (DMARDs) include methotrexate,
tumor necrosis factor (TNF)-blockers, and monoclonal antibodies.
What medications are commonly implicated in drug-induced SLE?
HIPPS
hydralazine
isoniazid
phenytoin
procainamide
sulfonamides
What antibodies are seen in SLE?
+anti-dsDNA
or
+anti-Sm
ANA+
How do complement and inflammatory markers change in acute SLE flares?
During acute flares, there is a decrease in C3, C4 levels but an increase in ESR and CRP levels.
What is treatment for SLE?
NSAIDs for arthritis, arthralgias, and serositis.
Hydroxychloroquine or chloroquine for rash, malaise, arthralgias.
Steroids for life-threatening manifestations, acute flares, and symptoms refractory to conservative therapy.
Moderate cases: azathioprine or methotrexate
Severe cases: immunosuppressive agents such as mycophenolate, cyclophosphamide, or rituximab.
What are the two types of scleroderma?
systemic sclerosis
limited cutaneous systemic sclerosis
CREST is a subgroup of limited cutaneous systemic sclerosis. What does it stand for?
Calcinosis cutis,
Raynaud phenomenon,
Esophageal dysmotility,
Sclerodactyly, and
Telangiectasia
What is treatment of CREST syndrome?
organ specific ie, ACE inhibitors for hypertensive
renal crisis; calcium channel blockers for Raynaud phenomenon
Immunosuppressive therapies are reserved for patients with severe disease
(like interstitial lung disease, myocarditis, severe arthritis) or diffuse skin involvement.
How is Giant Cell arteritis diagnosed?
Temporal artery biopsy, ESR > 50 mm/h
How is Behcet disease diagnosed?
Biopsy of affected tissue
How is Takayasu diagnosed?
Aortic arch arteriogram
What are the three main types of large vessel vasculitis?
Giant Cell arteritis
Behcet Disease
Takayasu arteritis
How is Giant Cell arteritis treated?
Prednisone 1-2 mg/kg/d immediately to present irreversible blindness +Low dose ASA
Which large vessel vasculitis presents as recurrent painful oral and genital ulcers?
Behcet syndrome
How is Behcet syndrome treated?
Prednisone
What are signs and symptoms of Takayasu arteritis?
Uveitis, iritis, or optic neuritis
What is treatment for Takayasu arteritis?
immunosuppressants
How is polyarteritis nodosa diagnosed?
Biopsy (skin, kidney)
Mesenteric angiogram
HBV/HCV testing
What is the treatment for polyarteritis nodosa?
Prednisone
cyclophosphamide
How is Wegener granulomatosis diagnosed?
c-ANCA
Lung biopsy
How is Wegener granulomatosis treated?
Prednisone
Cyclophosphamide
How is Buerger disease (throboangiitis obliterans) diagnosed?
MRA or angiography
What is the treatment for Buerger disease?
Smoking cessation
How is Microscopic polyangiitis diagnosed?
p-ANCA
Renal biopsy
How is microscopic polyangiitis treated?
cyclophosphamide
What are the 4 predominantly medium vessel vasculitis?
Polyarteritis Nodosa
Wegener Granulomatosis
Buerger Disease
Microscopic polyangiitis
How is hypersensitivity vasculitis diagnosed?
Skin biopsy
How is hypersensitivity vasculitis treated?
Prednisone
How is Henoch-Schonlein purpura diagnosed?
skin biopsy
rectal biopsy
How is Henoch Schonlein Purpura treated?
Supportive
Prednisone
How is Goodpasture Syndrome diagnosed?
Renal or lung biopsy showing basement membrane antibodies
How is Goodpasture syndrome treated?
supportive
prednisone
cyclophosphamide
plasmapheresis
Which 3 types of vasculitis is predominantly small vessel vasculitis?
Hypersensitivity vasculitis
Henoch-Shonlein Purpura
Goodpasture Syndrome
What are the two most common etiologies of infection in the first month after transplant?
- latent acute infections (ie, bacteremia, candida species, antimicrobial resistant bacteria, West Nile virus, HIV), that are in donor tissue infect the host; and
- postsurgical infection (cellulitis, abscess, pneumonia, etc).
What are the most common causes of infection 1-6 months after transplant?
CMV, EBV, P jiroveci, Chagas disease, endemic fungal disease, and tuberculosis (TB) all become common
What are the most common causes of infection->6 months after transplant?
Usually the lowest levels of immunosuppression so most infections are related to community-acquired agents.
How does cyclosporine toxicity present?
Acute toxicity causes reversible
vasoconstriction and renal ischemia
What medications can cause increase in cyclosporine levels?
Calcium channel blockers and antibiotics
(doxycycline, erythromycin)
What are side effects of mycophenolate (CellCept)?
diarrhea, n/v, leukopenia
What are side effects of Tacrolimus (Prograf)?
diabetes, nephrotoxicity, seizures, and neuropathy
What is the treatment for renal transplant rejection?
■ Methylprednisolone, 500 mg IV × 3 days.
■ May wait for results of biopsy before initiating steroids.
What are signs/symptoms of IgA deficiency?
recurrent sinus and pulmonary infections
Which Igs are low or dysfunctional in Common Variable Immunodeficiency (CVID)?
Low or dysfunctional levels of IgG, IgA, and IgM antibodies
