1
Q
What abnormalities are involved in DIC
A
- Thrombocytopenia
- Elevated (PT) Prothrombin Time
- Elevated (aPTT) activated Partial Thromboplastin Time
- Decreased Fibrinogen
- Increased Fibrin Split products
2
Q
List most common leukemia for young and elderly
A
Acute Lymphocytic Leukemia (ALL) is most common in children
Chronic Lymphocytic Leukemia (CLL) is most common in elderly
3
Q
List 8 DDx for leukopenia/decreased WBCs
A
Decreased Production:
- suppression of bone marrow
- chemotherapy
- radiation
- viral infections
Destruction of WBCs:
- beta-lactam abx
- rheumatoid arthritis
- AI diseases
Loss/Depletion:
- overwhelming bacterial infxn
Sequestration:
- ischemic reperfusion injury
- major trauma
- tissue insults
4
Q
List 10 Common Causes of Leukocytosis
A
PRIMARY:
Myeloproliferative disorders: Chronic myeloid leukemia (CML), Polycythemia vera
Hereditary neutrophilia
Familial myeloproliferative disease
Chronic idiopathic neutrophilia
Leukemoid reaction
SECONDARY:
Infection
Tissue necrosis: Cancer, Burns, Infarctions
Metabolic disorders: DKA, Thyrotoxicosis, Uremia
Non-hematologic malignant disease
Physiologic stress: Exercise, pain, surgery, hypoxia, seizures, trauma
Drugs: Epinephrine, corticosteroids, lithium, cocaine
Laboratory error: Automated counters, platelet clumping, precipitated cryoglobulin
5
Q
List 8 Causes of Lymphocytosis
A
VIRAL INFXN:
- Mono
- Rubeola
- Rubella
- VZV
- Toxoplasmosis
LYMPHOPROLIFERATIVE:
- ALL
- CLL
IMMUNOLOGIC:
- Immunization
- Autoimmune dz
- Graft rejection
6
Q
List 2 broad treatments for reduction of hyperleukocytosis
A
Chemotherapy
Leukapheresis
7
Q
List common cause of Chronic myeloid leukemia (CML)
A
Genetic Translocation = aberration known as Philadelphia chromosome
8
Q
List 3 phases of CML
A
Chronic
Accelerated
Blastic
9
Q
List clinical features of symptomatic chronic CML
A
Abdo pain
Nausea
Poor appetite
Early satiety from hepatosplenomegaly
LUQ pain 2/2 splenic infarction
Fatigue
Weight loss
Diaphoresis
Low grade fever
10
Q
List 4 clinical features of symptomatic accelerated + blastic CML
A
Abnormal bleed and bruise
Petechiae
Bone pain
Fever
11
Q
Define Blastic Crisis in CML and list clinical features
A
Sudden appearance of acute form of leukemia
- Rare, associated with poor outcomes
- Issues related to leukostasis + bone marrow infiltration
- Dyspnea
- Neurologic symptoms
- Anemia
- Thrombocytopenia
12
Q
Outline mgmt for CML
A
= Tyrosine Kinase Inhibitors (TKIs)
- may need stem cell transplant
13
Q
List 5 issues from hyperleukocytosis and leukostasis in CML
A
Hyperleukocytosis:
- Hyperuricemia
- Renal injury
- Severe anemia, leading to angina or HF
Leukostasis:
- Deafness
- Visual impairment
- Pulmonary ventilation-perfusion abnormalities
- Priapism
14
Q
Outline tx for hyperleukocytosis & leukostasis
A
- Hydration
- Leukapheresis
- Allopurinol
- Specific chemotherapy
15
Q
List 15 causes of Leukopenia
A
- Aplastic anemia
- Leukemia
- Cancer Chemotherapy (cyclophosphamide, azathioprine, methotrexate)
- Indomethacin
- Phenytoin
- Sulfonamides
- Viral infxn
- Mononucleosis
- Rubella
- Rubeola
- Rickettsia organisms
- TB
- Sepsis
- Folate deficiency
- B12 deficiency
- Chronic idiopathic neutropenia
- Starvation
- Sarcoidosis
- Portal HTN
- Malaria
- SLE
- AIDS
- Felty syndrome
- Lab error
16
Q
List 6 s/s of intravascular hemolytic transfusion reaction (such as from ABO incompatibility)
A
- fever/chills
- HA
- N/V
- sensation of chest restriction
- severe joint or low back pain
- burning sensation at site of infusion
- feeling of impending doom
17
Q
List 8 benefits of using stored whole blood early in resuscitation
A
- Physiologic balance of blood components
- Smaller volume anticoagulant/preservative sol’n
- PLT fnc significantly enhanced compared to component therapy
- Higher levels of hemostatic factors
- Fibrinogen delivery is higher
- Hemolytic transfusion reaction rate LOW (1:120,000)
- Confer fewer donor exposures
- Administration of all components together improves time to complete transfusion
- Errors associated w/ transfusion of type-specific blood minimized
18
Q
List 5 benefits of autologous blood transfusions
A
- immediate availability
- blood compatibility
- elimination of donor to patient disease transmission
- lower risk of circulatory overload
- fewer direct complications related to transfusion itself
19
Q
List 6 special populations who should get Irradiated pRBCs
A
= Irradiation of donor blood destroys WBCs thereby decreasing risk of transfusion-associated graft-versus-host disease
- Neonatal or intrauterine transfusion
- Hematologic malignancy
- Stem cell transplant patients or donors within a week prior to cell harvesting
- Hodgkin lymphoma
- Directed donations from family members (biological)
- Congenital cellular immune deficiency
- Transfusions from HLA-matched donors
- Patients treated with antithymocyte globulin or chemotherapy with purine analogs (e.g., fludarabine, bendamustine, etc.)
20
Q
List 3 special populations who should get washed pRBCs
A
= PRBCs are washed with saline to remove residual plasma and protein. Reduces allergic reactions to foreign proteins.
- History of severe allergic transfusion reactions
- IgA-deficiency
- Paroxysmal nocturnal hemoglobinuria
21
Q
List 3 special populations who should get Leukocyte Reduced pRBCs
A
= PRBCs are filtered to remove 99.99% of the leukocytes
- Patients undergoing chemotherapy
- Multiparous females
- Patients receiving multiple transfusions
22
Q
List 3 special populations who should get CMV Negative pRBCs
A
= CMV testing is performed on units of PRBCs
- Seronegative pts currently pregnant
- Fetal or intrauterine transfusion
- Solid organ, Stem cell, or BMT recipients who are CMV(-)
23
Q
List 4 indications for FFP administration
A
- Massive hemorrhage
- Component of a plasma exchange procedure
- Emergency reversal of Vitamin K antagonist in presence of clinically significant hemorrhage
- Treatment of ACEi-induced angioedema
24
Q
What is in FFP?
A
All clotting factors
25
Outline PLT transfusion thresholds before procedures and surgery
PLT <10 = General transfusion
PLT <20 = Central line procedures
PLT <50 = LPs and Non-neuraxial surgeries
PLT <100 = Neuraxial surgery
26
What is in Cryoprecipitate (5)?
- Fibrinogen 150mg
- Factor VIII 80 IU
- Factor XIII
- von Willebrand factor
- Fibronectin
27
List 5 indications for cryoprecipitate administration
- Fibrinogen deficiency
- Congenital afibrinogenemia
- Dysfibrinogenemia
- Hemophilia A when Fac8 not available
- vWD when Fac8 not available
NOT HELPFUL FOR HEMOPHILIA B (no Fac9)
28
What is in Prothrombin Complex Concentrate (PCC = Octaplex) ?
All Vitamin K–dependent clotting factors
= Factor II, VII, IX, X
2, 7, 9, 10
29
List indications for PCC (Octaplex) administration
- Reversal of elevated INR level in patients w/ life-threatening bleeding or ICH
Can reverse INR to 1.5 faster than FFP (and w/ less volume)
30
Outline dosing and effect of each blood product:
pRBCs, PLTs, FFP, PCC, Cryoprecipitate
pRBCs = 1 unit = 450ml
- raises HGB +10, Hct +30%
PLTs = 1 adult dose = "6-pack"
= Peds 1unit/10kg
- raises PLTs +40-60
FFP = 10-30mL/kg infusion
Cryoprecipitate = 10 bags for an adult
- raises fibrinogen +100mg/dL
PCC = Adults 2000IU
= Peds 25IU/kg
- max 3000IU at one time
31
Define 'massive transfusion'
Transfusion of 3units pRBCs over 1hr
or
Use of 4 components over 30min
32
List complications of massive transfusions
- Hypothermia
- hypoMg
- hypoCa
- hyperK or hypoK
- Acidosis
- or Metabolic alkalosis as citrate metabolized to HCO3
33
Outline algorithm for tx of transfusion rxns
34
What is first step if suspect transfusion related reaction?
STOP transfusion while investigating
35
Outline tx of minor allergic transfusion reaction
= Pt gets urticaria +/- wheezing & angioedema
= antibody-mediated response to donor plasma proteins
- Stop transfusion
- Antihistamines +/- steroids
- Resume if reaction limited to skin
36
Outline tx of anaphylactic transfusion reaction
= hTN, angioedema, dyspnea, bronchospasm, or laryngospasm
- Stop transfusion
- Tx like anaphylaxis
- If transfusion still required, pre-tx w/ steroids + antihistamines 30-60min before transfusion
- Use new product
- May need washed cellular products
37
Outline tx of febrile (nonhemolytic) transfusion reaction
= Temp elevation of >1degC occurring w/ transfusion, w/ no other medical explanation
- w/ rigors + chills
= Recipient anti-leukocyte antibodies that react with donor WBCs and from cytokines released during a storage lesion (damage to and loss of some RBCs over time during storage)
- Stop transfusion
- If 1st time, other VS instability, or temp rise >2degC, investigate for acute hemolytic rxn
- If hemolytic rxn ruled out, tx w/ acetaminophen (or ibuprofen or opioid)
- start new transfusion product
38
Outline tx of acute hemolytic transfusion reaction
MOST SERIOUS transfusion rxn
- usually from ABO incompatibility error
- immediately STOP transfusion
- vigourous crystalloid IVF resuscitation
- maintain U/O 1-2cc/kg/hr
- send blood bag for testing
- may need HD for hyperkalemia or renal failure as a result of hemolysis/DIC
39
List Lab Abnormalities in Acute Hemolytic Transfusion Reactions
- Decrease in HGB or HCT
- Hemoglobinemia (free HGB in blood)
- Hemoglobinuria (free HGB in urine)
- Increased serum LDH
- Increased indirect bilirubin
- Decreased haptoglobin
- Evidence of DIC, including: prolonged PT, PTT, decreased fibrinogen level, increased D-dimer
- Schistocytes or Spherocytes on peripheral smear
40
Outline 5 Criteria for TRALI
NEED ALL 5:
No evidence of acute lung injury before transfusion
Acute lung injury onset during or w/in 6hr of cessation of transfusion
Hypoxemia defined as either PaO2/FiO2 <300mmHg or O2 sat <90% on RA
Radiographic evidence of bilateral infiltrates
No evidence of left atrial HTN (circulatory overload)
41
What is TRALI (clinical features)?
Non-cardiogenic pulmonary edema
= increase in pulmonary capillary permeability leading to leakage of high protein fluid into alveoli
- dyspnea
- hypoxemia
- bilateral infiltrates on CXR
- fever
- hTN
- transient leukopenia
42
Outline tx of TRALI
- Stop transfusion
- Notify blood bank
- O2 support, NIPPV, or ETT
- can infuse new blood product
43
Outline 3 risk factors for developing TACO
- preexisting heart disease
- significant renal insufficiency
- extremes of age
44
Outline 4 s/s of TACO
- SOB
- HTN
- tachycardia
- other signs of volume overload
45
List 5 Acute Transfusion Reactions
Febrile non-hemolytic transfusion reaction
Acute hemolytic transfusion reaction
Anaphylaxis
TRALI
TACO
46
Outline tx of TACO
- Stop transfusion
- diuresis
- nitroglycerine (patch or infusion 50-100 mcg/min IV)
- NIPPV, or ETT
47
List features of Septic Transfusion Reaction (STR)
1) Fever >39degC
2) >1degC rise above pre-transfusion temp
3) hTN (SBP <90/DBP <60), or 15% decrease
4) Tachycardia (HR >100) or 15% increase
- Matching Cx's from Donor and recipient blood
- Rigors, N/V, dyspnea, shock
48
List 4 clinical features of Delayed Hemolytic Transfusion Reaction
- 3-10d after transfusion
- Fever
- Anemia
- Jaundice
49
List 5 clinical features of Transfusion-Associated Graft-versus-Host Disease
- 3-30d after transfusion
- fever
- erythematous skin rash
- diarrhea
- elevated liver enzymes
- pancytopenia
- 95% mortality
50
List 5 high-risk patients for Transfusion-Associated Graft-versus-Host Disease
Congenital immunodeficiency
Hematologic malignancy (Hodgkin disease)
Stem cell transplantation
Treatment with purine analogues (fludarabine)
Directed donor products from close relative
51
Outline tx options for Post-transfusion Purpura
= profound thrombocytopenia
- high dose IVIG
- plasmapheresis
- PLT transfusion
52
List 3 Delayed Transfusion Reactions
- Delayed Hemolytic Transfusion Reaction
- Transfusion-Associated Graft-versus-Host Disease
- Post-transfusion Purpura
53
List 3 basic mechanisms of anemia
1) RBC loss (bleeding)
2) Destruction of RBCs
3) Decreased production of RBCs
54
List 9 Causes of Rapid Intravascular Red Blood Cell Destruction
Mechanical hemolysis associated w/ DIC
Massive burns
Toxins (poisonous venoms: brown recluse spider, cobra)
Infections like Malaria or Clostridium sepsis
Severe G6PD deficiency w/ exposure to oxidant stress
ABO incompatibility transfusion reaction
Cold agglutinin hemolysis (Mycoplasma organisms, infectious mononucleosis)
Paroxysmal nocturnal hemoglobinuria exacerbated by transfusion
Immune complex hemolysis (quinidine)
55
List 4 sites of non-traumatic blood loss
- GI tract
- Retroperitoneal space
- Uterus
- Adnexa
56
List 4 causes of microcytic anemia
- Iron deficiency
- Thalassemia
- Sideroblastic anemia
- Toxins (lead poisoning)
- Defective heme synthesis
57
List causes of normocytic anemia
- Acute blood loss
- Chronic disease
- Chronic renal insufficiency
- Hypothyroidism
- Bone marrow suppression
- Hemolysis
- DIC
- G6PD deficiency
- Sickle cell disease
- Aplastic anemia
--------
the rest of this is expanded
1) Primary or Secondary bone marrow failure
2) Hemolytic or Non-Hemolytic
- Anemia of chronic disease = Non-Hemolytic
3) Intrinsic or Extrinsic hemolytic anemia
- Genetic mutations or enzyme deficiencies (sickle cell disease) = Intrinsic Hemolytic
- DIC = Extrinsic Hemolytic
58
List 8 causes of macrocytic anemia
- Folate deficiency
- B12 deficiency
- Alcoholism
- Liver disease
- Reticulocytosis
- Myelodysplastic syndrome
- Hydroxyurea
- Azothiaprine
- Chemotherapy
59
List BW to send in suspected acute blood loss
- CBC w/ peripheral smear
- Type + Crossmatch
- PT and INR
- PTT
- Electrolytes
- Glucose
- Cr
- Urinalysis for free hemoglobin
60
List 4 General Admission Criteria for Nonemergent Anemia
Cardiac symptoms (dyspnea or chest pain)
Neurologic symptoms (syncope)
Initial unexplained HGB < 80-100 or HCT < 25%–30% in select pts
Difficulty in obtaining Outpt care in pts w/ significantly low HGB or comorbidity present
61
List iron indices consistent with iron deficiency anemia
Serum Iron = LOW
TIBC = HIGH
Iron Saturation = LOW
Serum Ferritin = LOW
Bone Marrow Stainable Iron = ABSENT
62
List 3 conditions where IV Iron replenishes stores more effectively than PO
- CKD
- IBD
- Post-Partum
63
List 4 Non-Transfusion-Dependent Thalassemias (NTDT)
- Thalassemia minor (Beta)
- Mild HbE
- Alpha-thalassemia trait
- HbH disease
64
List 3 Transfusion-Dependent Thalassemias (TDT)
- Thalassemia major (Beta)
- Severe HbE/Beta-thalassemia
- Hb Barts hydrops (Alpha)
65
List clinical features of Homozygous β-chain Thalassemia (Thalassemia major)
- predominantly in Mediterranean populations
- no fnc'l beta chains
- severe anemia
- hepatosplenomegaly
- jaundice
- abnormal development
- premature death
- transfusion dependent
66
List clinical features of Heterozygous β-chain Thalassemia (Thalassemia minor or intermedia)
- prevalent in Asia, the Middle East, and Mediterranean countries
- some fnc'l beta chains
- mild-moderate anemia
- protection from falciparum malaria
67
List clinical features of Alpha Thalassemias
- Asians and African Americans
- Four gene loci responsible, severity depends on # of gene deletions
1/4 = silent carrier
2/4 = alpha thalassemia trait
3/4 = HbH disease
4/4 = Hb Barts (hydrops fetalis + fetal death)
68
List 3 smear findings of thalassemia
Hypochromia
Target cells
Basophilic stippling
69
List 5 mgmt options for thalassemias
- Blood transfusions target HGB 90-105
- Iron chelation therapy
- Hydroxyurea
- Splenectomy
- Hematopoietic stem cell transplantation
70
Briefly define sideroblastic anemia
= defect in porphyrin synthesis
- congenital, idiopathic, or acquired
- excess iron deposited in mitochondria of RBC precursor
- increased serum iron, ferritin, and transferrin saturation levels
71
List 6 acquired causes of sideroblastic anemia
- alcoholism
- copper deficiency
- lead poisoning
- zinc toxicity
- myelodysplastic syndrome
- myeloproliferative disorders
- chloramphenicol
- isoniazid
- linezolid
72
Name tx for sideroblastic anemia
Pyridoxine (Vit B6) 100mg PO TID
73
List 5 common causes of anemia of chronic disease
- malignancy
- arthritis
- renal insufficiency
- chronic heart failure
- chronic obstructive lung disease
- chronic infections (TB or osteomyelitis)
74
List iron indices consistent with anemia of chronic disease
Serum Iron = LOW
TIBC = LOW
Ferritin = HIGH or NORM
75
List Causes of Folate Deficiency
1) Inadequate dietary intake
- Poor diet or overcooked or processed food diet
- Alcoholism
2) Inadequate uptake
- Malabsorption with sprue and other chronic upper intestinal tract disorders
- drugs such as phenytoin and barbiturates
- blind loop syndrome
3) Inadequate use
- Metabolic block caused by drugs, (methotrexate or trimethoprim)
- Enzymatic deficiency, congenital or acquired
4) Increased requirement
- Pregnancy
- Increased RBC turnover: Ineffective erythropoiesis, hemolytic anemia, chronic blood loss
- Malignant disease: Lymphoproliferative disorders
5) Increased excretion or destruction or dialysis
76
List Causes of Vitamin B 12 Deficiency
1) Inadequate dietary intake
- Total vegan: No eggs, milk, or cheese
- Chronic alcoholism (rare)
2) Inadequate absorption
- Absent, inadequate, or abnormal intrinsic factor, as with pernicious anemia and gastrectomy
- Abnormal ileum, as can occur in sprue and IBD
3) Inadequate use
- Enzyme deficiency
- Abnormal vitamin B 12 –binding protein
4) Increased requirement by increased body metabolism
5) Increased excretion or destruction
77
List s/s of Vit B12 deficiency
- paresthesias of hands or feet
- decreased proprioception
- decreased vibratory sense
- weakness and spasticity of LEs w/ altered reflexes
- variable mental changes (depression, paranoid ideation, irritability, or forgetfulness)
78
List s/s of folate deficiency
neuropsychiatric manifestations = depression and forgetfulness
79
List non-hemolytic normocytic anemias
- anemia of chronic disease
- hypoendocrinism (hypothyroidism, hypoadrenalism, hypopituitarism)
- aplastic anemia
- myelodysplastic syndromes
- myeloproliferative syndromes
80
List 10 Causes of Aplastic Anemia
SLE
RA
Viral hepatitis
Radiation exposure
Chemotherapy
Parvovirus B19
HIV
EBV
CMV
VZV
Pregnancy (can improve after delivery)
Chloramphenicol
Carbamazepine
Phenytoin
Indomethacin
Methotrexate
Insecticides
Solvents
Toluene
Sulfonamides
Gold
Benzene
81
Outline Causes of Hemolytic Anemia
INTRINSIC
Enzyme defect:
- Pyruvate kinase deficiency
- G6PD deficiency
Membrane abnormality:
- Spherocytosis
- Paroxysmal nocturnal hemoglobinuria
HGB abnormality:
- Hemoglobinopathies
- Thalassemias
EXTRINSIC
Immunologic:
- Alloantibodies
- Autoantibodies
Mechanical:
- Microangiopathic hemolytic anemia
- Prosthetic valve disease
Environmental:
- Drugs
- Toxins
- Infections
- Thermal
Abnormal sequestrations
82
List 10 Drugs Associated With Hemolysis in G6PD
ASA
Primaquine
Quinine
Nitrofurantoin
Sulfa drugs
Naphthalene
Fava beans
Methylene blue
Phenylhydrazine
Isoniazid
Colchicine
Dapsone
Amyl nitrate
Rasburicase
Benzocaine
Lidocaine
83
List 15 Diseases Associated With Autoimmune Hemolytic Anemia
Neoplasms:
- Chronic lymphocytic leukemia
- Lymphoma
- Myeloma
- Thymoma
- Chronic myeloid leukemia
- Ovarian teratoma
- Dermoid cyst
Collagen Vascular Disease:
- Systemic lupus erythematosus
- Periarteritis nodosa
- Rheumatoid arthritis
Infections:
- Mycoplasma
- Syphilis
- Malaria
- Bartonella
- Mononucleosis
- Hepatitis
- Influenza
- Coxsackievirus
- CMV
Miscellaneous:
- Thyroid disorders
- Ulcerative colitis
- Drug immune reactions
84
List 10 Drugs Associated With Immune Hemolytic Anemia
- Penicillin
- Cephalosporins
- Tetracycline
- Hydrocortisone
- Metformin
- Quinine
- Quinidine
- Amphotericin B
- Thiopental
- Diclofenac
- Methyldopa
- Procainamide
- Carboplatin
- Cisplatin
- Insecticides
- Acetaminophen
- Ibuprofen
- Thiazides
- Erythromycin
85
List 2 treatments for hemolytic anemia
blood transfusion
prednisone 1mg/kg
86
List 5 neurologic complications of sickle cell pain crisis
TIA
Cerebral infarction
ICH
Spinal cord infarction
Vestibular + hearing problems
87
List s/s of acute chest syndrome in sickle cell disease
- fever
- cough
- hypoxia
- chest pain
- dyspnea
- new infiltrates on CXR
88
List 5 DDx for acute chest syndrome
PNA
PE
CHF
Fat embolism
ARDS
89
List 2 infections commonly associated with acute chest syndrome
Mycoplasma or Chlamydia species
90
List 4 considerations for exchange blood transfusions in acute chest syndrome
- multi-lobe involvement
- persistent or worsening hypoxemia
- neurologic abnormalities
- multi-organ failure
91
Outline tx for acute chest syndrome
- IVF hydration
- Analgesia
- Maintenance of adequate oxygenation and ventilation
- CTX + Azithro
92
List 15 organ damage complications seen in sickle cell disease
Skin
- Stasis ulcer
CNS
- CVA
Eye
- Retinal hemorrhage
- Retinopathy
Cardiac
- CHF
Pulmonary
- Intrapulmonary shunting
- Pulmonary HTN
- PE
- Pulmonary infarct
- Infection
Vascular
- Occlusive phenomenon at any site
Liver
- Hepatic infarct
- Hepatitis resulting from transfusion
- Hepatic sequestration
- Intrahepatic cholestasis
Gallbladder
- Increased incidence of bilirubin gallstones caused by hemolysis
Spleen
- Acute sequestration
Urinary
- Hematuria
- Glomerulosclerosis
- ESRD
Genital
- Decreased fertility
- Impotence
- Priapism
Skeletal
- Bone infarcts
- Osteomyelitis
- Aseptic necrosis
Placenta
- Insufficiency with fetal wastage
Leukocytes
- Relative immunodeficiency
Erythrocytes
- Chronic hemolysis
93
List 4 indications for acute exchange transfusion in sickle cell disease
- Acute chest syndrome
- Stroke
- Aplastic crisis
- Acute splenic sequestration
94
List clinical features of polycythemia
- HA
- vertigo
- dizziness
- blurred vision
- arterial thrombosis
- venous thrombosis
- epistaxis
- spontaneous bruising
- GI bleed
95
List 15 Causes of Absolute and Relative Polycythemia
ABSOLUTE Erythrocytosis:
- Right-to-left shunt
- Pulmonary disease
- Carboxyhemoglobinemia
- High-altitude acclimatization
- High affinity hemoglobins
- Sleep apnea syndrome
- Focal sclerosing glomerulonephritis
- Renal transplantation
- Hepatoma
- Adrenal tumors
- Meningioma
- Pheochromocytoma
- Hemangioblastoma
- Androgenic steroids
- Recombinant erythropoietin
- Polycythemia vera
RELATIVE Erythrocytosis:
Loss of fluid from vascular space:
- Emesis
- Diarrhea
- Diuretics
- Burns
- Hypoalbuminemia
Chronic plasma volume contraction:
- Hypoxia
- HTN
- Tobacco use
- EtOH abuse
96
Name cause of Primary polycythemia vera (PV)
Chronic myeloproliferative neoplasm caused by JAK2 mutations
97
List s/s of polycythemia vera
- headache
- weakness
- dizziness
- excessive sweating
- plethora
- pruritus after hot water exposure
98
List 4 complications of polycythemia vera
CVA
MI
DVT
Bleeding
Leukemic transformation
99
Outline Diagnostic Criteria for Polycythemia Vera
Major Criteria
1. HGB >165 in men or >160 in women or HCT >49% in men or >48% in women or increased RBC mass
2. Bone marrow tri-lineage proliferation w/ pleomorphic mature megakaryocytes
3. Presence of JAK2 mutation
Minor Criterion
- Subnormal serum erythropoietin level
100
Outline mgmt of polycythemia vera
Phlebotomy to HCT <45%
Daily low dose ASA
Hydroxyurea
101
List 4 heme disorders when PLT transfusion should be AVOIDED
TTP
HUS
HELLP
HIT
102
Define primary and secondary hemostasis
Primary = PLT plug formation
Secondary = Coagulation process
103
List 5 Roles of PLTs in Hemostasis
1) Adhesion to subendothelial connective tissue: Collagen, basement membrane, and noncollagenous microfibrils; serum factor VIII and von Willebrand factor (vWF) permit this function; adhesion creates the initial bleeding arrest plug
2) Release of ADP, thromboxane A, calcium, serotonin, epinephrine, and trace thrombin
3) Platelet aggregation over area of endothelial injury
4) Stabilization of hemostatic plug by interaction with coagulation system
5) Stimulation of limiting reactions of platelet activity
104
List Normal Controls of Coagulation
Removal and dilution of activated clotting factors through blood flow, which mechanically opposes growth of hemostatic plug
Alteration of platelet activity by endothelium-generated nitric oxide and prostacyclin
Removal of activated coagulation components by reticuloendothelial system
Regulation of clotting cascade by antithrombin III, protein C, protein S, and tissue factor pathway inhibitor (TFPI)
Activation of fibrinolytic system
105
List 5 Features of Coagulation Disorders That Differentiate From Platelet Disorders
The bleeding source is often an intramuscular or deep soft tissue hematoma from small arterioles.
The congenital form of disease occurs predominantly in men, via sex-linked inheritance.
Bleeding may occur after surgery or trauma but may be delayed in onset up to 72 hours.
Epistaxis, menorrhagia, and gastrointestinal sources of bleeding are rare, whereas hematuria or hemarthrosis are common in severe cases.
The bleeding time is normal except in patients with von Willebrand disease (vWD).
106
List causes of Decreased Platelet Count (Thrombocytopenia)
1) Decreased production
- Decreased megakaryocytes 2/2 drugs, toxins, or infection
- Normal megakaryocytes w/ megaloblastic hematopoiesis or hereditary origin
- Platelet pooling & splenic sequestration
2) Increased destruction
- Related to collagen vascular disease
- Lymphoma
- Leukemia
- Drug related
- Infection
- Post-transfusion
- ITP
- DIC
- TTP
- HUS
- HELLP in pregnancy
- Vasculitis
3) Dilutional secondary to massive blood transfusion
107
List causes of Platelet Dysfunction (Thrombocytopathy)
- von Willebrand disease (vWD)
- Acquired or drug related
- Aggregation defects, such as in thrombasthenia
108
List causes of Elevated Platelet Count (Thrombocytosis)
- Autonomous (primary thrombocythemia)
- Reactive (secondary thrombocythemia)
- Iron deficiency
- Infection or inflammation
- Trauma
- Nonhematologic malignant disease
- Post-splenectomy
- Rebound from alcohol, cytotoxic drug therapy, folate or vitamin B 12 deficiency
109
List 10 causes of Vascular Disorders
Inherited:
- Pseudoxanthoma elasticum
- Ehlers-Danlos syndrome
- Osteogenesis imperfecta
- Hemorrhagic telangiectasia
Acquired:
- Scurvy (vitamin C deficiency)
- Simple or senile purpura
- Purpura secondary to steroid use
- Meningococcemia
- HUS
- Hypoxemia
- TTP
- Dysproteinemic purpura
110
List 8 causes of Coagulation Disorders
Inherited:
- Von Willebrand disease
- Hemophilia A (factor VIII)
- Hemophilia B (factor IX)
- Factor XIII, factor XI, factor X, factor VII, factor V or factor II deficiency
- Afibrinogenemia & Hypofibrinogenemia
Acquired:
- Medication
- Snake bite (venom-induced consumptive coagulopathy)
- Liver disease
- DIC
- Autoimmune disorders (including autoAbs towards fibrinogen)
- Acquired factor inhibitors
111
What do PTT and INR test for?
INR = tests extrinsic pathway factors + common
- fibrinogen
- prothrombin
- F 5
- F 7
- F 10
PTT = tests intrinsic pathway + common
- F 8
- F 9
112
Outline clinical features of Primary ITP
= Acquired autoimmune thrombocytopenia that has no apparent trigger or associated condition
Acute (<3mos), Persistent (3-12mos), Chronic (>12mos)
Self-limited, 90% remission
113
Outline 8 causes of Secondary ITP
= acquired from various infections or chronic disease states
- SLE
- RA
- Leukemia
- Lymphoma
- post-HIV, HBV, HCV, EBV, VZV, rubella, rubeola
114
Outline 5 causes of Drug induced ITP
- Heparin
- Quinine
- Quinidine
- Digoxin
- Phenytoin
- Sulfonamides
- Beta-lactams
- ASA
115
Outline tx options for ITP
- Supportive
if <30:
- Dexamethasone 40mg PO/IV OD x4d
if <20:
- IVIG 1g/kg IV x1
- Splenectomy if medically refractory
116
List factors related to increased risk of HIT
Duration of exposure (>5 days)
Heparin type (UFH > LMWH)
Dosage (high risk with higher dose)
117
Outline 4Ts Score for HIT
1) Thrombocytopenia
2 = PLT count fall >50% and nadir ≥ 20
1 = PLT count fall 30–50% or nadir 10–19
0 = PLT count fall < 30% or nadir < 10
2) Timing
2 = Clear onset btwn days 5–10 or PLT fall ≤ 1 day (prior heparin exposure w/in 30 days)
1 = Consistent w/ days 5–10 fall, but not clear; Onset after day 10; or fall ≤ 1 day (prior heparin exposure 30–100 days ago)
0 = Platelet count fall <4 days w/out recent exposure
3) Thrombosis or Sequelae
2 = New thrombosis (confirmed) or skin necrosis; Acute systemic reaction post-IV UFH bolus
1 = Progressive or recurrent thrombosis; Non-necrotizing (erythematous) skin lesions; Suspected thrombosis (not proven)
0 = None
4) other Thrombocytopenia Causes
2 = None
1 = Possible
0 = Definite
118
Outline 4Ts Point Risk Stratification for HIT
<3 = Low probability
4-5 = Intermediate
6-8 = High probability
119
List tx options in HIT
= Non-heparin anti-coagulants
Rivaroxaban
Fondaparinux
+/- IVIG if severe
120
Define Post-transfusion purpura (PTP)
= causes a precipitous fall in platelets approximately one week following transfusion
121
List clinical features of TTP
= acquired autoAbs to ADAMTS13
- mostly adults
- thrombocytopenia
- MAHA (schistocytes seen on blood smear)
- fluctuating neurologic symptoms = mental clouding or confusion
- may have mesenteric ischemia, cardiac issues, proteinuria, hematuria
122
Outline PLASMIC score for TTP mgmt
*1 pt for each YES
1) PLT <30
2) HemoLysis (retics >2.5%, haptoglobin undetectable, indirect bili >34)
3) Active cancer or treated for cancer w/in past year
4) History of Solid organ or Stem cell transplant
5) MCV <90
6) INR <1.5
7) Cr <175
123
Outline PLASMIC risk stratification
0–4 = Low risk, Consider alternative dx
5 = Intermediate risk, Consult Heme & consider plasma exchange
6–7 = High risk, Consult Heme & immediate plasma exchange
124
List 4 associations with Primary Thrombocytosis
- polycythemia vera
- myelofibrosis
- CML
- Kawasaki disease
125
What defines thrombocytosis?
PLT >600
126
List 10 Indications for Factor Replacement in Hemophilia
Suspected bleeding into joint or muscle
Any significant injury to head, neck, mouth or eyes
Any new or unusual headache, particularly following trauma even if seemingly minor
Severe pain or swelling at any location
All wounds that require surgical closure (sutures, staples), wound adhesive, or Steri-Strip placement
History of blunt trauma that might result in bleeding
Prior to any invasive procedure or surgery
Suspicion of uncontrolled GI bleeding leading to anemia or signs or symptoms of hypovolemia
Acute fractures, dislocations or sprains
Suspicion of uncontrolled heavy menstrual bleeding, leading to anemia or signs or symptoms of hypovolemia
127
Outline Recommended Factor VIII Therapy & Dosing for Complications Associated With Hemophilia A
None:
- abrasion
- spontaneous epistaxis
- mucosa or minor tongue bite
25U/kg:
- superficial lac
- deep lac
- superficial muscle hematoma
- traumatic epistaxis
- traumatic oral lesions or dental extraction
- early-moderate hemarthrosis
- hematuria
50U/kg:
- deep muscle hematoma
- late hemarthrosis or nonresponsive to earlier treatment
- major & life threatening bleeding
128
Outline tx for Hemophilia B
Factor 9 100-140 U/kg IV
129
Outline tx for von Willebrand disease
Desmopressin 0.3mcg/kg IV
130
Outline dose of protamine in relation to UFH and LMWH
Protamine 1mg per 100u of UFH
Protamine 1mg per 1mg LMWH if <8h ago
Protamine 0.5mg per 1mg LMWH if >8hr ago
131
Name reversal agent for dabigatran
idarucizumab 5g IV
or PCC
of hemodialysis
132
Name reversal agent for apixaban or rivaroxaban
andexanet alfa
or PCC 2000 units IV
133
List 10 Critical Sites for Hemorrhage in Anticoagulated Patients
Intracranial
Intraocular
Spinal
Pericardial tamponade
Airway (including posterior epistaxis)
Thorax
Intra-abdominal bleeding
Retroperitoneal hematoma
Intramuscular
Intra-articular
134
Outline Treatment for Supratherapeutic INR
INR <4.5 w/ NO bleeding = Stop warfarin/hold next dose
INR 4.5-10 w/ NO bleeding = Stop warfarin/hold next dose
- may give Vit K 2.5mg PO if high risk to bleed
INR >10 w/ NO bleeding = Stop warfarin, give Vit K 5mg PO
INR >10 w/ ACTIVE bleeding = Stop warfarin, Vit K 10mg IV over 30min, PCC 50u/kg IV
Any INR w/ major LIFE THREATENING bleeding = Stop warfarin, Vit K 10mg IV over 30min, PCC 25-50u/kg IV
135
Outline PCC dose for Warfarin Reversal in Major Bleeding
INR 2-4 = 25 U/KG
- max dose 2500u
INR 4-6 = 35 U/KG
- max dose 3500u
INR >6 = 50 U/KG
- max dose 5000u
136
Outline DIC Abnormal Clotting Sequence
1) PLTs + coagulation factors consumed, including fibrinogen + factors V, VIII, and XIII.
2) Thrombin is formed, overwhelms its inhibitor system, & acts to accelerate coagulation process and directly activate fibrinogen.
3) Fibrin deposited in small vessels in multiple organs.
4) Fibrinolytic system by means of plasmin lyses fibrin + impairs thrombin formation.
5) Fibrin degradation products are released & affect PLT function & inhibit fibrin polymerization.
6) Coagulation inhibition levels (antithrombin III, protein C, tissue factor pathway inhibitor) are decreased.
137
Outline Lab Dx of DIC
Peripheral smear = low PLT, RBC fragments, schistocytes
PLT <100
Prolonged PT
Prolonged PTT
Prolonged Thrombin time
Low Fibrinogen
D-Dimer negligible to elevated
Cr may be abnormal
138
Outline tx options in DIC
PLTs
FFP
Cryprecipitate
+/- heparin if thrombosis is primary issue
139
Outline CISNE score for Febrile Neutropenia
ECOG status 2+ = 2
Stress induced hyperglycemia = 2
COPD = 1
Chronic CV disease = 1
Mucositis Grade 2+ = 1
Monocyte count <200/uL = 1
* Low = 0
* Intermediate = 1-2
* High risk = 3+
140
List 5 features of febrile neutropenic pts that can be tx'd as outpt
1) MASCC score of <21
2) No evidence of PNA, CLABSI, cellulitis, or organ failure
3) Reliable daily follow-up with oncologist
4) demonstrate clinical stability during observation in ED for >4 hr
5) Carry low suspicion of MDR infection
141
List 3 features suggestive of vertebral mets and spinal cord compression in cancer pts
- back pain
- peripheral strength or sensory loss
- bowel or bladder dysfunction
142
List 6 cancers most commonly causing metastatic spinal cord compression
Prostate
Breast
Lung
RCC
Non-Hodgkin lymphoma
Multiple Myeloma
143
List gold standard imaging for dx of metastatic spinal cord compression
MRI spine
144
Outline tx steps for pts with metastatic spinal cord compression
Dexamethasone 10mg IV x1
then 16mg PO/d
Surgical decompression
Radiation therapy
145
Outline tx of HyperCa
NS 1-2L bolus, then 200cc/hr
Bisphosphonates
- Pamidronate 90mg IV
- Zoledronate 4mg IV
Calcitonin 4-8u/kg IV q6h
- especially for cardiac and neurologic symptoms
Furosemide/Loop diuretics for volume mgmt
Hemodialysis
146
List 4 kinds of dysregulated calcium homeostasis in malignancy
1) Synthesis of PTH analog PTH-related protein (PTHrP)
2) Overproduction of calcitriol (activated Vit D)
3) Bone osteolysis 2/2 direct spread of tumour
4) Ectopic production of PTH
147
List clinical features of HyperCa
- weakness
- lethargy
- confusion
- abdominal pain
- nausea
- vomiting
- constipation
- polyuria
- polydipsia
- AKI
- dysrhythmias
- neurologic abnormalities
148
List metabolic abnormalities in Tumour Lysis Syndrome
HyperK
HyperPO4
HypoCa
HyperUricemia
+ often AKI
149
Outline tx for Tumour Lysis Syndrome
IVF
Correct HyperK
Rasburicase
PPX with Allopurinol
150
List 5 cancers with risk for TLS
Burkitt lymphoma
ALL
Breast
Testicular
Small cell lung Ca
151
List pt population who may be harmed from rasburicase tx in TLS
Pts with G6PD deficiency
- can trigger hemolytic crisis
152
List one adverse outcome of tx with rasburicase
Methemoglobinema
153
List clinical features of pulmonary leukostasis
Dyspnea
Tachypnea
Hypoxemia
Crackles on auscultation
Bilateral opacities on CXR
154
List clinical features of CNS leukostasis
Confusion
Vision + Hearing abnormalities
HA
Ataxia
Coma
May see ICH on CT brain
155
List 8 clinical (end-organ) manifestations of leukostasis
Pulmonary
CNS
Retinal hemorrhage
MI
Acute limb ischemia
Priapism
Renal vein thrombosis
Renal infarction
156
Outline tx for leukostasis
IVF to reduce blood viscosity
Leukapheresis
Hydroxyurea
Chemotherapy
157
List clinical features of SVC syndrome
Edema + Erythema to UE, Chest, Face
Dyspnea
Dysphagia
Chest pain
Cough
JVD
Pleural effusion
Vocal cord paralysis
Horner syndrome
Blurred vision
Cerebral edema
Tracheal compression
158
Outline mgmt of SVC syndrome in the ED
Elevate HOB
Supplemental O2
Airway protection prn
Anticoagulation if 2/2 thrombosis
159
List 4 potential adverse reactions 2/2 rituximab treatment
- Severe infusion reactions (appears similar to anaphylaxis)
- TLS
- Severe mucocutaneous reactions
- PML
160
List clinical features of Cytokine Release Syndrome after CAR-T therapy
= uncontrolled cytokine release leads to a potentially life-threatening inflammatory syndrome
- around 3 days after tx
fever
malaise
myalgias
fatigue
rash
hTN
resp failure
end-organ dysfunction
161
List clinical features of Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS) after CAR-T therapy
= central nervous system undergoes immune cell–mediated damage
- 4-7 days after tx
confusion
HA
*expressive aphasia (very specific)
tremor
behavioural change
peripheral numbness
weakness
GTC seizure
cerebral edema
162
List tx options for CRS and ICANS after CAR-T therapy
CALL ONCOLOGY
IVF
Vasopressors
Respiratory support
Corticosteroids
Tocilizumab
163
Outline Virchow triad
Blood stasis
Blood vessel wall abnormality
Hypercoagulable states
164
List 20 Common Causes of Methemoglobinemia
HEREDITARY
- Hemoglobin M
- NADH methemoglobin reductase deficiency (homozygote and heterozygote)
ACQUIRED
Medications:
- Amyl nitrite
- Antineoplastics (cyclophosphamide, flutamide)
- Dapsone
- Local anesthetics (benzocaine, lidocaine, prilocaine)
- Metoclopramide
- Nitroglycerin
- Nitroprusside
- Phenazopyridine
- Chloroquine
- Primaquine
- Rasburicase
- Sulfonamides
Chemical Agents:
- Aniline dye derivatives (shoe dyes, marking inks)
- Butyl nitrite
- Isobutyl nitrite
- Chlorobenzene
- Fire (heat-induced denaturation)
- Food high in nitrates
- Naphthalene (mothballs)
- Nitrophenol
- Nitrous gases (seen in arc welders)
- Paraquat
- Silver nitrate
- Trinitrotoluene
- Well water (nitrates)
165
List 3 general causes of polycythemia (elevated RBC mass)
1) Polycythema vera
2) Secondary polycythemia
- appropriate or inappropriate increase of Epo
- chronic hypoxemia (<92% O2 sat)
- cyanotic congenital heart disease
- cigarette smoking
- high-altitude exposures
- congenital MetHGB
3) Relative polycythemia
- dehydration
- reduced plasma volume
166
List tx options for MetHGB in pts with G6PD deficiency or pregnancy
G6PD def
- Ascorbic acid instead of methylene blue
Pregnancy
- C/S delivery
- HBOT
- Exchange transfusion
167
When to suspect Sulfhemoglobinemia
Elevated MetHGB w/ no response to methylene blue
AND
Ingestion of oxidizing drugs (dapsone, SULFONAMIDES, metoclopramide, nitrates)
Supportive care
Maybe exchange transfusion
168
List medications that increase & decrease the effectiveness of apixaban (5 each)
INCREASE:
Clarithromycin
Erythromycin
Ketoconazole
Irtaconazole
Amiodarone
DECREASE:
St. John's Wort
VPA
Carbamazepine
Phenytoin
Rifampin
Levetiracetam
Phenobarbital
Rosen's 10th
flashcards
Decks in class (23)
# Cards
-
Toxicology346
-
General3
-
Electrolytes, Metabolism, Endocrine, & Rheum197
-
Pediatrics207
-
GI258
-
Ortho394
-
Infectious Disease389
-
Trauma312
-
Psych89
-
Enviro313
-
Cardiovascular475
-
Respiratory157
-
Neuro418
-
Ophtho139
-
OBGYN + Urology316
-
Nephro24
-
Heme/Onc168
-
Dermatology116
-
Resuscitation146
-
Head & Neck94
-
Bonus Chapters107
-
Special Populations & Geriatrics49
-
Hard Stuff/High Yield93
