DDAVP is the appropriate initial therapy for this patient with von Willebrand's disease, Type I presenting with gastrointestinal bleeding. DDAVP causes release of von Willebrand factor and factor VIII from endothelial cells and is effective for type I von Willebrand's disease.

1. Project: Ghana Emergency Medicine Collaborative, 2013
Document Title: Hematologic and Oncologic Emergencies
Author(s): Joe Lex, MD, FACEP, FAAEM, MAAEM (Temple University)
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3. Hematologic and Oncologic
Emergencies
Joe Lex, MD, FACEP, FAAEM, MAAEM
Associate Professor of Emergency Medicine,
Department of Emergency Medicine
Temple University School of Medicine
Philadelphia, PA USA
3

4. 4

5. Menu
• Transfusions
• Bleeding disorders
• Platelet disorders
• Red cell disorders
• White cell disorders
• Oncologic emergencies
5

6. Questions
6

7. 7

8. Who Needs Blood?
• Most patients uncomfortable if
hemoglobin concentration <7 g/dL
• Patients with heart or pulmonary
disease may need hemoglobin
concentration of ≥10 g/dL to
safeguard adequate oxygen
transport
8

9. What’s Available?
• Packed Red Blood Cells:
centrifuged whole blood with 80%
of plasma removed
• Adult: 1 unit PRBC raises
hemoglobin by 1 gm/dL
• Child: Each mL/kg raises
hemoglobin by 1 gm/dL
9

10. What’s Available?
• Platelets: shelf life ~5 days
– ABO / Rh checks are needed
– “Six pack” raises count by ~30,000
• Fresh Frozen Plasma: ~1 year
– 1 unit / mL of each coagulation factor
– No cellular components
– 10–15 mL / kg (3–4 250 mL bags)
10

11. Special Needs
• All blood products now leukocytedepleted
• Washed cell products in patients
with confirmed deficiency of IgA
• Irradiated cell products used to
prevent graft-versus-host reactions
in immunosuppressed patients
11

12. Acute Intravascular Hemolytic
Transfusion Reaction
• Typically due to ABO
incompatibility (clerical error)
• Intravascular lysis of donor RBCs
12

13. Acute Intravascular Hemolytic
Transfusion Reaction
• Sudden fever, chills, headache,
flushing, low back pain, nausea,
tachycardia, hypotension
• Shortly after transfusion starts
• Hemoglobinuria, hemoglobinemia
13

14. Acute Intravascular Hemolytic
Transfusion Reaction
• Stop infusion
• Direct Coombs on recipient’s blood
detects host antibodies
• Look at plasma: if red…
• Look at urine: if red…
14

15. Acute Intravascular Hemolytic
Transfusion Reaction
• CBC, chemistries, liver panel,
coagulation profile, haptoglobin,
lactate dehydrogenase (LDH)
15

16. Acute Intravascular Hemolytic
Transfusion Reaction
• Send bag to blood bank
• IV fluids (new tubing)
• Consider furosemide, mannitol
16

17. Febrile Nonhemolytic
• Multiple prior transfusions or
multiparous women
• Fever, chills shortly after start
• Same workup as acute
intravascular hemolytic reaction
• Diagnosis of exclusion
17

18. Febrile Nonhemolytic
• Stop transfusion
• IV fluid through new tubing
• Antipyretic
• Broad-spectrum antibiotic(s)
• Future transfusions: probably
leukoreduced
18

19. Febrile Nonhemolytic
• MILD: if patient responds to
antihistamine, may resume
transfusion
• SEVERE: antihistamine, steroids,
epinephrine, IVF
19

20. Massive Transfusion
• Hyperkalemia or hypokalemia
• Citrate breakdown into bicarbonate
è metabolic alkalosis
• Citrate / serum calcium complex è
hypocalcemia
• Coagulopathy
• Hypothermia from cold blood
• Volume overload
20

21. Delayed Hemolytic
• Extravascular: antibodies react to
non-ABO antigens
• Antibody-coated RBCs removed
from circulation by liver and spleen
before they are lysed è
extravascular è no
hemoglobinemia, hemoglobinuria
21

22. Delayed Hemolytic
• Typically asymptomatic, may have
fever
• Same workup as acute
intravascular hemolytic reaction
22

23. TRALI
• Transfusion-associated acute lung
injury (TRALI)
• Increasingly recognized event
• Acute respiratory distress, often
associated with fever, noncardiogenic pulmonary edema, and
hypotension
• ~1 in 2000 transfusions
23

24. Transfusion-Associated Graftversus-Host Disease
• Donor lymphocytes recognize
immunocompromised recipient as
foreign, attack host tissues
• Usually 4–10d post transfusion
• Fever, N-V, rash, diarrhea
24

25. Transfusion-Associated Graftversus-Host Disease
• Same workup as acute
intravascular hemolytic reaction
• No effective treatment: possibly
stem cell transplant
25

26. Disease Transmission
• HIV: 1 in 2,000,000
• Hepatitis B: 1 in 137,000
• Hepatitis C: 1 in 1,000,000
26

27. Other Complications
• Hypothermia from cold blood
• Volume overload
• Breakdown of citrate into
bicarbonate è metabolic alkalosis
• Citrate / serum calcium complex è
hypocalcemia
27

28. 8. Your patient is profoundly anemic
and you believe she would benefit from
a blood transfusion. In weighing
benefits against risks, you tell her that
the most common adverse effect is:
a. hepatitis C transmission.
b. hepatitis B transmission.
c. human immunodeficiency virus (HIV)
transmission.
d. febrile nonhemolytic reaction.
e. graft versus host reaction.
28

29. 8. Your patient is profoundly anemic
and you believe she would benefit from
a blood transfusion. In weighing
benefits against risks, you tell her that
the most common adverse effect is:
a. hepatitis C transmission.
b. hepatitis B transmission.
c. human immunodeficiency virus (HIV)
transmission.
d. febrile nonhemolytic reaction.
e. graft versus host reaction.
29

30. 8. Most common transfusion adverse
Febrile non-hemolytic reaction is
estimated to occur once for every 200
units transfused. During the
transfusion or within a few hours after
its completion, the patient has a
temperature elevation of at least 1°C
and usually has chills. The usual
cause of this febrile reaction is an
antigen-antibody reaction involving the
plasma, platelets, or white blood cells
that are passively transfused to the
recipient along with the RBCs.
30

31. 8. Most common transfusion adverse
Once a febrile transfusion reaction is
recognized, the current transfusion
should be terminated because there is
not sufficient clinical evidence to
differentiate the simple febrile
nonhemolytic reaction from the more
serious immediate hemolytic reaction.
31

32. 32

33. Thrombus Formation
• Damaged epithelium è collagen
and tissue factor (TF) exposed to
flowing blood è adherence /
activation of platelets (relies on von
Willebrand Factor [vWF])
33

34. Thrombus Formation
• Tissue factor activates coagulation
cascade è generates thrombin è
converts fibrinogen to fibrin è
forms long, cross-linking strands
that trap platelets and RBCs to
form insoluble clot
34

35. Thrombus Formation
• Thrombin also triggers tissue
plasminogen activator è activates
plasmin
• Plasmin, anti-thrombin III, protein C
& protein S cause fibrinolysis
35

36. Warfarin
• Inhibits Vitamin K-dependent
coagulation factors II, VII, IX, X
– Half-lives 7h (FVII) to 50h (FII)
• Inhibits Vitamin K-dependent
anticoagulants Protein C & S
– Half-lives up to 40h
• 1st few days: may be procoaguable
36

37. Warfarin Overdose: No Bleed
• INR <5: omit next warfarin or ê
dose
• INR 5 – 9: omit next 1-2 doses,
give oral vitamin K (1 – 2.5 mg)
• INR >9: omit warfarin, give oral
vitamin K (2.5 – 5 mg)
• Avoid subcutaneous vitamin K
37

38. Warfarin Overdose: Bleed
• Vitamin K 10 mg slow IV infusion
• Fresh frozen plasma (FFP): start
with 4 – 6 units
– Each ml of FFP contains 1unit of
each coagulation factor
– INR will not correct beyond ~1.5
• Prothrombin complex concentrate
– Rapid, expensive, procoaguability
38

39. Heparin Overdose
• Heparin activates antithrombin III
• Short half-life: stopping drip will
normalize in few hours
• Can reverse with protamine sulfate:
1mg IV for every 100u heparin
unfractionated given in prior 2 hrs
– Works a little for LMWH
39

40. Liver Disease
• Liver synthesizes nearly all clotting
factors
• é PT/INR do not correlate well with
risk of bleeding
• Can reverse with FFP if active
bleeding, require invasive
procedure
• ± vitamin K
40

41. 41

42. Hemophilias
• Inherited: sex-linked recessive
• Factor VIII: hemophilia A (more
common)
• Factor IX: hemophilia B
• Clinically indistinguishable
• PTT elevated in both
42

43. Clinical Severity
• Related to activity level of factor
<1% - severe à frequent
spontaneous bleeds
1 – 5% - moderate à occasional
spontaneous, lots in trauma
>5% - mild à no spontaneous,
excessive in trauma, surgery
43

44. Presentation
• Vast majority in ED have known
disease, present with complications
• Most common: intramuscular, intraarticular bleeds
44

45. Treatment: Based on Complaint
• Minor bleeding: replace 25%
• Severe bleeding: replace 50%
• Life-threatening: replace 100%
• FVIII: 1U/kg é plasma level ~2%
• FIX: 1U/kg é plasma level ~1%
• In ED, assume baseline plasma
level to be zero
45

46. Replacement Factors
• Can be recombinant or derived
from human plasma
• Hemophilia A: mild to moderate à
start with DDAVP
– Causes release of vWF and FVIII
from endothelial cells
• Arthrocentesis rarely indicated
46

47. 5. The initial dose of factor VIII required
for a 60-kg male with severe
hemophilia A in whom you suspect a
ruptured spleen is:
a. 1,500 units
b. 2,850 units
c. 3,000 units
d. 6,000 units
e. 5,700 units
47

48. 5. The initial dose of factor VIII required
for a 60-kg male with severe
hemophilia A in whom you suspect a
ruptured spleen is:
a. 1,500 units
b. 2,850 units
c. 3,000 units
d. 6,000 units
e. 5,700 units
48

49. 5. …initial dose of factor VIII … severe
hemophilia A … ruptured spleen … 3,000
units.
A 60-kg patient with a life threatening
hemorrhage who requires 100%
correction will need 50 mL/kg = 3000
units of factor VIII
49

50. von Willebrand Disease
• Mucocutaneous bleeding more
likely
• Hemarthrosis less likely
• Humate F®: FVIII-vWF concentrate
• DDAVP only effective in Type 1
50

51. 15. A 38-year-old woman has von
Willebrand’s disease, Type I. She
complains of blood-tinged emesis and
epigastric pain. Her stool tests weakly
positive for blood. Appropriate initial
therapy includes:
a. vitamin K.
b. 6 units platelet concentrate.
c. factor IX concentrate.
d. desmopressin (DDAVP).
e. plasmapheresis.
51

52. 15. A 38-year-old woman has von
Willebrand’s disease, Type I. She
complains of blood-tinged emesis and
epigastric pain. Her stool tests weakly
positive for blood. Appropriate initial
therapy includes:
a. vitamin K.
b. 6 units platelet concentrate.
c. factor IX concentrate.
d. desmopressin (DDAVP).
e. plasmapheresis.
52

53. 15. von Willebrand’s disease, Type I ...
blood-tinged emesis … initial therapy…
Treatment of von Willebrand’s disease
depends on the type of disease that is
present and the severity of bleeding.
Desmopressin (DDAVP) treatment has
benefit in patients with mild to
moderately severe von Willebrand’s
disease, but should be given in
consultation with a hematologist.
Factor VIII (cryoprecipitate) or fresh
frozen plasma may be used in patients
with severe bleeding.
53

54. Disseminated Intravascular
Coagulation (DIC)
• Many potential causes: infection,
malignancy, trauma, OB
• Loss of hemostasis regulatory
mechanisms
• Thrombin overproduced è
promotes clotting
• Fibrin obstructs small vessels
• Consumed platelets and factors
54

55. Presentation
• May be lab abnormalities only: no
overt clinical signs
• Bleeding, organ dysfunction
possible
55

56. Presentation
• CBC: thrombocytopenia, possible
anemia
• Blood smear: schistocytes
• PT/INR, PTT: prolonged
• D-dimer/FSP: elevated
• Fibrinogen: diminished
56

57. Treatment
• Treat underlying cause
• Bleeding-predominant: FFP,
platelets, cryoprecipitate
• Clotting-predominant: heparin
– More common in chronic DIC
– Not appropriate for acute DIC
57

58. 3. The most helpful lab study in diagnosing
disseminated intravascular coagulation is
the:
a. D-dimer, which is elevated.
b. partial thromboplastin time (PTT), which
is decreased.
c. fibrinogen level, which is elevated.
d. prothrombin time, which is prolonged.
e. fibrin degradation products (FDP), which
are diminished.
58

59. 3. The most helpful lab study in diagnosing
disseminated intravascular coagulation is
the:
a. D-dimer, which is elevated.
b. partial thromboplastin time (PTT), which
is decreased.
c. fibrinogen level, which is elevated.
d. prothrombin time, which is prolonged.
e. fibrin degradation products (FDP), which
are diminished.
59

60. 3. Useful labs in DIC
MOST USEFUL:
• PT / INR – é
• Platelet count – usually ê
• Fibrinogen level – ê
HELPFUL:
• aPTT – usually é
• Thrombin clot time – é
• Fragmented RBCs – present
• FDP and D-dimers – é
60

61. 10. The cornerstone of Emergency
Department management of DIC is:
a. hemodynamic stabilization and
treatment of the underlying disorder.
b. rapid correction of thrombocytopenia.
c. aggressive resuscitation with colloid.
d. pan-culture and broad-spectrum
antibiotic coverage.
e. rapid intubation and hyperventilation.
61

62. 10. The cornerstone of Emergency
Department management of DIC is:
a. hemodynamic stabilization and
treatment of the underlying
disorder.
b. rapid correction of thrombocytopenia.
c. aggressive resuscitation with colloid.
d. pan-culture and broad-spectrum
antibiotic coverage.
e. rapid intubation and hyperventilation.
62

63. 10. Cornerstone of managing DIC
The primary cause of the DIC needs to be
determined and treated. The high
mortality rate in severe DIC is primarily
due to the underlying disorder. Many
patients with DIC require no specific
therapy if there is no evidence of
bleeding, or if thrombosis and laboratory
studies are not deteriorating. The first
principle of management is to stabilize
the patient hemodynamically, providing
oxygen, fluids, and life support as
needed.
63

64. 64

65. Platelet Disorders
ê platelets = thrombocytopenia
1. ê production
2. Splenic sequestration
3. é destruction: drugs, infection,
DIC, ITP, TTP
4. Dilution: massive blood
transfusion
65

66. Platelets
• Platelet life-span: 10 days
• Each day marrow produces /
releases ~10% of platelets
• Platelet count <20,000:
spontaneous bleed
• Platelet count >50,000: minimal
needed to avoid bleeding in
trauma / surgery
66

67. Platelets
• Aspirin blocks COX receptors for
life of platelet
• Withhold aspirin for 1 day è
~25,000 active platelets
• Withhold aspirin for 2 days è
~50,000 active platelets
• NSAIDs block COX receptors for
life of NSAID (~4 – 8 hours)
67

68. Thrombotic Thrombocytopenic
Purpura (TTP)
Classic Pentad in 40%
1.
2.
3.
4.
5.
Microangiopathic hemolysis
Thrombocytopenia
Neurologic symptoms
Fever
Renal dysfunction (usually mild)
68

69. Thrombotic Thrombocytopenic
Purpura (TTP)
More Common Triad in 75%
1. Microangiopathic hemolysis
2. Thrombocytopenic purpura
3. Neurologic symptoms
69

70. Presentation
• More common in women, adults in
4th decade of life
• 40% have URI / flu-like symptoms
prior to presentation
• Fatigue, malaise
• Fever
• Neurologic symptoms: headache,
confusion, seizure, stroke, coma
70

71. Diagnosis
• Peripheral blood: schistocytes
• CBC: anemia, thrombocytopenia
• LDH: markedly é (ischemia,
hemolysis)
• Creatinine: é
• Urine: blood, protein, casts
• PT/PTT typically normal
71

72. Treatment
• Plasma exchange: very effective
• Platelet transfusion CONTRAINDICATED (é thrombus
formation)
• Last resort: steroids, splenectomy
72

73. 6. A 44-year-old woman with a history of
TTP, in remission for 30 days, presents to
the ED complaining of lethargy. Laboratory
results would likely show:
a. é LDH, é reticulocyte count, é red
blood cell count.
b. é LDH, é reticulocyte count, é
creatinine.
c. ê platelet count, ê red blood cell
count, ê reticulocyte count.
d. ê platelet count, ê reticulocyte
count, ê LDH.
73

74. 6. A 44-year-old woman with a history of
TTP, in remission for 30 days, presents to
the ED complaining of lethargy. Laboratory
results would likely show:
a. é LDH, é reticulocyte count, é red
blood cell count.
b.  LDH,  reticulocyte count, 
creatinine.
c. ê platelet count, ê red blood cell
count, ê reticulocyte count.
d. ê platelet count, ê reticulocyte
count, ê LDH.
74

75. 6. TTP – Laboratory results
In TTP, laboratory studies will show an
anemia of variable degree,  LDH,
reticulocytosis,  indirect bilirubin,
negative Coombs’ test, and
schistocytes on peripheral smear.
Thrombocytopenia is often severe with
the count <20,000/mL in 50% of
patients. BUN and creatinine are
typically .
75

76. Hemolytic Uremic Syndrome (HUS)
• Similar to TTP, but worse renal
dysfunction, less severe neurologic
symptoms
– ~60% require hemodialysis
• “Typical” or “childhood”: follows
acute bloody diarrhea
– Most common: E coli O157:H7
– Usually 5 years and younger
76

77. Treatment
• Plasma exchange not as effective
as with TTP
• Avoid platelet transfusions as with
TTP
77

78. 1. A patient with anemia, thrombocytopenia,
renal failure, normal coagulation tests and a
clear sensorium probably has:
a.
b.
c.
d.
e.
idiopathic thrombocytopenic anemia.
thrombotic thrombocytopenic purpura.
hemolytic-uremic syndrome.
disseminated intravascular coagulation.
autoimmune hemolytic anemia.
78

79. 1. A patient with anemia, thrombocytopenia,
renal failure, normal coagulation tests and a
clear sensorium probably has:
a.
b.
c.
d.
e.
idiopathic thrombocytopenic anemia.
thrombotic thrombocytopenic purpura.
hemolytic-uremic syndrome.
disseminated intravascular coagulation.
autoimmune hemolytic anemia.
79

80. 1. Hemolytic Uremic Syndrome
ITP generally presents with isolated
thrombocytopenia. TTP causes
neurologic symptoms in addition to the
other symptoms. DIC will have
abnormal coagulation studies.
Autoimmune hemolytic anemia may
cause severe rapid anemia, which may
present with angina or congestive heart
failure.
80

81. 4. Hemolytic-uremic syndrome is most
commonly seen in:
a. neonates.
b. infants and children 6 months to 4
years of age .
c. adolescents.
d. women age 30 to 50.
e. both sexes, over age 75.
81

82. 4. Hemolytic-uremic syndrome is most
commonly seen in:
a. neonates.
b. infants and children 6 months to
4 years of age.
c. adolescents.
d. women age 30 to 50.
e. both sexes, over age 75.
82

83. 4. Hemolytic-uremic syndrome is most
commonly seen in infants and children.
Hemolytic-uremic syndrome (HUS) is a
disease mainly of infancy and early
childhood, with a peak incidence
between 6 months and 4 years of age.
83

84. Heparin-Induced
Thrombocytopenia (HIT)
• More common with unfractionated
• Heparin-dependent antibody
activates platelets
• Signs / symptoms occur 5 to 7 days
after starting heparin
• ~50% develop thrombosis
– Venous or arterial
– Life- and limb-threatening
84

85. Diagnosis & Treatment
• Moderate thrombocytopenia (~50%
reduction)
• HIT antibodies in serum
• Discontinue all heparins, avoid in
future
• Avoid warfarin: can progress to
gangrene
• Other medicines can also cause
85

86. 11. Heparin-induced thrombocytopenia:
a. does not occur with low molecular
weight heparins.
b. requires a minimum number of units,
so a heparin “flush” is always safe.
c. can paradoxically cause thrombosis,
ischemia, and amputation.
d. never occurs during the first 24 hours
of infusion.
e. is easily treated with warfarin and
fresh-frozen plasma.
86

87. 11. Heparin-induced thrombocytopenia:
a. does not occur with low molecular
weight heparins.
b. requires a minimum number of units,
so a heparin “flush” is always safe.
c. can paradoxically cause
thrombosis, ischemia, and
amputation.
d. never occurs during the first 24 hours
of infusion.
e. is easily treated with warfarin and
fresh-frozen plasma.
87

88. 11. HIT thrombosis
Heparin-induced thrombocytopenia
(HIT) is due to an antibody, usually
IgG, which attaches to and stimulates
platelets. This platelet activation
produces both thrombocytopenia and a
tendency for thrombosis. The
incidence of HIT is between 1 and 3%
in patients treated with unfractionated
heparin but significantly less in patients
treated with LMW products.
88

89. 11. HIT thrombosis
The onset of HIT is usually 5 to 12 days
after heparin treatment is started but
may be sooner for patients who
developed the antibody from a previous
exposure. Thrombosis may involve the
skin (similar to warfarin-induced
cutaneous necrosis), the arteries (e.g.,
femoral artery thrombosis), or the veins
(e.g., recurrent DVT or PE).
89

90. Idiopathic (Autoimmune)
Thrombocytopenic Purpura (ITP)
• Acute in children (age 2 – 6)
– Viral prodrome
– Self-limited: remission in 90%
– Treatment: supportive
• Chronic form: adult females
90

91. Signs and Symptoms
• Easy bruising, prolonged menses,
mucosal bleeding
• Petechiae, purpura
• Diagnosis: thrombocytopenia on
CBC
91

92. Treatment
• Steroids (?)
• If refractory: splenectomy or
immunosuppressive therapy
• Platelet transfusion ONLY if serious
bleeding
• Intravenous immunoglobulin G
(IVIG) in children with intracranial
hemorrhage (rare)
92

93. 14. A 5-year-old girl complains of weakness
and fatigue. Two weeks ago she saw her
family doctor and was diagnosed with an
upper respiratory infection. She received no
medicine at that time. Physical examination
shows only a scattered petechial rash
located in areas where her clothing is snug
against her skin, such as underwear elastic
lines. Laboratory studies show a white
blood cell count 11,000/mm3 , Hgb 10.5 mg/
dL, and platelet count of 16,000/mm3.
Appropriate management of this patient
should be:
93

94. 14. Recent URI … petechial rash …
platelet count of 16,000/mm3.
a. platelet concentrate transfusion.
b. discharge home with instructions to
limit contact sports.
c. admit for salicylate therapy.
d. admit for splenectomy.
e. admit for observation.
94

95. 14. Recent URI … petechial rash …
platelet count of 16,000/mm3.
a. platelet concentrate transfusion.
b. discharge home with instructions to
limit contact sports.
c. admit for salicylate therapy.
d. admit for splenectomy.
e. admit for observation.
95

96. 14. Recent URI … petechial rash …
platelet count of 16,000/mm3.
Acute idiopathic thrombocytopenic
purpura (ITP) is seen most often in
children 2 to 6 years old. A viral
prodrome is common, usually within 3
weeks of the onset. The platelet count
falls, usually to <20,000/mm3. The
course is self-limited, with a greater
than 90% rate of spontaneous
remission. Morbidity and mortality are
low. Treatment is supportive. Steroid
therapy does not alter disease course.
96

97. 97

98. Lymphoma: Hodgkin
• Lymphadenopathy: mostly above
diaphragm (lower neck,
subclavicular)
• Large mediastinal mass è chest
pressure, cough, dyspnea
• B symptoms: weight loss, fever,
night sweats
– May be presenting complaint
98

99. Lymphoma: Hodgkin
• Diagnosis: lymph node biopsy
showing Reed-Sternberg cells
• Treatment: chemotherapy /
radiation
99

100. Non-Hodgkin Lymphoma
• Proliferation of lymphoid cells from
lymph nodes OR lymphatic tissue
other than bone marrow
• B-Cell, T-Cell, NK-Cell: can be
indolent or aggressive
• Diagnosis: biopsy
• Treatment: chemotherapy /
radiation
100

101. Pancytopenia
• Anemia + thrombocytopenia +
neutropenia
• Bone marrow diseases: myelodysplasia, myelofibrosis, some
leukemias and lymphomas
• Systemic diseases: lupus, severe
infection, sarcoidosis, alcohol,
tuberculosis, êvitamin B12, folate
101

102. 102

103. Aplastic Anemia
• Pancytopenia with hypocellular
bone marrow
– Acquired: marrow stem cells
damaged by drugs, radiation, virus,
chemical, immune-related
– Inherited: Fanconi’s anemia,
dyskeratosis congenita
103

104. Signs & Symptoms
• Bleeding, easy bruising
• Fatigue, malaise, anemia è short
of breath
• Infection common
104

105. Diagnosis / Treatment
• CBC, reticulocyte count
• Bone marrow biopsy
• Immediate: depends on severity of
anemia / thrombocytopenia /
neutropenia ± complications
• Bone marrow transplant
105

106. Red Blood Cells (RBC)
• Normal life: ~120 days
• Marrow releases ~1% total count
daily
– “baby red cells” = nucleated =
reticulocytes
106

107. 7. The most helpful laboratory study to
differentiate poor red blood cell production
from increased red cell destruction is the:
a. sedimentation rate.
b. sideroblast level.
c. serum iron level.
d. total to direct bilirubin ratio.
e. reticulocyte count.
107

108. 7. The most helpful laboratory study to
differentiate poor red blood cell production
from increased red cell destruction is the:
a. sedimentation rate.
b. sideroblast level.
c. serum iron level.
d. total to direct bilirubin ratio.
e. reticulocyte count.
108

109. 7. ê production vs  destruction
Reticulocytes are RBCs of intermediate
maturity. They are an index of the
production of mature RBCs by the bone
marrow (reported as a percent of total
RBCs). ê reticulocyte count reflects
impaired RBC production; seen with
low levels of iron, vitamin B12, folate,
bone marrow failure.  reticulocyte
count reflects accelerated
erythropoeisis, the normal marrow
response to anemia; seen with blood
loss and hemolytic anemias.
109

110. Aplastic Anemia
• Normal MCV with ê reticulocyte
• Can be RBC aplasia alone
110

111. Sickle Cell Disease
• Inherited mutated hemoglobin: HbS
• Recessive gene: both parents need
to pass to offspring
• HbS + HbA: trait è asymptomatic
• HbS + HbC (beta-thalassemia):
chronic anemia + recurrent painful
crises
111

112. Sickle Cell Disease
• RBC life span 10 – 15 days
• Marrow on constant “overdrive”
• Reticulocyte “normal” 8 – 10%
• WBC “normal” at 15 – 20K
• Hemoglobin “normal” at 8 – 10
• Platelets “normal” >500K
112

113. Vaso-Occlusive Crisis
• AKA acute painful episode
• Pain in extremities, chest,
abdomen, back
• No lab test can confirm
• No vital sign can confirm
• Treatment: analgesia
– Avoid meperidine
113

114. Acute Chest Syndrome
• New infiltrate on chest x-ray +
fever, cough, ésputum, dyspnea,
tachypnea, hypoxia
• Many causes: fat embolism from
marrow ischemia, pulmonary vasoocclusion, infection, venous
thromboembolism, pulmonary
edema
114

115. Acute Chest Syndrome
• Children: fever & cough most
common
• Adults: fever & chest pain as
presenting complaint
– Some develop 2 – 3 days into
hospital stay
• ± hypoxemia
115

116. Acute Chest Syndrome
• Chest x-ray normal in ~50%
• Treatment supportive
• Empiric antibiotic: 3rd / 4th
generation cephalosporin +
macrolide
• Severe è exchange transfusion
116

117. Splenic Sequestration
• Etiology: unknown
• Typically occurs in infants
– Tender, enlarged spleen
– Signs of hypovolemia, shock
– Concurrent infection common
• Diagnosis: worsening anemia,
persistent reticulocytisis, tender
large spleen
117

118. Splenic Sequestration
• Treatment:
– Intravenous fluids
– Blood transfusion
– May need splenectomy after acute
episode resolves
118

119. Aplastic Crisis
• Marrow shuts down
• Abrupt ê hemoglobin
• Abrupt ê reticulocytes (<2%)
• Causes: folate deficiency, human
parvovirus B19 (in children)
• Blood transfusion: severe anemia,
cardiorespiratory symptoms
119

120. Hemolytic Crisis
• Abrupt ê hemoglobin
• Major increase reticulocyte
production
• May see worsening jaundice
120

121. Other Complications
• Functional asplenia: infected by
encapsulated organisms
• Strokes: CNS occlusive events
• Priapism: low-flow due to corpora
cavernosa occlusion
121

122. 2. The viral agent implicated in an aplastic
crisis of patients with sickle cell disease is:
a.
b.
c.
d.
e.
adenovirus (atypical).
herpes simplex.
parvovirus.
coxsackie virus.
HTLV-IV.
122

123. 2. The viral agent implicated in an aplastic
crisis of patients with sickle cell disease is:
a.
b.
c.
d.
e.
adenovirus (atypical).
herpes simplex.
parvovirus.
coxsackie virus.
HTLV-IV.
123

124. 2. Parvovirus & Sickle cell
Aplastic crises can be precipitated by
viral infections (particularly parvovirus
B19), folic acid deficiency, or the
ingestion of bone marrow toxins such
as phenylbutazone. Bone marrow
erythropoiesis is slowed or stopped.
The hematocrit falls to as low as 10%,
and the reticulocyte count falls to as
low as 0.5%. The white blood cell
count and platelet counts usually
remain stable.
124

125. 9. A 12-year-old girl with sickle cell disease is
brought by her mother after she passed out
twice. She was kept home from school the
last few days for a “cold.” When you ask
the child to stand, you must catch her to
prevent her from falling to the ground. This
is suspicious for:
a. salmonella sepsis.
b. sequestration crisis.
c. acute chest syndrome.
d. aplastic crisis.
e. hemolytic crisis.
125

126. 9. A 12-year-old girl with sickle cell disease is
brought by her mother after she passed out
twice. She was kept home from school the
last few days for a “cold.” When you ask
the child to stand, you must catch her to
prevent her from falling to the ground. This
is suspicious for:
a. salmonella sepsis.
b. sequestration crisis.
c. acute chest syndrome.
d. aplastic crisis.
e. hemolytic crisis.
126

127. 9. Sequestration crisis
Sequestration crisis occurs primarily in
children and is the second most
common cause of death in children with
SCD under the age of 5 years. Often
preceded by viral infections, sickled
cells block the splenic outflow, causing
pooling of peripheral blood and sickled
cells in the spleen. Such patients
present in hypovolemic shock with an
enlarged spleen.
127

128. Hemolytic Anemia
• RBC destruction
• Intravascular
– Smear à fragmented RBCs
(schistocytes)
– More acute than extravascular
• Extravascular
– Occurs in liver or spleen
– Smear à spherocytes
128

129. Hemolytic Anemia
• Intrinsic
– Enzyme defect (G6PD, pyruvate
kinase), abnormal membrane,
abnormal cell (sickle cell disease,
thalassemia)
– G6PD triggered by drugs (aspirin,
antimalarials, sulfa, nitrofurantoin,
phenazopyridine), foods (fava beans),
infection
129

130. Hemolytic Anemia
• Extrinsic
– Autoimmune
– Non-immune: HUS/TTP, HELLP,
prosthetic valve abnormality, arteriovenous malformation, malaria, drugs,
spider /snake venom
130

131. Signs & Symptoms
• Vary depending on disease
• Symptoms related to anemia
• Jaundice
• Hepatosplenomegaly
131

132. Diagnosis
• Smear à schisto-, spherocytes
• Reticulocytes should be é
• Haptoglobin: binds free Hgbà ê
• Bilirubin é
• LDH é (released from RBCs)
• Hemoglobinemia, hemoglobinuria
• Autoimmune è direct Coombs +
132

133. Hypochromic Microcytic Anemia
• ê iron à iron deficiency
• ê globin à thalassemia
• ê porphyrin à sideroblastic, lead
toxicity
• Chronic disease
133

134. 13. A healthy 12-year-old AfricanAmerican female complains of
weakness and fatigue 3 days after
starting a course of trimethoprimsulfamethoxasole and pyridium for
a urinary tract infection. Her
hemoglobin is 4.8 mg/dl, and her
urine is tea-colored, but you see no
red blood cells on microscopic
exam. She probably has
undiagnosed:
134

135. 13. 12-year-old African-American
female…weakness and fatigue… TMP/
SMZ … hgb 4.8 mg/dl … no RBCs in
urine. Undiagnosed:
a. hemolytic uremic syndrome.
b. G6PD deficiency.
c. idiopathic thrombocytopenic purpura.
d. thrombotic thrombocytopenic
purpura.
e. sickle cell disease.
135

136. 13. 12-year-old African-American
female…weakness and fatigue… TMP/
SMZ … hgb 4.8 mg/dl … no RBCs in
urine. Undiagnosed:
a. hemolytic uremic syndrome.
b. G6PD deficiency.
c. idiopathic thrombocytopenic purpura.
d. thrombotic thrombocytopenic
purpura.
e. sickle cell disease.
136

137. 13. G6PD
Deficiency of the RBC enzyme
glucose-6-phosphate dehydrogenase
(G-6-PD) is the most common human
enzyme defect, affecting nearly onetenth of the world’s population. The
RBC is unable to protect itself against
oxidant stress. Acute hemolytic crises
occur that are incited by bacterial and
viral infections, exposure to oxidant
drugs, metabolic acidosis (such as
diabetic ketoacidosis), and ingestion of
fava beans in some patients.
137

138. 13. G6PD
Within 1 to 3 days following oxidant
stress, the patient can develop
hemoglobinuria and the potential for
vascular collapse. These hemolytic
crises are generally well tolerated and
self-limited because only the older
RBCs will hemolyze. The drugs most
commonly associated with oxidant
stress are sulfa drugs, antimalarials,
phenazopyridine, and nitrofurantoin.
138

139. Diagnosis / Treatment
• ê serum iron level
• ê serum ferritin level
• é total iron binding capacity (TIBC)
• Treatment: iron supplements,
outpatient workup
139

140. Macrocytic Anemia
• Most important: megaloblastic
• ê folate (green vegetables, fruit,
cereals) or ê vitamin B12 (meat)
è impaired DNA synthesis
140

141. Macrocytic Anemia
• Petechiae, mucosal bleeding,
infections, sore mouth / tongue,
diarrhea, weight loss
• B12 can also have paresthesias,
ataxia
• Diagnosis: send levels
• Treatment: replace
141

142. Polycythemia
• éHct: >51% in M, >48% in F
• Apparent: ê plasma volume
• Secondary
– Appropriate: hypoxia
– Inappropriate: é erythropoietin
• Polycythemia vera: é production
RBCs, WBCs, platelets
– Can progress to myelofibrosis,
leukemia
142

143. Signs & Symptoms
• Headache, weakness, pruritus,
dizziness, ésweating, visual
changes, paresthesias, weight loss,
joint pain
• Ruddy complexion, éspleen,
éliver, éblood pressure
• Thrombosis: ACS, CVA, PE, etc
• Hemorrhage
143

144. Diagnosis / Treatment
• éRBCs, éWBCs, éplatelets
• Confirmed by non-ED studies
• Treatment: phlebotomy
144

145. 16. A 68-year-old man complains of
headache, dizziness, and blurred
vision. His blood pressure is
190/118 mmHg. He has a florid
face, normal fundi, and marked
splenomegaly. His hematocrit is
67%. Reasonable therapy
includes:
145

146. 16. … florid face … splenomegaly …
hematocrit = 67%. Therapy:
a. 250cc salt-poor albumin.
b. intravenous nitroprusside.
c. phlebotomy.
d. plasmapheresis.
e. sublingual nifedipine.
146

147. 16. … florid face … splenomegaly …
hematocrit = 67%. Therapy:
a. 250cc salt-poor albumin.
b. intravenous nitroprusside.
c. phlebotomy.
d. plasmapheresis.
e. sublingual nifedipine.
147

148. 16. … florid face … splenomegaly …
hematocrit = 67%. Therapy:
Emergency treatment of any form of
symptomatic polycythemia is
phlebotomy. Usually not more than
500 ml of blood is slowly removed as
the volume is replaced with a
comparable amount of normal saline.
148

149. Methemoglobinemia
• éproduction or êreduction
• Causes discussed in toxicology
• Cyanosis with normal oxygen
saturation
• Treatment:
– Congenital: usually none
– Toxic è symptomatic è treat with
intravenous methylene blue
149

150. 150

151. Leukemia
• éproduction undifferentiated
hematopoietic stem cells
• Acute Lymphocytic (ALL)
• Signs & symptoms: protean
– Related to abnormal cells crowding
out normal cells à êRBC, êWBC,
êplatelets
– Bacterial infections in 1/3 at time of
diagnosis
151

152. Leukemia
• Chronic Lymphocytic (CLL): most
common in patients >50 years
• Often no symptoms: may have
fatigue, large lymph nodes,
infections (esp. respiratory)
• Diagnosis: absolute lymphocyte
count >5000 cells/ml
• Treatment: monitor, chemo
152

153. Multiple Myeloma
• Abnormal éplasma cells
• Fatigue from anemia
• Bone pain from osteolytic lesions or
pathologic fractures
• Diagnosis: écalcium, écreatinine
• Bone marrow: >10% plasma cells
• Serum / urine protein electrophoresis (SPEP, UPEP)
153

154. Treatment
• Chemotherapy
• Plasmapheresis for hyperviscosity
syndrome
• If comatose: temporize by removing
1 liter blood, replace with normal
saline
• écalcium: IV saline, steroids
154

155. 155

156. Malignancy Complications
• Hyperviscosity syndrome
• Leukostasis (sludging)
• Neutropenic fever
• Spinal cord compressions
• Superior vena cava syndrome
• Tumor lysis syndrome
• Hypercalcemia
• Pericardial effusion / tamponade
156

157. Hyperviscosity Syndrome
• éabnormal serum proteins
• Waldenstrom macroglobulinemia
• Multiple myeloma (less common)
• Most common symptoms:
neurologic, visual
• May see mucosal or GI bleeding
• CHF from é plasma volume
• Plasmapheresis, exchange
157

158. Leukostasis
• WBC sludging in microcirculation
• Usually acute leukemia
• Can be seen with chronic, NHL
• Neurologic symptoms
• Can see respiratory failure
• Treatment: leukapheresis,
hydroxyurea, chemotherapy
158

159. Neutropenic Fever
• Absolute neutrophil count (ANC) =
neutrophils + bands
• ANC <500 cells/ml
• Signs and symptoms: fever
• Treatment: IV antibiotics
– Ceftazidime or cefepime ± aminoglycoside or –penem
– Add vancomycin if appropriate
159

160. Spinal Cord Compression
• Lymphoma, metastasis, primary
• S&S: back pain, weakness,
numbness, bowel / bladder / sexual
dysfunction
• Diagnosis: MRI
– CT myelogram if MRI not available
• Treatment
– Dexamethasone
– Radiation therapy
160

161. Superior Vena Cava Syndrome
• Tumor obstructs SVC è venous
hypertension, congestion
• Early signs: face edema that
improves through day
• SOB, cough, chest pain
• Distension of chest, neck veins
• Cyanosis
• Diagnosis: chest CT
• Treatment: radiation therapy
161

162. Acute Tumor Lysis Syndrome
• Usually after chemotherapy
• Lysed cells è metabolic changes
• Hyperuricemia: N/V, renal failure
due to renal precipitation
• Hyperphosphatemia: N/V, lethargy,
seizures, renal impair
– Also binds with Ca+ à êcalcium
• Hypocalcemia: tetany, arrhythmia
162

163. Acute Tumor Lysis Syndrome
• Hyperkalemia: N/V, muscle
weakness, cramps, arrhythmias,
heart block è asystole
• Acute renal failure: possible
hemodialysis; do NOT alkalinize
urine, worsens éphosphorus and
êcalcium
163

164. Others
• Hypercalcemia: see EndocrineMetabolic Emergencies
• Pericardial Effusion / Tamponade:
see Cardiovascular Emergencies
164

165. 12. A 42-year-old woman with adult T-cell
lymphoma-leukemia complains of back pain,
abdominal pain, and confusion. Laboratory
evaluation shows a total calcium of 15.8 mg/
dl. Appropriate management of this patient
should include:
a. plasmapheresis.
b. IV bicarbonate.
c. IV hypertonic saline / oral
Kayexalate®.
d. IV normal saline and IV furosemide.
e. glucagon.
165

166. 12. A 42-year-old woman with adult T-cell
lymphoma-leukemia complains of back pain,
abdominal pain, and confusion. Laboratory
evaluation shows a total calcium of 15.8 mg/
dl. Appropriate management of this patient
should include:
a. plasmapheresis.
b. IV bicarbonate.
c. IV hypertonic saline / oral Kayexalate®.
d. IV normal saline and IV
furosemide.
e. glucagon.
166

167. 12. Hypercalcemia of malignancy
Patients with severe hypercalcemia
(>14 mg/dl) require immediate
treatment regardless of symptoms.
The four basic goals of therapy are
(1) restore intravascular volume,
(2) enhance renal calcium elimination
(3) reduce osteoclastic activity
(4) treat primary disorder.
167

168. 12. Hypercalcemia of malignancy
Isotonic saline is the first step. Once
volume is restored, the calcium will
usually have ê by 1.6 to 2.4 mg/dl, but
hydration alone rarely leads to
complete normalization. Loop diuretics
inhibit resorption of calcium in the thick
ascending loop of Henle, é the
calciuric effect of hydration. Volume
expansion must precede administration
of furosemide, because the drug’s
effect depends on the delivery of
calcium to the distal nephron.
168

169. Pearls
• The first step in managing any
transfusion reaction to to stop the
transfusion
• Hemarthrosis in hemophiliacs:
factor replacement, never
arthrocentesis
• Minor head injury in hemophilia:
replace factor, head CT, admit for
observation
169

170. Pearls
• Initial treatment in mild-moderate
hemophilia A: DDAVP
• NO PLATELET TRANSFUSION in
patients with TTP, HUS
• Once a patient has HIT, no heparin
can ever again be used, including
LMWH
170

171. Thank You
171