GEMC: Hematologic and Oncologic Emergencies: Resident Training

Project: Ghana Emergency Medicine Collaborative, 2013 Document Title: Hematologic and Oncologic Emergencies Author(s): Joe Lex, MD, FACEP, FAAEM, MAAEM (Temple University) License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/

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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

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Menu

•  Transfusions •  Bleeding disorders •  Platelet disorders •  Red cell disorders •  White cell disorders •  Oncologic emergencies

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Questions

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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

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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

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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)

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Special Needs

•  All blood products now leukocyte-depleted

•  Washed cell products in patients with confirmed deficiency of IgA

•  Irradiated cell products used to prevent graft-versus-host reactions in immunosuppressed patients

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Acute Intravascular Hemolytic Transfusion Reaction

•  Typically due to ABO incompatibility (clerical error)

•  Intravascular lysis of donor RBCs

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•  Sudden fever, chills, headache, flushing, low back pain, nausea, tachycardia, hypotension

•  Shortly after transfusion starts •  Hemoglobinuria, hemoglobinemia

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•  Stop infusion •  Direct Coombs on recipient’s blood

detects host antibodies •  Look at plasma: if red… •  Look at urine: if red…

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•  CBC, chemistries, liver panel, coagulation profile, haptoglobin, lactate dehydrogenase (LDH)

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•  Send bag to blood bank •  IV fluids (new tubing) •  Consider furosemide, mannitol

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Febrile Nonhemolytic

•  Multiple prior transfusions or multiparous women

•  Fever, chills shortly after start •  Same workup as acute

intravascular hemolytic reaction •  Diagnosis of exclusion

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

leukoreduced

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•  MILD: if patient responds to antihistamine, may resume transfusion

•  SEVERE: antihistamine, steroids, epinephrine, IVF

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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

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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

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Delayed Hemolytic

•  Typically asymptomatic, may have fever

•  Same workup as acute intravascular hemolytic reaction

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TRALI

•  Transfusion-associated acute lung injury (TRALI)

•  Increasingly recognized event •  Acute respiratory distress, often

associated with fever, non-cardiogenic pulmonary edema, and hypotension

•  ~1 in 2000 transfusions 23

Transfusion-Associated Graft-versus-Host Disease

•  Donor lymphocytes recognize immunocompromised recipient as foreign, attack host tissues

•  Usually 4–10d post transfusion •  Fever, N-V, rash, diarrhea

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Transfusion-Associated Graft-versus-Host Disease

•  Same workup as acute intravascular hemolytic reaction

•  No effective treatment: possibly stem cell transplant

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Disease Transmission

•  HIV: 1 in 2,000,000 •  Hepatitis B: 1 in 137,000 •  Hepatitis C: 1 in 1,000,000

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Other Complications

•  Hypothermia from cold blood •  Volume overload •  Breakdown of citrate into

bicarbonate è metabolic alkalosis •  Citrate / serum calcium complex è

hypocalcemia

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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.

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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.

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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

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.

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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])

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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

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Thrombus Formation

•  Thrombin also triggers tissue plasminogen activator è activates plasmin

•  Plasmin, anti-thrombin III, protein C & protein S cause fibrinolysis

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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

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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

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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

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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

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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

Hemophilias

•  Inherited: sex-linked recessive •  Factor VIII: hemophilia A (more

common) •  Factor IX: hemophilia B •  Clinically indistinguishable •  PTT elevated in both

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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

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•  Vast majority in ED have known disease, present with complications

•  Most common: intramuscular, intra-articular bleeds

Presentation

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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

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

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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

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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

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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

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von Willebrand Disease

•  Mucocutaneous bleeding more likely

•  Hemarthrosis less likely •  Humate F®: FVIII-vWF concentrate •  DDAVP only effective in Type 1

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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.

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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.

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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.

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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

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Presentation

•  May be lab abnormalities only: no overt clinical signs

•  Bleeding, organ dysfunction possible

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Presentation

•  CBC: thrombocytopenia, possible anemia

•  Blood smear: schistocytes •  PT/INR, PTT: prolonged •  D-dimer/FSP: elevated •  Fibrinogen: diminished

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Treatment

•  Treat underlying cause •  Bleeding-predominant: FFP,

platelets, cryoprecipitate •  Clotting-predominant: heparin

– More common in chronic DIC – Not appropriate for acute DIC

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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

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

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

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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.

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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.

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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.

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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

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

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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)

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Thrombotic Thrombocytopenic Purpura (TTP)

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

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Thrombotic Thrombocytopenic Purpura (TTP)

More Common Triad in 75% 1.  Microangiopathic hemolysis 2.  Thrombocytopenic purpura 3.  Neurologic symptoms

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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

Diagnosis

•  Peripheral blood: schistocytes •  CBC: anemia, thrombocytopenia •  LDH: markedly é (ischemia,

hemolysis) •  Creatinine: é •  Urine: blood, protein, casts •  PT/PTT typically normal

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Treatment

•  Plasma exchange: very effective •  Platelet transfusion CONTRA-

INDICATED (é thrombus formation)

•  Last resort: steroids, splenectomy

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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

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

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 .

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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

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Treatment

•  Plasma exchange not as effective as with TTP

•  Avoid platelet transfusions as with TTP

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1.  A patient with anemia, thrombocytopenia, renal failure, normal coagulation tests and a clear sensorium probably has:

a. idiopathic thrombocytopenic anemia. b. thrombotic thrombocytopenic purpura. c.  hemolytic-uremic syndrome. d.  disseminated intravascular coagulation. e.  autoimmune hemolytic anemia.

78

1. A patient with anemia, thrombocytopenia, renal failure, normal coagulation tests and a clear sensorium probably has:

a. idiopathic thrombocytopenic anemia. b. thrombotic thrombocytopenic purpura. c.  hemolytic-uremic syndrome. d.  disseminated intravascular coagulation. e.  autoimmune hemolytic anemia.

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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

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.

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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

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

•  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

Heparin-Induced Thrombocytopenia (HIT)

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•  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

Diagnosis & Treatment

85

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

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

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.

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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

•  Acute in children (age 2 – 6) – Viral prodrome – Self-limited: remission in 90% – Treatment: supportive

•  Chronic form: adult females

Idiopathic (Autoimmune) Thrombocytopenic Purpura (ITP)

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•  Easy bruising, prolonged menses, mucosal bleeding

•  Petechiae, purpura •  Diagnosis: thrombocytopenia on

CBC

Signs and Symptoms

91

•  Steroids (?) •  If refractory: splenectomy or

immunosuppressive therapy •  Platelet transfusion ONLY if serious

bleeding •  Intravenous immunoglobulin G

(IVIG) in children with intracranial hemorrhage (rare)

Treatment

92

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

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.

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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.

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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.

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•  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

Lymphoma: Hodgkin

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•  Diagnosis: lymph node biopsy showing Reed-Sternberg cells

•  Treatment: chemotherapy / radiation

Lymphoma: Hodgkin

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•  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

Non-Hodgkin Lymphoma

100

•  Anemia + thrombocytopenia + neutropenia

•  Bone marrow diseases: myelo-dysplasia, myelofibrosis, some leukemias and lymphomas

•  Systemic diseases: lupus, severe infection, sarcoidosis, alcohol, tuberculosis, êvitamin B12, folate

Pancytopenia

101

•  Pancytopenia with hypocellular bone marrow – Acquired: marrow stem cells

damaged by drugs, radiation, virus, chemical, immune-related

– Inherited: Fanconi’s anemia, dyskeratosis congenita

Aplastic Anemia

103

•  Bleeding, easy bruising •  Fatigue, malaise, anemia è short

of breath •  Infection common

Signs & Symptoms

104

•  CBC, reticulocyte count •  Bone marrow biopsy •  Immediate: depends on severity of

anemia / thrombocytopenia / neutropenia ± complications

•  Bone marrow transplant

Diagnosis / Treatment

105

Red Blood Cells (RBC)

•  Normal life: ~120 days •  Marrow releases ~1% total count

daily – “baby red cells” = nucleated =

reticulocytes

106

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

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

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

Aplastic Anemia

•  Normal MCV with ê reticulocyte •  Can be RBC aplasia alone

110

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

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

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

Acute Chest Syndrome

•  New infiltrate on chest x-ray + fever, cough, ésputum, dyspnea, tachypnea, hypoxia

•  Many causes: fat embolism from marrow ischemia, pulmonary vaso-occlusion, infection, venous thromboembolism, pulmonary edema

114


•  Children: fever & cough most common

•  Adults: fever & chest pain as presenting complaint – Some develop 2 – 3 days into

hospital stay •  ± hypoxemia

115


•  Chest x-ray normal in ~50% •  Treatment supportive •  Empiric antibiotic: 3rd / 4th

generation cephalosporin + macrolide

•  Severe è exchange transfusion

116

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

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Splenic Sequestration

•  Treatment: – Intravenous fluids – Blood transfusion – May need splenectomy after acute

episode resolves

118

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

Hemolytic Crisis

•  Abrupt ê hemoglobin •  Major increase reticulocyte

production •  May see worsening jaundice

120

Other Complications

•  Functional asplenia: infected by encapsulated organisms

•  Strokes: CNS occlusive events •  Priapism: low-flow due to corpora

cavernosa occlusion

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2. The viral agent implicated in an aplastic crisis of patients with sickle cell disease is:

a.  adenovirus (atypical). b.  herpes simplex. c.  parvovirus. d.  coxsackie virus. e.  HTLV-IV.

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2. The viral agent implicated in an aplastic crisis of patients with sickle cell disease is:

a.  adenovirus (atypical). b.  herpes simplex. c.  parvovirus. d.  coxsackie virus. e.  HTLV-IV.

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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

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.

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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.

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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.

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Hemolytic Anemia

•  RBC destruction •  Intravascular

– Smear à fragmented RBCs (schistocytes)

– More acute than extravascular •  Extravascular

– Occurs in liver or spleen – Smear à spherocytes

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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

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Hemolytic Anemia

•  Extrinsic – Autoimmune – Non-immune: HUS/TTP, HELLP,

prosthetic valve abnormality, arterio-venous malformation, malaria, drugs, spider /snake venom

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Signs & Symptoms

•  Vary depending on disease •  Symptoms related to anemia •  Jaundice •  Hepatosplenomegaly

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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 +

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Hypochromic Microcytic Anemia

• ê iron à iron deficiency • ê globin à thalassemia • ê porphyrin à sideroblastic, lead

toxicity •  Chronic disease

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13. A healthy 12-year-old African-American female complains of weakness and fatigue 3 days after starting a course of trimethoprim-sulfamethoxasole 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:

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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.

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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.

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13. G6PD Deficiency of the RBC enzyme glucose-6-phosphate dehydrogenase (G-6-PD) is the most common human enzyme defect, affecting nearly one-tenth 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.

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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.

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• ê serum iron level • ê serum ferritin level • é total iron binding capacity (TIBC) •  Treatment: iron supplements,

outpatient workup

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Macrocytic Anemia

•  Most important: megaloblastic • ê folate (green vegetables, fruit,

cereals) or ê vitamin B12 (meat) è impaired DNA synthesis

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Macrocytic Anemia

•  Petechiae, mucosal bleeding, infections, sore mouth / tongue, diarrhea, weight loss

•  B12 can also have paresthesias, ataxia

•  Diagnosis: send levels •  Treatment: replace

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Polycythemia

• éHct: >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

Signs & Symptoms

•  Headache, weakness, pruritus, dizziness, ésweating, visual changes, paresthesias, weight loss, joint pain

•  Ruddy complexion, éspleen, éliver, éblood pressure

•  Thrombosis: ACS, CVA, PE, etc •  Hemorrhage

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• éRBCs, éWBCs, éplatelets •  Confirmed by non-ED studies •  Treatment: phlebotomy

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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:

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16. … florid face … splenomegaly … hematocrit = 67%. Therapy:

a. 250cc salt-poor albumin. b. intravenous nitroprusside. c. phlebotomy. d. plasmapheresis. e. sublingual nifedipine.

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a. 250cc salt-poor albumin. b. intravenous nitroprusside. c. phlebotomy. d. plasmapheresis. e. sublingual nifedipine.

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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.

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Methemoglobinemia

• éproduction or êreduction •  Causes discussed in toxicology •  Cyanosis with normal oxygen

saturation •  Treatment:

– Congenital: usually none – Toxic è symptomatic è treat with

intravenous methylene blue

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Leukemia

• éproduction undifferentiated hematopoietic stem cells

•  Acute Lymphocytic (ALL) •  Signs & symptoms: protean

– Related to abnormal cells crowding out normal cells à êRBC, êWBC, êplatelets

– Bacterial infections in 1/3 at time of diagnosis

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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

Multiple Myeloma

•  Abnormal éplasma cells •  Fatigue from anemia •  Bone pain from osteolytic lesions or

pathologic fractures •  Diagnosis: écalcium, écreatinine •  Bone marrow: >10% plasma cells •  Serum / urine protein electro-

phoresis (SPEP, UPEP) 153

Treatment

•  Chemotherapy •  Plasmapheresis for hyperviscosity

syndrome •  If comatose: temporize by removing

1 liter blood, replace with normal saline

• écalcium: IV saline, steroids

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Malignancy Complications

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

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Hyperviscosity Syndrome

• éabnormal 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

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Leukostasis

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

hydroxyurea, chemotherapy

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Neutropenic Fever

•  Absolute neutrophil count (ANC) = neutrophils + bands

•  ANC <500 cells/ml •  Signs and symptoms: fever •  Treatment: IV antibiotics

– Ceftazidime or cefepime ± amino-glycoside or –penem

– Add vancomycin if appropriate

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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

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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

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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 êcalcium

•  Hypocalcemia: tetany, arrhythmia 162

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 éphosphorus and êcalcium

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Others

•  Hypercalcemia: see Endocrine-Metabolic Emergencies

•  Pericardial Effusion / Tamponade: see Cardiovascular Emergencies

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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.

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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.

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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.

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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

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

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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

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Thank You

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GEMC: Hematologic and Oncologic Emergencies: Resident Training

Education

Transcript of GEMC: Hematologic and Oncologic Emergencies: Resident Training