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GEMC: Hematologic and Oncologic Emergencies: Resident Training

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This is a lecture by Dr. Joe Lex from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, …

This is a lecture by Dr. Joe Lex from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. 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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  • 1. 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/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. These lectures have been modified in the process of making a publicly shareable version. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/privacy-and-terms-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers. 1
  • 2. Attribution Key for more information see: http://open.umich.edu/wiki/AttributionPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair. 2
  • 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