Hematology Emergencies Intensive Course Final Year MMED Candidates 2009-2010 Chew Keng Sheng School of Medical Sciences UN...
Whole Blood <ul><li>Rarely used today (individual blood components provided separately) </li></ul><ul><li>Indications </li...
Packed Red Blood Cells <ul><li>Preparation </li></ul><ul><li>Plasma removed from whole blood and remaining RBC mass is was...
<ul><li>Production of anti-D antibody occurs in Rh– individuals who have exposure to small amounts of D antigen </li></ul>...
<ul><li>Indications </li></ul><ul><li>Generally, transfusion is rarely indicated when Hb >10 g/dL and is almost always ind...
<ul><li>Indications </li></ul><ul><li>Transfusion for Hb >6 g/dL in healthy nonsurgical patients is generally not indicate...
<ul><li>Indications </li></ul><ul><li>In acute hemorrhage, up to 40% of the blood volume in a bleeding, otherwise  healthy...
<ul><li>Comments </li></ul><ul><li>Each unit of PRBCs has approximate volume of 250 mL </li></ul><ul><li>In adults, 1 unit...
Fresh Frozen Plasma <ul><li>Frozen fluid product of centrifuged and separated whole blood </li></ul><ul><li>FFP is frozen ...
<ul><li>Before use, should be thawed in warm water which between 30°C to 37°C.  </li></ul><ul><li>Higher temperatures will...
<ul><li>Indications </li></ul><ul><li>Clotting factor deficiencies </li></ul><ul><ul><li>Hemophilia A </li></ul></ul><ul><...
<ul><li>Requires ABO-compatibility; but not crossmatched </li></ul><ul><li>Amount to transfuse: 3 to 10 mL/kg or as needed...
Cryoprecipitate <ul><li>Cryoprecipitate prepared from precipitants of slowly thawed FFP between 1-6C. The cold insoluble p...
<ul><li>Indications </li></ul><ul><li>Hypofibrinogenemia (congenital, DIC, cancer, </li></ul><ul><li>Cirrhosis </li></ul><...
<ul><li>It is preferable to use cryoprecipitate that is ABO-compatible with the recipient’s red cells, but not crossmatche...
Platelets <ul><li>Obtained from centrifuged whole blood </li></ul><ul><li>Indications </li></ul><ul><li>Thrombocytopenia <...
<ul><li>Not indicated in diseases with ongoing consumption of platelets: ITP, TTP, untreated DIC & thrombocytopenia associ...
<ul><li>Thienopyridine platelet ADP receptor inhibitors and direct glycoprotein IIb/IIIa inhibitors impair platelet functi...
<ul><li>Amount to transfuse: 1 unit per 10 kg body weight (6 to 10 units of platelets for the average adult) </li></ul><ul...
COMPLICATIONS OF TRANSFUSION
Massive Transfusion <ul><li>Definition </li></ul><ul><li>No strict definition but commonly referred as the replacement of ...
<ul><li>Complications </li></ul><ul><li>Metabolic alkalosis and hypocalcemia secondary to citrated blood </li></ul><ul><li...
<ul><li>Administer via blood warmer (no microwave) </li></ul><ul><li>Calcium gluconate (if ECG changes occur) </li></ul>Ma...
Hemolytic Crisis (Acute Transfusion Reaction) <ul><li>Most commonly caused by ABO incompatibility </li></ul><ul><li>May re...
<ul><li>Management </li></ul><ul><li>Stop transfusion </li></ul><ul><li>IV fluids </li></ul><ul><ul><li>Maintain urine out...
Other Complications <ul><li>Febrile transfusion reaction </li></ul><ul><li>Etiology: recipient antibody response to donor ...
SPECIFIC DRUG THERAPIES AFFECTING HEMOSTASIS
Aspirin <ul><li>Mechanism </li></ul><ul><li>Irreversibly blocks conversion of arachidonic acid into thromboxane A2 (platel...
<ul><li>Mechanism </li></ul><ul><li>Irreversibly blocks ADP receptor on platelets </li></ul><ul><li>Deforms the fibrinogen...
Clopidogrel and Ticlopidine (2) <ul><li>Complications </li></ul><ul><li>Dyspepsia, rash, diarrhea </li></ul><ul><li>Ticlop...
Heparin <ul><li>Mechanism </li></ul><ul><li>Reduced thrombin and fibrin formation by binding and activating antithrombin I...
Heparin <ul><li>Low Molecular Weight Heparin </li></ul><ul><li>Derived from porcine intestinal mucosa </li></ul><ul><li>Hi...
<ul><li>Complications </li></ul><ul><li>HIT </li></ul><ul><li>Reversal </li></ul><ul><li>Reversed with protamine sulfate (...
Heparin Induced Thrombocytoenia <ul><li>HIT is a syndrome of antibody-mediated thrombocytopenia that paradoxically is ofte...
<ul><li>Platelet factor 4, a small peptide stored within the alpha granules of platelets,  binds to heparin  and is releas...
<ul><li>Typically, HIT begins with the appearance of thrombocytopenia about a week after the start of heparin therapy. </l...
HIT Type 1 and 2
Warfarin <ul><li>Mechanism </li></ul><ul><li>I nhibits synthesis of vitamin K-dependent coagulation factors (factors II, V...
Warfarin (2) <ul><li>Reversal </li></ul><ul><li>Reversed with FFP or prothrombin complex concentrate </li></ul><ul><li>May...
GP IIb and GP IIIa Receptor Inhibitors <ul><li>Examples:  abciximab,  eptifibatide, tirofiban </li></ul><ul><li>Mechanism ...
ONCOLOGIC EMERGENCIES
Neutropenic Fever <ul><li>Definition </li></ul><ul><li>Single oral temperature of ≥38.3°C (101°F) </li></ul><ul><li>or sus...
<ul><li>Diagnosis </li></ul><ul><li>All neutropenic patients with fever should be managed as if they have a serious bacter...
<ul><li>Management </li></ul><ul><li>Admission, Start prophylactic empiric antibiotic therapy </li></ul><ul><ul><li>Monoth...
<ul><li>Complications </li></ul><ul><li>Untreated neutropenic fever associated with  20%  mortality rate compared to  <2% ...
Tumor Lysis Syndrome <ul><li>Definition </li></ul><ul><ul><li>Electrolyte abnormalities that result from the breakdown pro...
<ul><li>Symptoms and signs </li></ul><ul><li>Occurs most commonly within 1 to 5 days of initiating chemotherapy or radiati...
<ul><li>Diagnosis (constellation of the following metabolic disturbances) </li></ul><ul><li>Hyperuricemia (>7 or 8 mg/dL) ...
<ul><li>Diagnosis (constellation of the following metabolic disturbances) </li></ul><ul><li>Hyperphosphatemia </li></ul><u...
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A Review On Hematology and Oncology Emergencies

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Slides on the discussion points during Intensive Course for Final MMed (Emergency Medicine) 2010

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A Review On Hematology and Oncology Emergencies

  1. 1. Hematology Emergencies Intensive Course Final Year MMED Candidates 2009-2010 Chew Keng Sheng School of Medical Sciences UNIVERSITI SAINS MALAYSIA
  2. 2. Whole Blood <ul><li>Rarely used today (individual blood components provided separately) </li></ul><ul><li>Indications </li></ul><ul><ul><li>Autologous transfusion </li></ul></ul><ul><ul><li>Exchange transfusion (ie, sickle cell anemia) </li></ul></ul><ul><li>Comments </li></ul><ul><li>Risk of transfusion reaction is >2 times than with packed red blood cells (PRBCs) </li></ul><ul><li>Risk of allergic reaction is 1% </li></ul>
  3. 3. Packed Red Blood Cells <ul><li>Preparation </li></ul><ul><li>Plasma removed from whole blood and remaining RBC mass is washed </li></ul><ul><li>Washing RBCs removes leukocytes, platelets, proteins, and other antigenic components of whole blood </li></ul><ul><li>Type and cross-match </li></ul><ul><li>ABO blood group antigen system and Rhesus system </li></ul>
  4. 4. <ul><li>Production of anti-D antibody occurs in Rh– individuals who have exposure to small amounts of D antigen </li></ul><ul><li>A) Maternal-fetal mixing (Rh– mother and Rh+ fetus) </li></ul><ul><li>B) Anti-D immunoglobulin required in Rh– mothers with exposure to D antigen within 72 hours of exposure </li></ul>Packed Red Blood Cells (2)
  5. 5. <ul><li>Indications </li></ul><ul><li>Generally, transfusion is rarely indicated when Hb >10 g/dL and is almost always indicated in when Hb level < 6 g/dL </li></ul><ul><li>The determination of transfusion in patients whose Hb is 6-10 g/dL should be based on any ongoing indication of organ ischemia, the rate and magnitude of any potential or actual bleeding and the patient’s intravascular volume status. </li></ul>Packed Red Blood Cells (3)
  6. 6. <ul><li>Indications </li></ul><ul><li>Transfusion for Hb >6 g/dL in healthy nonsurgical patients is generally not indicated because oxygen delivery in healthy adults is maintained even with Hb as low as 6-7 g/dL. </li></ul><ul><li>Transfusion usually recommended prior to major surgery when hemoglobin levels are <10 g/dL </li></ul>Packed Red Blood Cells (4)
  7. 7. <ul><li>Indications </li></ul><ul><li>In acute hemorrhage, up to 40% of the blood volume in a bleeding, otherwise healthy young adult can be replaced with crystalloid without the need for red cell transfusion. </li></ul>Packed Red Blood Cells (5)
  8. 8. <ul><li>Comments </li></ul><ul><li>Each unit of PRBCs has approximate volume of 250 mL </li></ul><ul><li>In adults, 1 unit of PRBCs increases Hb level by ~1 g/dL and hematocrit by ~ 3% </li></ul><ul><li>In children, PRBCs increase the hematocrit by 1% for each mL/kg transfused </li></ul>Packed Red Blood Cells (6)
  9. 9. Fresh Frozen Plasma <ul><li>Frozen fluid product of centrifuged and separated whole blood </li></ul><ul><li>FFP is frozen at -18C or colder within 6-8h of collection </li></ul><ul><li>Contains normal plasma levels of stable clotting factors, albumin and immunoglobulin, but variably reduced levels of Factor V and Factor VIII </li></ul>
  10. 10. <ul><li>Before use, should be thawed in warm water which between 30°C to 37°C. </li></ul><ul><li>Higher temperatures will destroy clotting factors and proteins. </li></ul><ul><li>Once thawed, to be infused immediately (best within 6hr) or re-stored at 1-6C for up to 24 hours, which will be relabeled as Thawed Plasma, and to be used as a source of stable coagulation factors for up to 5 days </li></ul>Fresh Frozen Plasma (2)
  11. 11. <ul><li>Indications </li></ul><ul><li>Clotting factor deficiencies </li></ul><ul><ul><li>Hemophilia A </li></ul></ul><ul><ul><li>Hemophilia B </li></ul></ul><ul><ul><li>von Willebrand disease </li></ul></ul><ul><li>Cirrhosis (lack factors II, VII, IX, and X) </li></ul><ul><li>Massive blood transfusion – may transfuse 1 unit of FFP for every 5 to 6 units of PRBCs </li></ul><ul><li>Coagulopathy secondary to super-therapeutic warfarin </li></ul><ul><ul><li>Transfusion of 5 to 10 mL/kg of FFP will reverse the effects of supertherapeutic warfarin </li></ul></ul>Fresh Frozen Plasma (3)
  12. 12. <ul><li>Requires ABO-compatibility; but not crossmatched </li></ul><ul><li>Amount to transfuse: 3 to 10 mL/kg or as needed </li></ul><ul><li>Each unit of FFP has a volume of ~200 to 250 mL </li></ul><ul><li>Each unit of FFP increases coagulation factor levels by 2% to 3% </li></ul>Fresh Frozen Plasma (4)
  13. 13. Cryoprecipitate <ul><li>Cryoprecipitate prepared from precipitants of slowly thawed FFP between 1-6C. The cold insoluble precipitant then collected and refrozen within 1 hour. </li></ul><ul><li>Contains factor VIII, factor XIII, vWF, fibrinogen, and fibronectin </li></ul>
  14. 14. <ul><li>Indications </li></ul><ul><li>Hypofibrinogenemia (congenital, DIC, cancer, </li></ul><ul><li>Cirrhosis </li></ul><ul><li>Reversal of tissue plasminogen activator </li></ul><ul><li>Coagulopathy from massive transfusion </li></ul>Cryoprecipitate (2)
  15. 15. <ul><li>It is preferable to use cryoprecipitate that is ABO-compatible with the recipient’s red cells, but not crossmatched. </li></ul><ul><li>Infuse within 6 hours of thawing </li></ul><ul><li>Each bag of cryoprecipitate contains 10 to 25 mL of fluid </li></ul>Cryoprecipitate (3)
  16. 16. Platelets <ul><li>Obtained from centrifuged whole blood </li></ul><ul><li>Indications </li></ul><ul><li>Thrombocytopenia <10,000 cells/mm3 in asymptomatic patients </li></ul><ul><li>Thrombocytopenia <20,000 cells/mm3 with active hemorrhage </li></ul><ul><li>Thrombocytopenia <50,000 cells/mm3 undergoing invasive procedure </li></ul><ul><li>Dilutional thrombocytopenia (with massive blood transfusions) </li></ul>
  17. 17. <ul><li>Not indicated in diseases with ongoing consumption of platelets: ITP, TTP, untreated DIC & thrombocytopenia associated with septicaemia, until Rx has commenced or in cases of hypersplenism. </li></ul>Platelets (2)
  18. 18. <ul><li>Thienopyridine platelet ADP receptor inhibitors and direct glycoprotein IIb/IIIa inhibitors impair platelet function. </li></ul><ul><li>Platelets should not be transfused prophylactically without thrombocytopenia, but high dose therapeutic transfusion may be required for life threatening hemorrhage in patients on these drugs. </li></ul>Platelets (3)
  19. 19. <ul><li>Amount to transfuse: 1 unit per 10 kg body weight (6 to 10 units of platelets for the average adult) </li></ul><ul><li>Cross-matching is unnecessary, but all transfused platelets should be ABO and Rh compatible </li></ul><ul><li>1 unit increases the platelet count by 5000 to 10,000 cells/mm3 </li></ul>Platelets (4)
  20. 20. COMPLICATIONS OF TRANSFUSION
  21. 21. Massive Transfusion <ul><li>Definition </li></ul><ul><li>No strict definition but commonly referred as the replacement of entire body blood volume within 24 hours, or >10 units of PRBC transfusions within a few hours </li></ul>
  22. 22. <ul><li>Complications </li></ul><ul><li>Metabolic alkalosis and hypocalcemia secondary to citrated blood </li></ul><ul><li>Hyperkalemia or hypokalemia </li></ul><ul><li>Hypothermia </li></ul><ul><li>Dilutional coagulopathy </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Acute respiratory distress syndrome (ARDS) </li></ul>Massive Transfusion (2)
  23. 23. <ul><li>Administer via blood warmer (no microwave) </li></ul><ul><li>Calcium gluconate (if ECG changes occur) </li></ul>Massive Transfusion (3)
  24. 24. Hemolytic Crisis (Acute Transfusion Reaction) <ul><li>Most commonly caused by ABO incompatibility </li></ul><ul><li>May result in activation of coagulation cascade (DIC) </li></ul><ul><li>Symptoms and signs </li></ul><ul><ul><li>Headache, back pain, joint pain, anxiety, fever, tachycardia, hypotension, wheezing, pulmonary edema, and renal failure </li></ul></ul><ul><ul><li>Delayed reactions occur in extravascular space, most commonly spleen, liver, or bone marrow </li></ul></ul><ul><ul><li>Pink serum or urine </li></ul></ul>
  25. 25. <ul><li>Management </li></ul><ul><li>Stop transfusion </li></ul><ul><li>IV fluids </li></ul><ul><ul><li>Maintain urine output at 30 to 100 cc/h </li></ul></ul>Hemolytic Crisis (Acute Transfusion Reaction) (2)
  26. 26. Other Complications <ul><li>Febrile transfusion reaction </li></ul><ul><li>Etiology: recipient antibody response to donor leukocytes, and release of cytokines that are produced in storage </li></ul><ul><li>Difficult to differentiate from hemolytic reaction </li></ul><ul><li>Management: stop transfusion until hemolytic reaction excluded </li></ul>
  27. 27. SPECIFIC DRUG THERAPIES AFFECTING HEMOSTASIS
  28. 28. Aspirin <ul><li>Mechanism </li></ul><ul><li>Irreversibly blocks conversion of arachidonic acid into thromboxane A2 (platelet aggregation agent) by inhibiting cyclooxygenase (COX) </li></ul><ul><li>Effect on platelets irreversible, lasts for entire platelet life span (~7 to 10 days) </li></ul>
  29. 29. <ul><li>Mechanism </li></ul><ul><li>Irreversibly blocks ADP receptor on platelets </li></ul><ul><li>Deforms the fibrinogen receptor on platelet, that renders the platelet unable to aggregate via the GP IIb and GP IIIa pathway </li></ul>Clopidogrel and Ticlopidine
  30. 30. Clopidogrel and Ticlopidine (2) <ul><li>Complications </li></ul><ul><li>Dyspepsia, rash, diarrhea </li></ul><ul><li>Ticlopidine is associated with hematologic effects </li></ul><ul><ul><li>Neutropenia </li></ul></ul><ul><ul><li>ITP </li></ul></ul><ul><ul><li>TTP </li></ul></ul><ul><li>Reversal </li></ul><ul><li>Platelet transfusion </li></ul>
  31. 31. Heparin <ul><li>Mechanism </li></ul><ul><li>Reduced thrombin and fibrin formation by binding and activating antithrombin III (potentiate activities of antithrombin III) </li></ul><ul><li>Unfractionated Heparin </li></ul><ul><ul><ul><li>Derived from bovine lung tissue </li></ul></ul></ul><ul><ul><ul><li>Inhibits factors Xa and IIa in roughly equal proportions </li></ul></ul></ul><ul><ul><ul><li>Requires frequent monitoring of aPTT (target generally between 1.5 and 2.5 times baseline) </li></ul></ul></ul>
  32. 32. Heparin <ul><li>Low Molecular Weight Heparin </li></ul><ul><li>Derived from porcine intestinal mucosa </li></ul><ul><li>Higher ratio of antifactor Xa to antifactor Iia activity than unfractionated heparin </li></ul><ul><li>Activity onset within 3 to 5 hours </li></ul>
  33. 33. <ul><li>Complications </li></ul><ul><li>HIT </li></ul><ul><li>Reversal </li></ul><ul><li>Reversed with protamine sulfate (derived from fish sperm; beware hypotension and anaphylaxis) </li></ul>Heparin
  34. 34. Heparin Induced Thrombocytoenia <ul><li>HIT is a syndrome of antibody-mediated thrombocytopenia that paradoxically is often associated with thrombosis [thrombotic risk is more than 30 times that in control populations] </li></ul>
  35. 35. <ul><li>Platelet factor 4, a small peptide stored within the alpha granules of platelets, binds to heparin and is released into the blood during treatment with heparin. </li></ul><ul><li>These complexes then activate platelets [contributes to the thrombotic complications of heparin-induced thrombocytopenia] </li></ul>Heparin Induced Thrombocytoenia
  36. 36. <ul><li>Typically, HIT begins with the appearance of thrombocytopenia about a week after the start of heparin therapy. </li></ul><ul><li>Patients who have HIT should not be treated with low-molecular-weight heparins, since these have high cross-reactivity with circulating PF4–heparin antibodies. </li></ul>Heparin Induced Thrombocytoenia
  37. 37. HIT Type 1 and 2
  38. 38. Warfarin <ul><li>Mechanism </li></ul><ul><li>I nhibits synthesis of vitamin K-dependent coagulation factors (factors II, VII, IX, and X) </li></ul><ul><li>Also inhibits the anticoagulants protein C and protein S </li></ul><ul><li>Ingredient in many rodenticides or “superwarfarins” </li></ul>
  39. 39. Warfarin (2) <ul><li>Reversal </li></ul><ul><li>Reversed with FFP or prothrombin complex concentrate </li></ul><ul><li>May be reversed with vitamin K </li></ul><ul><ul><li>Oral route preferred, unless rapid reversal required (may administer intravenously) </li></ul></ul><ul><ul><li>Delay (up to 24 hours) in onset </li></ul></ul>
  40. 40. GP IIb and GP IIIa Receptor Inhibitors <ul><li>Examples: abciximab, eptifibatide, tirofiban </li></ul><ul><li>Mechanism </li></ul><ul><ul><ul><li>Inhibit platelet aggregation and activation by preventing activated fibrinogen binding to GP IIb/IIIa receptors </li></ul></ul></ul><ul><li>Effects typically last 24 to 48 hours </li></ul><ul><li>Complications </li></ul><ul><ul><ul><li>Thrombocytopenia, Hemorrhage </li></ul></ul></ul><ul><li>Reversal </li></ul><ul><ul><ul><li>Platelet transfusion, Desmopressin (may be beneficial) </li></ul></ul></ul>
  41. 41. ONCOLOGIC EMERGENCIES
  42. 42. Neutropenic Fever <ul><li>Definition </li></ul><ul><li>Single oral temperature of ≥38.3°C (101°F) </li></ul><ul><li>or sustained temperature elevation of 38°C (100.4°F) for 1 hour and </li></ul><ul><li>Polymorphonuclear leukocyte count <500 to 1000 cells/mm3 </li></ul>
  43. 43. <ul><li>Diagnosis </li></ul><ul><li>All neutropenic patients with fever should be managed as if they have a serious bacterial infection </li></ul><ul><li>Cultures (blood, urine, and other areas as indicated) </li></ul><ul><li>Radiographic imaging as indicated (eg, chest radiographs, CT sinuses, etc.) </li></ul>Neutropenic Fever (2)
  44. 44. <ul><li>Management </li></ul><ul><li>Admission, Start prophylactic empiric antibiotic therapy </li></ul><ul><ul><li>Monotherapy </li></ul></ul><ul><ul><ul><ul><li>Imipenem and cilastatin </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Ceftazidime </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Cefipime </li></ul></ul></ul></ul><ul><ul><li>Combination therapy </li></ul></ul><ul><ul><ul><li>Ceftazidime or cefepime or imipenem/ cilastatin and vancomycin </li></ul></ul></ul><ul><ul><ul><ul><li>For suspected MRSA (recent hospitalizations) or with indwelling catheter </li></ul></ul></ul></ul>Neutropenic Fever (3)
  45. 45. <ul><li>Complications </li></ul><ul><li>Untreated neutropenic fever associated with 20% mortality rate compared to <2% if treated promptly </li></ul><ul><ul><li>Infections are the number one cause of cancer death </li></ul></ul><ul><ul><li>Remember: Although fever may result from the malignancy itself, 55% to 70% of fevers in this patient population will have an infectious etiology </li></ul></ul>Neutropenic Fever
  46. 46. Tumor Lysis Syndrome <ul><li>Definition </li></ul><ul><ul><li>Electrolyte abnormalities that result from the breakdown products of dying cancer cells </li></ul></ul><ul><li>Etiology </li></ul><ul><ul><li>Typically following chemotherapy of Leukemias and lymphomas (especially Burkitt lymphoma) </li></ul></ul><ul><ul><li>Small cell lung carcinoma </li></ul></ul><ul><ul><li>Following steroid administrations </li></ul></ul>
  47. 47. <ul><li>Symptoms and signs </li></ul><ul><li>Occurs most commonly within 1 to 5 days of initiating chemotherapy or radiation therapy for rapidly growing tumors </li></ul><ul><li>Reflect the presenting electrolyte abnormality </li></ul>Tumor Lysis Syndrome (2)
  48. 48. <ul><li>Diagnosis (constellation of the following metabolic disturbances) </li></ul><ul><li>Hyperuricemia (>7 or 8 mg/dL) </li></ul><ul><ul><li>Secondary to DNA degradation </li></ul></ul><ul><ul><li>Acute renal failure </li></ul></ul><ul><li>Hyperkalemia </li></ul><ul><ul><li>Susceptible to arrhythmias </li></ul></ul><ul><ul><li>Exacerbated by renal failure </li></ul></ul>Tumor Lysis Syndrome
  49. 49. <ul><li>Diagnosis (constellation of the following metabolic disturbances) </li></ul><ul><li>Hyperphosphatemia </li></ul><ul><ul><li>Secondary to protein degradation </li></ul></ul><ul><ul><li>Precipitation with calcium in heart and kidney </li></ul></ul><ul><li>Hypocalcemia </li></ul><ul><ul><li>Secondary to hyperphosphatemia </li></ul></ul><ul><ul><li>Muscle weakness and cramps </li></ul></ul>Tumor Lysis Syndrome
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